Revista Brasileira de Cirurgia Cardiovascular 28.1 - 2013 by Revista Brasileira de Cirurgia Cardiovascular

28.1 JANEIRO/MARÇO 2013

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR | BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

VOL. 28 Nº 1 JANEIRO/MARÇO 2013

RBCCV na era da tecnologia

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28/01/2013 16:48:57

RBCCV REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

EDITOR/EDITOR Prof. Dr. Domingo M. Braile - PhD São José do Rio Preto - SP - Brasil domingo@braile.com.br

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

EDITORES ANTERIORES/FORMER EDITORS • Prof. Dr. Adib D. Jatene PhD - São Paulo (BRA) [1986-1996] • Prof. Dr. Fábio B. Jatene PhD - São Paulo (BRA) [1996-2002]

EDITOR EXECUTIVO EXECUTIVE EDITOR Ricardo Brandau Pós-graduado em Jornalismo Científico - S. José do Rio Preto (BRA) brandau@sbccv.org.br

ASSESSORA EDITORIAL/EDITORIAL ASSISTANT Rosangela Monteiro PhD - São Paulo (BRA) rosangela.monteiro@incor.usp.br

EDITORES ASSOCIADOS/ASSOCIATE EDITORS • Antônio Sérgio Martins • Gilberto Venossi Barbosa • José Dario Frota Filho • José Teles de Mendonça • Luciano Cabral Albuquerque • Luis Alberto Oliveira Dallan • Luiz Felipe Pinho Moreira

Botucatu (BRA) Porto Alegre (BRA) Porto Alegre (BRA) Aracaju (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA)

• Manuel Antunes • Mario Osvaldo P. Vrandecic • Michel Pompeu B. Oliveira Sá • Paulo Roberto Slud Brofman • Ricardo C. Lima • Ulisses A. Croti • Walter José Gomes

Coimbra (POR) Belo Horizonte (BRA) Recife (BRA) Curitiba (BRA) Recife (BRA) S.J. Rio Preto (BRA) São Paulo (BRA)

EDITOR DE ESTATÍSTICA/STATISTICS EDITOR • Orlando Petrucci Jr.

Campinas (BRA)

CONSELHO EDITORIAL/EDITORIAL BOARD • Adib D. Jatene • Adolfo Leirner • Adolfo Saadia • Alan Menkis • Alexandre V. Brick • Antônio Carlos G. Penna Jr. • Bayard Gontijo Filho • Borut Gersak • Carlos Roberto Moraes • Christian Schreiber • Cláudio Azevedo Salles • Djair Brindeiro Filho • Eduardo Keller Saadi • Eduardo Sérgio Bastos • Enio Buffolo • Fábio B. Jatene • Fernando Antônio Lucchese • Gianni D. Angelini • Gilles D. Dreyfus • Ivo A. Nesralla • Jarbas J. Dinkhuysen • José Antônio F. Ramires • José Ernesto Succi • José Pedro da Silva • Joseph A. Dearani

São Paulo (BRA) São Paulo (BRA) Buenos Aires (ARG) Winnipeg (CAN) Brasília (BRA) Marília (BRA) Belo Horizonte (BRA) Ljubljana (SLO) Recife (BRA) Munique (GER) Belo Horizonte (BRA) Recife (BRA) Porto Alegre (BRA) Rio de Janeiro (BRA) São Paulo (BRA) São Paulo (BRA) Porto Alegre (BRA) Bristol (UK) Harefield (UK) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Rochester (USA)

VERSÃO PARA O INGLÊS/ENGLISH VERSION • Alexandre Werneck • Fernando Pires Buosi • Marcelo Almeida • Pablo Sebastian Maluf

• Joseph S. Coselli • Luiz Carlos Bento de Souza • Luiz Fernando Kubrusly • Mauro Paes Leme de Sá • Miguel Barbero Marcial • Milton Ary Meier • Nilzo A. Mendes Ribeiro • Noedir A. G. Stolf • Olivio Souza Neto • Otoni Moreira Gomes • Pablo M. A. Pomerantzeff • Paulo Manuel Pêgo Fernandes • Paulo P. Paulista • Paulo Roberto B. Évora • Pirooz Eghtesady • Protásio Lemos da Luz • Reinaldo Wilson Vieira • Renato Abdala Karam Kalil • Renato Samy Assad • Roberto Costa • Rodolfo Neirotti • Rui M. S. Almeida • Sérgio Almeida de Oliveira • Tomas A. Salerno

Houston (USA) São Paulo (BRA) Curitiba (BRA) Rio de Janeiro (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Salvador (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Belo Horizonte (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Ribeirão Preto (BRA) Cincinatti (USA) São Paulo (BRA) Campinas (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) Cambridge (USA) Cascavel (BRA) São Paulo (BRA) Miami (USA)

ÓRGÃO OFICIAL DA SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR DESDE 1986 OFFICIAL ORGAN OF THE BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SINCE 1986

ENDEREÇO/ADDRESS

Sociedade Brasileira de Cirurgia Cardiovascular

Rua Beira Rio, 45 • 7º andar - Cj. 72 • Vila Olímpia • Fone: 11 3849-0341. Fax: 11 5096-0079. Cep: 04548-050 • São Paulo, SP, Brasil E-mail RBCCV: revista@sbccv.org.br • E-mail SBCCV: sbccv@sbccv.org.br • Site SBCCV: www.sbccv.org.br • Sites RBCCV: www.scielo.br/rbccv / www.rbccv.org.br (também para submissão de artigos)

Publicação trimestral/Quarterly publication Edição Impressa - Tiragem: 250 exemplares (*)

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR (Sociedade Brasileira de Cirurgia Cardiovascular) São Paulo, SP - Brasil. v. 119861986, 1: 1,2 1987, 2: 1,2,3 1988, 3: 1,2,3 1989, 4: 1,2,3 1990, 5: 1,2,3 1991, 6: 1,2,3 1992, 7: 1,2,3,4 1993, 8: 1,2,3,4 1994, 9: 1,2,3,4

1995, 10: 1,2,3,4 1996, 11: 1,2,3,4 1997, 12: 1,2,3,4 1998, 13: 1,2,3,4 1999, 14: 1,2,3,4 2000, 15: 1,2,3,4 2001, 16: 1,2,3,4 2002, 17: 1,2,3,4 2003, 18: 1,2,3,4

2004, 19: 1,2,3,4 2005, 20: 1,2,3,4 2006, 21: 1 [supl] 2006, 21: 1,2,3,4 2007, 22: 1 [supl] 2007, 22: 1,2,3,4 2008, 23: 1 [supl] 2008, 23: 1,2,3,4 2009, 24: 1 [supl]

2009, 24: 1,2,3,4 2009, 24: 2 [supl] 2010, 25: 1,2,3,4 2010, 25: 1 [supl] 2011, 26: 1,2,3,4 2011, 26: 1 [supl] 2012, 27: 1,2,3,4 2012, 27: 1 [supl] 2013, 28: 1

ISSN 1678-9741 - Publicação online ISSN 0102-7638 - Publicação impressa RBCCV 44205

CDD 617.4105 NLM18 WG 168

(*) ASSOCIAÇÃO PAULISTA DE BIBLIOTECÁRIOS. Grupo de Bibliotecários Biomédicos. Normas para catalogação de publicações seriadas nas bibliotecas especializadas. São Paulo, Ed. Polígono, 1972

INDEXADA EM • Thomson Scientific (ISI) http://science.thomsonreuters.com • PubMed/Medline www.ncbi.nlm.nih.gov/sites/entrez • SciELO - Scientific Library Online www.scielo.br • Scopus www.info.scopus.com • LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde. www.bireme.org

• ADSAUDE - Sistema Especializado de Informação em Administração de Saúde www.bibcir.fsp.usp.br/html/p/pesquisa_em_ bases_de_dados/programa_rede_adsaude • Index Copernicus www.indexcopernicus.com • Google scholar http://scholar.google.com.br/scholar • EBSCO www2.ebsco.com/pt-br

• LATINDEX -Sistema Regional de Información en Línea para Revistas Cientificas de America Latina, el Caribe, España y Portugal www.latindex.uam.mx

Distribuída gratuitamente aos sócios da Sociedade Brasileira de Cirurgia Cardiovascular

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY DEPARTAMENTO DE CIRURGIA DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA DEPARTMENT OF SURGERY OF THE BRAZILIAN SOCIETY OF CARDIOLOGY

“Valorizando o profissional em prol do paciente” DIRETORIA 2011 - 2013 Presidente: Vice-Presidente: Secretário Geral: Tesoureiro: Diretor Científico:

Walter José Gomes (SP) João Alberto Roso (RS) Marcelo Matos Cascudo (RN) Eduardo Augusto Victor Rocha (MG) Fábio Biscegli Jatene (SP)

Conselho Deliberativo:

Bruno Botelho Pinheiro (GO) Henrique Barsanulfo Furtado (TO) José Glauco Lobo Filho (CE) Rui M.S. Almeida (PR) Henrique Murad (RJ)

Editor da Revista: Editor do Site: Editores do Jornal:

Domingo Marcolino Braile (SP) Vinicius José da Silva Nina (MA) Walter José Gomes (SP) Fabricio Gaburro Teixeira (ES) Josalmir José Melo do Amaral (RN) Luciana da Fonseca (SP)

Presidentes das Regionais Afiliadas Norte-nordeste: Rio de Janeiro: São Paulo: Minas Gerais: Centro-Oeste: Rio Grande do Sul: Paraná: Santa Catarina:

Maurílio Onofre Deininger (PB) Marcelo Sávio da Silva Martins Carlos Manuel de Almeida Brandão AntonioAugusto Miana Luiz Carlos Schimin (DF) Marcela da Cunha Sales Rodrigo Mussi Milani Lourival Bonatelli Filho

Departamentos DCCVPED: DECAM: DECA: DECEN: DEPEX: DECARDIO:

Marcelo B. Jatene (SP) Alfredo Inácio Fiorelli (SP) Luiz Paulo Rangel Gomes da Silva (PA) Rui M. S. Almeida (PR) Melchior Luiz Lima (ES) Miguel Angel Maluf (SP)

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

ISSN 1678-9741 - Publicação online ISSN 0102-7638 - Publicação impressa RBCCV 44205

Fator de Impacto: 1,239

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brasil) jan/mar - 2013;28(1) 001-164

SUMÁRIO/CONTENTS

EDITORIAIS/EDITORIALS

A Medicina e a Fé Domingo M. Braile...............................................................................................................................................................................I

Avaliação cardíaca fetal por meio da ultrassonografia 3D/4D (STIC): qual a sua real aplicabilidade no diagnóstico das doenças cardíacas congênitas? Edward Araujo Júnior, Liliam Cristine Rolo, Luciano Marcondes Machado Nardozza, Antonio Fernandes Moron....................... III

ARTIGOS ORIGINAIS/ORIGINAL ARTICLES 1436 Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery Impacto na mortalidade precoce e tardia após transfusão de hemácias em cirurgia de revascularização miocárdica Antonio Alceu dos Santos, Alexandre Gonçalves Sousa, Hugo Oliveira de Souza Thomé, Roberta Longo Machado, Raquel Ferrari Piotto.................................................................................................................................................................................................... 1 1437 Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta Risk factors for pre, intra, and postoperative hospital mortality in patients undergoing aortic surgery Mário Issa, Álvaro Avezum, Daniel Chagas Dantas, Antonio Flávio Sanches de Almeida, Luiz Carlos Bento de Souza, Amanda Guerra de Moraes Rego Sousa........................................................................................................................................................... 10 1438 Impact of coronary artery bypass grafting in elderly patients Impacto da cirurgia de revascularização do miocárdio em pacientes idosos Priscila Aikawa, Angélica Rossi Sartori Cintra, Cleber Aparecido Leite, Ricardo Henrique Marques, Claudio Tafarel Mackmillan da Silva, Max dos Santos Affonso, Felipe da Silva Paulitsch, Evandro Augusto Oss....................................................................... 22 1439 Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center Tratamento cirúrgico para endocardite infecciosa e mortalidade hospitalar em centro único brasileiro Maurício Nassau Machado, Marcelo Arruda Nakazone, Jamil Ali Murad-Júnior, Lilia Nigro Maia................................................ 29 1440 Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino Surgical repair of chordae tendineae rupture after degenerative valvular regurgitation using standardized bovine pericardium Francisco Gregori Júnior, Moacir Fernandes de Godoy, Celso Otaviano Cordeiro, Alexandre Noboru Murakami, Rogerio Teruya, Sergio Shigueru Hayashi, Wallace Kohata de Aquino, Luiz Eduardo Gallina................................................................................... 36 1441 Correlação entre a qualidade de vida, classe funcional e idade em portadores de marca-passo cardíaco Correlation between quality of life, functional class and age in patients with cardiac pacemaker Juliana Bassalobre Carvalho Borges, Rubens Tofano de Barros, Sebastião Marcos Ribeiro de Carvalho, Marcos Augusto de Moraes Silva.................................................................................................................................................................................................... 47

1442 Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos Yong Cao, Lie Wang, Hong Chen, Zhiqian Lv.................................................................................................................................. 54 1443 Coping strategies after heart transplantation: psychological implications Estratégias de enfrentamento pós-transplante cardíaco: implicações psicológicas Paula Moraes Pfeifer, Patricia Pereira Ruschel, Solange Bordignon................................................................................................. 61 1444 Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization Análise da função ventricular esquerda de pacientes com insuficiência cardíaca submetidos à ressincronização cardíaca Ricardo Adala Benfatti, Felipe Matsushita Manzano, José Carlos Dorsa Vieira Pontes, Amaury Edgardo Mont’Serrat Ávila Souza Dias, João Jackson Duarte, Guilherme Viotto Rodrigues da Silva, Jandir Ferreira Gomes Junior, Neimar Gardenal...................... 69 1445 O uso de recuperador de sangue em cirurgia cardíaca com circulação extracorpórea The use of cell saver system in cardiac surgery with cardiopulmonary bypass Rui M. S. Almeida, Luciano Leitão................................................................................................................................................... 76

ARTIGOS DE REVISÃO/REVIEW ARTICLES 1446 Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients Desfechos de 5 anos do tratamento de lesões de TCE por stents farmacológicos versus CRM: meta-análise e meta-regressão de 2914 pacientes Michel Pompeu Barros de Oliveira Sá, Paulo Ernando Ferraz, Rodrigo Renda Escobar, Eliobas Oliveira Nunes, Alexandre Magno Macário Nunes Soares, Frederico Browne Correia de Araújo e Sá, Frederico Pires Vasconcelos, Ricardo Carvalho Lima............ 83 1447 Criss-cross heart: report of two cases, anatomic and surgical description and literature review Coração entrecruzado (criss-cross heart): relato de dois casos, descrição anatomocirúrgica e revisão de literatura Ítalo Martins de Oliveira, Vera Demarchi Aiello, Marcela Maria Aguiar Mindêllo, Yasmin de Oliveira Martins, Valdester Cavalcante Pinto Jr................................................................................................................................................................................................ 93

ARTIGOS ESPECIAIS/SPECIAL ARTICLES 1448 Religion, spirituality and cardiovascular disease: research, clinical implications, and opportunities in Brazil Religião, espiritualidade e doença cardiovascular: pesquisa, implicações clínicas e oportunidades no Brasil Fernando A. Lucchese, Harold G. Koenig....................................................................................................................................... 103 1449 Cardiac surgery: the infinite quest. Part II Cirurgia cardiaca: a busca infinita. Parte II Rodolfo A. Neirotti........................................................................................................................................................................... 129 1450 Revascularização miocárdica no século XXI Myocardial revascularization in the XXI century Luís Alberto Oliveira Dallan, Fabio Biscegli Jatene........................................................................................................................ 137 COMUNICAÇÃO BREVE/SHORT COMMUNICATION 1451 Correção endovascular de dissecção de aorta ascendente Endovascular repair of ascending aortic dissection José Carlos Dorsa Vieira Pontes, Amaury Mont'Serrat Ávila Souza Dias, João Jackson Duarte, Ricardo Adala Benfatti, Neimar Gardenal........................................................................................................................................................................................... 145

DIVULGAÇÃO CIENTÍFICA/SCIENTIFIC 1452 Erros em artigos científicos brasileiros são mais conceituais do que de expressão Mistakes in Brazilian papers are more from concepts than of expression Elton Alisson/Agência Fapesp......................................................................................................................................................... 148

CARTAS/LETTERS 1453 Cartas ao Editor Letters to the Editor ......................................................................................................................................................................... 150

Errata ............................................................................................................................................................................................. 155 Revisores RBCCV 28.1 ................................................................................................................................................................. 156 Normas para publicação na Revista Brasileira de Cirurgia Cardiovascular .......................................................................... 157 Calendário de Eventos/Meetings Calendar ................................................................................................................................. 161

Impresso no Brasil Printed in Brazil

Projeto Gráfico: Heber Janes Ferreira Impressão e acabamento:

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

Editorial

A Medicina e a Fé Domingo M. Braile* DOI: 10.5935/1678-9741.20130001

o contrário do que muitos ainda imaginam, a ciência, em sua eterna busca de compreender e explicar o mundo de forma racional, com fatos que precisam ser comprovados e demonstrados, e a Fé, cuja definição de Paulo (São Paulo para os que praticam o catolicismo), na sua epístola aos Hebreus é: “...o firme fundamento das coisas que se esperam, e a prova das coisas que se não veem”, não são incompatíveis. Nas palestras e aulas para as quais tenho a honra de ser convidado, exponho aos que me dão o prazer de sua audiência que, nas últimas décadas, vários estudos têm demonstrado que pacientes que têm algum tipo de fé, mesmo que não necessariamente ligada a uma doutrina religiosa, costumam ter mais chances de cura do que os materialistas. Entre as pesquisas científicas realizadas, um estudo prospectivo de 6 anos com 557 idosos, conduzido por Lutgendorf et at. [1], em 2004, apontou que, entre aqueles que frequentavam serviços religiosos, o risco relativo de morte reduzia-se 78% e os níveis de interleucina-6 eram 66% menores durante o período de seguimento.

para o paciente. O entendimento maior das necessidades do paciente, não apenas físicas, mas também espirituais, é fator primordial para que o tratamento tenha condições de ser mais eficaz e, também, se encaixa dentro da “humanização” da Medicina, um conceito tão caro e que ainda resiste, apesar de um mundo cada vez mais corrido e impessoal.

Artigo dos Drs. Fernando Lucchese e Harold Koenig (pág. 103)

Também não posso deixar de destacar a bem embasada retrospectiva sobre a revascularização do miocárdio, escrita pelos Drs. Luis Dallan e Fabio Jatene. Em um texto rico em detalhes, eles narram desde os primórdios até as perspectivas dessa hoje consagrada técnica e que deve ser de conhecimento de todos que lidam com a cirurgia cardíaca.

Os cirurgiões cardiovasculares, que lidam com pacientes em situações-limite, também devem acompanhar com interesse as pesquisas que abordam esse tema. Nesse sentido, a RBCCV/BJCVS (Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery) publica, nesta edição, um artigo dos Drs. Fernando Lucchese e Harold Koenig, com título “Religion, spirituality and cardiovascular disease: research, clinical implications, and opportunities in Brazil”. O texto faz uma revisão das pesquisas sobre a relação entre religião, espiritualidade e doença cardiovascular, discute mecanismos que ajudam a explicar as associações relatadas, examina as implicações clínicas desses achados e aborda a necessidade de futuras pesquisas no Brasil sobre esse tema. Mesmo com todos os obstáculos, como o tempo curto e condições de trabalho aquém das ideais, entre outros, nós, médicos, temos o compromisso de procurar o melhor

Segunda parte do ensaio do Dr. Rodolfo Neirotti (pág. 129) Ainda, nesta edição, publicamos a segunda das três partes do ensaio do Dr. Rodolfo Neirotti, denominado “Cardiac Surgery: the infinite quest”. O tópico enfatiza como a cirurgia cardiovascular pode aprender com lições de outros sistemas complexos que identificaram soluções para impasses intrincados, e que a especialidade deve estar sempre aberta às inovações. Artigo de revisão sobre cirurgia das coronárias do Dr. Luis Dallan e Dr. Fábio Jatene (pág. 137)

40º Congresso da Sociedade Brasileira de Cirurgia Cardiovascular Uma oportunidade que teremos para conversar e nos aprofundar sobre esses temas será no 40º Congresso da Sociedade Brasileira de Cirurgia Cardiovascular (SBCCV), que acontecerá no período de 18 a 20 de abril, no Costão do Santinho, em Florianópolis, SC, local que recebeu o evento em 2007. Também haverá a presença de profissionais de áreas afins, como Perfusão, Enfermagem e Fisioterapia, além dos acadêmicos. Mantendo a tradição dos últimos anos, teremos a I

presença de convidados internacionais que, com seu conhecimento e expertise, vão mostrar as inovações e perspectivas da cirurgia cardíaca internacional. Haverá, como sempre, várias atividades de grande interesse, com destaque para o “Hands On”, que a cada ano se aprimora e, por meio de treinamento prático do implante de novas órteses e próteses possibilita aos cirurgiões atualizar seus conhecimentos dentro do que há de mais novo no estado da arte da cirurgia cardíaca, sempre no intuito de proporcionar maiores benefícios aos pacientes. Toda essa gama de atrações só foi possível graças ao empenho de todos os sócios e da atual Diretoria da Sociedade Brasileira de Cirurgia Cardiovascular (SBCCV), presidida pelo Dr. Walter Gomes, com apoio dos demais membros. Também não há como deixar de citar o trabalho incessante da Comissão Organizadora, liderada pelo Dr. Lourival Bonatelli Filho, ladeado pelo Dr. Milton de Miranda Santoro, Dr. Renato Bastos Pope e Dr. Ricardo José Choma, a fim de que os participantes possam usufruir das atrações e atividades da melhor maneira possível. Reunião Corpo Editorial da RBCCV com os Editores Associados e Membros do Conselho Editorial No dia 18 de abril, das 11h às 12h, na Sala Faial I e II, ocorrerá a já tradicional reunião do Corpo Editorial da RBCCV com os Editores Associados e membros do Conselho Editorial também aberta a todos os sócios que desejem participar. Teremos a oportunidade de debater as perspectivas da Revista, que foi indexada na base de dados EBSCO e está finalizando o processo para a entrada no PUBMED Central. A presença nas novas mídias e a divulgação por meio das redes sociais, bem como meios de aumentar o Fator de Impacto, atualmente de 1,239, também serão temas de discussão. Artigo publicado na RBCCV tem 100 citações no Google Acadêmico (pág. 153) Temos o prazer de informar o trabalho “Noções básicas

de variabilidade da frequência cardíaca e sua aplicabilidade clínica”, publicado na RBCCV 24.2, atingiu a marca de 100 citações. Parabenizamos aos autores Luiz Carlos Marques Vanderlei, Carlos Marcelo Pastre, Rosângela Akemi Hoshi, Tatiana Dias de Carvalho e Moacir Fernandes de Godoy pela conquista. Fatos como este nos incentivam a continuar nosso empenho a fim de que a RBCCV/BJCVS se consolide como um dos mais importantes periódicos da cirurgia cardiovascular em todo o mundo. Os artigos disponíveis para os testes pelo sistema de Educação Médica Continuada (EMC), nesta edição, são os seguintes: "Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery" (pág. 1), "Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center" (pág. 29), "Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino" (pág. 36) e "Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and meta-regression of 2914 patients" (pág. 83). Recebam meu abraço,

Domingo Braile Editor-Chefe - RBCCV/BJCVS

REFERÊNCIA 1. Lutgendorf SK, Russell D, Ullrich P, Harris TB, Wallace R. Religious participation, interleukin-6, and mortality in older adults. Health Psychol. 2004;23(5):465-75.

Editorial

Avaliação cardíaca fetal por meio da ultrassonografia 3D/4D (STIC): qual é sua real aplicabilidade no diagnóstico das doenças cardíacas congênitas? Edward Araujo Júnior1, Liliam Cristine Rolo2, Luciano Marcondes Machado Nardozza3, Antonio Fernandes Moron4 DOI: 10.5935/1678-9741.20130002

As doenças cardíacas congênitas (DCC) são as malformações maiores mais frequentes ao nascimento [1], com prevalência que varia de 0,6% a 5% dos recémnascidos vivos [2]. Apesar de grandes esforços e avanço tecnológico da ecocardiografia bidimensional (2D) nas duas décadas passadas, a acurácia na detecção de DCC no pré-natal está entre 31% e 96% [3]. Em 2003, com o desenvolvimento do Spatio-Temporal Image Correlation (STIC), iniciou-se a utilização da ultrassonografia de terceira e quarta dimensões (3D/4D) na avaliação cardíaca fetal [4]. O STIC é um software que permite a aquisição volumétrica do coração fetal com suas conexões vasculares, cujas imagens podem ser avaliadas tanto no modo multiplanar quanto no renderizado ou de superfície, de forma estática ou em movimento (4D), por meio de uma sequência de cineloop, que simula um ciclo cardíaco completo [4]. Esse software oferece uma novidade inexistente na ultrassonografia 2D, que é o armazenamento do volume cardíaco para uma análise off-line, ou seja, na ausência da paciente. Dessa forma, a avaliação detalhada da anatomia e do funcionamento cardíaco fetal é possível sem haver a necessidade de causar maior desconforto à gestante, situação relativamente frequente diante de

estudos ultrassonográficos mais prolongados. Além disso, o armazenamento permite o envio dos volumes para centros especializados por meio de um link de internet, fortalecendo a telemedicina e potencializando o melhor rastreamento durante o pré-natal [5]. Já existem padronizações para o armazenamento dos volumes obtidos, de forma que o examinador responsável pela análise off-line tenha o real conhecimento da posição das câmaras cardíacas com relação ao eixo fetal (lados direito e esquerdo), para avaliar inclusive a presença de possíveis isomerismos cardíacos. Por isso, sempre que o feto estiver em apresentação cefálica, deve-se considerar que o lado cardíaco corresponde ao lado fetal, diferentemente dos fetos pélvicos, cujos lados são opostos [6]. A escala de cinzas e o Doppler colorido são aplicações também presentes no STIC, utilizadas para melhorar a avaliação das vias de saída dos ventrículos, dos arcos aórtico e ductal, além de auxiliar na localização dos defeitos septais [7]. A tecnologia 3D permitiu o desenvolvimento de novas técnicas conhecidas como inversion mode (técnica de análise de estruturas líquidas que inverte os voxels da escala de cinzas, ou seja, estruturas anecoicas, como câmaras cardíacas, lúmen de vasos, estômago, bexiga e

1. Professor Adjunto da Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil – Autor principal. 2. Doutor em Ciências do Departamento de Obstetrícia, UNIFESP, São Paulo, SP, Brasil – Contribuição na redação. 3. Professor Adjunto do Departamento de Obstetrícia, São Paulo, SP, Brasil – Revisão do artigo. 4. Professor Titular do Departamento de Obstetrícia, UNIFESP, São Paulo, SP, Brasil – Revisão do artigo.

Endereço para correspondência: Setor de Cardiologia Fetal, Departamento de Obstetrícia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil. Edward Araujo Júnior Rua Carlos Weber, 956 apto. 113 – Visage – Alto da Lapa – São Paulo, SP, Brasil – CEP: 05303-000 E-mail: araujojred@terra.com.br Artigo recebido em 22 de janeiro de 2013 Artigo aprovado em 28 de janeiro de 2013

III

Abreviaturas, acrônimos e símbolos 2D 3D 4D DCC STIC TUI

Bidimensional Terceira dimensão Quarta dimensão Doenças cardíacas congênitas Spatio-Temporal Image Correlation Tomographic Ultrasound Imaging

pelve renal, com a inversão de modo se tornam ecogênicas, ao passo que estruturas normalmente ecogênicas, como os ossos, se tornam anecoicas) [8] (Figura 1) e o B-flow imaging (técnica que melhora os sinais fracos refletidos do sangue e suprime os sinais fortes das estruturas ao redor) [9]. O inversion mode permite a reconstrução de câmaras cardíacas, arcos aórtico e ductal, além de anomalias de conexões venosas [8]. O B-flow imaging apresenta alta sensibilidade e ângulo independência, sendo potencialmente vantajoso em relação ao Doppler colorido para a visualização de grandes vasos e retorno venoso ao coração, permitindo a identificação de pequenos vasos de fino calibre e com baixa velocidade de fluxo como as veias pulmonares, potencializando a detecção de anomalias de retorno venoso pulmonar [9].

Fig. 1 – Visibilização do plano de quatro câmaras cardíacas utilizando o inversion mode

Outra técnica também abordada pelo STIC é o Tomographic Ultrasound Imaging (TUI), que possibilita a obtenção de todos os planos axiais do coração desde o abdome até o ápice do tórax, potencializando o rastreamento e a análise das cardiopatias fetais [10] (Figura 2). O STIC também permite a mensuração dos volumes das câmaras cardíacas, assim como o cálculo do volume sistólico, da fração de ejeção e do débito cardíaco. Dessa forma, a obtenção de informações relevantes sobre o funcionamento cardíaco é possível diante das DCC [11]. Mais recentemente, uma nova abordagem da análise pelo modo renderizado do STIC obteve medidas das áreas IV

das valvas mitral e tricúspide e do septo interventricular, determinando valores de referência para esses parâmetros, tornando viável sua aplicação em casos suspeitos ou patológicos [12,13].

Fig. 2 – Uso do TUI com visibilização simultânea de planos axiais sequenciais do tórax fetal ao nível coração (3VT, 5C, 4C). TUI: tomographic ultrasound imaging. 3VT: três vasos e traqueia; 5C: cinco câmaras; 4C: quatro câmaras

Recentemente, alguns estudos tentaram correlacionar as técnicas 3D/4D (STIC) e 2D (ecocardiografia) no diagnóstico das DCC, contudo, esses estudos demonstraram resultados contraditórios [14,15]. Em um desses estudos, sendo o STIC realizados por obstetras gerais, sem conhecimento específico na metodologia, o STIC mostrou-se inferior à ecocardiografia 2D, realizada por especialista, no diagnóstico de DCC [14]. Já no outro estudo, que o STIC foi realizado por examinadores experientes nessa metodologia, a acurácia no diagnóstico de DCC foi semelhante à obtida pela ecocardiografia 2D [15]. Com base em estudos recentes, ainda é precoce afirmar se a ultrassonografia 3D/4D (STIC) irá superar a ecocardiografia 2D como método padrão-ouro no diagnóstico pré-natal das DCC. Em nosso meio, os maiores entraves são a necessidade de equipamentos sofisticados e ainda caros e de pessoas com treinamento específico em ultrassonografia 3D/4D. Contudo, algumas vantagens já são vislumbradas, como menor dependência do operador e a possibilidade de envio dos volumes para centros de referência em cardiologia fetal e pediátrica, de fundamental importância em um país como o nosso, em que esses centros estão localizados nas grandes cidades. Em síntese, somente a realização de estudos multicêntricos, com examinadores experientes na tecnologia 3D/4D, poderá comprovar o real benefício do STIC no diagnóstico pré-natal das DCC.

REFERÊNCIAS

1. Hoffmann JI. Incidence of congenital heart disease: I. Postnatal incidence. Pediatr Cardiol. 1995;16(3):103-13. 2. Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study. Am J Obstet Gynecol. 1999;181(2):446-54. 3. Stümpflen I, Stümpflen A, Wimmer M, Bernaschek G. Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease. Lancet. 1996;348(9031):854-7. 4. DeVore GR, Falkensammer P, Sklansky MS, Platt LD. Spatio-temporal image correlation (STIC): new technology for evaluation of the fetal heart. Ultrasound Obstet Gynecol. 2003;22(4):380-7. 5. Gonçalves LF, Nien JK, Espinoza J, Kusanovic JP, Lee W, Swope B, et al. What does 2-dimensional imaging add to 3and 4-dimensional obstetrics ultrasonography? J Ultrasound Med. 2006;25(6):691-9. 6. Paladini D. Standardization of on-screen fetal heart orientation prior to storage of spatio-temporal image correlation (STIC) volume datasets. Ultrasound Obstet Gynecol. 2007;29(6):605-11. 7. Gonçalves LF, Lee W, Chaiworapongsa T, Espinoza J, Schoen ML, Falkensammer P. Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation. Am J Obstet Gynecol. 2003;189:1792-802. 8. Lee W, Gonçalves LF, Espinoza J, Romero R. Inversion mode: a new volume analysis tool for 3-dimensional ultrasonography. J Ultrasound Med. 2005;24(2):201-7. 9. Pooh PK, Korai A. B-flow and B-flow spatio-temporal image

correlation in visualizing fetal cardiac blood flow. Croat Med J. 2005;46(5):808-11. 10. Yagel S, Cohen SM, Rosenak D, Messing B, Lipschuetz M, Shen O, et al. Added value of three-/four-dimensional ultrasound in offline analysis and diagnosis of congenital heart disease. Ultrasound Obstet Gynecol. 2011;37(4):432-7. 11. Simioni C, Nardozza LM, Araujo Júnior E, Rolo LC, Zamith M, Caetano AC, et al. Heart stroke volume, cardiac output, and ejection fraction in 265 normal fetus in the second half of gestation assessed by 4D ultrasound using spatiotemporal image correlation. J Matern Fetal Neonatal Med. 2011;24(9):1159-67. 12. Rolo LC, Nardozza LM, Araujo Júnior E, Hatanaka AR, Rocha LA, Simioni C, et al. Reference ranges of atrioventricular valve areas by means of four-dimensional ultrasonography using spatiotemporal image correlation in the rendering mode. Prenat Diagn. 2013;33(1):50-5. 13. Nardozza LM, Rolo LC, Araujo Júnior E, Hatanaka AR, Rocha LA, Simioni C, et al. Reference range for fetal interventricular septum area by means of four-dimensional ultrasonography using spatiotemporal image correlation. Fetal Diagn Ther. 2013 [ahead of print]. 14. Wanitpongpan P, Kanagawa T, Kinugasa Y, Kimura T. Spatio-temporal image correlation (STIC) used by general obstetricians is marginally clinically effective compared to 2D fetal echocardiography scanning by experts. Prenat Diagn. 2008;28(10):923-8. 15. Bennasar M, Martínez JM, Gómez O, Bartrons J, Olivella A, Puerto B, et al. Accuracy of four-dimensional spatiotemporal image correlation echocardiography in the prenatal diagnosis of congenital heart defects. Ultrasound Obstet Gynecol. 2010;36(4):458-64.

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2013;28(1):1-9

Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery Impacto na mortalidade precoce e tardia após transfusão de hemácias em cirurgia de revascularização miocárdica

Antonio Alceu dos Santos1, Alexandre Gonçalves Sousa2, Hugo Oliveira de Souza Thomé3, Roberta Longo Machado4, Raquel Ferrari Piotto5 DOI: 10.5935/1678-9741.20130003

RBCCV 44205-1436

Abstract Objective: To assess the 30-day and 1-year mortality associated to the red blood cell transfusion after coronary artery bypass grafting surgery. This procedure has been questioned by the international medical community, but it is still widely used in cardiac surgery. Therefore, it is needed more evidence of this medical practice in our country. Methods: We retrospectively analyzed 3,004 patients who underwent coronary artery bypass grafting surgery between June 2009 and July 2010. Patients were divided into two groups: non-transfused and transfused. Results: The transfused group totaled 1,888 (63%) and non-transfused 1,116 (37%). There were 129 deaths in 30 days, with 108 (84%) in the transfused group and 21 (16%) in the non-transfused (P<0.001). One year mortality totaled 249 distributed in 212 (85%) among transfused patients and 37 (15%) in non-transfused (P<0.001). The adjusted odds ratio for mortality in patients transfused was 2.00 (P=0.007) in 30 days and 2.31 (P=0.003) in 1 year. Even in low risk patients (age < 60 years and EuroSCORE ≤ 2 points), and so with fewer comorbidities, both outcomes, 30 day and 1 year mortality were significantly higher in the transfused patients (7.0% vs. 0.0%, P< 0.001) and (10.0% vs. 0.0%, P< 0.001), respectively.

Conclusion: The perioperative red blood cell transfusions after coronary artery bypass grafting surgery increased significantly the 30-day and 1-year mortality, even after the adjustments for comorbidities and other factors. So, new therapeutic options and autologous blood management and conservation strategies should be encouraged to reduce blood products transfusions.

1. Specialist Cardiologist with the title of AMB and the Brazilian Society of Cardiology Physician Assistant Team Dr. Pedro José da Silva, São Paulo, SP, Brazil. 2. Cardiologist with a specialist title by SBC/AMB, Medical Research Center of the Hospital of Charity of St. Paul Portuguese, São Paulo, SP, Brazil. 3. Cardiology, Charitable Portuguesa de São Paulo / Graduate Diploma in Intensive Care, Hospital Albert Einstein, São Paulo, SP, Brazil. 4. Cardiology, Charitable Portuguesa de São Paulo / Graduate Diploma in Intensive Care - Brazilian Association of Intensive Care Medicine (AMIB), São Paulo, SP, Brazil. 5. Doctorate in cardiology by the Faculty of Medicine of Ribeirão Preto, São Paulo, SP, Brazil.

Work carried out at Portuguese Beneficent Hospital of São Paulo, São Paulo, SP, Brazil.

Descriptors: Blood transfusion. Mortality. Blood cells. Coronary artery bypass. Myocardial revascularization. Postoperative complications. Resumo Objetivo: Avaliar a mortalidade em 30 dias e em 1 ano associada à transfusão de glóbulos vermelhos após cirurgia de revascularização miocárdica. Esse procedimento já vem sendo questionado pela comunidade médica internacional, mas ainda é utilizado em grande escala em cirurgias cardíacas. Portanto, faz-se necessário mais evidência dessa prática médica em nosso meio. Métodos: Analisamos retrospectivamente 3004 pacientes submetidos à cirurgia de revascularização miocárdica entre

Correspondence address: Alceu Antonio dos Santos Rua Maestro Cardim, 769 – Block I – Room 202 – Bela Vista São Paulo, SP, Brazil – Zip code: 01323-001 E-mail: antonioalceu@cardiol.br Article received on June 29th, 2012 Article accepted on July 30th, 2012

Rev Bras Cir Cardiovasc 2013;28(1):1-9

Santos AA, et al. - Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery

Abbreviations, Acronyms & Symbols AF CABG CPB EuroSCORE HF ICU KF RBCT

Atrial fibrillation Coronary artery bypass grafting Cardiopulmonary bypass European System for Cardiac Operative Risk Evaluation Heart failure Intensive care unit Kidney failure Red blood cells transfusion

junho de 2009 e julho de 2010. Os pacientes foram divididos em dois grupos: Transfundidos e Não transfundidos. Resultados: O grupo de pacientes transfundidos totalizaram 1888 (63%) e o grupo não transfundidos 1116 (37%). Foi observado 129 óbitos em 30 dias, sendo 108 (84%) no grupo transfundidos e 21 (16%) no grupo não transfundidos (P<0,001). Os óbitos em um ano totalizaram 249 distribuídos

INTRODUCTION Blood transfusions are among the greatest scientific discoveries of medical history. Since the nineteenth century they are used on a large scale worldwide. In Brazil, for example, about four million units of blood and derivatives are transfused annually [1]. The reason for this clinical practice is that the anemic patients have adverse outcomes due to reduced capacity to transport oxygen to the tissues, and hence the replacement of red cells through transfusion could prevent these deleterious outcomes [2]. Other indications, such as getting volemic expansion and blood pressure restoration, have no scientific support [3]. However, as evidenced in the worldwide medical literature, the blood transfusions have been questioned for several reasons. Firstly, we still do not have a specific, safely and effectively hemoglobin level able to set the trigger to indicate a blood transfusion [4], moreover there is a huge discrepancy of its use among physicians and hospitals [5]. Another worrying factor is the increased risk of heart failure (HF) [6], atrial fibrillation (AF), kidney failure (KF), stroke, respiratory infection, severe sepsis, and longer hospital stays [7], in the postoperative cardiac surgery, besides the malignant diseases [8], potential transmission of 68 infectious agents [9], multiple organ failure [10]. But what really has concerned the medical community according to recent studies is the mortality increase in general [11] and cardiac surgery [6,12,13]. Another important factor is the reduction of blood donations, leading to blood bank stocks below than what would be the ideal in Brazil [14] and abroad [15]. 2

em 212 (85%) hemotransfundidos e 37 (15%) sem transfusão (P<0,001). O odds ratio ajustado para mortalidade nos pacientes transfundidos foi de 2,00 (P=0,007) em 30 dias e 2,31 (P=0,003) em 1 ano. Mesmo em pacientes de baixo risco (idade<60 anos e com EuroSCORE ≤ 2%), portanto com menos comorbidades, temos significativamente mais óbitos no grupo transfundidos em 30 dias (7,0% vs. 0,0%; P<0,001) e também em 1 ano (10,0% vs. 0,0%; P<0,001). Conclusão: A transfusão de glóbulos vermelhos após cirurgia de revascularização miocárdica aumenta significativamente a mortalidade em 30 dias e em um ano, mesmo após correção de comorbidades e outros fatores. Novas opções terapêuticas e estratégias de gerenciamento e conservação do sangue autólogo devem ser estimuladas para reduzir as transfusões de hemoderivados. Descritores: Transfusão de sangue. Mortalidade. Células sanguíneas. Ponte de artéria coronária. Revascularização miocárdica. Complicações pós-operatórias.

Based on these findings the use of homologous blood has been proposed more narrowly in cardiovascular surgery [16]. Therefore, it is necessary to have more evidence of this medical practice in our country. Thus, the aim of this study is to assess the 30-day and 1-year mortality associated with the red blood cells transfusion (RBCT) after coronary artery bypass grafting (CABG). METHODS We performed a retrospective cohort study using data from the cardiac surgery service of the Beneficência Portuguesa Hospital of São Paulo. The CABG surgeries database is powered by 14 teams, composed of 3,004 patients who were followed-up during the period of June 8, 2009 to July 26, 2010. For the study, were considered patients undergoing CABG with or without associated procedures, age ≥ 18 years; with no restriction on gender or race. We excluded patients who underwent any other surgery, including cardiac, without CABG. The data collection form presented a total of 243 variables. For this study were assessed nine: age, gender, comorbidities, European System for Cardiac Operative Risk Evaluation (EuroSCORE), type of surgery, packed red blood cells transfusion, length of stay (in hospital and Intensive Care Unit - ICU), acquired comorbidities after surgery, and intraoperative and postoperative complications. We present in Tables 1 and 2 the variables assessed in this study in each group.

Rev Bras Cir Cardiovasc 2013;28(1):1-9

Santos AA, et al. - Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery

Table 1. Mean values and standard deviation (for age) and absolute frequencies (%), according to group of death (30 days) Group

30-days mortality (n=129) 66,9 ± 9,6 51 (40)

No death (n=2755) 61,7 ± 9,4 1099 (40)

P < 0,001

59 (46) 19 (5)

1230 (45) 426 (16)

0,961

108 (84)

1676 (61)

< 0,001

55 (43)

981 (36)

0,111

Dyslipidemia

39 (30)

1247 (45)

< 0,001

CKF

22 (17)

126 (5)

< 0,001

SAH

109 (85)

2271 (82)

0,564

Previous Stroke

10 (8)

137 (5)

0,161

COPD

16 (12)

168 (6)

0,004

Peripheral arterial disease

10 (8)

118 (4)

0,062

Cerebrovascular disease

5 (4)

41 (1)

0,052

13 (10)

301 (11)

0,762

Previous CABG

3 (2)

41 (1)

0,446

Previous valvar surgery

1 (1)

7 (0,3)

0,307

Other surgeries

0 (0)

3 (0,1)

1,000

Angioplasty

9 (7)

243 (9)

0,469

Previous AMI

52 (40)

1299 (47)

0,128

CHF

13 (10)

55 (2)

< 0,001

Arrhythmia

15 (12)

134 (5)

< 0,001

2 (2)

22 (1)

0,323

Arterial

13 (10)

484 (18)

Graft type

34 (26)

309 (11)

82 (64)

1961 (71)

8 (6)

337 (12)

89 (69)

2503 (91)

Variable Age

Category Former

Smoker

No Yes

Transfusion

Coronary intervention

Surgical indication-Urgent

Venous

Venous + Arterial CPB use Isolate CABG

With heart surgery

9 (7)

138 (5)

With other surgeries

10 (8)

27 (1)

21 (16)

87 (3)

With valvar

< 0,001

0,039

< 0,001

DM – diabetes mellitus; CKF – chronic kidney failure; SAH – systemic arterial hypertension; COPD - chronic obstructive pulmonary disease; CABG – coronary artery bypass graft; AMI – acute myocardial infarction; CHF – congestive heart failure; CPB – cardiopulmonary bypass

Rev Bras Cir Cardiovasc 2013;28(1):1-9

Santos AA, et al. - Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery

Table 2. Mean values and standard deviation (for age) and absolute frequencies (%), according to group of death (1 year) Group

1-Year mortality (n=249) 67,5 ± 9,1 101 (40)

No death (n=2755) 61,7 ± 9,4 1099 (40)

P < 0,001

114 (46) 34 (14)

1230 (45) 426 (16)

0,749

212 (85)

1676 (61)

< 0,001

117 (47)

981 (36)

< 0001

Dyslipidemia

89 (36)

1247 (45)

0,004

CKF

44 (18)

126 (5)

< 0,001

SAH

214 (86)

2271 (82)

0,160

Previous Stroke

30 (12)

137 (5)

< 0,001

COPD

40 (16)

168 (6)

< 0,001

Peripheral arterial disease

28 (11)

118 (4)

< 0,001

Cerebrovascular disease

13 (5)

41 (1)

< 0,001

Coronary intervention

26 (10)

301 (11)

0,814

Previous CABG

6 (2)

41 (1)

0,278

Previous valvar surgery

1 (1)

7 (0,3)

0,500

Other surgeries

1 (1)

3 (0,1)

0,293

Angioplasty

18 (7)

243 (9)

0,393

Previous AMI

109 (44)

1299 (47)

0,307

CHF

28 (11)

55 (2)

< 0,001

Arrhythmia

31 (13)

134 (5)

< 0,001

6 (2)

22 (1)

0,024

Arterial

32 (13)

484 (18)

Graft type

54 (22)

309 (11)

163 (65)

1961 (71)

21 (8)

337 (12)

180 (72)

2503 (91)

Variable Age

Category Former

Smoker

No Yes

Transfusion

Surgical indication-Urgent

Venous

Venous + Arterial CPB use Isolate CABG

With heart surgery

18 (7)

138 (5)

With other surgeries

15 (6)

27 (1)

36 (14)

87 (3)

With valvar

< 0,001

0,076

< 0,001

Santos AA, et al. - Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery

Rev Bras Cir Cardiovasc 2013;28(1):1-9

The patients were divided among two groups: 1) transfused, patients who received one or more units of packed red blood cells during and / or after surgery, and 2) non-transfused. We adjusted two models for assessing the mortality in these two groups: a model for 30-day mortality and another for the 1-year mortality. Quantitative variables were described as means and standard deviations or medians, and qualitative variables by absolute and relative frequencies. For the data analysis in both groups we used the t-Student test and Mann-Whitney nonparametric test. For checking homogeneity between ratios we used the chi-square or Fisher's exact test. To obtain mortality prognostic factors the multivariate logistic regression model [17] was used with "stepwise" variable selection process, based on variables that presented P<0.25 in the univariate analysis. The significance level used for the tests was 5%. This study was assessed and approved by the Ethics Committee in Research of the Hospital Beneficência Portuguesa of São Paulo, under No 700-11, according to the Helsinki Declaration.

in the group receiving RBCT, against only 1.9% deaths among non-transfused group (P <0.001). So we have a risk reduction of 3.8%, which is equivalent to state that every 26 RBCT restrictions we avoid one death in 30 days. As shown in the Figure 1, the difference between the two groups became well evident when assessed the adjusted Kaplan-Meier survival curves of 30-day mortality (P <0.001). According to this study, the RBCT also showed to be a predictor of 1-year mortality. After a follow up period of 1 year deaths totaled 249 distributed in 212 (85%) in transfused group against 37 (15%) in non-transfused group (P <0.001) (Table 3). The adjusted odds ratio for 1-year mortality after red blood cell transfusion was 2.31 (95% CI 1.31 to 4.04, P=0.003). So, we also observed differences between groups for RBC transfusion in relation to the presence of death at 1 year, being significantly higher in the transfused group. In terms of percentage, we observed a 1-year mortality rate of 11.2% in the group receiving RBCT against only 3.3% in non-transfused group (P<0.001). Thus, we have a reduced risk of 7.9%, which is equivalent to say that, every 13 RBCT restrictions we avoid a death in one year. Another data analysis in our study allows us to conclude that in both outcomes 30-day and 1-year, the nontransfused group presents significantly greater percentage of alive patients when compared to the transfused group (log-rank test P<0.001), as shown in Figure 2. Even in low risk patients (expected mortality by EuroSCORE ≤ 2%) we have significantly more deaths within 30 days in the transfused group (5% vs. 1%, P=0.007). In one year we also observed survival reduction in patients with low euroSCORE in transfused group (7% vs. 1%, P=0.001) (Table 4). When we separate a specific group of younger patients (<60 years) and EuroSCORE ≤ 2%, and hence less comorbidity, we also have significantly more deaths among transfused, as shown in Table 5. Based on these results, our study objectively shows that the RBCTs are associated with a reduction, adjusted risk, on survival in patients undergoing CABG in both 30day and 1-year outcomes.

RESULTS The group of transfused patients was 1,888 (63%) and non-transfused 1,116 (37%). There was a predominance of male patients (69.9%) and whites (84.6%) with mean age of 62.2 ± 9.5 years. The survival rate was 94.4% at hospital discharge (in four cases to another hospital) and only 0.2% (seven cases) of intraoperative death. Firstly, we found that the RBCT proved to be a predictor of 30-day mortality. The adjusted odds ratio for 30-day mortality in transfused was 2 (95% CI 1.21 to 3.31, P=0.007). The study showed a total of 129 deaths in 30 days, with 108 (84%) in transfused group and 21 (16%) in non-transfused (P<0.001). Thus, the transfusion group showed a significantly greater percentage of deaths in 30 days when compared to non-transfused (Table 3). On the other hand, we observed a mortality rate of 5.7%

Table 3. Association between transfusion and death at 30 days and 1 year Total 30-day Mortality % 1-year Mortality % No Death Non-transfused 1116 21 16 37 15 1079 Transfused 1888 108 84 212 85 1676 Total 3004 129 100 249 100 2755 30-day Mortality vs. No Death: chi-square test, P <0.001; 1-year Mortality vs. No Death: chi-square test, P <0.001

% 39 61 100

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Santos AA, et al. - Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery

Fig. 1 – Kaplan-Meier survival curve in the study of death at 30 days (y-axis starts at 60%)

Fig. 2 – Adjusted survival risk after coronary artery bypass grafting (y-axis starts at 60%)

Table 4. Mortality study in patients with low risk (EuroSCORE ≤ 2) Mortality No (n=308) 30-days 1 (1%) 1-year 3 (1%) (*) descriptive level of the chi square probability

Transfused

Yes (n=317) 14 (5%) 22 (7%)

P* 0,007 0,001

Table 5. Mortality study in patients with low risk (EuroSCORE ≤ 2) and age less than 60 years Transfused Mortality No (n=188) Yes (n=154) 30-days 0 (0,0%) 11 (7%) 1-year 0 (0,0%) 15 (10%) * significant difference; † descriptive level of the Fisher's exact test probability. ‡ descriptive level of the chi-square test probability.

DISCUSSION The real purpose of the red blood cell transfusion is to maintain adequate tissue oxygenation. Blood is a living tissue that circulates through the body delivering oxygen and nutrients to all organs. The blood has its classification into groups with the presence or absence of an antigen on the red blood cells surface. Although the ABO and Rh groups (positive and negative) are the most important, there are countless others. A transplant is the transfer of cells, tissues or organs from a living individual (donor) to another (recipient) with the aim at restoring a lost function. Thus, we can say that blood transfusions are the most common type of transplantation [18]. As it occurs with any 6

P* < 0,001† < 0,001‡

transplant, there is an acute immune reaction and it also occurs in long term. We have evidence to support a role of immunomodulatory effect on the transfusion with changes in the blood cells (such as a reduction in the number of circulating lymphocytes, modification in T-cells and activation of immune cells) [19]. The cardiac surgery related traumas together with RBCTs promote a noninfectious inflammatory response reflected by an increase in the inflammatory mediator concentrations. In these circumstances cytokine levels are very high. Other limitations in respect to the blood transfusions is related to the stored blood that have a reduced tissue oxygen delivery and as the storage time increases, the

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red cells undergo to cellular, biochemical, hormonal and inflammatory structural changes, resulting in the inability of the stored blood to perfuse the microcirculation [20]. Recently, a study reported an association between blood transfusions and the pulmonary coagulation activation, as well as intraoperative thromboembolic complications [11]. These and other still unknown factors, respond largely the negative outcomes associated with blood transfusions, specifically the early mortality of patients undergoing CABG. This study showed that the death risk presented a most influential early impact of the blood transfusion for the first 30 days after surgery, as we can see by comparing the survival curves (Figures 1 and 2). When assessing the graphs it is possible to observe an association between the RBCT and reduced survival, statistically and significantly different, from those who did not receive a RBCT at 30 days (P<0.001). The RBCT effect on the risk of early mortality (first 6 months after surgery) was also found by Koch et al. [13]. Thus, though, an analysis of survival curve in one year it is also possible to observe higher mortality among the transfused group (Figure 2). The long-term mortality related to red blood cell transfusions is still speculative. Some of the mechanisms responsible for this effect would be the systemic inflammatory response and the immunomodulation [19]. But, we also can state that comorbidities (such as: HF, AF, stroke, KF, infectious agents transmission, pulmonary thromboembolism, and other malignancies) [6-11], caused by the transfusions also influence the late mortality. The higher early mortality increase is believed to be related with cardiopulmonary dysfunction, and as well as the infections increase, higher inflammatory response, and the transfusion immunomodulatory effect. With respect to different response we found with a large increase in short term mortality, and then, a sustained increase in long-term mortality in transfused patients, suggesting two distinct processes. One of these processes is the hypothesis that a transfused patient is sicker. However, the increased mortality, also in long term, discards the argument that transfusion is an indicator of hospitalized patients (Figure 2). Other information from our study, contrary to the idea that the higher mortality after a RBCT is due to the patientâ&#x20AC;&#x2122;s more severe condition, was provided by the EuroSCORE calculation, a simple and objective index, but it has been shown as a satisfactory predictor of mortality in patients undergoing CABG [21]. When we have an EuroSCORE â&#x2030;¤ 2%, the mortality is low, but in our study when we provide RBCT the death risk increased significantly in both at 30-day and 1-year mortality (Table 4). Interestingly, when we have patients younger than 60 years and an EuroSCORE â&#x2030;¤ 2%, and so with fewer comorbidities and/or aggravating risk factors for heart

surgery, we had no deaths in the non-transfused group (Table 5), unlike the group that received RBCT, where we had a significant mortality, in both early and late period. It is known that intraoperative allogeneic transfusion, which is usually based on hemoglobin levels and not on the patient's clinical status (symptoms and signs), is also a risk factor for the increased mortality [12]. Thus, we can state that the blood product transfusion is not necessarily an indicator factor of sicker patient, but it is an independent factor of early and late mortality. The potential adverse influence of blood transfusions on early and long term survival is indeed alarming, as was also demonstrated by Kuduvalli et al. [22]. Our findings were also evidenced by Michalopoulos et al. [23], which reported an independent association of blood transfusions with early and late mortality after CABG. Engoren et al. [12] also studying the effects of blood transfusions in patients undergoing CABG alone, also reported that transfused patients had twice the mortality of non-transfused. Even after the adjustment for comorbidities and other factors, the blood transfusion was still independently associated with an increase of 70% in mortality. Other authors also reported an association between RBCT and increased mortality in a series of clinical scenarios, both in cardiac and general surgery [6,11,12]. There is a global real need in making more decisions based on evidence, in relation to the RBCTs. The proposal to maintain certain hemoglobin level via blood transfusions has no strong support in the medical literature. Several randomized and controlled studies have shown that lowering the hemoglobin threshold for recommending a blood transfusion in cardiac surgery [16] and in critically ill patients [4] do not adversely affect patient outcome. In 2010 was published a large study that identified a dramatic variability on RBCT rates (7.8% to 92.8%) in patients undergoing CABG in several hospitals [5], demonstrating thereby that is often the physician and not the patient who does not tolerate low hemoglobin and/or hematocrit levels during or after a surgery [24]. Researchers have found that a hematocrit level between 17% and 21% during CABG together with moderate hypothermia, are well tolerated and have no adverse impact on the outcomes. In our study, even within a single center (hospital) we also recorded a wide variation in blood transfusion rates. Among the fourteen teams that perform CABG, the team who most indicated transfusion had 85.7% of their patients receiving RBCT and that who less indicated transfusion had 54.1%. This demonstrates that blood products are still used on a large scale in our country, hence the relevance of this study that adds itself to several others in highlighting the adverse effects of this medical practice. Various techniques and strategies to reduce the blood 7

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use have been studied; one of these is the blood products during cardiopulmonary bypass (CPB) associated with a reduced hydric balance, proposed by Souza & Braile [25]. Other proposed measures are the use of antifibrinolytic agent, aminocaproic acid [26], minimum use of CPB, especially in relation to its duration [27]. Others relevant care include preoperative patient meticulous assessment, implementation of intraoperative and postoperative measures for reducing blood loss and transfusion, active involvement of the surgeon, physician, anesthesiologist and intensivist, and as well as the use of algorithms for patients assessment and treatment, can significantly reduce transfusion need and prove to be lifesaving in cases of serious bleeding. This was evidenced by previous studies that reported a reduction of up to 50% in transfusion rates with the implementation of the cardiac surgery multidisciplinary protocols [28]. The tolerance of anemia in the perioperative period is one of the three main pillars of the blood conservation, and it does not increase the risk of complications and death in cardiac surgery [29]. Another important pillar is to optimize the erythrocyte mass by stimulating the red blood cell production through specific medication (ferrous sulfate, folic acid, vitamin B12, and erythropoietin). The third pillar, also equally important, involves the blood loss reduction by using all available resources such as electrocautery, argon beam coagulation, heparin-coated circuits, leukocyte filter, anti-fibrinolytic drugs, buffer fibrin glue, hemostatic agents, normothermia, induced hypotension, meticulous hemostasis, phlebotomy, acute normovolemic hemodilution [27], and especially the intraoperative cell salvage (cell saver). The allogeneic blood is expensive, difficult to obtain, transport and store. The local and global shortages are imminence [14,15]. Currently, there are no demonstrated real benefits of blood transfusions, and adverse effects are increasingly described. Thus, alternatives to this procedure provide many advantages, and its use is likely to improve the outcomes, as the safer and more effective agents are developed. Therefore, they should be encouraged worldwide. There are some limitations in our study. The first is that by being a retrospective database study, by its nature, we can only find associations between variables and outcomes, without however showing the causality. A second limitation is the fact that there was not a well-established rule for transfusion in both intra and postoperative period, and the transfusion triggers were dependent on the physician responsible for the patient. Another limitation is that we use all-cause of mortality as a final outcome, not differentiating causes of cardiac and non-cardiac death. A final limitation is that we have no data to differentiate transfusions, both from intraoperative

data to the postoperative period, since intraoperative transfusions, especially in surgery with CPB, are more triggered by levels of hemoglobin or hematocrit rather than patient's clinical status, and having added this parameter in our study probably would reinforce our conclusion.

CONCLUSION The red blood cell transfusion after coronary artery bypass grafting surgery increases significantly the 30day and 1-year mortality, even after the adjustment for comorbidities and other factors. Other therapeutic options and strategies for autologous blood management and conservation should be encouraged to reduce the transfusion need of blood products.

REFERENCES 1. Boletin de Hemovigilância Nº 2-ANVISA-2009; P:7. Accessed in 01/July/2012: http://portal.anvisa.gov.br/wps/wcm/connect /3a17a980474585998f47df3fbc4c6735/boletim_hemo_2009. pdf?MOD=AJPERES. 2. Practice Guidelines for blood component therapy: a report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology. 1996;84(3):73247. 3. American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105(1):198-208. 4. Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, et al; American College of Critical Care Medicine of the Society of Critical Care Medicine; Eastern Association for the Surgery of Trauma Practice Management Workgroup. Crit Care Med. 2009;37(12):3124-57. 5. Bennett-Guerrero E, Zhao Y, O’Brien SM, Ferguson TB Jr, Peterson ED, Gammie JS, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA. 2010;304(14):1568-75. 6. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116(22):2544-52. 7. Dorneles CC, Bodanese LC, Guaragna JCVC, Macagnan FE, Coelho JC, Borges AP, et al. O impacto da hemotransfusão na

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morbimortalidade pós-operatória de cirurgias cardíacas. Rev Bras Cir Cardiovasc. 2011;26(2):222-9.

19. Blajchman MA. Immunomodulation and blood transfusion. Am J Ther. 2002;9(5):389-95.

8. Silverman RH, Nguyen C, Weight CJ, Klein EA. The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. Nat Rev Urol. 2010;7(7):392-402.

20. Spiess BD. Red cell transfusions and guidelines: work in progress. Hematol Oncol Clin North Am. 2007;21(1):185-200.

9. Stramer SL, Hollinger FB, Katz LM, Kleinman S, Metzel PS, Gregory KR, et al. Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion. 2009;49(Suppl 2):1S-29S. 10. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg. 1997;132(6):620-4. 11. Glance LG, Dick AW, Mukamel DB, Fleming FJ, Zollo RA, Wissler R, et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology. 2011;114(2):283-92. 12. Engoren MC, Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg. 2002;74(4):1180-6. 13. Koch CG, Li L, Duncan AI, Mihaljevic T, Loop FD, Starr NJ, et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg. 2006;81(5):1650-7. 14. Novaretti MCZ. Importância dos carreadores de oxigênio livre de células. Rev Bras Hematol Hemoter. 2007;29(4):394-405. 15. Sojka BN, Sojka P. The blood donation experience: selfreported motives and obstacles for donating blood. Vox Sang. 2008;94(1):56-63. 16. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-67. 17. Hosmer Jr. DW, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons;1989. p.307. 18. Berkow R, Fletcher AJ, Bondy PK, Faling LJ, Feinstein AR, Frenkel EP, et al. Transfusão de sangue. Manual Merck. 15ª ed. 1987:p.1246.

21. Moraes Neto F, Duarte C, Cardoso E, Tenório E, Pereira V, Lampreia D, et al. Avaliação do EuroSCORE como preditor de mortalidade em cirurgia de revascularização miocárdica no Instituto do Coração de Pernambuco. Rev Bras Cir Cardiovasc. 2006;21(1):29-34. 22. Kuduvalli M, Oo AY, Newall N, Grayson AD, Jackson M, Desmond MJ, et al. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2005;27(4):592-8. 23. Michalopoulos A, Tzelepis G, Dafni U, Geroulanos S. Determinants of hospital mortality after coronary artery bypass grafting. Chest. 1999;115(6):1598-603. 24. Senay S, Toraman F, Karabulut H, Alhan C. Is it the patient or the physician who cannot tolerate anemia? A prospective analysis in 1854 non-transfused coronary artery surgery patients. Perfusion. 2009;24(6):373-80. 25. Souza DD, Braile DM. Avaliação de nova técnica de hemoconcentração e da necessidade de transfusão de hemoderivados em pacientes submetidos à cirurgia cardíaca com circulação extracorpórea. Rev Bras Cir Cardiovasc. 2004;19(3):287-94. 26. Benfatti RA, Carli AF, Silva GVR, Dias AEMAS, Goldiano JA, Pontes JCDV. Influência do ácido épsilon aminocapróico no sangramento e na hemotransfusão pós-operatória em cirurgia valvar mitral. Rev Bras Cir Cardiovasc. 2010;25(4):510-5. 27. Souza HJB, Moitinho RF. Estratégias para redução do uso de hemoderivados em cirurgia cardiovascular. Rev Bras Cir Cardiovasc. 2008;23(1):53-9. 28. Van der Linden P, Dierick A. Blood conservation strategies in cardiac surgery. Vox Sang. 2007;92(2):103-12. 29. Moskowitz DM, McCullough JN, Shander A, Klein JJ, Bodian CA, Goldweit RS, et al. The impact of blood conservation on outcomes in cardiac surgery: is it safe and effective? Ann Thorac Surg. 2010;90(2):451-8.

ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2013;28(1):10-21

Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta Risk factors for pre, intra, and postoperative hospital mortality in patients undergoing aortic surgery

Mário Issa1, Álvaro Avezum2, Daniel Chagas Dantas3, Antonio Flávio Sanches de Almeida4, Luiz Carlos Bento de Souza5, Amanda Guerra de Moraes Rego Sousa6

DOI: 10.5935/1678-9741.20130004

RBCCV 44205-1437

Resumo Objetivos: O objetivo primário deste estudo é identificar preditores de óbito hospitalar em pacientes submetidos à cirurgia de aorta. O objetivo secundário é identificar fatores associados ao desfecho clínico composto hospitalar (óbito, sangramento, disfunção ventricular ou complicações neurológicas). Métodos: Delineamento transversal com componente longitudinal; por meio de revisão de prontuários, foram incluídos 257 pacientes. Os critérios de inclusão foram: dissecção crônica de aorta tipo A de Stanford e aneurisma de aorta ascendente. Foram excluídos casos de dissecção aguda de aorta, qualquer tipo, e aneurisma de aorta não envolvendo segmento ascendente. As variáveis avaliadas foram demografia, fatores pré, intra e pós-operatórios. Resultados: Variáveis com risco aumentado de óbito hospitalar (RC; IC95%; P valor): etnia negra (6,8; 1,5430,2; 0,04), doença cerebrovascular (10,5; 1,12-98,7; 0,04), hemopericárdio (35,1; 3,73-330,2; 0,002), operação de Cabrol (9,9; 1,47-66,36; 0,019), cirurgia de revascularização miocárdica simultânea (4,4; 1,31-15,06; 0,017), revisão

de hemostasia (5,72; 1,29-25,29; 0,021) e circulação extracorpórea (CEC) [min] (1,016; 1,007-1,026; 0,001). Dor torácica associou-se com risco reduzido de óbito hospitalar (0,27; 0,08-0,94; 0,04). Variáveis com risco aumentado do desfecho clínico composto hospitalar foram: uso de antifibrinolítico (3,2; 1,65-6,27; 0,0006), complicação renal (7,4; 1,52-36,0; 0,013), complicação pulmonar (3,7; 1,5-8,8; 0,004), EuroScore (1,23; 1,08-1,41; 0,003) e tempo de CEC [min] (1,01; 1,00-1,02; 0,027). Conclusão: Etnia negra, doença cerebrovascular, hemopericárcio, operação de Cabrol, revascularização miocárdica simultânea, revisão de hemostasia e tempo de CEC associaram-se com risco aumentado de óbito hospitalar. Dor torácica associou-se com risco reduzido de óbito hospitalar. Uso de antifibrinolítico, complicação renal, complicação pulmonar, EuroScore e tempo de CEC associaram-se ao desfecho clínico composto hospitalar.

1. Cirurgião do Instituto Dante Pazzanese de Cardiologia (IDPC), Doutor em Cardiologia pela Universidade de São Paulo (USP)/IDPC São Paulo, SP, Brasil. 2. Doutor em Cardiologia pela USP, Diretor da Divisão de Ensino e Pesquisa do IDPC, São Paulo, SP, Brasil. Orientador da Tese de Doutorado, base do artigo. 3. Residente de Cirurgia Cardiovascular do IDPC, São Paulo, SP, Brasil. Levantamento dos dados de prontuário. 4. Doutor em Ciências pela USP, cirurgião cardiovascular do IDPC, São Paulo, SP, Brasil. Compilação de dados. 5. Doutor em Medicina pela Unoversidade Federal de São Paulo (UNIFESP), Diretor da Divisão de Cirurgia do IDPC, São Paulo, SP, Brasil. Orientação no artigo. 6. Livre-Docente pela USP, Diretora Técnica do Departamento de Saúde do IDPC, Orientação do artigo.

Trabalho realizado no Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil.

Descritores: Aneurisma aórtico/cirurgia. Aneurisma da aorta torácica. Aneurisma aórtico.

Endereço para correspondência: Mário Issa Av. Dante Pazzanese 500 – Vila Mariana São Paulo, SP. Brasil – CEP: 04012-909 E-mail: drmarioissa@yahoo.com.br

Artigo recebido em 27 de novembro de 2012 Artigo aprovado em 28 de dezembro de 2012

Rev Bras Cir Cardiovasc 2013;28(1):10-21

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Abreviações, acrônimos & símbolos AVC CEC cm DP FEVE IC Min RC

Acidente vascular cerebral Circulação extracorpórea Centímetros Desvio padrão Fração de ejeção do ventrículo esquerdo Intervalo de confiança Minutos Razão de chance

Abstract Objectives: The primary objective was to identify predictors of hospital mortality in patients undergoing aortic surgery. The secondary objective was to identify factors associated with clinical outcome composed hospital (death, bleeding, neurologic complications or ventricular dysfunction). Methods: A cross-sectional design with longitudinal component. Through chart review, 257 patients were included. Inclusion criteria were: aortic dissection Stanford type A and ascending aortic aneurysm. Exclusion criteria were acute aortic dissection, of any kind, and no aortic aneurysm involving the ascending segment. Variables assessed: demographics, preoperative factors, intraoperative and postoperative.

INTRODUÇÃO Nos Estados Unidos, aproximadamente 15 mil pessoas ao ano são diagnosticadas como portadoras de aneurisma da aorta torácica. Adicionalmente, mais de 47 mil indivíduos por ano morrem vítimas de doenças da aorta; mais do que câncer de mama, AIDS, homicídios ou acidentes automobilísticos, fazendo da doença aórtica uma epidemia silenciosa [1]. Aneurismas e dissecções constituem as principais doenças da aorta, os quais podem ser submetidos a princípios e técnicas de tratamento cirúrgico comuns. O manuseio cirúrgico continua sendo um desafio nos procedimentos eletivos, bem como em casos de emergência. A decisão quanto à cirurgia é baseada no equilíbrio entre o risco cirúrgico e a chance de ruptura da aorta, podendo ser particularmente difícil em casos eletivos. Por outro lado, entre pacientes com ruptura de aorta torácica, a mortalidade é extremamente elevada, situando-se acima de 94% [2]. O objetivo primário deste estudo foi identificar preditores associados independentemente ao óbito hospitalar em pacientes submetidos à cirurgia para correção de doenças de aorta. O obetivo secundário foi identificar variáveis asssociadas independentemente ao desfecho

Results: Variables with increased risk of hospital mortality (OR, 95% CI, P value): black ethnicity (6.8, 1.54-30.2; 0.04), cerebrovascular disease (10.5, 1.12-98.7; 0.04), hemopericardium (35.1, 3.73-330.2; 0.002), Cabrol operation (9.9, 1.47-66.36; 0.019), CABG simultaneous (4.4; 1.31 to 15.06; 0.017), bleeding (5.72, 1.29-25.29; 0.021) and cardiopulmonary bypass (CPB) time [min] (1.016; 1.0071.026; 0.001). Thoracic pain was associated with reduced risk of hospital death (0.27, 0.08-0.94, 0.04). Variables with increased risk of hospital clinical outcome compound were: use of antifibrinolytic (3.2, 1.65-6.27; 0.0006), renal complications (7.4, 1.52-36.0; 0.013), pulmonary complications (3.7, 1.58.8, 0.004), EuroScore (1.23; 1.08-1.41; 0.003) and CPB time [min] (1.01; 1.00 to 1.02; 0.027). Conclusion: Ethnicity black, cerebrovascular disease, hemopericardium, Cabrol operation, CABG simultaneous, hemostasis review and CPB time was associated with increased risk of hospital death. Chest pain was associated with reduced risk of hospital death. Use of antifibrinolytic, renal complications, pulmonary complications, EuroScore and CPB time were associated with clinical outcome hospital compound. Descriptors: Aortic Aneurysm. Thoracic. Aortic Aneurysm, surgery.

Aortic

Aneurysm,

clínico composto na fase hospitalar (óbito, sangramento, disfunção ventricular ou complicações neurológicas). MÉTODOS Esta pesquisa envolve um delineamento transversal, com coleta de dados retrospectiva e prospectiva e com um componente longitudinal. Pacientes consecutivos, com diagnóstico confirmado de aneurisma de aorta ascendente ou dissecção crônica tipo A de Stanford, foram incluídos a partir da revisão de prontuários, por meio de coleta de dados retrospectiva, com início em janeiro de 2004. A partir de janeiro de 2009, pacientes consecutivos foram incluídos por meio de coleta de dados prospectiva, até dezembro de 2010. A amostra observada incluiu 257 pacientes cujos eventos óbito hospitalar e desfecho clínico composto foram avaliados em função de medidas quantitativas e qualitativas. Os critérios de inclusão foram pacientes operados por dissecção crônica de aorta tipo A de Stanford e aneurisma de aorta ascendente, envolvimento da aorta ascendente em todos os pacientes, comprometimento presente ou não de outros segmentos da aorta, ambos os sexos e sem limite de idade. Os critérios de exclusão foram: pacientes com 11

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Rev Bras Cir Cardiovasc 2013;28(1):10-21

dissecção aguda de aorta (de qualquer tipo), pacientes com aneurisma envolvendo outros segmentos de aorta que não fossem aorta ascendente e dissecção de aorta tipo B de Stanford. O desfecho clínico composto refere-se à presença de óbito hospitalar ou complicação neurológica (acidente vascular cerebral – AVC ou coma > 24 horas) ou disfunção ventricular (insuficiência cardíaca sintomática e/ou choque cardiogênico) ou sangramento clinicamente relevante (presença de revisão de hemostasia e/ou necessidade de transfusão de concentrado de hemácias ≥ 3U), ou seja, o paciente que apresentou pelo menos um desses eventos foi caracterizado como portador de desfecho clínico composto. Para análise estatística, a amostra de pacientes estudada foi descrita por frequências absolutas (n) e relativas (%) das medidas qualitativas (fatores) e estatísticas sumárias de média, mediana, desvio padrão (DP) e percentis 25 e 75 das medidas quantitativas (covariáveis). A associação entre medidas qualitativas e os grupos (óbito e desfecho clínico composto) foi avaliada por teste qui-quadrado de Pearson ou exato de Fisher. Para a comparação de medidas quantitativas entre dois grupos foi aplicado teste não-paramétrico de Mann-Whitney. Para o óbito após a cirurgia, foram observadas as curvas de sobrevivência de Kaplan-Meier ou de sobrevivência média e, inicialmente, os efeitos de fatores avaliados por teste de Log-Rank e os de covariáveis por regressão de Cox. Os efeitos de fatores e covariáveis, considerados estatisticamente relevantes (P<0,10) ou clinicamente relevantes, foram também observados, todos presentes, num modelo de regressão logística para múltiplas variáveis no óbito hospitalar e no desfecho clínico composto. Para o óbito tardio, no longo prazo após a cirurgia, múltiplas variáveis foram avaliadas por modelo de regressão de Cox. O nível de significância dos testes foi arbitrado em 5%, ou seja, diferenças foram consideradas significativas quando o valor de P dos testes foi menor que 5%. Os casos em que o valor de P se manteve entre 5% e <10% sugeriram tendências de efeito significativo. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa do Instituto Dante Pazzanese de Cardiologia, em outubro de 2010, sob o protocolo de número 3994.

pacientes, o diagnóstico de Síndrome de Marfan em 2,7%, sendo a fração de ejeção do ventrículo esquerdo (FEVE) média avaliada em 57,8%, EuroScore médio de 6,12. Nesta casuística, 55 (21,4%) pacientes foram submetidos a reoperações, sendo que, em 29 (50,9%) deles, foi realizada apenas a troca valvar aórtica no primeiro procedimento, em nove (16,4%), cirurgia para revascularização do miocárdio, em cinco (9,1%), correção de dissecção aguda da aorta, em quatro (7,3%), correção de coarctação de aorta, em três (5,4%), correção de aneurisma de aorta, e apenas um caso em cada uma das situações seguintes: troca da valva mitral, plastia da valva tricúspide, correção de persistência do canal arterial, de comunicação interventricular, de tetralogia de Fallot e de interrupção do arco aórtico. A cirurgia simultânea para revascularização do miocárdio foi necessária em 49 (19,1%) pacientes. Os dados demográficos de todos os pacientes incluídos no presente estudo encontram-se descritos na Tabela 1. Medidas quantitativas estão resumidas em amplitude, média e desvio padrão; as medidas qualitativas, em frequência absoluta e percentual. As Tabelas 2 a 7 sintetizam as análises realizadas no presente estudo.

RESULTADOS Foram incluídos 257 pacientes, no período de janeiro de 2004 a dezembro de 2010, sendo 33,9% do sexo feminino, 7% de etnia negra, com idade média de 57,7 anos. Desta população, 75% tinham diagnóstico de aneurisma de aorta ascendente e 25% de dissecção crônica de aorta tipo A de Stanford, estando o tabagismo presente em 40,5%, a diabetes mellitus em 13,2% e a hipertensão arterial sistêmica em 78,6%. A dor torácica esteve presente em 41,6% dos 12

DISCUSSÃO Nesta análise incluindo 257 pacientes consecutivos, operados durante o período de janeiro de 2004 a dezembro de 2010, a taxa de mortalidade total hospitalar de 8,17%. Por meio de análise multivariada, o modelo logístico identificou os seguintes fatores associados independentemente ao óbito durante a fase hospitalar: pacientes de etnia negra, revascularização do miocárdio associada, operação de Cabrol, presença de doença cerebrovascular, necessidade de revisão de hemostasia, tempo prolongado de circulação extracorpórea (CEC) e a presença de hemopericárdio. A presença de dor torácica foi identificada como fator protetor. Fatores como sítio de canulação axilar, uso de antifibrinolítico, complicação neurológica, presença de arritmia grave, EuroScore, tempo de anóxia (min) e sangramento nas primeiras 24 horas, por meio de análise multivariada, estiveram associados independentemente à ocorrência do desfecho clínico composto. Séries cirúrgicas contemporâneas envolvendo pacientes portadores de doença da aorta ascendente, com a utilização de modernas técnicas de enxertos e métodos de proteção cerebral e miocárdica, apresentam taxas de mortalidade hospitalar variando de 1,7% a 17,1%, provavelmente devido à heterogeneidade da população de pacientes avaliada. As causas de mortalidade incluem hemorragia, AVC e insuficiência respiratória, sendo que a insuficiência cardíaca é considerada a causa mais comum de morte prematura nessa população [3-5].

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Rev Bras Cir Cardiovasc 2013;28(1):10-21

Gazoni et al. [5] compararam resultados imediatos de cirurgia eletiva de aneurisma de aorta torácica, entre centros de baixo volume (<40 cirurgias/ano) e de alto volume (> 80 cirurgias/ano). A mortalidade operatória foi de 8,3% e 3,7%, respectivamente (P=0,02). Na análise de regressão logística, centros de baixo volume estiveram significativamente associados com aumento nas taxas de complicações e de mortalidade (P<0,05). Neste estudo, 66,1% dos pacientes eram do sexo masculino e dentre os óbitos hospitalares, 57,1% eram do sexo masculino. O sexo e a idade não apresentaram impacto com significância estatística nas taxas de mortalidade hospitalar e tardia, após o ajuste entre as diferentes variáveis no modelo multivariado. Deve ser comentado que a idade apresenta-se como fator de risco independente para mortalidade em outros cenários da doença cardiovascular, como síndrome coronária

aguda, fibrilação atrial ou insuficiência cardíaca, como também, pacientes do sexo feminino apresentam maiores taxas de mortalidade quando submetidas à cirurgia de revascularização miocárdica, em comparação aos pacientes do sexo masculino. Os resultados da pesquisa em questão podem ser explicados por meio de duas considerações: idade e sexo não representam fatores preditores independentemente associados com mortalidade em pacientes com doenças da aorta avaliadas neste trabalho ou devido à falta de poder estatístico, não foi possível demonstrar o efeito dessas duas variáveis sobre desfechos clinicamente relevantes. A inclusão de número adicional de pacientes poderia esclarecer as considerações supracitadas. Apesar dessas diferenças, quando todas as variáveis são inseridas no modelo logístico, na pesquisa atual, essas variáveis não emergiram como preditoras independentes de mortalidade.

Tabela 1. Fatores demográficos e pré-operatórios. Idade (anos) Peso (kg) Sexo Etnia Classe funcional (NYHA) Diagnóstico Métodos diagnósticos Tabagismo Diabetes mellitus DAOP HAS (mmHg) PAS PAD IRC IRC dialítica AVC prévio DPOC Doença cerebrovascular Síndrome de Marfan Síncope Derrame pericárdico Dor torácica Sintomas neurológicos Cirurgia cardíaca prévia Doença coronária RM associada FE (%) FE Creatinina EuroScore Eletiva

18 a 81 41 a 115 Masc. 170 (66,1%) Negra 18 (7%) I 70 (27,2%) Aneurisma 193 (75%) Ecocardiograma 242 (94,2%) 104 (40,5%) 34 (13,2%) 11 (4,3%) 202 (78,6%) 110 a 220 40 a 130 21 (8,2%) 1 (0,4%) 15 (5,8%) 7 (2,7%) 4 (1,6%) 7 (2,7%) 7 (2,7%) 3 (1,2%) 107 (41,6%) 4 (1,6%) 55 (21,4%) 53 (20,6%) 49 (19,1%) 20 a 80 Ecocardiograma 256 (99,6%) 0,5 a 2,4 3 a 17 247 (96,1%)

Média 57,7 Média 72,8 Fem. 87 (33,9%) Não Negra 239 (93%) II 119 (46,3%) Dissecção 64 (24,9%) TC 162 (63%)

DP 13 DP 13,27 III 65 (25,3%)

IV 3 1,2%)

Cateterismo 181 (70,4%)

RNM 2 (0,8%)

Média 151,5 Média 85,5

DP 20,1 DP 14,9

Média 57,8 RNM 1 (0,4%) Média 1,13 Média 6,12

DP 11,6 DP 0,32 DP 2,52

AVC: Acidente vascular cerebral; DAOP: Doença arterial obstrutiva periférica; DP: Desvio padrão; DPOC: Doença pulmonar obstrutiva crônica; FE: Fração de ejeção; Fem.: Feminino; HAS: Hipertensão arterial sistêmica; IRC: Insuficiência renal crônica; kg: quilograma; Masc.: Masculino; mmHg: milímetros de mercúrio; NYHA: New York Heart Association; PAD: Pressão arterial diastólica; PAS: Pressão arterial sistólica; RM: Revascularização miocárdica; RNM: Ressonância nuclear magnética; TC: Tomografia computadorizada

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Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Tabela 2. Fatores demográficos e pré-operatórios e óbito hospitalar

n (%) Feminino Negra Dissecção ECO Tabagismo Diabetes DAOP HAS IRC AVC prévio DPOC Doença cerebrovascular Síndrome de Marfan Síncope Derrame pericárdico Dor torácica Sintomas neurológicos Cirurgia cardíaca prévia Doença coronária Eletiva Canulação da aorta Valva aórtica bicúspide Insuficiência aórtica Hemopericárdio Média (DP) Mediana (Per25;Per75) Idade (anos) Última Creatinina

Variáveis Óbito hospitalar Não (N=236) Sim (N=21) 78 (33,05%) 9 (42,86%) 14 (5,93%) 4 (19,05%) 54 (22,88%) 10 (47,62%) 226 (95,76%) 16 (76,19%) 96 (40,68%) 8 (38,1%) 29 (12,29%) 5 (23,81%) 8 (3,39%) 3 (14,29%) 183 (77,54%) 19 (90,48%) 17 (7,2%) 4 (19,05%) 13 (5,51%) 2 (9,52%) 6 (2,54%) 1 (4,76%) 2 (0,85%) 2 (9,52%) 7 (2,97%) 0 (0%) 6 (2,54%) 1 (4,76%) 2 (0,85%) 1 (4,76%) 102 (43,22%) 5 (23,81%) 3 (1,27%) 1 (4,76%) 46 (19,49%) 9 (42,86%) 45 (19,07%) 8 (38,1%) 226 (95,76%) 21 (100%) 170 (72,34%) 14 (66,67%) 37 (15,68%) 2 (9,52%) 147 (62,29%) 13 (61,9%) 3 (1,27%) 2 (9,52%)

Total (N=257) 87 (33,85%) 18 (7%) 64 (24,9%) 242 (94,16%) 104 (40,47%) 34 (13,23%) 11 (4,28%) 202 (78,6%) 21 (8,17%) 15 (5,84%) 7 (2,72%) 4 (1,56%) 7 (2,72%) 7 (2,72%) 3 (1,17%) 107 (41,63%) 4 (1,56%) 55 (21,4%) 53 (20,62%) 247 (96,11%) 184 (71,88%) 39 (15,18%) 160 (62,26%) 5 (1,95%)

P valor 0,360 (P) 0,085 (F) 0,012 (P) 0,004 (F) 0,810 (P) 0,170 (F) 0,018 (P) 0,160 (P) 0,058 (P) 0,450 (P) 0,540 (P) 0,002 (P) 0,420 (P) 0,540 (P) 0,220 (F) 0,084 (P) 0,290 (F) 0,012 (P) 0,039 (P) 0,330 (P) 0,580 (P) 0,450 (P) 0,970 (P) 0,055 (F)

57,5 (13,13) 59 (48,25;68) 1,11 (0,33) 1 (0,9;1,3)

57,56 (12,95) 59 (48;67,25) 1,13 (0,32) 1 (0,9;1,3)

0,471

59,9 (11,62) 60 (53,5;67,5) 1,26 (0,29) 1,2 (1,05;1,45)

0,019

F: teste de Fisher; P: teste de Pearson. AVC: Acidente vascular cerebral; DAOP: Doença arterial obstrutiva periférica; DP: Desvio padrão; DPOC: Doença pulmonar obstrutiva crônica; HAS: Hipertensão arterial sistêmica; IRC: Insuficiência renal crônica

Numa pesquisa sobre a qualidade de vida dos pacientes operados de aneurisma de aorta, Lohse et al. [6] demonstraram conexão altamente significativa entre a operação cardíaca prévia e morte no pós-operatório (P=0,001). Houve também associação significativa entre morte e infarto do miocárdio (P<0,001), AVC (P=0,001), tempo de ventilação prolongada (P<0,001), aumento do uso de produtos de transfusão (P=0,016) e tempos cirúrgicos prolongados (P<0,001). A alta incidência de infarto do miocárdio peri-operatório esteve associada à grande porcentagem de pacientes com doença arterial coronariana. No que diz respeito à qualidade de vida, a classe funcional melhorou segundo a classificação da Canadian Cardiovascular Society. Um dos maiores impactos na redução da qualidade de vida desses pacientes foi a presença de AVC, assim como a internação prolongada. 14

Em estudo publicado por Czerny et al. [7], a idade não esteve associada a risco aumentado de mortalidade e lesão neurológica em pacientes submetidos a correção cirúrgica de doenças agudas ou crônicas da aorta torácica com parada circulatória hipotérmica, achado concordante com os resultados deste estudo. Em nossa casuística, 55 (21,4%) pacientes eram reoperações, sendo que em 29 (51%) foi realizada apenas a troca valvar aórtica no primeiro procedimento, em nove (16,4%), cirurgia para revascularização do miocárdio, em cinco (9,1%), correção de dissecção aguda da aorta, em quatro (7,3%), correção de coarctação de aorta, em três (5,5%), correção de aneurisma de aorta. Cada um dos seguintes eventos: troca da valva mitral, plastia da valva tricúspide, correção de persistência do canal arterial, de comunicação interventricular, de tetralogia de Fallot e de interrupção do arco aórtico ocorreram em apenas um caso.

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Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Tabela 3. Fatores intra e pós-operatórios e óbito hospitalar.

n (%) Cirurgia de coronárias Hemiarco Bentall Cabrol Tubo supracoronariano Tirone David Yacoub Stent aorta descendente Reimplante de vasos da base bloco Reimplante separados Aortoplastia Revisão de hemostasia Hemoderivados Antifibrinolítico Complicação neurológica Complicação renal Complicação infecciosa Complicação pulmonar Complicação vascular Complicação gastrointestinal Arritmia Falência múltiplos órgãos Insuficiência cardíaca Choque cardiogênico Síndrome má perfusão AAS Clopidogrel IECA/BRA Betabloqueador Estatina Antiarrítmico Diurético Espironolactona Média (DP) Mediana (Per25;Per75) Sangramento nas primeiras 24 horas (ml) Tempo de CEC (min) Tempo de anóxia (min) EuroScore

Não (N=236) 42 (17,8%) 18 (7,63%) 85 (36,02%) 7 (2,97%) 125 (52,97%) 4 (1,69%) 4 (1,69%) 19 (8,05%) 11 (4,66%)

Variáveis Óbito hospitalar Sim (N=21) 7 (33,33%) 2 (9,52%) 6 (28,57%) 2 (9,52%) 12 (57,14%) 1 (4,76%) 0 (0%) 3 (14,29%) 3 (14,29%)

Total (N=257) 49 (19,07%) 20 (7,78%) 91 (35,41%) 9 (3,5%) 137 (53,31%) 5 (1,95%) 4 (1,56%) 22 (8,56%) 14 (5,45%)

P valor 0,082 (P) 0,750 (P) 0,490 (P) 0,110 (P) 0,710 (P) 0,340 (F) 1,000 (F) 0,320 (P) 0,060 (P)

2 (0,85%) 3 (1,27%) 15 (6,36%) 178 (75,42%) 84 (35,59%) 13 (5,51%) 13 (5,51%) 31 (13,14%) 33 (13,98%) 1 (0,42%) 4 (1,69%) 66 (27,97%) 0 (0%) 12 (5,08%) 2 (0,85%) 0 (0%) 165 (69,92%) 1 (0,42%) 193 (81,78%) 169 (71,61%) 58 (24,58%) 44 (18,64%) 92 (38,98%) 13 (5,51%)

0 (0%) 0 (0%) 4 (19,05%) 20 (95,24%) 11 (52,38%) 4 (19,05%) 9 (42,86%) 10 (47,62%) 14 (66,67%) 6 (28,57%) 0 (0%) 14 (66,67%) 14 (66,67%) 13 (61,9%) 15 (71,43%) 16 (76,19%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

2 (0,78%) 3 (1,17%) 19 (7,39%) 198 (77,04%) 95 (36,96%) 17 (6,61%) 22 (8,56%) 41 (15,95%) 47 (18,29%) 7 (2,72%) 4 (1,56%) 80 (31,13%) 14 (5,45%) 25 (9,73%) 17 (6,61%) 16 (6,23%) 165 (64,2%) 1 (0,39%) 193 (75,1%) 169 (65,76%) 58 (22,57%) 44 (17,12%) 92 (35,8%) 13 (5,06%)

1,000 (F) 1,000 (F) 0,033 (P) 0,039 (P) 0,120 (P) 0,017 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) 1,000 (F) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) 1,000 (F) < 0,001 (P) < 0,001 (P) 0,010 (P) 0,030 (P) < 0,001 (P) 0,270 (P)

509,39 (303,3) 434 (320;640) 138,83 (45,25) 137,5 (105;162,25) 101,44 (32,87) 101 (79;123) 5,98 (2,5) 6 (4;7)

594,62 (465,31) 450 (275;999) 185,95 (90,31) 180 (122,5;195) 115,95 (57) 99 (86,5;138,5) 7,62 (2,18) 7 (6;9)

516,35 (319,23) 438 (320;650) 142,67 (50,24) 140 (110;170) 103,6 (35,29) 103 (80;125) 6,05 (2,47) 6 (4;7,25)

0,756 0,006 0,464 0,002

F: teste de Fisher; P: teste de Pearson. AAS: Ácido acetilsalicílico; BRA: Bloqueadores dos receptores da angiotensina; CEC: Circulação extracorpórea; DP: Desvio padrão; IECA: Inibidores da enzima conversora de angiotensina; min = minutos; ml: mililitros

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Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Tabela 4. Modelo logístico para óbito hospitalar. Etnia negra Doença cerebrovascular Dor torácica Hemopericárdio Tipo de operação: Cabrol Cirurgia de coronárias Revisão de hemostasia Tempo de CEC (min) Constante

Efeito 1,92 2,35 -1,32 3,56 2,29 1,49 1,74 0,02 -5,8

EP 0,76 1,14 0,64 1,14 0,97 0,62 0,76 0 1,01

RC 6,82 10,51 0,27 35,08 9,86 4,43 5,72 1,016 0

1,54 1,12 0,08 3,73 1,47 1,31 1,29 1,007

IC95%

30,2 98,7 0,94 330,2 66,36 15,06 25,29 1,026

P valor 0,011 0,04 0,04 0,002 0,019 0,017 0,021 0,001 < 0,001

Valor de P (Hosmer e Lemeshow)=0,553. CEC: Circulação extracorpórea; EP: Erro Padrão; IC: Intervalo de confiança; RC: Razão de Chances

Tabela 5. Fatores pré-operatórios e desfecho clínico composto.

n (%) Feminino Etnia negra Dissecção Tabagismo Diabetes DAOP HAS IRC AVC prévio DPOC Doença cerebrovascular Síndrome de Marfan Síncope Derrame pericárdico Dor torácica Sintomas neurológicos Cirurgia cardíaca prévia Doença coronária Eletiva Canulação da aorta Valva aórtica bicúspide Insuficiência aórtica Hemopericárdio Média (DP) Mediana (Per25;Per75) Idade (anos) Última Creatinina

Variáveis Evento combinado Não (N=159) Sim (N=98) 103 (64,78%) 67 (68,37%) 11 (6,92%) 7 (7,14%) 33 (20,75%) 31 (31,63%) 69 (43,4%) 35 (35,71%) 18 (11,32%) 16 (16,33%) 3 (1,89%) 8 (8,16%) 125 (78,62%) 77 (78,57%) 11 (6,92%) 10 (10,2%) 8 (5,03%) 7 (7,14%) 5 (3,14%) 2 (2,04%) 2 (1,26%) 2 (2,04%) 4 (2,52%) 3 (3,06%) 3 (1,89%) 4 (4,08%) 1 (0,63%) 2 (2,04%) 68 (42,77%) 39 (39,8%) 2 (1,26%) 2 (2,04%) 23 (14,47%) 32 (32,65%) 27 (16,98%) 26 (26,53%) 155 (97,48%) 92 (93,88%) 121 (76,58%) 63 (64,29%) 28 (17,61%) 11 (11,22%) 103 (64,78%) 57 (58,16%) 1 (0,63%) 4 (4,08%)

57,35 (12,38) 59 (49;67) 1,08 (0,31) 1 (0,9;1,2)

58,26 (14,01) 60,5 (48,75;69) 1,19 (0,34) 1,2 (1;1,4)

Total (N=257) 170 (66,15%) 18 (7%) 64 (24,9%) 104 (40,47%) 34 (13,23%) 11 (4,28%) 202 (78,6%) 21 (8,17%) 15 (5,84%) 7 (2,72%) 4 (1,56%) 7 (2,72%) 7 (2,72%) 3 (1,17%) 107 (41,63%) 4 (1,56%) 55 (21,4%) 53 (20,62%) 247 (96,11%) 184 (71,88%) 39 (15,18%) 160 (62,26%) 5 (1,95%)

P valor 0,550 (P) 0,560 (F) 0,500 (P) 0,220 (P) 0,250 (P) 0,016 (P) 0,990 (P) 0,350 (P) 0,480 (P) 0,710 (F) 0,630 (F) 1,000 (F) 0,430 (F) 0,560 (F) 0,630 (P) 0,630 (F) 0,001 (P) 0,066 (P) 0,140 (P) 0,033 (P) 0,160 (P) 0,280 (P) 0,071 (F)

57,7 (13,01) 59 (49;68) 1,13 (0,32) 1 (0,9;1,3)

0,393 0,004

Teste de Mann-Whitney; F: teste de Fisher; P: teste de Pearson. AVC: Acidente vascular cerebral; DAOP: Doença arterial obstrutiva periférica; DP: Desvio padrão; DPOC: Doença pulmonar obstrutiva crônica; HAS: Hipertensão arterial sistêmica; IRC: Insuficiência renal crônica

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Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Tabela 6 - Fatores intra e pós-operatório e desfecho clínico composto.

n(%) Cirurgia de coronárias Hemiarco Bentall Cabrol Tubo supracoronariano Tirone David Yacoub Stent aorta descendente Reimplante de vasos da Base Bloco Reimplante separados Aortoplastia Revisão de hemostasia Hemoderivados Antifibrinolítico Complicação neurológica Complicação renal Complicação infecciosa Complicação pulmonar Complicação vascular Complicação gastrointestinal Arritmia Falência de múltiplos órgãos Insuficiência cardíaca Choque cardiogênico Síndrome de má perfusão AAS Clopidogrel IECA/BRA Betabloqueador Estatina Antiarrítmico Diurético Espironolactona Média (DP) Mediana (Per25;Per75) Tempo de CEC (min) Sangramento nas primeiras 24 horas (ml) Tempo de Anóxia (min) EuroScore

Variáveis Evento combinado Não (N=159) Sim (N=98) 24 (15,09%) 25 (25,51%) 10 (6,29%) 10 (10,2%) 52 (32,7%) 39 (39,8%) 3 (1,89%) 6 (6,12%) 89 (55,97%) 48 (48,98%) 4 (2,52%) 1 (1,02%) 4 (2,52%) 0 (0%) 12 (7,55%) 10 (10,2%) 9 (5,66%) 5 (5,1%)

Total (N=257) 49 (19,07%) 20 (7,78%) 91 (35,41%) 9 (3,5%) 137 (53,31%) 5 (1,95%) 4 (1,56%) 22 (8,56%) 14 (5,45%)

P valor 0,039 (P) 0,250 (P) 0,240 (P) 0,073 (P) 0,270 (P) 0,650 (F) 0,300 (F) 0,460 (P) 0,840 (P)

0 (0%) 1 (0,63%) 0 (0%) 101 (63,52%) 37 (23,27%) 1 (0,63%) 2 (1,26%) 10 (6,29%) 11 (6,92%) 1 (0,63%) 1 (0,63%) 44 (27,67%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 110 (69,18%) 1 (0,63%) 132 (83,02%) 114 (71,7%) 40 (25,16%) 33 (20,75%) 51 (32,08%) 7 (4,4%)

2 (2,04%) 2 (2,04%) 19 (19,39%) 97 (98,98%) 58 (59,18%) 16 (16,33%) 20 (20,41%) 31 (31,63%) 36 (36,73%) 6 (6,12%) 3 (3,06%) 36 (36,73%) 14 (14,29%) 25 (25,51%) 17 (17,35%) 16 (16,33%) 55 (56,12%) 0 (0%) 61 (62,24%) 55 (56,12%) 18 (18,37%) 11 (11,22%) 41 (41,84%) 6 (6,12%)

0,140 (F) 0,560 (F) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) 0,013 (F) 0,150 (F) 0,120 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) < 0,001 (P) 0,034 (P) 1,000 (F) < 0,001 (P) 0,011 (P) 0,200 (P) 0,049 (P) 0,110 (P) -

130,72 (39,96) 130 (100;155) 430,84 (187,27) 380 (290;520) 96,72 (31,05) 98 (75;116) 5,55 (2,2) 6 (4;7)

162,09 (62,19) 152,5 (123,75;185) 655,1 (424,72) 540 (350;873,75) 112,19 (40,12) 111 (83;137,5) 7,04 (2,73) 7 (5,75;8)

142,68 (51,81) 140 (110;170) 516,35 (319,23) 438 (320;650) 102,62 (35,52) 101 (80;123) 6,12 (2,52) 6 (4;8)

< 0,001 < 0,001 0,002 < 0,001

Teste de Mann-Whitney; F: teste de Fisher; P: teste de Pearson. AAS: ácido acetilsalicílico; BRA: Bloqueadores dos receptores da angiotensina; CEC: Circulação extracorpórea; DP: Desvio padrão; IECA: Inibidores da enzima conversora de angiotensina; min = minutos; ml: mililitros

Rev Bras Cir Cardiovasc 2013;28(1):10-21

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Tabela 7. Modelo logístico para desfecho clínico composto. Sítio canulação: axilar Antifibrinolítico Tipo de operação: Cabrol Complicação renal** Complicação pulmonar*** Arritmia grave**** EuroESCORE Tempo de CEC (min)

Efeito 1,011 1,169 1,662 2,001 1,295 1,196 0,209 0,009

EP 0,54 0,34 0,857 0,81 0,45 0,64 0,07 0,004

RC 2,75 3,22 5,27 7,40 3,65 3,31 1,23 1,01

Constante

-4,183

0,768

0,02

0,95 1,65 0,98 1,52 1,51 0,95 1,08 1

IC95%

7,96 6,27 28,25 36,01 8,84 11,51 1,41 1,02

P valor 0,062 0,0006 0,0524 0,0132 0,0041 0,0602 0,0026 0,0265 < 0,0001

Valor de P (Hosmer e Lemeshow) =0,432; Complicação Renal**: creatinina >2 mg/dl ou 2x> pré-operatório; Complicação Pulmonar***: necessidade de ventilação invasiva em período > 48h; Arritmia grave****: TV,FV e BAVT. CEC: Circulação extracorpórea; EP: Erro Padrão; IC: Intervalo de confiança; min = minutos; RC: Razão de Chances

Embora na análise univariada para óbito hospitalar a variável cirurgia cardíaca prévia tivessem demonstrado significância estatística (P= 0,012), na análise multivariada não houve persistência do nível de significância dessa variável, demonstrando não ser um preditor independente. Como demonstraram Estrera et al. [8], pacientes com dissecção aguda tipo A após cirurgia cardíaca prévia apresentaram riscos semelhantes de má-perfusão, hipotensão e tamponamento cardíaco. Esse achado sugere que as aderências formadas após a operação não eliminam o risco de tamponamento cardíaco por ruptura de aorta. Embora os resultados sejam plausíveis, a mortalidade hospitalar foi maior (31% vs. 13,8%, P<0,007) do que entre os pacientes sem história prévia de cirurgia cardíaca. Recomenda-se a substituição profilática da aorta ascendente, mesmo que aparentemente normal, onde houver alguma dilatação, nos casos de troca de valva aórtica bicúspide. Mesmo na ausência de doença significativa da valva aórtica, existe associação frequente com a dilatação da raiz da aorta, ectasia ânulo-aórtica e dissecção da aorta. Após a substituição da valva aórtica bicúspide, esse achado é relatado como fator de risco para dissecção aguda tardia e aneurisma de aorta ascendente [9-11]. Para pacientes com valva aórtica bicúspide normofuncionante e dilatação da aorta ascendente, recomenda-se a operação para aqueles com diâmetro > 5 cm e conduta diferenciada para pacientes sob vigilância na ausência de aumento significativo (>0,5 cm/ano). A sobrevida global é considerada equivalente àquela de uma população considerada normal da mesma idade e sexo. A operação foi necessária em aproximadamente 10% dos pacientes acompanhados a cada ano [12]. Com relação aos fatores de risco para mortalidade hospitalar, Ogeng’o et al. [13] estudaram o padrão de aneurismas entre a população jovem negra do Quênia. Os pacientes foram divididos em dois grupos: ≤ 40 anos (Grupo I) e > 40 anos (Grupo II). Localizados na aorta, 18

49,6% eram do grupo I e 68,6% do grupo II. A maioria na aorta abdominal (64,9%), especialmente no segmento infrarrenal. No segmento ascendente da aorta, abaixo de 5%, sendo equivalente nos dois grupos. A proporção entre os sexos é de 2,7:1, com predominância para o sexo masculino. Nos segmentos intracraniano e aórtico, a maior incidência ocorreu entre 31 e 40 anos, e entre 21 e 30 na periferia. As comorbidades associadas em ambos os grupos foram: hipertensão arterial, tabagismo, AIDS, alcoolismo, obesidade e síndrome de Marfan. Entretanto, apenas no grupo de pacientes com idade acima de 40 anos, aterosclerose e dislipidemia estiveram presentes, estando diabetes mellitus relacionado com aneurismas periféricos e intracranianos, mas não na aorta. A prevalência de fatores de risco tradicionais aterotrombóticos variou significativamente entre os grupos étnicos. O uso de terapias médicas para reduzir o risco foi comparável entre todos os grupos. Em menos de 2 anos de seguimento, a taxa de mortalidade cardiovascular foi significativamente maior em negros (6,1%) em comparação a todos os outros grupos étnicos (3,9%; P=0,01), segundo relato de Meadows et al. [14]. Em estudos prévios, observou-se que o procedimento simultâneo para correção da aorta ascendente e revascularização do miocárdio pode ser realizado com segurança e com resultados satisfatórios. Ueda et al. [15] demonstraram que a revascularização coronária incompleta foi identificada como fator de risco para eventos cardiovasculares (P=0,016). Em uma análise para o tratamento cirúrgico da raiz da aorta, comparando o tubo valvulado com a preservação da valva aórtica, Dias et al. [16] demonstraram, de maneira consistente com os achados da presente pesquisa, que a Operação de Cabrol é um dos preditores independentes de mortalidade hospitalar e tardia. Murphy et al. [17], em recente publicação, observaram que a transfusão sanguínea em pacientes submetidos

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Rev Bras Cir Cardiovasc 2013;28(1):10-21

à cirurgia cardíaca esteve fortemente associada com infecção e morbidade pós-operatória isquêmica, tempo de internação prolongado, aumento da mortalidade precoce e tardia e aumento de custos hospitalares. Os custos foram substancialmente maiores em pacientes que necessitaram de re-exploração por sangramento, como demonstrado por Alstrom et al. [18]. Como relatado por Svensson et al. [19], pacientes submetidos a procedimentos cirúrgicos em aorta ascendente e arco aórtico, e que participaram de técnicas de conservação de sangue, apresentaram significativamente (P<0,05) menor incidência de transfusões homólogas, foram extubados em tempo mais precoce, apresentaram menor tempo de internação e receberam alta hospitalar em melhor classe funcional. A análise multivariada desses 60 pacientes mostrou que os preditores de transfusão homóloga intra-hospitalar, com valor de P<0,05, foram: idade, tempo de CEC e drenagem aumentada no pósoperatório. O derrame pericárdico é mais comum na dissecção aguda de aorta ou durante a agudização de uma dissecção crônica. Mehta et al. [20] afirmaram que a taxa de mortalidade hospitalar em dissecção aguda de aorta tipo A de Stanford é alta e pode ser prevista com o uso de um modelo clínico incorporado em uma ferramenta simples de previsão de risco. O derrame pericárdico na apresentação clínica desses pacientes foi identificado como preditor independente (P=0,07), como também a complicação tamponamento cardíaco (P<0,0001). No modelo preditor proposto, o desfecho composto hipotensão arterial, choque e tamponamento esteve associado a maior mortalidade (RC=2,97; IC 95% 1,83-4,81; P<0,001). Ranucci et al. [21] sugerem que a abordagem multifatorial parece ser mais adequada para responder às reações complexas que conduzem a lesões inflamatórias e ativação da cascata de coagulação durante as operações cardíacas. Provavelmente, a questão fundamental seja a formação de trombina que, ao mesmo tempo, é um marcador da ativação da cascata de coagulação e um gatilho para as reações de base endotelial, incluindo o consumo de antitrombina e proteína C, ativação, agregação e adesão plaquetária, expressão de adesão de moléculas e de ativação e adesão de leucócitos. O aparecimento de dor torácica com um fator protetor, reduzindo o risco de mortalidade hospitalar em 73% (P=0,04), pode ser interpretado e consubstanciado por plausibilidade epidemiológica e clínica, pelo fato de o tempo de espera para a realização da operação ser abreviado, independentemente do diâmetro da aorta, evitando-se assim ruptura, dissecção ou tamponamento cardíaco. No que diz respeito ao desfecho clínico composto, na série publicada por Souza & Moitinho [22], medidas adotadas, com o uso de antifibrinolíticos, hemodiluição

normovolêmica e reposição total do perfusato, permitiram a redução da necessidade de hemotransfusão no pósoperatório de cirurgia cardíaca. Pacientes com tempo de CEC maior que 120 minutos tenderam a necessitar de hemotransfusão. A associação de cirurgia em pacientes idosos e tempo de CEC superior a 120 minutos resultou em maior utilização de sangue e hemoderivados no período pós-operatório. Brown et al. [23] realizaram meta-análise para comparar aprotinina, ácido épsilon-aminocapróico e ácido tranexâmico. Os resultados incluíram a perda de sangue total, transfusão de concentrado de hemácias, reexploração, mortalidade, AVC, infarto do miocárdio, insuficiência renal dialítica e disfunção renal. Todos os antifibrinolíticos foram eficazes na redução da perda de sangue e transfusão. Não houve riscos significativos ou benefícios para a mortalidade, AVC, infarto do miocárdio ou insuficiência renal. No entanto, a dose alta de aprotinina foi associada a risco aumentado de disfunção renal estatisticamente significativo. O EuroScore demonstrou associação clara com a ocorrência de desfechos clínicos compostos, nessa população estudada, devendo ser considerado importante ferramenta na determinação do risco desses pacientes, mesmo tendo sido elaborado em outros países, com serviços médicos e população distintos. Chertow et al. [24] avaliaram 42.773 pacientes submetidos à cirurgia cardíaca valvar ou revascularização do miocárdio para determinar a associação entre insuficiência renal aguda e necessidade de diálise e mortalidade operatória. Insuficiência renal aguda ocorreu em 1,1% dos pacientes. A mortalidade operatória foi de 63,7% nesses pacientes, comparados a 4,3% nos pacientes sem essa complicação. Após o ajuste para fatores relacionados a comorbidades, a RC foi de 27; IC 95% 22-34. Foi concluído que insuficiência renal aguda esteve associada independentemente com mortalidade precoce após cirurgia cardíaca e que intervenções para previnir ou melhorar o tratamento dessa condição são necessárias, devendo ser implementadas com brevidade dentro desse cenário clínico-cirúrgico. Wynne & Botti [25] descreveram a frequência de complicações pulmonares após cirurgia cardíaca: derrame pleural (25-95%), atelectasia (17-88%), paralisia do nervo frênico (30-75%), ventilação mecânica prolongada (658%), disfunção diafragmática (2-54%), pneumonia (420%), paralisia diafragmática (9%), embolia pulmonar (0,4-3,2%), síndrome do desconforto respiratório agudo (0,4-2%), aspiração (1,9%) e pneumotórax (1,4%). CONCLUSÃO 1. Etnia negra, doença cerebrovascular, hemopericárdio, operação de Cabrol, revascularização miocárdica cirúrgica 19

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

Rev Bras Cir Cardiovasc 2013;28(1):10-21

associada, revisão de hemostasia e tempo de CEC associaram-se independentemente com risco aumentado de óbito hospitalar. A presença de dor torácica associou-se independentemente com risco reduzido de óbito hospitalar. 2. Uso de antifibrinolítico, complicação renal, complicação pulmonar, EuroScore e tempo de CEC prolongado associaram-se independentemente com risco aumentado de desfecho clínico composto hospitalar (óbito, sangramento, disfunção ventricular ou complicações neurológicas).

and transverse aortic arch. Factors influencing survival in 717 patients. J Thorac Cardiovasc Surg. 1989;98(5 Pt 1):659-73.

AGRADECIMENTOS Os autores agradecem à estatística Roberta de Souza, à secretária da Divisão de Epidemiologia Translacional, Simone Batista da Cruz, e ao analista de sistemas, Wellington Cícero de Carvalho.

5. Gazoni LM, Speir AM, Kron IL, Fonner E, Crosby IK. Elective thoracic aortic aneurysm surgery: better outcomes from highvolume centers. J Am Coll Surg. 2010;210(5):855-9. 6. Lohse F, Lang N, Schiller W, Roell W, Dewald O, Preusse CJ, et al. Quality of life after replacement of the ascending aorta in patients with true aneurysms. Tex Heart Inst J. 2009;36(2):104-10. 7. Czerny M, Krähenbühl E, Reineke D, Sodeck G, Englberger L, Weber A, et al. Mortality and neurologic injury after surgical repair with hypothermic circulatory arrest in acute and chronic proximal thoracic aortic pathology: effect of age on outcome. Circulation. 2011;124(13):1407-13. 8. Estrera AL, Miller CC, Kaneko T, Lee TY, Walkes JC, Kaiser LR, et al. Outcomes of acute type a aortic dissection after previous cardiac surgery. Ann Thorac Surg. 2010;89(5):1467-74.

REFERÊNCIAS 1. Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/ AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010;121(13):e266-369. 2. Johansson G, Markström U, Swedenborg J. Ruptured thoracic aortic aneurysms: a study of incidence and mortality rates. J Vasc Surg. 1995;21(6):985-8. 3. Kouchoukos NT, Wareing TH, Murphy SF, Perrillo JB. Sixteen-year experience with aortic root replacement. Results of 172 operations. Ann Surg. 1991;214(3):308-18. 4. Crawford ES, Svensson LG, Coselli JS, Safi HJ, Hess KR. Surgical treatment of aneurysm and/or dissection of the ascending aorta, transverse aortic arch, and ascending aorta

9. Nistri S, Sorbo MD, Martin M, Palisi M, Scognamiglio R, Thiene G. Aortic root dilatation in young men with normally functioning bicuspid aortic valves. Heart. 1999;82(1):19-22. 10. Russo CF, Mazzetti S, Garatti A, Ribera E, Milazzo A, Bruschi G, et al. Aortic complications after bicuspid aortic valve replacement: long-term results . Ann Thorac Surg. 2002;74(5):S1773-6. 11. Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt TM 3rd. Should the proximal arch be routinely replaced in patients with bicuspid aortic valve disease and ascending aortic aneurysm? J Thorac Cardiovasc Surg. 2011;142(3):602-7. 12. Chaturvedi N. Ethnic differences in cardiovascular disease. Heart 2003;89(6):681-6. 13. Ogeng’o JA, Obimbo MM, Olabu BO, Sinkeet RA. Pattern of aneurysms among young black Kenyans. Indian J Thorac Cardiovasc Surg. 2011;27(2):70-5. 14. Meadows TA, Bhatt DL, Cannon CP, Gersh BJ, Röther J, Goto S, et al; the REACH Registry Investigators. Ethnic differences in cardiovascular risks and mortality in atherothrombotic disease: insights from the Reduction of Atherothrombosis for Continued Health (REACH) registry. Mayo Clin Proc. 2011;86(10):960-7. 15. Ueda T, Shimizu H, Shin H, Kashima I, Tsutsumi K, Iino Y, et al. Detection and management of concomitant coronary artery disease in patients undergoing thoracic aortic surgery. Japan J Thorac Cardiovasc Surg. 2001;49(7):424-30. 16. Dias RR, Mejia OAV, Fiorelli AI, Pomerantzeff PMA, Dias AR, Mady C, et al. Análise do tratamento cirúrgico da raiz

Issa M, et al. - Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta

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da aorta com tubo valvulado e com a preservação da valva aórtica. Rev Bras Cir Cardiovasc. 2010;25(4):491-9.

A systematic review of biocompatible cardiopulmonary bypass circuits and clinical outcome. Ann Thorac Surg. 2009;87(4):1311-9.

17. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116(22):2544-52. 18. Alström U, Levin LA, Stahle E, Svedjeholm R, Friberg Ö. Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery. Br J Anaesth. 2011;108(2):216-22. 19. Svensson LG, Sun J, Nadolny E, Kimmel WA. Prospective evaluation of minimal blood use for ascending aorta and aortic arch operations Ann Thorac Surg. 1995;59(6):1501-8. 20. Mehta RH, Suzuki T, Hagan PG, Bossone E, Gilon D, Llovet A, et al; International Registry of Acute Aortic Dissection (IRAD) Investigators. Predicting death in patients with acute type A aortic dissection. Circulation. 2002;105(2):200-6. 21. Ranucci M, Balduini A, Ditta A, Boncilli A, Brozzi S.

22. Souza HJ, Moitinho RF. Estratégias para redução do uso de hemoderivados em cirurgia cardiovascular. Rev Bras Cir Cardiovasc. 2008;23(1):53-9. 23. Brown JR, Birkmeyer NJ, O’Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation. 2007;115(22):2801-13. 24. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med. 1998;104(4):343-8. 25. Wynne R, Botti M. Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice. AM J Crit Care. 2004;13(5):384-93.

Aikawa P, et al. - Impact of coronary artery bypass grafting in elderly ORIGINAL ARTICLE patients

Rev Bras Cir Cardiovasc 2013;28(1):22-8

Impact of coronary artery bypass grafting in elderly patients Impacto da cirurgia de revascularização do miocárdio em pacientes idosos

Priscila Aikawa1, Angélica Rossi Sartori Cintra2, Cleber Aparecido Leite3, Ricardo Henrique Marques4, Claudio Tafarel Mackmillan da Silva5, Max dos Santos Afonso5, Felipe da Silva Paulitsch6, Evandro Augusto Oss7 DOI: 10.5935/1678-9741.20130005

RBCCV 44205-1438

Abstract Objective: To analyze the results of isolated on-pump coronary artery bypass graft surgery (CABG) in patients ≥ 65 years-old. Methods: Patients undergoing isolated on-pump CABG from December 1st 2010 to July 31th 2012 were divided in two groups: GE (elderly ≥ 65 years-old, n=103) and GA (adults < 65 years-old, n=150). Preoperative data, intraoperative (as cardiopulmonar bypass time, aortic clamping time, time length of stay in mechanical ventilation - MV - and number of grafts), and postoperative variable (as morbidity, mortality and time length of stay in hospital) were analyzed during hospitalization. Results: In GE, the morbidity rate was greater than in GA (30% vs. 14%, P=0.004), but there was no difference in the mortality rate (5.8% vs. 2.0%, P=0.165). In GA, there was higher prevalence DM (39.6% vs. 27%, P=0.043) and smoking (32.2% versus 19.8%, P=0.042); and in GE, higher prevalence of stroke (17% vs. 6.7%, P=0.013). There was no difference between the groups regarding intraoperative variables. After multivariate analysis, age ≥ 65-year-old was associated with greater morbidity, but it was not independent

predictive factor for in-hospital mortality. Considering in-hospital mortality, stay in ward time length (P=0.006), cardiac (P=0.011) and respiratory complications (P=0.026) were independent predictive factors. Conclusion: This study suggests that patients ≥ 65-yearold were at increased risk of postoperative complications when submitted to isolated on-pump CABG in comparison to patients < 65-year-old, but not under increased risk of death.

1. PhD - Faculty of Medicine of University of Sao Paulo, Faculty Anhanguera of Rio Grande, Associação de Caridade da Santa Casa do Rio Grande, Rio Grande do Sul, Brazil. 2. PhD - Faculty of Medicine of University of Campinas, Faculty Anhanguera of Campinas, São Paulo, Brazil. 3. PhD – Federal University of Sao Paulo, Faculty Anhanguera of Santo Andre I, São Paulo, Brazil. 4. PhD - Faculty Anhanguera of Santo Andre III, University of Mogi das Cruzes, São Paulo, Brazil. 5. Student of Physicaltherapist of Faculty Anhanguera of Rio Grande, Rio Grande do Sul, Brazil. 6. PhD in Cardiology (Faculty of Medicine of University of Sao Paulo), Faculty of Medicine of Federal University of Rio Grande, Rio Grande do Sul, Brazil. 7. Cardiovascular surgeon of Associação de Caridade da Santa Casa do Rio Grande, Rio Grande do Sul, Brazil.

Work carried out at Hospital de Cardiologia Doutor Pedro Bertoni da Associação de Caridade da Santa Casa do Rio Grande, Rio Grande, RS, Brasil.

Descriptors: Myocardial revascularization. Hospital mortality. Postoperative complications.

Elderly.

Resumo Objetivo: Analisar os desfechos da cirurgia de revascularização do miocárdio (CRM) isolada com circulação extracorpórea em pacientes com idade ≥ 65 anos em comparação àqueles com < 65 anos. Métodos: foram analisados 253 pacientes submetidos consecutivamente à CRM isolada entre 1º de dezembro de 2010 a 31 de julho de 2012. Os pacientes foram separados em dois grupos: GI (idosos ≥ 65 anos) e GA (adultos < 65 anos).

Correspondence address Priscila Aikawa Rua General Câmara, 432 – Centro – Rio Grande, RS, Brasil – Zip code: 96200-320 E-mail: priaikawa@hotmail.com Supported by FUNADESP, Sao Paulo/Brazil, protocol number 5500255.

Article received on October 30th, 2012 Article accepted on December 18th, 2012

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Aikawa P, et al. - Impact of coronary artery bypass grafting in elderly patients

Abbreviations, Acronyms & Symbols AMI CABG CAD CAT CHF CPB CRF DM GA GE ICU MV PVD SD SPSS

Acute myocardial infarction Coronary artery bypass grafting Coronary artery disease Coronary arteriography Chronic heart failure Cardiopulmonary bypass Chronic renal failure Diabetes mellitus Group of adult (patients < 65years-old) Group of elderly (patients ≥ 65years-old) Intensive care unit Mechanical ventilation Peripheral vascular disease Standard deviation Statistical Package for the Social Science

Foram analisadas variáveis pré-operatórias, intraoperatórias (tempo de CEC, tempo de pinçamento aórtico, tempo de submissão à VM e número de enxertos) e pós-operatórias (morbidade, mortalidade e tempo de internação). Resultados: Dos 253 pacientes, 103 pertenciam ao GI

INTRODUCTION The growth of the elderly population, in absolute and relative numbers, is a worldwide phenomenon and is occurring at an unprecedented level. Currently, one in ten people aged 60 or older. In year 2050, it is estimated that the ratio will be one to five in the world, and one to three in developed countries. In Brazil, life expectancy has increased more than ten years (62.57 years to 73.17 years) and it is estimated that in 2050, the Brazilian population over 15% of people have 70 years or older [1]. Advanced age is a risk factor for development of coronary artery disease (CAD), diabetes mellitus, hypertension, dyslipidemia, smoking, obesity and family history of CAD. Elderly population has greater prevalence of CAD, and more inclinable to major coronary procedures as coronary artery bypass surgery (CABG). Additionally, cardiovascular disease is the major factor contributing to death, especially in elderly [2-4]. CABG is a safe procedure performed around the world with low rates of mortality and morbidity in the general population. The number of octogenarians undergoing CABG increased from 0.13%, in 1986, to 3.5%, in 2001, at the Heart Institute of the Clinical Hospital

(40,7%) e 150 ao GA (59,3%). A taxa de morbidade foi significativamente maior no GI quando comparada ao GA (30% vs. 14%, P=0,004), porém não houve diferença na taxa de mortalidade (5,8% vs. 2,0%, P=0,165). No GA havia maior prevalência DM (39,6% vs. 27%, P=0,043) e tabagismo (32,2% vs. 19,8%, P=0,042); e no GI, maior prevalência de acidente vascular encefálico prévio (17% vs. 6,7%, P=0,013). Não houve diferença entre os grupos quanto às variáveis intraoperatórias. Na análise multivariada: tempo de internação na enfermaria (P=0,006), complicações cardíacas (P=0,011) e complicações respiratórias (P=0,026) foram variáveis preditoras de risco para maior mortalidade intrahospitalar. No entanto, a idade ≥ 65 anos não foi um fator preditor de risco associada a variável óbito. Conclusão: Este estudo sugere que pacientes com idade igual ou superior a 65 anos possuem um maior risco de complicações intra-hospitalares no pós-operatório de CRM isolada com CEC em comparação com pacientes mais jovens. Descritores: Revascularização miocárdica. Idoso. Mortalidade hospitalar. Complicações pós-operatórias.

of the Faculty of Medicine, University of São Paulo, the last 16 years (1986-2001) [5]. Thus, recent studies demonstrate the concern of evaluating the outcomes of CABG in elderly patients and comparison with younger individuals to verify the risks to which the elderly are more vulnerable because they are considered high risk patients for this surgery [6,7]. Another important fact is that in the last decade, there have been many changes in surgical techniques, such as the advent of minimally invasive surgery, off-pump CABG, and new devices. Thus, the indication of CABG for elderly patients is increasing because it provides better survival and quality of life [8-12]. The aim of this study was to analyze the outcomes of CABG in patients aged 65 years or older compared with younger patients (<65 years) at a regional reference hospital in Southern Brazil. METHODS The project was approved by the Research Ethics Committee of the Hospital Associação de Caridade Santa Casa Rio Grande (RS, Brazil) under protocol number 001/2011. 23

Aikawa P, et al. - Impact of coronary artery bypass grafting in elderly patients

Rev Bras Cir Cardiovasc 2013;28(1):22-8

This is a prospective study in which all patients who consecutively underwent CABG alone between 1st December 2010 to 31th July 2012 were analyzed at the Cardiology Hospital Doutor Pedro Bertoni of the Associação de Caridade Santa Casa Rio Grande (RS / Brazil). Patients undergoing CABG or associated with other cardiac surgery were excluded from the study. We included patients who needed surgery elective and urgent or emergency according to the criteria of the American Heart Association and the American College of Cardiology. Patients were divided into two groups, the group of elderly (GE) consisted of patients aged greater than 65 years and the adult group (GA) with patients under the age of 65. Data were collected daily directly from medical records and interviews with patients since its admission to discharge through a pre-structured form. All patients were elucidated on the research and signed an informed consent form. The variables collected from the medical records and through interviews with patients were: sex, age, weight, height, race, comorbidities, prior CABG, prior coronary angiography, angioplasty surgery, sedentary lifestyle, smoking, alcohol consumption, number of grafts, time CPB, aortic clamping time, time of submission to mechanical ventilation (MV), length of stay in the Intensive Care Unit (ICU) and in the ward, postoperative complications and progression to hospital discharge or death. The data were analyzed with the Statistical Package for Social Science (SPSS, version 13.0, Inc., Chicago, IL, USA). Continuous variables were expressed as means and standard deviations (SD), while categorical variables by proportions. Normality was checked using the Kolmogorov-Smirnov test. In the statistical analysis we used the Student t test to compare the means, and the chi-square or Fisher exact test to compare proportions. To determine which factors independently influence the development outcomes of the study was analyzed using multivariate logistic regression "stepwise forward". To verify the correlation between risk factors preoperative, intraoperative variables, postoperative variables and mortality was used the Spearman test. In all analyzes were considered significant when P <0.05.

lifestyle, acute myocardial infarction (AMI), coronary angiography (CAT), previous angina pectoris, previous peripheral vascular disease (PVD), previous CABG, chronic renal failure (CRF) and failure chronic heart failure (CHF) and dyslipidemia. However, patients in the GA had a higher prevalence of diabetes mellitus (DM) (39.6% vs. 27%, P=0.043) and smoking (32.2% vs. 19.8%, P=0.042), whereas the GE patients had a higher prevalence of stroke prior (17% vs. 6.7%, P=0.013). Table 2 shows the results of the surgery. There was no significant difference in mortality between the groups (P=0.165), but the rate of hospital morbidity was significantly higher in GE (30% vs. 14%, P=0.004).

RESULTS During the study period, 253 consecutive patients submitted isolated on-pump CABG was assigned either Elderly Group (GE, n=103, 41%) or Adult Group (GA, n=150, 59%). The clinical and demographic characteristics of the patients are summarized in Table 1, which demonstrates a higher prevalence of males in both groups: GE = 61% and GA = 70%; no difference regarding gender, history of CAD in the family, hypertension, alcohol consumption, sedentary 24

Table 1. Clinical and demographic preoperative characteristics. Male (%) Age (mean ± SD years) Hypertension (%) DM (%) CAD family history (%) Smoking (%) Alcoholism (%) Sedentary Lifestyle (%) Previous AMI (%) Previous CAT (%) Previous stroke (%) Angina pectoris (%) PVD (%) Previous CABG (%) CRF (%) CHF (%) Dyslipidemia (%)

GA (150) 70 57 ± 6 81.2 39.6 68 32.2 23.6 68.2 49.7 27.7 6.7 72.3 12.2 3.4 5.4 13.5 42.9

GE (103) 61 72 ± 5 79 27 61.6 19.8 20 67 45 24 17 75 10 3 9 8 50

P 0.175 0.000 0.745 0.043 0.339 0.042 0.536 0.890 0.518 0.558 0.013 0.663 0.685 1.000 0.310 0.221 0.299

GA= adult group; GE= elderly group; DM= diabetes mellitus; CAD= coronary artery disease; AMI= acute myocardial infarction; CAT= coronary arteriography; PVD= peripheral vascular disease; CABG= coronary artery bypass grafting; CRF= chronic renal failure; CHF= chronic heart failure

Table 2. Surgical outcomes. Mortality (%) Morbidity (%) Complications categories: Respiratory (%) Cardiac (%) Gastrintestinal (%) Neurological (%) Other (%)

GA (150) 2.0 14

GE (103) 5,8 30

P 0.165 0.004

2 8 0 0 4

5 13 3 2 7

0.277 0.191 0.066 0.165 0.389

GA= adult group; GE= elderly group

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Complications were divided into five categories: (1) pulmonary complications: respiratory infection, (2) cardiac complications: arrhythmia, cardiac arrest, reinfarction, precordial pain and atrial fibrillation, (3) gastrointestinal complications: abdominal distension, (4) neurological complications: stroke, and (5) other complications: increased postoperative bleeding, mediastinitis, septic shock and sternal instability. There was no significant difference between the categories of complications comparing the groups. Intraoperative data, MV and length of stay for both groups are shown in Table 3. There was no significant difference between groups in the time length of stay on MV <24 hours (P=0.096), MV between 24 and 48 hours (P=0.071) and MV> 48 hours (P=1.000); time of CPB (P=0.334) and aortic clamping (P=0.214), number of grafts (P=0.412), length of stay in ICU (P=0.140) and total time in hospital (P=0.144). However, the GE patients had more days hospitalized than patients in GA (P=0.036). In Table 4, we analyzed the in-ICU and total in-

hospitalization time in the two groups. In-ICU ≥ 5 days was greater in GE group (P = 0.010), but there is no difference in total in-hospital time between groups (P = 0.141). After univariate analysis, the risk factors associated with hospital mortality were chronic renal failure, dyslipidemia, lin-ICU time ≥ 5 days, in-ICU time, in-ward time, MV for more than 24 hours, CPB time, cardiac and respiratory complications. However, the age ≥ 65 years was not a risk factor (Table 5). After multivariate logistic regression analysis, the inward time (P=0.006), cardiac complications (P=0.011) and respiratory complications (P=0.026) were predictors of risk (P≤0.05) for hospital mortality (Table 6). In GE, we found that hospital mortality was positively correlated with length of stay in ICU ≥ 5 days (P=0.008), MV ≥ 48 hours (P<0.001), postoperative complications (P<0.001) and cardiac complications (P=0.004). Already in GA, hospital mortality showed positive correlation with DM (P=0.031), chronic renal failure (P=0.030), dyslipidemia (P=0.044), MV ≥ 48 hours (P=0.029), postoperative complications (P<0.001) and respiratory complications (P<0.001).

Table 3. Intraoperative data, mechanical ventilation and length of stay. MV 24 hours (%) MV > 24and ≤ 48 hours (%) MV > 48hours (%) CPB (mean ± SD, minutes) Aortic clamping time (mean ± SD, minutes) Grafts (%)

Lenght of stay in ICU (mean ± SD, days) Lenght of stay in ward (mean ± SD, days) Total time in-hospital (mean ± SD, days)

1 2 3 4

GA (150) 80 15 5.3 63 ± 19 40 ± 14 12.7 40.7 34 12.7 3.74 ± 3,91 5.71 ± 2.57 10.28 ± 5.79

GE (103) 70 25 5 60 ±16 37 ± 12 7.8 36.9 42.7 12.6 4.60 ± 5.27 6.48 ± 3.23 11.48 ± 7.09

P 0.096 0.071 1.000 0.334 0.214 0.412 0.140 0.036 0.144

GA= adult group; GE= elderly group; MV= mechanical ventilation; CPB= cardiopulmonary bypass; ICU= intensive care unit

Table 4. Results of the length of stay in the ICU and total time in-hospital. Lenght of stay in ICU ≥ 5 days (%)

GA (150) 14.8

GE (103) 28.7

P 0,010

Total time in-hospital ≥ 11 days (%)

22.1

30.7

0.141

GA= adult group; GE= elderly group; ICU= intensive care unit

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Aikawa P, et al. - Impact of coronary artery bypass grafting in elderly patients

Table 5. Univariate analysis. Variable Age ≥ 65 anos BMI Gender CAD Grafts DM Smoking Alcoholism Sedentary lifestyle Previous AMI Previous CAT Previous stroke Angina pectoris PVD Hypertension Previous CABG CRF CHF Dyslipidemia Lenght of stay in ICU ≥ 5 dias Lenght of stay in ICU Lenght of stay in ward Total time in-hospital Total time in-hospital ≥ 11 days MV > 24 hours Time in CPB Aortic clamping time Cardiac complications Respiratory complications Other complications Gastrintestinal complications Neurological complications

OR 3.031 0.941 1.610 1.064

IC 0.740 – 12.407 0.789 – 1.124 0.421 – 6.157 0.191 – 5.931

3.927 2.797 1.783 0.951 1.095 1.421 1.662

0.705 – 21.887 0.550 – 14.212 0.318 – 10.002 0.171 – 5.305 0.217 – 5.532 0.254 – 7.945 0.187 – 14.776

4.154 1.231

0.725 – 23.795 0.141 – 10.781

5.675 4.154

1.020 – 31.578 0.725 – 23.795

7.174 1.091 0.499 1.030 1.800 4.101 1.047 1.036 8.960 11.333 2.417

1.655 – 31.103 1.018 – 1.170 0.337 – 0.737 0.944 – 1.123 0.418 – 7.754 1.065 – 15.784 1.014 – 1.081 0.993 – 1.081 2.227 – 36.048 1.934 – 66.405 0.279 – 20.920

P 0.123 0.503 0.487 0.943 0.038* 0.119 0.215 0.511 0.955 0.913 0.689 0.649 0.346* 0.110 0.851 0.999* 0.047 0.110 0.009* 0.008 0.014 < 0.001 0.509 0.430 0.040 0.005 0.104 0.002 0.007 0.423 0.999* 0.999*

BMI= body mass index; CAD= coronary artery disease; DM= diabetes mellitus; AMI= acute myocardial infarction; CAT= coronary arteriography; PVD= peripheral vascular disease; CABG= coronary artery bypass grafting; CRF= chronic renal failure; CHF= chronic heart failure; ICU= intensive care unit; MV= mechanical ventilation; CPB= cardiopulmonary bypass; * Fisher exact test

Table 6. Predictive factors of hospital mortality by logistic regression analysis. Lenght of stay in ward Cardiac complications Respiratory complications

DISCUSSION This study in patients undergoing CABG alone suggests that patients aged ≥ 65 years are subject to greater risk of postoperative complications than patients under 65, but there was no difference between the mortality rate between the groups. 26

OR 0.542 10.580 12.819

IC95% 0.350 – 0.840 1.722 – 64.999 1.352 – 121.586

P 0.006 0.011 0.026

Regarding to mortality rate, a study examining predictors of hospital mortality in patients undergoing CABG in acute myocardial analyzed that advanced age is a risk factor related to mortality [13]. Rocha et al. [14] also reported on a study conducted at the National Institute of Cardiology of Rio de Janeiro that the variables: age ≥ 70 years, need for reoperation for revision of homeostasis,

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sepsis and respiratory complications postoperatively were associated with hospital mortality. As well, in another study in Santa Catarina/Brazil, the authors found the same relationship [15]. In our study, we found that age ≥ 65 years was not a predictor of mortality, similar to other reported by Ng et al. [16] in a retrospective study with 1594 patients undergoing CABG alone, where no significant difference in hospital mortality between patients aged ≥ 70 years (5.4%) compared to those with less than 70 years (3.8%). Even after 30 days of surgery, the mortality of patients aged ≥ 70 years was 3.8% compared with 3.3% of patients aged <70 years (P<0.740). The morbidity rate in hospital was higher in the GE compared to the GA. This data is in according to other study, which were also investigated the outcomes of CABG in elderly patients [14,17,18]. Pivatto et al. [19] observed that the morbidity rate was 34.4% in octogenarian patients undergoing CABG alone. We observed a morbidity rate of 30% in GE that was significantly higher compared to patients in the GA (14%). These data support the hypothesis that elderly patients have more postoperative complications. In the GE, we founded that the prevalence of respiratory, cardiac, gastrointestinal, neurological, and other complications were higher compared to the GA, but there was no significant difference. Rocha et al. [14] observed that these complications were more developed for patients aged ≥ 70 years, which had more respiratory complications (21.4% vs. 9.1%, P<0.001), mediastinitis (5.1% vs. 1.9%, P=0.013), stroke (3.9% vs. 1.3%, P=0.016), acute renal failure (7.8% vs. 1.3%, P<0.001), sepsis (3.9% vs. 1.9%, P=0.003), atrial fibrillation (15.6% vs. 9.8%, P=0.016) and 3rd degree atrioventricular block (3.5% vs. 1.2%, P=0.023) in the postoperative period compared to patients < 70 years-old. In a retrospective study, Machado et al. [5] reported 10% mortality rate in octogenarian patients undergoing CABG, and observed the occurrence of cardiac arrhythmias (especially atrial fibrillation), cerebrovascular, and respiratory complications in the postoperative period. In our study, the cardiac complications were also major postoperative complications (12.6%). However, it was followed by respiratory complications (4.9%), and a lower incidence of neurological complications (1.9%). Anderson et al. [20] observed predictors of mortality in patients undergoing cardiac surgery comparing septuagenarians and octogenarians, there was no significant difference in mortality rate between the groups. As observed in our study, preoperative variables did not increase the risk to death, but researchers have shown that cardiopulmonary bypass time > 75 minutes has 3.2 times (CI: 1.3 - 7.9) greater chance of to death than patients with cardiopulmonary bypass time < 75 minutes, and

postoperative variables such as prolonged mechanical ventilation above 12 hours, length of stay in ICU, reoperation, inotropic support more than 48 hours, and the need for blood products are associated with increased mortality. In this study, we found that postoperative variables such as length of stay in hospital, and cardiac and respiratory postoperative complications are associated with higher mortality, suggesting that patients who had postoperative complications remained more time hospitalized, increasing the risk of mortality hospital. Recently, in a retrospective study [14] with 655 patients undergoing CABG, the authors observed that length of stay in ICU ≥ 3 days had positive correlation with death, but this study did not examine this relationship by age, and yes, total population sample. Our results show that length of stay ≥ 5 days had positive correlation with death in GE, emphasizing the importance of studies that evaluate the outcomes of CABG in elderly patients. Analyzing the most recent data in the literature, there is disagreement about what age, in elderly patients, the morbimortality appears to be significantly higher compared to adult patients. We found studies that described their groups of elderly with age ≥ 65 years-old [12], ≥ 70 yearsold [13-17], ≥ 75 years-old [6,21], ≥ 80 years-old [22] and ≥ 85 years-old [23]. Therefore we will suggest that more studies to be made in order to can to conclude in which age the risks factors of this surgery appear enlarged, whether preoperative, intraoperative or postoperative outcomes. CONCLUSION This study suggests that patients with 65 years old or more undergoing isolated on-pump coronary artery bypass surgery have a higher risk of postoperative complications in comparison with younger patients. The highest prevalence was heart complications, followed by respiratory complications; and lower prevalence of gastrointestinal and neurological complications.

REFERENCES 1. Brasil. Instituto Brasileiro de Geografia e Estatística (homepage). Brasília, DF. Ministério do Planejamento, Orçamento e Gestão; (tábuas completas de mortalidade 2008; comunicação social em 27.09.2008). Disponível em: http:// www.ibge.gov.br Acesso em 01/10/2012. 2. Kurlansky P. Do octogenarians benefit from coronary artery bypass surgery: a question with a rapidly changing answer? Curr Opin Cardiol. 2012;27(6):611-9.

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3. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117(4):e25-e146.

13. Mejía OAV, Lisboa LAF, Tiveron MG, Santiago JAD, Tineli RA, Dallan LAO, et al. Cirurgia de revascularização miocárdica na fase aguda do infarto: análise dos fatores preditores de mortalidade intra-hospitalar. Rev Bras Cir Cardiovasc. 2012;27(1):66-74.

4. Veeranna V, Pradhan J, Niraj A, Fakhry H, Afonso L. Traditional cardiovascular risk factors and severity of angiographic coronary artery disease in the elderly. Prev Cardiol. 2010;13(3):135-40. 5. Machado LB, Chiaroni S, Vasconcelos Filho PO, AulerJúnior JOC, Carmona MJC. Incidência de cirurgia cardíaca em octogenários: estudo retrospectivo. Rev Bras Anestesiol. 2003;53(5):646-53. 6. Rocha ASC, Pittella FJM, Lorenzo AR, Barzan V, Colafranceschi AS, Brito JOR, et al. A idade influencia os desfechos em pacientes com idade igual ou superior a 70 anos submetidos à cirurgia de revascularização miocárdica isolada. Rev Bras Cir Cardiovasc. 2012;27(1):45-5. 7. Al-Alao BS, Parissis H, McGovern E, Tolan M, Young VK. Propensity analysis of outcome in coronary artery bypass graft surgery patients >75 years old. Gen Thorac Cardiovasc Surg. 2012;60(4):217-24. 8. Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1991 guidelines for coronary artery bypass graft surgery). Circulation. 1999;100(13):1464-80. 9. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, Di Mario C, Falk V, Folliguet T. Guidelines on myocardial revascularization. Eur J Cardiothorac Surg. 2010;38(Suppl):S1-S52. 10. Braile DM, Leal JCF, Soares MJ, Godoi MF, Paiva O, Petrucci Júnior O, et al. Revasculação do miocárdio com cirurgia minimamente invasiva (MIDCAB): resultados em 46 pacientes. Rev Bras Cir Cardiovasc. 1998;13(3):194-7. 11. Shroyer AL, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E, et al; Veterans Affairs Randomized On/Off Bypass (ROOBY) Study Group. On-pump versus off-pump coronaryartery bypass surgery. N Engl J Med. 2009;361(19):1827-37. 12. Blacher C, Ribeiro JP. Cirurgia de revascularização miocárdica sem circulação extracorpórea: uma técnica em busca de evidências. Arq Bras Cardiol. 2003;80(6):656-62.

14. Rocha ASC, Pittella FJM, Lorenzo AR, Barzan V, Colafranceschi AS, Brito JOR, et al. A idade influencia os desfechos em pacientes com idade igual ou superior a 70 anos submetidos à cirurgia de revascularização miocárdica isolada. Rev Bras Cir Cardiovasc. 2012;27(1):45-51. 15. Oliveira EL, Westphal GA, Mastroeni MF. Características clínico-demográficas de pacientes submetidos à cirurgia de revascularização do miocárdio e sua relação com a mortalidade. Rev Bras Cir Cardiovasc. 2012;27(1):52-60. 16. Ng CY, Ramli MF, Awang Y. Coronary bypass surgery in patients aged 70 years and over: mortality, morbidity, length of stay and hospital cost. Asian CardiovascThorac Ann. 2004;12(3):218-23. 17. Johnson WM, Smith JM, Woods SE, Hendy MP, Hiratzha LF. Cardiac surgery in octogenarians: does age alone influence outcomes? Arch Surg. 2005;140(11):1089-93. 18. Alves Jr. L, Rodrigues AJ, Évora PRB, Basseto S, Scorzoni Filho A, Luciano PM, et al. Fatores de risco em septuagenários ou mais idosos submetidos à revascularização do miocárdio e ou operações valvares. Rev Bras Cir Cardiovasc. 2008;23(4):550-5. 19. Pivatto Jr F, Kalil RAK, Costa AR, Pereira EMC, Santos EZ, Valle FH, et al. Morbimortalidade em octogenários submetidos à cirurgia de revascularização miocárdica. Arq Bras Cardiol. 2012;95(1):41-6. 20. Anderson AJPG, Barros-Neto FXR, Costa MA, Dantas LD, Hueb AC, Prata MF. Preditores de mortalidade em pacientes acima de 70 anos na revascularização miocárdica ou troca valvar com circulação extracorpórea. Rev Bras Cir Cardiovasc. 2011;26(1):69-75. 21. MacDonald P, Stadnyk K, Cossett J, Klassen G, Johnstone D, Rockwood K. Outcomes of coronary artery bypass surgery in elderly people. Can J Cardiol. 1998;14(10):1215-22. 22. Peterson ED, Cowper PA, Jollis JG, Bebchuk JD, DeLong ER, Muhlbaier LH, et al. Outcomes of coronary artery bypass graft surgery in 24,461 patients aged 80 years or older. Circulation. 1995;92(9 Suppl):II85-91. 23. Guimarães IN, Moraes F, Segundo JP, Silva I, Andrade TG, Moraes CR. Fatores de risco para mortalidade em octogenários submetidos à cirurgia de revascularização miocárdica. Arq Bras Cardiol. 2011;96(2):94-98.

Machado MN, et al. - Surgical treatment for infective endocarditis and ORIGINAL ARTICLE hospital mortality in a Brazilian single-center

Rev Bras Cir Cardiovasc 2013;28(1):29-35

Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center Tratamento cirúrgico para endocardite infecciosa e mortalidade hospitalar em centro único brasileiro

Maurício Nassau Machado1,2, Marcelo Arruda Nakazone1-3, Jamil Ali Murad-Júnior1, Lilia Nigro Maia4 DOI: 10.5935/1678-9741.20130006

RBCCV 44205-1437

Abstract Objective: We evaluated patients underwent cardiac valve surgery in the presence of infective endocarditis in an attempt to identify independent predictors of 30-day mortality. Methods: We evaluated 837 consecutive patients underwent cardiac valve surgery from January 2003 to May 2010 in a tertiary hospital in São José do Rio Preto, São Paulo (SP), Brazil. The study group comprised patients who underwent intervention in the presence of infective endocarditis and was compared to the control group (without infective endocarditis), evaluating perioperative clinical outcomes and 30-day all cause mortality. Results: In our series, 64 patients (8%) underwent cardiac valve surgery in the presence of infective endocarditis, and 37.5% of them had surgical intervention in multiple valves. The study group had prolonged ICU length of stay (16%), greater need for dialysis (9%) and higher 30-day mortality (17%) compared to the control group (7%, P=0.020; 2%, P=0.002 and 9%, P=0.038; respectively). In a Cox regression analysis, age (P = 0.007), acute kidney injury (P = 0.004), dialysis (P = 0.026), redo surgery (P = 0.026), re-exploration for bleeding (P = 0.013), tracheal reintubation (P <0.001) and type I neurological injury (P <0.001) were identified as independent predictors for death. Although the manifestation of infective endocarditis influenced on mortality in univariate

analysis, multivariate Cox regression analysis did not confirm such variable as an independent predictor of death. Conclusion: Age and perioperative complications stand out as predictors of hospital mortality in Brazilian population. Cardiac valve surgery in the presence of active infective endocarditis was not confirmed itself as an independent predictor of 30-day mortality.

1. Cardiologist Assistant at the Postoperative Cardio Surgery Care Unit and Coronary Care Unit from Hospital de Base, São José do Rio Preto Medical School (FAMERP). Specialist in Cardiology by SBC/AMB, São José do Rio Preto, SP, Brazil. 2. Post-graduation program in Health Sciences, FAMERP, São José do Rio Preto, SP, Brazil. 3. Technical Scientific Coordinator at Centro Integrado de Pesquisas – Hospital de Base /FAMERP, São José do Rio Preto, SP, Brazil. 4. Professor from São José do Rio Preto Medical School. Chief of the Coronary Care Unit and Medical Clinical Research Coordinator at Centro Integrado de Pesquisas – Hospital de Base /FAMERP, São José do Rio Preto, SP, Brazil.

Some results were presented in XXXII Congress from Sociedade de Cardiologia do Estado de São Paulo, SP, Brazil.

This work was developed in Cardiac Intensive Care Unit from Hospital de Base, São José do Rio Preto Medical School, São José do Rio Preto, SP, Brazil.

Descriptors: Bacterial endocarditis. Cardiac surgical procedures. Hospital mortality. Resumo Objetivo: Avaliamos pacientes submetidos à cirurgia valvar em vigência de endocardite infecciosa na tentativa de identificar preditores independentes de mortalidade intrahospitalar em 30 dias. Métodos: Foram avaliados 837 pacientes consecutivamente submetidos à cirurgia valvar, no período de janeiro de 2003 a maio de 2010, em um hospital terciário de São José do Rio Preto, SP, Brasil. O Grupo de Estudo compreendeu indivíduos submetidos à intervenção em vigência de endocardite infecciosa e foi comparado ao Grupo Controle, considerando complicações clínicas perioperatórias e óbito por todas as causas em 30 dias.

Correspondence address: Maurício Nassau Machado Hospital de Base de São José do Rio Preto Av. Brigadeiro Faria Lima, 5544 – 5° floor – Unidade Coronária (UCor) – São José do Rio Preto, SP, Brazil – Zip code: 15090-000 E-mail: maunmac@gmail.com

Article received on July15th, 2012 Article accepted on September 25th, 2012

Rev Bras Cir Cardiovasc 2013;28(1):29-35

Machado MN, et al. - Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center

Abbreviations, Acronyms & Symbols CG CI CVS SG EuroSCORE HR ICU IE SD

Control group Confidence interval Cardiac valve surgery Study group European System for Cardiac Operative Risk Evaluation Hazard ratio Intensive care unit Infective endocarditis Standard deviation

Resultados: Em nossa casuística, 64 (8%) pacientes foram submetidos à cirurgia valvar em vigência de endocardite infecciosa, sendo 37,5% deles com indicação de intervenção cirúrgica em múltiplas valvas. O Grupo de Estudo apresentou maior permanência em Unidade de Terapia Intensiva (16%),

INTRODUCTION Surgical mortality for infective endocarditis (IE), while declining in the last decades, stands out as an important cause of death in native or prosthetic valve interventions [1-3], justifying early diagnosis and appropriate antibiotic therapy as key points to the success of the treatment [4]. Clinical complications and treatment failure may suggest surgical valve replacement for IE by up to 60% of cases [5-7]. However, due to possible association between increased incidence of postoperative complications and mortality, the real benefit of early surgical intervention on IE remains doubtful [8]. In the absence of adequate treatment, IE can be fatal. Despite the medical and surgical treatment being able to modify the course of disease, mortality remains high, ranging from 17% to 36% of cases according to the population studied [9,10]. In this context, this study evaluated the mortality of patients undergoing cardiac valve surgery (CVS) in the presence of IE in an attempt to identify independent predictors of 30-day mortality in a regional referral center. METHODS This study evaluated 837 patients admitted to the São José do Rio Preto Medical School Cardiac Surgery Postoperative Intensive Care Unit after CVS from January 2003 to May 2010. This Brazilian Hospital is a regional tertiary referral service with 540 beds for a population demand of 1.5 million inhabitants. In this research, patients were divided into two groups: (SG) study group, subjects undergoing CVS in the presence of 30

necessidade de diálise (9%) e maior mortalidade em 30 dias (17%) comparado ao Grupo Controle (7%, P=0,020; 2%, P=0,002 e 9%, P=0,038; respectivamente). A análise de regressão de Cox confirmou idade (P=0,007), lesão renal aguda (P=0,004), diálise (P=0,026), reoperação (P=0,026), reintervenção por sangramento (P=0,013), reintubação orotraqueal (P<0,001) e lesão neurológica tipo I (P<0,001) como preditores independentes para óbito. Embora a manifestação de endocardite infecciosa influencie na mortalidade na análise univariada, a regressão de Cox não confirmou tal variável como preditor independente de óbito em nossa casuística. Conclusão: Idade e complicações perioperatórias destacam-se como preditores de mortalidade hospitalar em população brasileira. Cirurgia valvar em vigência de infecção ativa não se confirma como preditor independente de óbito nesta casuística. Descritores: Endocardite bacteriana. Procedimentos cirúrgicos cardíacos. Mortalidade hospitalar.

IE; and (CG) control group, consisting of patients with CVS performed in the absence of IE. The analysis was conducted as a prospectively historical type, including gathering information on the local computer database. The constitution of SG considered the recent recommendations of the American College of Cardiology / American Heart Association for IE surgical approach [11]. This study was approved by the São José do Rio Preto Medical School Ethics Committee (6079/2010) and, because of its observational nature, the informed consent was waived. We evaluated demographic data, clinical outcomes and complications occurred in the postoperative period, and 30-day all cause mortality. Categorical data are presented as absolute numbers and percentages, and continuous variables as mean ± standard deviation (SD) or median and interquartile, when applicable. Categorical data were compared by chi-square test or Fisher's exact test and continuous variables were compared using the nonparametric Mann-Whitney test. Survival curve was constructed to demonstrate the outcome of 30-day mortality for both groups. The Cox regression analysis was used to determine independent predictors of 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated for predictors of mortality. The analysis was performed with the SPSS software (version 20) and P value <0.05 (two-tailed) was considered statistically significant. RESULTS In our series, 64 (8%) patients underwent CVS in the presence of IE, and 37.5% had surgical intervention in multiple valves. In the SG there was predominance of males (67%) lower body mass index (23 kg/m2), greater value for

Machado MN, et al. - Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center

Rev Bras Cir Cardiovasc 2013;28(1):29-35

European System for Cardiac Operative Risk Evaluation (EuroSCORE) (9 points), and greater cardiopulmonary bypass time (100.5 min) compared to CG (47%, P = 0.002, 24 kg/m2, P = 0.028, 90 min, P = 0.020 and 4 points, P <0.001, respectively). Table 1 shows the demographic and baseline characteristics of all groups. The analysis of clinical outcomes demonstrated that the EG had a higher percentage of subjects with prior cardiac valve surgery (47%), higher prolonged intensive care unit (ICU) length of stay (over 14 days) (16%) and need for dialysis (9%) compared to CG (28%, P = 0.001; 7%, P = 0.020 and 2%, P = 0.002, respectively, Table 2). Consequently, patients undergoing CVS in the presence of IE had higher 30-day mortality (17%) compared to those without active infection (9%, P = 0.038). The following variables were included in the univariate Cox analysis: age (years), male gender, body mass index

(kg/m2), readmission to intensive care, diabetes mellitus, CVS in the presence of IE, multiple valve surgery, acute kidney injury, dialysis, left ventricular systolic dysfunction moderate or severe, redo surgery, reoperation for bleeding, tracheal reintubation and type I neurological injury. Table 3 shows the variables associated with 30day mortality, highlighting age (P = 0.007), acute kidney injury (P = 0.004), dialysis (P = 0.026), redo surgery (P = 0.026), reoperation for bleeding (P = 0.013), tracheal reintubation (P <0.001) and type I neurological injury (P <0.001) as independent predictors of death determined by multivariate Cox regression model. Cardiac valve surgery in the presence of infective endocarditis was a predictor of death in the non adjusted analysis (HR = 1.96, 95% CI = 1.04 - 3.70, P = 0.038, Figure 1). However, after adjustment for predictors in the multivariate model, this variable was not independent (P = 0.06).

Table 1. Demographic data and baseline characteristics of patients. Baseline Characteristics Age (median, Q1 e Q3) Men [n (%)] BMI (median, Q1 e Q3) Diabetes Mellitus [n (%)] Mitral Valve Surgery [n (%)] Aortic Valve Surgery [n (%)] Tricuspid Valve Surgery [n (%)] Multiple Valve Surgery [n (%)] LV Dysfunction moderate/severe [n (%)] ECC Time (median, Q1 e Q3) Additive EuroScore (median, Q1 e Q3)

All Patients n 837 52 (40 – 61) 405 (48%) 24 (22 – 28) 46 (5%) 602 (72%) 374 (45%) 213 (25%) 300 (36%) 121 (14%) 91 (76 – 113) 5 (3 – 6)

Endocarditis ( + ) n 64 52,5 (40 – 61) 43 (67%) 23 (20 – 26) 4 (6%) 43 (67%) 33 (52%) 17 (27%) 24 (37,5%) 10 (16%) 100,5 (80 – 125) 9 (6 – 11)

Endocarditis ( - ) n 773 52 (40 – 61) 362 (47%) 24 (22 – 28) 42 (5%) 559 (72%) 341 (44%) 196 (25%) 276 (36%) 111 (14%) 90 (75 – 111,5) 4 (3 – 6)

P 0.902 0.002 0.028 0.773 0.380 0.249 0.831 0.854 0.782 0.020 <0.001

n= number of individuals; Q1 and Q3 in reference to Quartis 25% and 75%; BMI= body mass index; LV= left ventricle; ECC= extracorporeal circulation

Table 2. Perioperative clinical complications. Clinical complication Length of ICU stay (median, Q1 e Q3) ICU Readmission [n (%)] Length of ICU stay > 14 days [n (%)] Reoperation [n (%)] Reintervention for bleeding [n (%)] AF [n (%)] Reintubation for lung complications [n (%)] Acute Renal Failure [n (%)] Dialysis [n (%)] Mediastinitis [n (%)] Neurological disorder type I [n (%)] Death in 30 days [n (%)]

All Patients n 837 2 (2 – 4) 47 (6%) 61 (7%) 246 (29%) 33 (4%) 78 (9%) 106 (13%) 222 (27%) 19 (2%) 23 (3%) 39 (5%) 82 (10%)

Endocarditis ( + ) n 64 4 (2 – 11) 2 (3%) 10 (16%) 30 (47%) 0 (0%) 1 (2%) 9 (14%) 20 (31%) 6 (9%) 0 (0%) 2 (3%) 11 (17%)

Endocarditis ( - ) n 773 2 (2 – 4) 45 (6%) 51 (7%) 216 (28%) 33 (4%) 77 (10%) 97 (13%) 202 (26%) 13 (2%) 23 (3%) 37 (5%) 71 (9%)

P 0.006 0.571 0.020 0.001 0.168 0.026 0.726 0.373 0.002 0.248 0.761 0.038

n= number of individuals; ICU= Intensive Care Unit; Q1 and Q3 in reference to Quartis 25% and 75%; AF= atrial fibrillation

Rev Bras Cir Cardiovasc 2013;28(1):29-35

Machado MN, et al. - Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center

Table 3. Independent predictors for hospital mortality in 30 days. Independent predictors for hospital mortality Univariate analysis Infective endocarditis Age (years) Men BMI (kg/m2) Readmission in ICU Diabetes Mellitus Multiple valve surgery Acute renal failure Dialysis LV Dysfunction Moderate/Severe Reoperation Reintervention for bleeding Reintubation Neurological dysfunction type I

Wald

CI 95%

P Value

0.673 0.035 -0.135 -0.018 0.954 0.641 0.493 1.767 2.419 0.197 0.927 1.943 2.162 1.885

4.318 18.339 0.372 0.554 8.668 2.969 9.644 57.483 63.101 0.452 17.597 46.110 95.180 49.689

1.96 1.04 0.87 0.98 2.60 1.90 1.64 5.85 11.24 1.22 2.53 6.98 8.69 6.59

1.04 – 3.70 1.02 – 1.05 0.57 – 1.35 0.94 – 1.03 1.38 – 4.90 0.92 – 3.94 1.20 – 2.23 3.71 – 9.24 6.19 – 20.41 0.69 – 2.17 1.64 – 3.89 3.98 – 12.23 5.63 – 13.41 3.90 – 11.12

0.038 <0.001 0.542 0.457 0.003 0.085 0.002 <0.001 <0.001 0.501 <0.001 <0.001 <0.001 <0.001

Multivariate analysis Age Acute renal failure Dialysis Reoperation Reintervention for bleeding Reintubation Neurological dysfunction type I

0.024 0.806 0.771 0.528 0.769 1.076 1.093

7.214 8.389 4.946 4.937 6.217 16.580 14.531

1.03 2.24 2.16 1.70 2.16 2.93 2.98

1.01 – 1.04 1.30 – 3.86 1.10 – 4.27 1.06 – 2.70 1.18 – 3.95 1.75 – 4.92 1.70 – 5.24

0.007 0.004 0.026 0.026 0.013 <0.001 <0.001

HR=Hazard Ratio; CI= Confidence Interval; BMI= body mass index; k=kilogram; m=meter; ICU= intensive care unit

Fig. 1 – In-hospital survival curve following 30 days

DISCUSSION Despite the current knowledge including prevention, diagnosis and treatment, IE remains a not rare cause of hospitalization with high morbidity and mortality [12,13]. 32

In our analysis, we found 8% of valve-related surgery approaching to IE, percentage similar to that observed in national, North American and European casuistic [14-16]. Moreover, we confirmed high 30-day mortality (17%) for patients undergoing CVS in the presence of active infection, as recently reported by Prendergast & Tornos (ranging from 6% to 25%) [17]. However, the surgical approach in the presence of IE wasn’t confirmed as an independent predictor of death in our series. Our series of patients considered subjects with high severity disease transferred from other hospitals for surgery treatment with established diagnosis of IE, justified by the infection refractory to medical treatment. In this context, factors such as age, comorbidities, clinical presentation and surgical technique used in valve approach can influence the postoperative results [18,19]. Although there is no statistical difference between the groups in age, this variable was found as an independent predictor of 30-day mortality in patients with IE, reinforcing results of Murdoch et al. [20]. Furthermore, in contrast to data of Chirillo et al. [21], the prevalence of diabetes mellitus was similar between the groups do not representing a risk factor for poor clinical outcome in patients with active IE

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Rev Bras Cir Cardiovasc 2013;28(1):29-35

undergoing CVS. Although evidenced greater proportion of male gender and lower body mass index in EG, these parameters were not associated with worse postoperative prognosis. The higher cardiopulmonary bypass duration in this group may reflect the greater surgical difficulty for a complete removal of the cardiac valve in patients with IE [17]. The International Collaboration on EndocarditisProspective Cohort Study [20] reported 17.7% of overall in-hospital mortality for patients with IE, while Wallace et al. [22] reported 15% mortality in the group undergoing medical treatment and 22% for those who underwent additional surgery. Still, the hospital mortality in patients with valvular abscess due to complications of IE has been reported as 19.2% in Brazilian patients [23]. Similarly, the present study found a hospital mortality rate of 17% at 30 days for patients undergoing CVS due to IE and prolonged ICU length of stay, probably reflecting the severity of sepsis in these individuals [24-26]. However, the anatomical location of the valve infection was similar among the groups, confirming the absence of its association with clinical complications, including mortality, reflecting results previously presented by Rostagno et al. [13]. In this context, the presence of signs of heart failure, persistent infection, acute kidney injury, thrombocytopenia, paravalvular abscess at echocardiography and need for urgent surgery are indicated as predictors of hospital mortality [27-29]. Several studies have associated renal dysfunction with worse prognosis in the evolution and treatment of IE, reporting sepsis, lesions in glomerular architecture and antibiotic toxicity as etiologic factors [22,30,31]. Results of this analysis confirmed the acute kidney injury requiring dialysis as independent predictors of hospital mortality. This study demonstrated that reoperation, including re-exploration due to postoperative bleeding, was also a predictor of 30-day mortality. Attempting to decrease perioperative mortality for valve replacement surgery in the presence of IE, Musci et al. [32] recently proposed valvuloplasty as an effective alternative in previously selected cases, with consequent reduction in the need for reoperation and recurrent infections, but this surgical modality was not evaluated in this analysis. Besides these factors, the type I neurological injury and tracheal reintubation stood out as predictors of mortality in patients undergoing CVS in the presence of IE, in agreement with previous studies [33,34]. In this case, the manifestation of encephalopathy due to cardiovascular surgical procedure or severe sepsis, characterized by altered mental status or focal neurological deficit without evidence of impairment in anatomical imaging methods may have contributed definitely to returning to invasive mechanical ventilation and consequent high risk of in-hospital deaths.

Study limitations Studies related to IE approach are limited by its low relative frequency, the huge variability of the population affected and their underlying risk factors, represented mostly by series of case reports or single centers experience. In our sample, due to the small number of valve involvement by IE, there was limitation in demonstrating the relationship between prognosis, native or prosthetic valve involvement and etiologic agent identified in blood cultures, a fact worsen by the wide range of pathogens involved in its manifestation, affecting the scope and statistical power to draw definitive conclusions. Further investigations are needed to evaluate whether more sensitive prognostic markers may improve the detection of high-risk patients for whom aggressive surgical valve treatment during an IE can really contribute to the reduction of in-hospital mortality. CONCLUSION Although hospital mortality rate for patients undergoing cardiac valve surgery due to refractory infective endocarditis remains high in the Brazilian population, the surgical approach during an active infection is not confirmed as an independent predictor of death in our series. In this case, age, acute kidney injury, dialysis, redo surgery, re-exploration for bleeding, tracheal reintubation and type I neurological injury stand out as predictors of inhospital mortality (30 days) in this population.

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15. Daneshmand MA, Milano CA, Rankin JS, Honeycutt EF, Shaw LK, Davis RD, et al. Influence of patient age on procedural selection in mitral valve surgery. Ann Thorac Surg. 2010;90(5):1479-85. 16. Holzhey DM, Shi W, Borger MA, Seeburger J, Garbade J, Pfannmüller B, et al. Minimally invasive versus sternotomy approach for mitral valve surgery in patients greater than 70 years old: a propensity-matched comparison. Ann Thorac Surg. 2011;91(2):401-5. 17. Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation. 2010;121(9):1141-52. 18. Nunes MC, Gelape CL, Ferrari TC. Profile of infective endocarditis at a tertiary care center in Brazil during a sevenyear period: prognostic factors and in-hospital outcome. Int J Infect Dis. 2010;14(5):e394-8. 19. Arnoni AS, Castro Neto J, Arnoni RT, Almeida AFS, Abdulmassih Neto C, Dinkhuysen JJ, et al. Endocardite infecciosa: 12 anos de tratamento cirúrgico. Rev Bras Cir Cardiovasc. 2000;15(4):308-19. 20. Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, et al; International Collaboration on EndocarditisProspective Cohort Study (ICE-PCS) Investigators. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009;169(5):463-73. 21. Chirillo F, Bacchion F, Pedrocco A, Scotton P, De Leo A, Rocco F, et al. Infective endocarditis in patients with diabetes mellitus. J Heart Valve Dis. 2010;19(3):312-20. 22. Wallace SM, Walton BI, Kharbanda RK, Hardy R, Wilson AP, Swanton RH. Mortality from infective endocarditis: clinical predictors of outcome. Heart. 2002;88(1):53-60. 23. Pomerantzeff PM, Almeida Brandão CM, Albuquerque JM, Oliveira JL Jr, Dias AR, Mansur AJ, et al. Risk factor analysis of hospital mortality in patients with endocarditis with ring abscess. J Card Surg. 2005;20(4):329-31. 24. Gabbieri D, Dohmen PM, Linneweber J, Grubitzsch H, von Heymann C, Neumann K, et al. Early outcome after surgery for active native and prosthetic aortic valve endocarditis. J Heart Valve Dis. 2008;17(5):508-24. 25. Ribeiro DGL, Silva RP, Rodrigues Sobrinho CRM, Andrade PJN, Ribeiro MVV, Mota RMS, et al. Infective valve endocarditis treated by surgery: analysis of 64 cases. Rev Bras Cir Cardiovasc. 2005;20(1):75-80.

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26. Dias AR, Pomerantzeff PM, Brandão CMA, Dias RR, Grinberg M, Lahoz EV, et al. Surgical treatment of active infectious endocarditis: a study of 361 surgical cases. Rev Bras Cir Cardiovasc. 2003;18(2):172-7.

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27. Revilla A, López J, Vilacosta I, Villacorta E, Rollán MJ, Echevarría JR, et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J. 2007;28(1):65-71. 28. Hanai M, Hashimoto K, Mashiko K, Sasaki T, Sakamoto Y, Shiratori K, et al. Active infective endocarditis: management and risk analysis of hospital death from 24 years' experience. Circ J. 2008;72(12):2062-8. 29. Alonso-Valle H, Fariñas-Alvarez C, García-Palomo JD, Bernal JM, Martín-Durán R, Gutiérrez Díez JF, et al. Clinical course and predictors of death in prosthetic valve endocarditis over a 20-year period. J Thorac Cardiovasc Surg. 2010;139(4):887-93. 30. Netzer RO, Zollinger E, Seiler C, Cerny A. Infective

31. Oakley CM, Hall RJ. Endocarditis: problems: patients being treated for endocarditis and not doing well. Heart. 2001;85(4):470-4. 32. Musci M, Hübler M, Pasic M, Amiri A, Stein J, Siniawski H, et al. Surgery for active infective mitral valve endocarditis: a 20-year, single-center experience. J Heart Valve Dis. 2010;19(2):206-14. 33. Heiro M, Nikoskelainen J, Engblom E, Kotilainen E, Marttila R, Kotilainen P. Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland. Arch Intern Med. 2000;160(18):2781-7. 34. Tugtekin SM, Alexiou K, Wilbring M, Daubner D, Kappert U, Knaut M, et al. Native infective endocarditis: which determinants of outcome remain after surgical treatment? Clin Res Cardiol. 2006;95(2):72-9.

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na ARTIGO ORIGINAL insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino Surgical repair of chordae tendineae rupture after degenerative valvular regurgitation using standardized bovine pericardium

Francisco Gregori Júnior1, Moacir Fernandes de Godoy2, Celso Otaviano Cordeiro3, Alexandre Noboru Murakami3, Rogerio Teruya3, Sergio Shigueru Hayashi4, Wallace Kohata de Aquino5, Luiz Eduardo Gallina6

DOI: 10.5935/1678-9741.20130007

RBCCV 44205-1440

Resumo Objetivo: Avaliar, clinicamente e pelo ecodopplercardiograma, o funcionamento da valva mitral em 22 pacientes submetidos à correção do refluxo valvar com substituição das cordas tendíneas nativas por cordas padronizadas de pericárdio bovino. Métodos: Os pacientes apresentavam insuficiência mitral degenerativa. Quatorze (63,6%) pacientes eram do gênero masculino e a idade variou de 19 a 76 anos (média 56,8±13,8 anos). As cordas de pericárdio bovino foram tratadas com glutaraldeído, com reforço de suas extremidades transversais formando um trapézio. Resultados: Um (4,5%) paciente faleceu no pósoperatório imediato em síndrome de baixo débito cardíaco e três (13,6%) no pós-operatório tardio. Uma (4,5%) paciente foi reoperada. As curvas atuariais de sobrevivência livre de

óbitos por causa cardiovascular e livres de reoperações para os pacientes que deixaram o hospital (21) demonstraram taxas de 82,0±9,8% e 83,9±10,4%, aos 70 meses de pósoperatório, respectivamente. Dezessete (77,3%) pacientes estão vivos com a própria valva. Dos 17 pacientes vivos com a própria valva 16 (94,1%) estão em classe funcional I. O ecodoppler pós-operatório (média de 41 meses; 4 a 70 meses) demonstrou ausência de regurgitação mitral em 11 (64,7%) pacientes e regurgitação discreta em cinco (29,4%). Conclusão: A técnica de implante de cordas padronizadas de pericárdio bovino para substituição de cordas tendíneas da valva mitral em pacientes com insuficiência mitral degenerativa demonstrou resultados bastante satisfatórios.

1. Professor Associado, Chefe da Disciplina de Cirurgia Cardíaca da Universidade Estadual de Londrina, Londrina, PR, Brasil – Idealizador do estudo; coleta de dados; discussão; redação. 2. Professor Adjunto e Livre-Docente no Departamento de Cardiologia e Cirurgia Cardiovascular da Faculdade de Medicina de São José do Rio Preto (Famerp), Diretor Adjunto de Ensino da Famerp, São José do Rio Preto, SP, Brasil – Análise Estatística / Discussão. 3. Cirurgião do Hospital Evangélico de Londrina e Hospital João de Freitas de Arapongas, Londrina, PR, Brasil – Coleta de dados; discussão. 4. Cardiologista do Hospital Evangélico de Londrina, Londrina, PR, Brasil – Coleta de Dados; discussão. 5. Cardiologista do Hospital Evangélico de Londrina, Londrina, PR, Brasil – Discussão. 6. Cardiologista do Hospital João de Freitas de Arapongas, Arapongas, PR, Brasil – Discussão.

Trabalho realizado no Departamento de Clínica Cirúrgica da Universidade Estadual de Londrina (UEL), Hospital Evangélico de Londrina e Hospital Regional João de Freitas de Arapongas, Paraná, Brasil. Departamento de Cardiologia e Cirurgia Cardiovascular da Faculdade de Medicina de São José do Rio Preto (Famerp), São José do Rio Preto, SP, Brasil.

Descritores: Insuficiência da valva mitral. Músculos papilares. Cordas tendinosas. Pericárdio.

Endereço para correspondência Moacir F. Godoy Rua Garabed Karabashian, 570 São José do Rio Preto, SP, Brasil – CEP: 15070-600 E-mail: mf60204@gmail.com Artigo recebido em 27 de janeiro de 2013 Artigo aprovado em 28 de fevereiro de 2013

Rev Bras Cir Cardiovasc 2013;28(1):36-46

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Abreviações, acrônimos & símbolos AE AVM FE GTVM NYHA PD2VE PTFE VDFVE

Diâmetro átrio esquerdo Área valvar mitral Fração de ejeção Gradiente transvalvar médio mitral New York Heart Association Pressão diastólica final do ventrículo esquerdo Politetrafluoretileno Volume diastólico final do ventrículo esquerdo

Abstract Objective: To evaluate clinically and by Doppler Echocardiography 22 patients submitted to mitral valve repair after valvular regurgitation using standardized bovine pericardium chordae. Methods: The patients had degenerative mitral regurgitation. Fourteen (63.6%) patients were male and the age ranged from 19 to 76 years (mean 56.8 ± 13.8 years). The strings of bovine pericardium treated with glutaraldehyde were reinforced in its transverse ends forming a trapezoid.

INTRODUÇÃO Se não a mais frequente, seguramente uma das mais importantes causas da insuficiência mitral tem sido a ruptura de cordas tendíneas, estando presente em todas as etiologias, especialmente na degenerativa. As rupturas de cordas, levando ao prolapso da cúspide correspondente, foram tratadas cirurgicamente no início da cirurgia com circulação extracorpórea por McGoon [1], por meio da plicatura da porção prolapsada da cúspide. Os resultados iniciais foram bons, porém em longo prazo culminaram com a diminuição da mobilidade da cúspide, especialmente a anterior. Merendino et al. [2] propuseram a ressecção da cúspide posterior da valva mitral, eliminando assim o prolapso e suturando borda a borda essa cúspide, precedida de plicatura posterior do anel mitral. Essa técnica tem sido empregada até os dias atuais, com excelentes resultados, limitando-se, porém, às rupturas de cordas da cúspide posterior [3]. Os maus resultados com as ressecções da cúspide anterior da valva mitral levaram Carpentier et al. [4] a introduzirem a técnica de transferência de cordas da cúspide posterior para a cúspide anterior da valva mitral em casos de ruptura de cordas tendíneas. A criação de nova corda a partir de retalho de tecido da cúspide anterior foi proposta por Gregori et al. [5], para a correção de prolapso, nos casos de ruptura de cordas da cúspide anterior. No entanto, essa técnica ficou reservada para os casos em que há exuberância de tecidos, fato comum na doença degenerativa. Desde janeiro de 1991, temos empregado uma técnica para a correção do prolapso da cúspide anterior da valva mitral secundário

Results: One patient (4.5%) died in the immediate postoperative period with in low cardiac output syndrome and three (13.6%) in the late postoperative period. One patient (4.5%) was reoperated. The actuarial curves for survival free of death from cardiovascular causes and free from reoperation for patients who left the hospital (21), showed rates of 82.0 ± 9.8% and 83.9 ± 10.4% at 70 months postoperatively, respectively. Seventeen patients (77.3%) are alive with native valves. Of the 17 patients alive with native valves 16 (94.1%) were in functional class I. The Doppler Echocardiography postoperatively (mean 41 months, 4-70 months), showed no mitral regurgitation in 11 (64.7%) patients and mild regurgitation in five (29.4%). Conclusion: The technique of standard cords of bovine pericardium implantation to replace chordae tendineae of the mitral valve in patients with degenerative mitral regurgitation showed satisfactory results. Descriptors: Mitral valve insufficiency. Papillary muscles. Chordae Tendineae. Pericardium.

à ruptura de cordas tendíneas, com bons resultados. Consiste no fornecimento de cordas tendíneas a partir da transferência parcial da valva tricúspide para a valva mitral [6]. O prolapso valvar tem sido tratado por outras técnicas que tentam evitar qualquer tipo de restrição à mobilidade da cúspide anterior da valva mitral, como a confecção de cordas artificiais de pericárdio bovino [7] ou de politetrafluoretileno (PTFE) [8]. Desde 2006, temos empregado uma prótese para substituição de cordas tendíneas rotas [9,10]. Trata-se de cordas tendíneas pré-moldadas de pericárdio bovino conservado em glutaraldeído. A técnica empregada é similar à transferência parcial da valva tricúspide para a valva mitral para o fornecimento de novas cordas [6]. O objetivo deste estudo é apresentar a evolução pósoperatória de uma série consecutiva de pacientes portadores de insuficiência mitral degenerativa secundária a ruptura de cordas tendíneas, submetidos à cirurgia reparadora com implante de cordas pré-moldadas de pericárdio bovino tratado em glutaraldeído e anticalcificantes. MÉTODOS Foram estudados, prospectivamente, 22 pacientes submetidos à cirurgia reparadora da valva mitral insuficiente de causa degenerativa, no período de maio de 1996 a maio de 2012. Esses pacientes eram portadores de prolapso da valva mitral por ruptura de cordas tendíneas levando a regurgitação valvar. Foram operados, consecutivamente, pelo mesmo cirurgião, no Hospital Evangélico de Londrina (Londrina, PR, Brasil) e Hospital João de Freitas de Arapongas (Arapongas, PR, 37

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

Brasil), pela técnica de substituição de cordas tendíneas rotas pelo implante de cordas premoldadas de pericárdio bovino tratado em glutaraldeido e anticalcificantes (Braile Biomédica, São José do Rio Preto, SP, Brasil). Os dados clínicos pré-operatórios dos pacientes encontram-se na Tabela 1. Quatorze (63,6%) pacientes eram do sexo masculino e oito (36,4%), do sexo feminino. A idade dos pacientes variou de 19 a 76 anos, com média de 56,8±13,8 anos. Todos os pacientes apresentavam insuficiência mitral de etiologia degenerativa, sendo degeneração fibroelástica em 16 (72,7%) pacientes e síndrome de Barlow em seis (27,3%). Quinze (68,2%) pacientes encontravam-se na classe funcional III e sete (31,8%) na classe IV da New York Heart Association (NYHA). A ausculta da valva mitral demonstrou sopro sistólico regurgitativo em todos os pacientes, sendo importante em 13 (59,1%) e muito importante em nove (40,9%). A fibrilação atrial estava presente em quatro (18,2%) pacientes. O diagnóstico clínico foi comprovado pelo estudo ecodopplercardiográfico e hemodinâmico quando

então a cirurgia foi indicada. Cinco (22,7%) pacientes apresentavam insuficiência tricúspide, um (4,5%), comunicação interatrial e um (4,5%), insuficiência coronária crônica. Os dados hemodinâmicos pré-operatórios encontramse na Tabela 2. Ao exame hemodinâmico, realizado em 21 pacientes, a regurgitação mitral era moderada em cinco (23,8%) e importante em 16 (76,2%) pacientes. Quanto à contratilidade do ventrículo esquerdo observada pela cineventriculografia encontramos: normal em oito (38,1%) pacientes, hipocinesia discreta do ventrículo esquerdo em cinco (23,8%), moderada em seis (28,6%) e hipocinesia importante em dois (9,5%). A média da pressão diastólica final do ventrículo esquerdo (PD2VE) era de 19,8 mmHg (variando de 12 a 31 mmHg). Em todos os pacientes, duas alterações estiveram sempre presentes, ruptura de cordas tendíneas e dilatação do anel da valva mitral. Em 13 (59,1%) pacientes, a ruptura de cordas era na cúspide anterior da valva mitral, em oito (36,4%), na cúspide posterior e em um (4,5%), em ambas as cúspides.

Tabela 1. Dados clínicos pré-operatórios dos pacientes No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Média ± DP

Paciente

Sexo

Idade

Diag

DiagAssoc

Etiol

SSFM

VG CLSF JR AM AMB SFN ATF GMG JAO PSM AC SM NAN GAL JC MAT MLPS AR HJA JAL RF ABR

M F M M M F F F M M M M F M M F F M M F M M

61 51 59 58 53 23 68 69 61 19 72 76 45 55 66 53 62 53 55 70 62 58 56,8 ± 13,8

IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM IM

IT CIA IT ICO IT IT IT -

DFE DFE DFE DFE DFE DFE DFE DFE DFE DFE DFE BARLOW DFE DFE BARLOW DFE DFE BARLOW DFE BARLOW BARLOW BARLOW

IV III III III III III III III IV IV III IV III III IV III III IV IV III III III

++++ +++ +++ +++ +++ +++ +++ +++ ++++ ++++ +++ ++++ +++ +++ ++++ +++ +++ ++++ +++ ++++ ++++ ++++

M = Masculino, F = Feminino, CF = Classe Funcional (NYHA), Diag = Diagnóstico, Diag Assoc = Diagnóstico Associado, Etiol = Etiologia, SSFM = Sopro Sistólico no Foco Mitral, IM = Insuficiência Mitral, IT = Insuficiência Tricúspide, CIA = Comunicação Interatrial, ICO = Insuficiência Coronária, DFE = Degeneração Fibroelástica, Barlow = Síndrome de Barlow, DP = desvio=padrão

Rev Bras Cir Cardiovasc 2013;28(1):36-46

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Tabela 2. Dados hemodinâmicos pré-operatórios. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Média

Paciente

Sexo

Data Cat

Data Cir

Cont VE

PD2VE

VG CLSF JR AM AMB SFN ATF GMG JAO PSM AC SM NAN GAL JC MAT MLPS AR HJA JAL RF ABR

M F M M M F F F M M M M F M M F F M M F M M

15/05/06 04/08/06 06/06/06 26/09/06 17/04/06 08/11/06 03/05/06 22/12/06 12/01/07 14/02/07 21/05/07 02/08/08 28/11/08 13/07/09 10/09/09 08/10/09 12/03/10 28/09/10 20/10/10 05/01/11 28/02/12

31/05/06 29/08/06 20/09/06 09/10/06 16/10/06 14/11/06 04/12/06 06/12/06 29/01/07 12/02/07 27/02/07 30/05/08 19/08/08 15/12/08 19/08/09 17/09/09 31/03/10 20/05/10 06/10/10 03/11/10 16/03/11 05/03/12

Hipo Import Normal Normal Normal HipoDisc Normal Normal HipoMod HipoMod HipoDisc HipoDisc HipoDisc HipoMod Normal HipoDisc Normal HipoMod HipoMod HipoMod Hipo Import Normal

Import Import Import Mod Mod Import Import Import Import Import Import Mod Import Import Import Import Mod Import Import Import Mod

30 18 31 15 16 25 20 16 28 20 15 14 24 15 12 24 12 15 22 23 21 19,8 [12 a 31]

Hipo Disc = Hipocinesia discreta, HipoMod = Hipocinesia moderada, Hipo import = Hipocinesia importante, Data cat = Data do cateterismo, Data Cir = Data da cirurgia, Cont VE = Contratilidade do ventrículo esquerdo, RM = Regurgitação mitral, PD2VE = Pressão diastólica final do ventrículo esquerdo

A Prótese As cordas pré-moldadas de pericárdio bovino foram confeccionadas em monobloco (Braile Biomédica, São José do Rio Preto, SP, Brasil), com a forma de um trapézio, com reforço de pericárdio bovino ou Dacron nas suas traves superior e inferior. As cordas pré-moldadas são em número de cinco a sete, com comprimento variando de 20 a 35 mm. Sua largura é de 2 mm e distam entre si por 3 mm. A padronização das cordas foi confirmada pelo uso de medidores de aço, correspondendo ao tamanho das próteses. O pericárdio bovino foi tratado com glutaraldeído a 0,5%, submetido a tratamento anticalcificante com ácido glutâmico e preservado em solução de formaldeído a 4%. Testes de resistência e durabilidade demonstraram níveis de ruptura de aproximadamente 15 kg/cm2 [11]. As próteses foram implantadas em números 35, 30, 25 e 20 em um (4,5%), 12 (54,5%), sete (31,8%) e dois (9,1%) pacientes, respectivamente. O tamanho da prótese foi determinado baseado na distância do topo do músculo papilar ao bordo livre da cúspide em sua posição original, não prolapsada. Treze (59,1%) pacientes receberam próteses para a cúspide anterior, oito (36,4%) para a cúspide posterior e um (4,5%) para ambas. O implante da prótese começa com

a fixação da parte menor do trapézio no topo do músculo papilar associado às cordas rotas, utilizando-se um ponto em U de polipropileno 5-0, ancorado em almofada de Dacron. Em sequência, a trave maior do trapézio será suturada no bordo livre da cúspide mitral comprometida, com suturas interrompidas de polipropileno 5-0. A prótese com cinco a sete cordas no seu formato original pode ser reduzida para até duas cordas, se necessário. Pode também ter sua haste superior (maior) dividida, podendo, assim, serem as duas partes superiores suturadas às cúspides anterior e posterior ao mesmo tempo, corrigindo ocasionais prolapsos das duas cúspides. Técnicas Reparadoras Associadas (Tabela 3) Anuloplastia – A dilatação do anel mitral, presente em todos os casos, foi corrigida com o emprego do anel protético Gregori-Braile® [12]. Em associação, em dois (91%) casos, foi realizada plicatura do anel mitral próximo à comissura póstero-mediana pela técnica de Wooler et al. [13]. Essa prótese é uma hemi-elipse industrializada e disponível comercialmente (Braile Biomédica, São José do Rio Preto, SP, Brasil). Sua forma assemelha-se ao anel de Carpentier sem a haste anterior, e apresenta 39

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

uma modificação na sua metade direita. Trata-se de uma retificação de curva do anel. Assim sendo, a prótese tem a forma de uma hemi-elipse, sendo a curvatura direita retificada. O material empregado é aço inoxidável 316, de grau médico, revestido por uma camada de borracha de silicone e, finalmente, por veludo de Dacron. Apresenta-se em vários tamanhos, de acordo com diversas dimensões do anel mitral. A escolha do anel ideal baseou-se, exclusivamente, na distância entre os trígonos fibrosos, que, em geral, correspondem às projeções das comissuras no anel mitral do paciente, não importando o diâmetro ântero-posterior. A fixação da prótese ao anel mitral foi feita com fios de poliéster 2-0 passados em “U”, inicialmente no anel mitral 1 a 2 mm afastados e, em seguida, na parte externa do anel protético. Os dois pontos iniciais que correspondem aos extremos da prótese são aplicados no anel mitral, na altura da projeção das comissuras, de tal forma que, após a fixação da prótese, a cúspide posterior vá ao encontro da anterior, e o que é importante, a porção póstero-medial desloca-se mais acentuadamente em sentido ântero-lateral,

corrigindo dessa maneira a dilatação existente. Em dois (9,1%) pacientes, foi realizada anuloplastia de Wooler et al. [13], para corrigir a dilatação exagerada do anel posterior da valva mitral próximo à comissura póstero-medial. Encurtamento de cordas – O encurtamento de cordas foi realizado em oito (36,4%) pacientes. Em dois (9,1%) desses pacientes, o encurtamento de cordas foi realizado segundo Carpentier et al. [14], com incisão longitudinal do músculo papilar e sepultamento intrapapilar da corda alongada. Em dois (9,1%) pacientes, foi empregado encurtamento segundo método descrito por Gregori Júnior et al. [15]. Realizamos uma pequena incisão na cúspide anterior próximo ao feixe de cordas alongadas, sendo tracionado através da incisão e, em seguida, fixado à superfície da cúspide anterior. Em quatro (18,2%) pacientes, empregamos a técnica de Frater et al. [7], ou seja, a fixação da corda alongada na face interna da cúspide anterior. Menores encurtamentos são conseguidos com essa técnica. Eventualmente, utilizamos os três métodos descritos para o encurtamento de cordas alongadas em um mesmo paciente.

Tabela 3. Técnicas reparadoras associadas No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Média

Paciente

Data Cir

Anulo

VG CLSF JR AM AMB SFN ATF GMG JAO PSM AC SM NAN GAL JC MAT MLPS AR HJA JAL RF ABR

31/05/06 29/08/06 20/09/06 09/10/06 26/10/06 14/11/06 04/12/06 06/12/06 29/01/07 12/02/07 27/02/07 30/05/08 19/08/08 15/12/08 19/08/09 17/09/09 31/03/10 20/05/10 06/10/10 03/11/10 16/03/11 05/03/12

ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL ANEL + WOOLER ANEL ANEL + WOOLER

Técnicas

Cordas No.

DeVega A 30 ENC. CORDAS GREGORI A 20 RES. CALCIF ENC. CORDAS FRATER/CARP A 30 ENC. CORDAS CARP/ FECH CIA P 30 MERENDINO + RES. CUSP ANT P 30 ENC. CORDAS FRATER P 20 MERENDINO + MMDA P 30 ENC. CORDAS CARP+DeVega P 30 MERENDINO + ENC. CORDAS GREGORI A 30 MERENDINO P 35 AMPL CUSP POST A 25 A+P 30 ENC. CORDAS FRATER A 25 A 30 P 25 A 25 A 25 MERENDINO P 30 A 25 DeVega A 30 MERENDINO ENC. CORDAS CARP + DeVega A 25 MERENDINO A 30

TCEC

TAM

94 98 98 92 117 90 87 75 100 81 182 120 71 99 97 67 82 100 85 86 121 151 100

41 63 66 52 62 27 48 26 58 44 123 61 37 52 57 22 42 41 34 51 59 79 52

Data Cir = Data da cirurgia, Anulo = Tipo de anuloplastia, TCEC = Tempo de circulação extracorpórea, TAM = Tempo de anóxia do miocárdio, Enc = Encurtamentos, RES = Ressecção, Calcif = Calcificação, Carp = Carpentier, CuspAnt = Cúspide anterior, Cusp Post = Cúspide posterior, MMDA = Mamaria/artéria coronária descendente anterior, Amplcusp post = Ampliação da cúspide posterior, A = Anterior, P = Posterior, Fech CIA = Fechamento de Comunicação Interatrial

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

Ressecção de cúspide – Em oito (36,4%) pacientes, realizamos ressecções de cúspides, sendo quadrangulares na cúspide posterior [2] em sete pacientes e triangular na cúspide anterior em um [1]. Evitamos esse último procedimento na cúspide anterior, pois poderia levar a estenose mitral, por diminuição da mobilidade da mesma cúspide. Após ressecção quadrangular da cúspide posterior e prolapso da cúspide posterior corrigido, os dois bordos da cúspide foram aproximados e suturados com pontos separados de polipropileno 5-0. Ampliação de cúspide – Em um (4,5%) paciente, realizamos ampliação de cúspide posterior da valva mitral com retalho de pericárdio bovino, para, com isso, facilitar a melhor coaptação da cúspide posterior à anterior.

(VDFVE). O tempo médio de avaliação pós-operatória dos 17 pacientes sobreviventes foi de 47 meses (variando de 4 a 70 meses).

Outras Técnicas Cirúrgicas Associadas Quatro (18,2%) pacientes com insuficiência funcional da valva tricúspide foram submetidos à anuloplastia segundo a técnica descrita por DeVega [16], que consiste na cerclagem do anel tricúspide para fugir da zona correspondente à passagem do feixe de condução junto ao nó atrioventricular. Um (4,5%) paciente teve sua comunicação interatrial fechada e outro (4,5%) foi submetido à revascularização do miocárdio com artéria torácica interna para o ramo interventricular anterior da artéria coronária esquerda. Avaliação Clínica Pós-Operatória Foram observadas as mortalidades hospitalar e tardia, o índice de reoperação decorrente de falha da cirurgia reparadora, além da morbidade pós-operatória. Os pacientes sobreviventes (17) foram avaliados, clinicamente, num tempo médio de pós-operatório de 47 meses (variando de 4 a 70 meses). Assim como no préoperatório, os pacientes foram classificados de acordo com o estado clínico, segundo a classificação sintomatológica da NYHA. Ao exame físico, neste mesmo período, a ausculta da valva mitral foi analisada quanto à presença de sopros. Avaliação Ecodopplercardiográfica Dezessete pacientes foram submetidos ao estudo ecodopplercardiográfico para avaliação de função ventricular esquerda, diâmetro do átrio esquerdo, área da valva mitral, gradiente transvalvar médio, volume diastólico final do ventrículo esquerdo e grau de refluxo valvar. A classificação ecodopplercardiográfica da insuficiência mitral foi baseada na extensão e magnitude do jato regurgitante na sístole do ventrículo esquerdo. Foram analisados os seguintes índices: fração de ejeção (FE) do ventrículo esquerdo, diâmetro do átrio esquerdo (AE), área valvar mitral (AVM), gradiente transvalvar médio mitral (GTVM) e volume diastólico final do ventrículo esquerdo

Análise Estatística Foram obtidas a curva atuarial de sobrevivência livre de óbitos e a curva atuarial de sobrevivência livre de reoperações para o total (22) de pacientes e para os 21 pacientes que receberam alta hospitalar e acompanhados ambulatorialmente [17]. RESULTADOS Os dados clínicos pós-operatórios estão apresentados na Tabela 4. Ocorreu um óbito no pós-operatório imediato (4,5%), em síndrome de baixo débito cardíaco, em paciente de 70 anos, com diagnóstico de insuficiência mitral e insuficiência tricúspide associada e portadora de síndrome de Barlow. A anuloplastia mitral consistiu no emprego do anel Gregori-Braile e a anuloplastia tricúspide realizada com técnica de DeVega [6]. Não ocorreram fenômenos tromboembólicos nem hemólise no pós-operatório. Quatro pacientes que apresentavam fibrilação atrial no pré-operatório continuaram com arritmia no pós-operatório tardio. Duas (9,1%) pacientes necessitaram de reoperação aos 35 e 46 meses, para substituição da valva mitral, esta última falecendo em síndrome de baixo débito cardíaco nas primeiras horas após chegar ao Centro de Terapia Intensiva. Em ambas as pacientes, a técnica de encurtamento de cordas foi associada e em nenhuma delas havia comprometimento das cordas de pericárdio bovino implantadas na cúspide posterior. Houve evolução da degeneração fibroelástica, comprometendo principalmente a cúspide anterior da valva mitral que não recebeu cordas artificiais. Dois pacientes faleceram com um mês e aos 12 meses de pós-operatório, subitamente, estando previamente em classe funcional I, um deles sem refluxo mitral e o outro com refluxo discreto ao ecodopplercardiograma. No primeiro paciente, foi documentada fibrilação ventricular ao monitor do eletrocardiógrafo da UTI móvel. Esses pacientes apresentavam hipocontratilidade grave do ventrículo esquerdo à cineventriculografia préoperatória, além de elevada pressão diastólica final do ventrículo esquerdo. O total de óbitos tardios, portanto, foi de 3 (13,6%) pacientes, se somados estes dois óbitos ao da reoperação após troca valvar. Dezoito (81,8%) pacientes estão vivos e 17 (77,3%) vivos com própria valva. Dezesseis (94,1%) de 17 pacientes sobreviventes encontram-se em classe funcional I e um (5,9%) em classe funcional II (NYHA). Em quinze (88,2%) pacientes não há sopros na valva mitral e, em dois (11,8%), há presença de sopro sistólico discreto, um (5,9%) deles associado a sopro 41

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

diastólico no foco mitral. A curva atuarial de sobrevivência livre de óbitos dos 22 pacientes por causa cardiovascular demonstrou probabilidade de sobrevivência aos 70 meses de 78,3±10,1% (Figura 1).

A curva atuarial de sobrevivência dos pacientes que deixaram o hospital e permanecerm em acompanhamento ambulatorial (21) demonstrou probabilidade de sobrevivência aos 70 meses de 82,0±9,8% (Figura 2).

Tabela 4. Dados clínicos pós-operatórios No.

Paciente

Sexo

Idade

Data Cir

Data Evol

Evol

SSFM

SDFM

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

VG CLSF JR AM AMB SFN ATF GMG JAO PSM AC SM NAN GAL JC MAT MLPS AR HJA JAL RF ABR

M F M M M F F F M M M M F M M F F M M F M M

61 51 59 58 53 23 68 69 61 19 72 76 45 55 66 53 62 53 55 70 62 58

31/05/06 29/08/06 20/09/06 09/10/06 16/10/06 14/11/06 04/12/06 06/12/06 29/01/07 12/02/07 27/02/07 30/05/08 19/08/08 15/12/08 19/08/09 17/09/09 31/03/10 20/05/10 06/10/10 03/11/10 16/03/11 05/03/12

12 M 16/06/12 15/05/12 18/07/12 19/06/12 22/10/09 20/04/12 05/08/10 11/06/12 11/06/12 20/07/12 20/07/12 12/06/12 13/03/12 05/07/12 03/01/12 04/06/12 15/06/12 11/07/12 1M 04/07/12

OB TARDIO SÚBITO BOA BOA BOA BOA REOP. P/TVM BOA OB TARDIO NA REOP TVM BOA BOA BOA BOA BOA BOA BOA BOA BOA BOA BOA OB IMED SBDC OB TARDIO FV BOA

I I I I I I II I I I I I I I I I I

0 0 0 0 0 0 0 + + 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 + 0 0 0 0 0 0 0 0 0 0

Evol = Evolução, Data Evol = Data da Evolução, CF = Classe Funcional, SSFM = Sopro Sistólico Foco Mitral, SDFM = Sopro Diastólico Foco Mitral, M = Masculino, F = Feminino, Ob Tardio = Óbito tardio, Ob Imed = Óbito Imediato, Reop = Reoperação, TVM = Troca Valvar Mitral, FV = Fibrilação Ventricular, SBDC = Síndrome de Baixo Débito

Fig. 1 – Curva atuarial de sobrevivência do total de pacientes (22). Observa-se que 78,3 ± 10,1% dos pacientes estão vivos após 70 meses de seguimento

Fig. 2 – Curva atuarial de sobrevivência dos pacientes que deixaram o hospital e foram acompanhados ambulatorialmente (21). Observa-se que 82,0 ± 9,8% estão vivos aos 70 meses de pós-operatório

Gregori Junior F, et al. - Correção da ruptura de cordas tendíneas na insuficiência mitral degenerativa pelo emprego de cordas padronizadas de pericárdio bovino

Rev Bras Cir Cardiovasc 2013;28(1):36-46

A avaliação ecodopplercardiográfica foi realizada nos 17 pacientes sobreviventes, entre os meses de janeiro e julho de 2012, com tempo médio de evolução pósoperatória de 47 meses (variando de 4 a 70 meses). A função ventricular esquerda medida pela FE mostrou um índice médio de 0,59 (variando de 0,27 a 0,76). O diâmetro médio do átrio esquerdo foi de 4,5 cm (variando de 3,0 a 6,9 cm). A média da AVM avaliada foi de 2,9 cm2 (variando de 1,6 a 4,5 cm2), sendo satisfatória em todos, exceto em um (1,6 cm2) paciente. A média do GTVM foi de 3,3 mmHg (variando de 1 a 9 mmHg), com valores insignificantes em todos os pacientes, exceto um. A média do VDFVE foi de 141 ml (variando de 83 a 247 ml), estando normal em 12 (70,5%).

A análise da competência valvar mostrou ausência de regurgitação mitral em 11 (64,7%) dos 17 pacientes sobreviventes analisados, regurgitação discreta em cinco (29,4%) e discreta/moderada em um (5,9%). Portanto, competência satisfatória da valva mitral foi observada em 94,1% dos casos. Regurgitação discreta da valva tricúspide foi observada em quatro (23,5%) pacientes e regurgitação discreta da valva aórtica em quatro (23,5%). A curva atuarial de livres de reoperações após o implante de cordas padronizadas de pericárdio bovino tratado com glutaraldeído e com anticalcificantes, para substituição de cordas tendíneas rotas da valva mitral era aos 70 meses de pós-operatório, 83,9±10,4% (Figura 3). A curva atuarial de livres de reoperações para os 21 pacientes que receberam alta hospitalar e seguidos, ambulatorialmente aos 70 meses de pós-operatório mostrou taxa de 83,9±10,4% (Figura 4). DISCUSSÃO

Fig. 3 – Curva atuarial de sobrevivência do método cirúrgico, ou seja, da prótese implantada na valva mitral (22 pacientes). Observa-se que 83,9 ± 10,4% das próteses estão livres de disfunção aos 70 meses de pós-operatório

Fig. 4 – Curva atuarial livre de reoperações para os 21 pacientes que receberam alta hospitalar e foram seguidos ambulatorialmente, aos 70 meses de pós-operatório (83,9 ± 10,4%)

Várias técnicas foram descritas ao longo dos anos visando à reconstrução valvar mitral. Para tanto, um profundo conhecimento da anatomopatologia faz-se necessário. A valva mitral é composta por um anel fibroso incompleto, que vai do trígono fibroso direito ao trígono fibroso esquerdo – sua porção anterior é ocupada pelo anel da valva aórtica e que se pensava não se dilatar até que Hueb et al. [18] demonstraram alterações anatomopatológicas dessa porção do anel mitral em corações com doença degenerativa e isquêmica. De qualquer forma, alterando ou não essa parte, a dilatação anular deve ser corrigida – e esse é o último passo da reconstrução, devolvendo a forma original do anel que é de uma cuba, culminando com a perfeita aproximação das cúspides anterior, posteriores e comissuras. São seis as válvulas que compõem a valva mitral, uma anterior e três posteriores (póstero-lateral, póstero-medial e posterior, propriamente dita), além das duas comissuras que contêm cúspides e cordas tendíneas presas a músculos papilares e/ou à parede livre do ventrículo esquerdo. Durante a sístole do ventrículo esquerdo, o anel mitral contrai, similarmente a um esfíncter – assume a forma de um rim ao mesmo tempo em que alivia a via de saída do ventrículo esquerdo. Nas dilatações do ventrículo esquerdo (seja nas sobrecargas de volume, seja na cardiomiopatia), o anel dilata-se posteriormente, adquirindo a forma ovoide, porém, mais intensamente à direita, próximo à comissura póstero-medial. Daí a razão de termos empregado o anel por nós desenvolvido [12], que com a forma de uma hemi-elipse aproxima as cúspides posteriores da cúspide anterior e, por ter uma retificação no seu lado direito, aproxima mais essa 43

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parte do anel mitral, frequentemente mais dilatada. Mesmo sendo aberto, em sua porção anterior, as extremidades superiores da prótese, fixadas junto aos trígonos, impedem a dilatação anular nesse local, ocupado pelo anel fibroso da valva aórtica. O alongamento e a ruptura de cordas são as complicações mais frequentes nas doenças degenerativas da valva mitral. Acompanham-se também de alterações nas cúspides, com flacidez e proliferação do tecido conetivo podendo ser exageradas, como na síndrome de Barlow (seis pacientes deste estudo), muito mais difícil de serem tratadas que na degeneração fibroelástica, quando não há sobra de tecido. Diante de casos de ruptura de cordas, os cirurgiões comumente têm comportamento distinto, se esta se localiza na cúspide anterior da valva mitral. A ruptura de cordas da cúspide anterior é um grande desafio, já que, nesses casos, a insuficiência valvar costuma ser significativa. A cúspide anterior tem, basicamente, função de excursão e as posteriores, função de contenção e de amparo para a cúspide anterior. Prolapsos valvares por rupturas de cordas são mais fáceis de serem tratados quando presentes na cúspide posterior. A plástica de Merendino et al. [2], desde há muito tempo empregada com sucesso, costuma resolver o problema, nesses casos. Ao contrário do que demonstra a literatura, nos nossos casos, a correção da ruptura de cordas da cúspide anterior foi mais frequente que a da cúspide posterior. A técnica cirúrgica a ser utilizada depende do nível de comprometimento e da localização das cordas lesadas. São vários os procedimentos que podem ser adotados nas rupturas de cordas tendíneas. A transferência de cordas da cúspide posterior para cúspide anterior da valva mitral proposta por Carpentier et al. [4] tem sido utilizada, inclusive no nosso Serviço. A construção de uma neocorda por meio da retirada de um retalho da cúspide anterior da valva mitral para, quando baixada no topo do músculo papilar, substituir as cordas tendíneas rotas é uma alternativa técnica [5], porém, seu emprego restringe-se aos pacientes com a cúspide anterior bastante desenvolvida, o que não ocorre na doença reumática, isquêmica ou mesmo nas endocardites. É, portanto, quase exclusividade da doença degenerativa. A transferência parcial da valva tricúspide (cúspide posterior na maioria das vezes) para a valva mitral, fornecendo cordas para a cúspide anterior, foi por proposta por Gregori et al., em 1992 [6], com resultados bastante satisfatórios. Estas técnicas requerem manuseio de cúspides e cordas com anatomia normal e, em geral, são temidas pelos cirurgiões que se iniciam na cirurgia reconstrutora da valva mitral. Materiais sintéticos e biológicos têm sido usados para a substituição das cordas tendíneas. Os fios de PTFE, propostos por David et al. [8], têm sido o material mais frequentemente empregado em todo o mundo. Um estudo

recente utilizando PTFE demonstrou excelentes resultados aos cinco e 10 anos de pós-operatório, com ausência de reoperação em 93,3% e 81,7%, respectivamente [19]. No entanto, o emprego dessas técnicas requer enorme grau de subjetividade, exigindo alto grau de habilidade individual. Dang et al. [20] descreveram um método simplificado para o uso do PTFE, facilitando um pouco sua implantação. Com materiais biológicos, Frater et al. [7] foram os primeiros a empregar o pericárdio bovino para substituição de cordas tendíneas, com resultado inicial satisfatório. Seu estudo foi interrompido devido ao temor da calcificação ao longo dos anos. No entanto, em seu trabalho original, foram compados dois grupos de pacientes submetidos a implantes de cordas de PTFE e de pericárdio bovino. É preciso enfatizar que os retalhos de pericárdio bovino mediam 4 mm de largura, não sendo cordas premoldadas, nem tampouco padronizadas por instrumentos (medidores). Além disso, o tempo de seguimento foi maior no grupo em que se empregou pericárdio bovino do que no grupo em que se empregou o PTFE. Mesmo assim, não houve diferença significativa na evolução tardia dos dois grupos e tampouco calcificação dos pericárdios bovinos implantados. Calcificação realmente é um problema e deve ser motivo de preocupação. Muitos esforços têm sido realizados para a melhoria da durabilidade do pericárdio bovino implantado com a introdução de novos reagentes químicos, como o utilizado em nossos casos, o ácido glutâmico. Tem sido muito frequente a utilização do pericárdio bovino em cirurgia cardiovascular. É comum seu emprego na confecção de biopróteses, nas oclusões de orifício nas cardiopatias congênitas, nas reconstruções da via de saída ventricular, nas ventriculorrafias pós-correção de aneurismas do ventrículo esquerdo, entre outros procedimentos. Nas cirurgias da valva mitral, o pericárdio bovino tem sido empregado como corda para manter a tensão, entre o topo dos músculos papilares e o anel mitral nas trocas valvares, com melhora significativa da função ventricular [21]. O emprego das próteses padronizadas de pericárdio bovino torna o procedimento mais fácil e, portanto, rápido, objetivo e reprodutível. Os testes laboratoriais das cordas artificiais revelaram nível de ruptura em 15 kg/cm2. Deve ser lembrado que, em um paciente com nível pressórico de 140 mmHg na sístole de seu ventrículo esquerdo, a tensão a que estão submetidas as cordas tendíneas é de, aproximadamente, 0,5 kg/cm2, portanto, trinta vezes menor. A técnica de implante de cordas é semelhante à descrita por nós nos casos de transferência parcial da valva tricúspide (cúspide posterior, geralmente) para a valva mitral [6]. Neste estudo, em todos os pacientes foi realizada anuloplastia com anel aberto e rígido Gregori-Braile [12], precedida, em dois casos, de anuloplastia à Wooler [13], junto à comissura pósteromedial. Boa evolução clínica foi observada nos pacientes

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sobreviventes, tanto com relação à classe funcional (16 deles em classe funcional I e um em classe funcional II) quanto a excelente ausculta da valva mitral (15 sem sopros e dois com sopro sistólico no foco mitral discreto, um deles associado à sopro diastólico no foco mitral). Objetivando uniformização dos dados laboratoriais, analisamos hemodinamicamente os pacientes no préoperatório, uma vez que os ecocardiogramas foram realizados por diferentes clínicos, o que não aconteceu no pós-operatório. Note-se que, nos dois pacientes com morte súbita no pós-operatório tardio, a cineventriculografia pré-operatória demonstrava hipocinesia importante do ventrículo esquerdo, além de pressão diastólica final do ventrículo esquerdo alta. O estudo ecodopplercardiográfico tem sido o melhor método para a avaliação pós-operatória da valva mitral e, nos pacientes deste estudo, o implante de cordas padronizadas de pericárdio bovino associado à anuloplastia com anel aberto e a outras técnicas apresentou evolução pós-operatória bastante satisfatória. Atribuímos esses resultados a significativa maior linha de coaptação entre as cúspides, uma vez que extensas ressecções são evitadas. Os dados pós-operatórios deste estudo prospectivo confirmaram os achados clínicos observados. Exceto em um caso, os gradientes transvalvares médios foram normais; em mais de 70% dos casos, o volume diastólico final do ventrículo esquerdo foi normal e a área valvar mitral foi satisfatória. Também foram constatados resultados satisfatórios na análise da competência valvar mitral em vista da ausência de regurgitação ou apenas regurgitação mitral discreta em 16 dos 17 pacientes. O benefício do implante de cordas artificiais é mais evidente nos casos de ruptura de cordas tendíneas da cúspide anterior, situação em que a ressecção deve ser evitada, pois poderá prejudicar sua principal função, que é a de excursão. Porém, não deixa de ser interessante sua aplicação também na cúspide posterior. Falk et al. [22] corroboraram essa afirmação num estudo prospectivo randomizado comparando o uso de cordas de PTFE com a ressecção de prolapso da cúspide posterior. Assim, os bons resultados tardios são técnicodependentes. A análise prospectiva dos nossos casos é válida porque a série é consecutiva, os pacientes apresentavam lesões da valva mitral de mesma etiologia (degenerativa) e foram operados pelo mesmo cirurgião. As curvas atuariais livres de óbito e reoperação apresentaram probabilidade de sobrevivência aos 70 meses de pós-operatório de mais de 80%, corroborando nossas publicações anteriores [9,10]. Mais de 90% dos 17 pacientes sobreviventes apresentaram valva mitral competente no pós-operatório e, nenhum demonstrou sinais de calcificação da prótese implantada. Além disso, em nenhum paciente com eventos de óbito ou reoperação foi confirmada disfunção da prótese de

pericárdio bovino conservada em glutaraldeído para substituição de cordas tendíneas rotas. O óbito imediato na primeira cirurgia e o óbito imediato em um paciente reoperado para substituição da valva mitral foram decorrentes de síndrome de baixo débito cardíaco, estando as próteses funcionando normalmente. Nos dois pacientes que faleceram subitamente, no pós-operatório tardio, a causa mais provável teria sido a fibrilação ventricular – documentada em um na UTI móvel. Nas rupturas de cordas da valva mitral, os pacientes apresentam, geralmente, nos casos graves, edema agudo dos pulmões. No ato operatório do paciente reoperado para troca valvar mitral, com boa evolução pós-operatória, foi observado que a valva mitral apresentava intensa degeneração da cúspide anterior, estando com bom aspecto o implante das cordas de pericárdio bovino na cúspide posterior. CONCLUSÃO Apesar de um seguimento pós-operatório não extenso, os resultados obtidos, tanto clínicos quanto ecodopplercardiográficos, permitem-nos afirmar ser satisfatória a evolução clínica após utilização da técnica da substituição de cordas tendíneas por cordas premoldadas de pericárdio bovino conservado em glutaraldeído em pacientes com insuficiência mitral de etiologia degenerativa.

REFERÊNCIAS 1. McGoon DC. Repair of mitral insufficiency due to ruptured chordae tendineae. J Thorac Cardiovasc Surg. 1960;39:357-62. 2. Merendino KA, Thomas GI, Jesseph JE, Herron PW, Winterscheid LC, Vetto RR. The open correction of rheumatic mitral regurgitation and/or stenosis; with special reference to regurgitation treated by posterormedial annuloplasty utilizing a pump-oxygenator. Ann Surg. 1959;150(1):5-22. 3. Pomerantzeff PAM, Brandão CMA, Rossi EG, Cardoso LF, Tarasoutchi F, Grimberg M, et al. Quadrangular resection without ring annuloplasty in mitral valve repair. Eur Cardiovasc Surg. 1997;2:271-3. 4. Carpentier A, Relland J, Deloche A, Fabiani JN, D'Allaines C, Blondeau P, et al. Conservative management of the prolapsed mitral valve. Ann Thorac Surg, 1978;26(4):294-302. 5. Gregori F Jr, Takeda R, Silva S, Façanha L, Meier MA. A new technique for mitral insufficiency caused by ruptured chordae of the anterior leaflet. J Thorac Cardiovasc Surg, 1988;96(5):765-8.

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6. Gregori F Jr, Cordeiro C, Croti UA, Hayashi SS, Silva SS, Gregori TE. Partial tricuspid valve transfer for repair of mitral insufficiency due to ruptured chordae tendineae. Ann Thorac Surg, 1999;68(5):1686-91.

15. Gregori Júnior F, Silva S, Façanha L, Cordeiro C, Aquino W, Moure O. Preliminary results with a new technique for repairing elongated chordae tendineae of the anterior mitral valve leaflet. J Thorac Cardiovasc Surg. 1994;107(1):321-3.

7. Frater RW, Gabbay S, Shore D, Factor S, Strom J. Reproducible replacement of elongated or ruptured mitral valve chordae. Ann Thorac Surg. 1983;35(1):14-28.

16. DeVega NF. La anuloplastia selectiva, regulable y permanente. Rev Esp Cardiol. 1972;25:555-6.

8. David TE, Bos J, Rakowski H. Mitral valve repair by replacement of chordae tendineae with polytetrafluorethylene sutures. J Thorac Cardiovasc Surg. 1991;101(3):495-501. 9. Leal JCF, Gregori Jr. F, Galina LE, Thevenard RS, Braile DM. Avaliação ecocardiográfica em pacientes submetidos à substituição de cordas tendíneas rotas. Rev Bras Cir Cardiovasc. 2007;22(2):184-91. 10. Gregori F Jr, Leal JC, Braile DM. Premolded bovine pericardial chords for replacement of ruptured or elongated chordae tendineae. Heart Surg Forum. 2010;13(1):E17-20. 11. Braile DM, Ardito RV, Pinto GH, Santos JLV, Zaiantchik M, Souza DRS, et al.. Plástica mitral. Rev Bras Cir Cardiovasc. 1990;5(2):86-98. 12. Gregori F, Silva SS, Hayashi SS, Aquino W, Cordeiro C, Silva LR. Mitral valvuloplasty with a new prosthetic ring. Analysis of the first 105 cases. Eur J Cardiothorac Surg. 1994;8(4):168-72. 13. Wooler GH, Nixon PG, Grimshaw VA, Watson DA. Experience with the repair of the mitral valve in mitral in competence. Thorax. 1962;17:49-57. 14. Carpentier A, Deloche A, Dauptain J, Soyer R, Blondeau PH, Piwinica A, et al. A new reconstructive operation for correction of mitral and tricuspid insufficiency. J Thorac Cardiovasc Surg. 1971;61(1):1-13.

17. Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Statist Assoc. 1958;53:457-8. 18. Hueb AC, Jatene FB, Moreira LF, Pomerantzeff PM, Kallás E, Oliveira SA. Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: new insights from anatomic study. J Thorac Cardiovasc Surg. 2002;124(6):1216-24. 19. Kobayashi J, Sasako Y, Bando K, Minatoya K, Niwaya K, Kitamura S. Ten-year experience of chordal replacement with expanded polytetrafluoroethylene in mitral valve repair. Circulation. 2000;102(19 Suppl 3):III30-4. 20. Dang NC, Stewart AS, Kay J, Mercando ML, Kruger KH, Topkara VK, et al. Simplified placement of multiple artificial mitral valve chords. Heart Surg Forum. 2005;8(3):E129-31. 21. Gomes OM, Pitchon M, Barros MVL. Utilização de cordas tendíneas de pericárdio bovino em cirurgia da valva mitral. Coração. 1990;2:20-2. 22. Falk V, Seeburger J, Czesla M, Borger MA, Willige J, Kuntze T, et al. How does the use of polytetrafluoroethylene neochordae for posterior mitral valve prolapse (loop technique) compare with leaflet resection? A prospective randomized trial. J Thorac Cardiovasc Surg. 2008;136(5):1205. 23. Gregori Junior F. Conservative surgical management of mitral insufficiency: an alternative approach. Rev Bras Cir Cardiovasc. 2012;27(2):312-7.

Borges JBC, et al. - Correlação entre a qualidade de vida, classe funcional ARTIGO ORIGINAL e idade em portadores de marca-passo cardíaco

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Correlação entre a qualidade de vida, classe funcional e idade em portadores de marca-passo cardíaco Correlation between quality of life, functional class and age in patients with cardiac pacemaker

Juliana Bassalobre Carvalho Borges1, Rubens Tofano de Barros2, Sebastião Marcos Ribeiro de Carvalho3, Marcos Augusto de Moraes Silva4

DOI: 10.5935/1678-9741.20130008

RBCCV 44205-1441

Resumo Objetivo: Avaliar se existe correlação entre qualidade de vida e classe funcional em pacientes no pós-implante de marca-passo cardíaco, e sua relação com idade. Métodos: Investigados 107 pacientes de ambos os sexos (49,5% do sexo feminino e 50,5% do sexo masculino), tempo médio de implante 6,36 ±2,99 meses e média de idade 69,3 ±12,6 anos. Para avaliação da classe funcional, foi utilizada escala proposta por Goldman e para qualidade de vida, questionário AQUAREL associado ao SF-36. Realizada análise estatística pela correlação de Spearman, com significância de 5%. Resultados: Foram observadas correlações negativas entre qualidade de vida e classe funcional: AQUAREL nos três domínios, desconforto no peito (r=-0,197, P=0,042), dispneia (r=-0,508, P =0,000), arritmia (r=-0,271, P=0,005) e, no SF-36 nos oito domínios. Em relação à idade, correlação negativa com Capacidade Funcional do SF-36 (r=-0,338, P=0,000) e não se observou correlação com AQUAREL. Entre idade e classe funcional observou-se correlação positiva (r=0,237, P=0,014).

Conclusão: Neste estudo, encontrou-se correlação negativa entre qualidade de vida e classe funcional, evidenciando nesta amostra que os pacientes pertencentes a melhor classe funcional apresentaram melhor qualidade de vida. Conforme maior idade, pior a qualidade de vida em Capacidade Funcional e em classe funcional. Sugere-se, que idade e classe funcional influenciam qualidade de vida e as escalas de classificação funcional podem constituir um dos instrumentos que integram a avaliação e refletem a qualidade de vida em portadores de marca-passo.

1. Pós-doutorado Universidade Estadual Paulista, Faculdade de Medicina de Botucatu (FMB-UNESP); Professor Adjunto do Curso de Fisioterapia da Universidade Federal de Alfenas - UNIFAL, Alfenas, MG, Brasil. Pesquisadora Responsável. 2. Mestre, Santa Casa de Misericórdia de Marília, Marília, SP, Brasil. Pesquisador. 3. Doutor / Unesp-FFC, Campus de Marília, Marília, SP, Brasil. Pesquisador. 4. Professor Adjunto / Unesp-FMB, Campus de Botucatu, Botucatu, SP, Brasil. Pesquisador.

Trabalho realizado no Programa de Pós-Doutorado em Bases Gerais da Cirurgia da Faculdade de Medicina de Botucatu/UNESP, Botucatu, SP, Brasil.

Descritores: Qualidade de vida. Marca-passo artificial. Indicadores de qualidade de vida. Abstract Objective: To evaluate whether there is a correlation between quality of life and functional class in early heart pacemaker in patients, and its relationship with age. Methods: 107 patients of both sexes (49.5% female

Endereço para correspondência: Juliana Bassalobre Carvalho Borges Rua Prof. Carvalho Júnior, 53/201. Alfenas, MG, Brasil – CEP: 37130-000. E-mail: jubassalobre@ig.com.br Artigo recebido em 15 de outubro de 2012 Artigo aprovado em 19 de dezembro de 2012

Borges JBC, et al. - Correlação entre a qualidade de vida, classe funcional e idade em portadores de marca-passo cardíaco

Abreviaturas, acrônimos & siglas CF QV CDI

classe funcional qualidade de vida cardioversor desfibrilador implantável

/50.5% male) were investigated, average implant time of 6.36 months (±2.99), and average age of 69.3 years (±12.6). To assess the FC, a scale suggested by Goldman was used; for QoL the AQUAREL questionnaire was used, associated with SF-36. Statistical analysis was conducted using Spearman's correlation with 5% significance. Results: Negative correlations were observed between QoL and FC: AQUAREL in the three domains, chest discomfort (r=-0.197, P=0.042), dyspnea (r=-0.508, P=0.000), arrhythmia

INTRODUÇÃO O complexo estimulante cardíaco é resultante de um processo de especialização celular e traduz o esforço de milhões de anos na evolução filogenética para a manutenção da vida. Naturalmente, a substituição de componentes desse sistema de condução, com a manutenção das suas propriedades, sempre constituiu um desafio importante no campo da eletroterapia cardíaca [1]. O processo normal de condução do coração é lesado quando um dos vasos coronarianos é interditado, ficando parte dessa condução bloqueada. Quando esse tipo de anormalidade é detectado, pode-se indicar o implante de marca-passo cardíaco, que consiste em mecanismos de estimulação cardíaca artificial, com objetivo de corrigir ou diminuir as alterações [2]. Esses dispositivos elétricos têm como função proporcionar a atividade elétrica cardíaca mais fisiológica possível, contribuindo, basicamente, para a correção da frequência cardíaca e ressincronização de câmaras cardíacas [1,3]. A estimulação cardíaca elétrica artificial, modernamente, deixou de ser apenas uma forma de salvar a vida de portadores de bloqueios atrioventriculares, passando a ser um modo de corrigir os distúrbios do ritmo cardíaco e do sincronismo atrioventricular [4]. A preocupação foi além da inicial de apenas prolongar a vida, mas também permitir a esses pacientes atingirem qualidade de vida compatível com a média da população. Para isso vários estudos foram desenvolvidos focando a qualidade de vida de pacientes com marca-passo [3,5-11]. O termo qualidade de vida possui várias definições. Segundo a Organização Mundial de Saúde, qualidade de vida é a “percepção do indivíduo da sua posição na vida 48

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(r=-0.271, P=0.005), and the SF-36 in the eight domains. Regarding age, there was a negative correlation with the SF36 Functional Capacity (r=-0.338, P=0.000) and no correlation was found with AQUAREL. Positive correlation (r=0.237, P=0.014) was observed between age and FC. Conclusion: In this study we found a significant negative correlation between QoL and FC, indicating that patients in this sample who belong to a better FC demonstrated better QoL. The older the patient, QoL is worse in functional capacity and FC. It is suggested that age and FC influence QoL, and the functional classification scales may be established as one of the assessment tools and reflect QoL in patients with pacemakers. Descriptors: Quality of life. Pacemaker, artificial. Indicators of quality of life.

dentro do contexto cultural e de valores que ele vive, bem como em relação a seus objetivos, expectativas, padrões e preocupações” [12]. A avaliação da qualidade de vida e sua mensuração, inicialmente, tinham por objetivo complementar as análises de sobrevida, somando-se aos demais parâmetros clínicos. Entretanto, essa avaliação teve seu escopo ampliado quando passou a integrar as análises de custo-efetividade [13]. A preocupação com o conceito de “qualidade de vida” vem resgatar aspectos mais amplos que o controle de sintomas, diminuição da mortalidade ou aumento da expectativa de vida. A qualidade de vida relacionada à saúde refere-se a uma visão subjetiva do paciente sobre o seu estado de saúde, e pode contrastar com avaliações fisiológicas, com interpretações clínicas relativas ao bemestar do paciente e sua capacidade funcional [13,14]. Vários instrumentos têm sido propostos para avaliar a qualidade de vida em saúde, os questionários mais utilizados são os genéricos e os específicos [3,14-16]. Para pacientes com marca-passo a literatura recomenda o uso de um questionário específico associado às questões gerais de saúde contidas num questionário genérico [5-8]. Segundo Cunha et al. [9], o rápido desenvolvimento, nas últimas décadas, de sofisticados dispositivos e o aumento do número de indicações para implante de marca-passo chamam a atenção para o uso de medidas que avaliem a qualidade de vida e o nível de atividade diária desses pacientes. Observaram em seus estudos importantes aspectos de correlação entre duas formas de avaliação: qualidade de vida e classificação funcional. Escalas de classificação funcional frequentemente são utilizadas durante as avaliações do paciente com marcapasso com objetivo de categorizar o grau de disfunção

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cardiovascular. Dentre elas, destaca-se a escala proposta por Goldman [3,5,17]. Os instrumentos para avaliação da qualidade de vida e classificação funcional são uma forma complementar para a avaliação dos aspectos físicos, emocionais e funcionais dos pacientes. Entretanto, ainda é discutível a correlação entre classe funcional e qualidade de vida em usuários de marca-passo definitivo cardíaco. Esse questionamento é o alicerce do presente estudo, justifica-se na necessidade de discussão aprofundada sobre a temática “capacidade funcional e qualidade de vida em pacientes portadores de marca-passo”, como sugerido por estudos de Stofmeel et al. [18]; Oliveira et al. [8] e Cunha et al. [9]. O objetivo do presente estudo foi avaliar se existe correlação entre qualidade de vida e classe funcional em pacientes no pós-implante de marca-passo cardíaco, e sua relação com idade.

metabólicos próprios. Os pacientes responderam às perguntas com “SIM” ou “NÃO” de acordo com a ficha de classificação funcional para a referida escala e foram organizados em classes funcionais: I (capacidade de executar todas as atividades questionadas equivalente a consumos metabólicos ≥ 7 mets), II (executar atividades com consumo metabólico ≥ 5 mets), III (capacidade de executar atividades com consumo metabólico ≥ 2 mets) e IV (não conseguem executar atividades que requerem consumo acima de 2 mets) [3,8,9,17]. Na avaliação da qualidade de vida foram utilizados dois questionários que devem ser aplicados em conjunto aos pacientes de marca-passo: questionário de qualidade de vida específico para portadores de marca-passo, o Assessment of QUality of life and RELetad events – AQUAREL e o questionário genérico The Medical Study 36-item Short-Form Health Survey – SF-36, [3,8,9]. Ambos os instrumentos já foram traduzidos e adaptados para a língua portuguesa e possuem validade, confiabilidade e reprodutibilidade bem estabelecidas na população brasileira [8,15]. O questionário AQUAREL é composto por 20 questões distribuídas em três domínios: desconforto no peito, arritmia e dispneia ao exercício. [3,6-8]. O domínio Desconforto no peito envolve as questões: 1 a 6 (referentes à dor no peito) e questões 11 e 12 (referentes à dispneia ao repouso). O domínio Arritmia engloba as questões de 13 a 17. O domínio Dispneia ao exercício compreende as questões de 7 a 10 (referentes à dispneia ao exercício) e 18 a 20, (referentes à fadiga) [3]. Cada domínio é constituído de itens específicos que apresentam cinco categorias de resposta, com valores de 1 a 5. Os escores individuais, obtidos para cada domínio do questionário foram somados e computados pela fórmula apresentada na análise dos dados. Os escores finais podem variar de zero (todas as queixas) a 100 (sem queixas), este último valor representa perfeita qualidade de vida [8]. O SF-36 é um questionário multidimensional formado por 36 itens, agrupados em oito domínios: capacidade funcional, aspectos físicos, dor, estado geral de saúde, vitalidade, aspectos sociais, aspectos emocionais e saúde mental. Apresenta um escore final de 0 a 100, no qual 0 corresponde a pior estado geral de saúde e 100 a melhor estado de saúde [15]. Em relação a somatória dos escores, cada questionário poderia variar sua pontuação final de 0 a 100, dessa forma, foi estipulado um valor de corte de 50 (valor médio) para determinar os domínios que estão melhores e os que estão piores. Os domínios que pontuaram menos de 50 estariam com a qualidade de vida pior e aqueles que pontuaram 50 ou mais estariam com boa qualidade de vida [20]. Os questionários AQUAREL e SF-36 foram aplicados sob a forma de entrevista, por um único examinador

MÉTODOS Foi realizado estudo observacional transversal, quantitativo e descritivo, em pacientes portadores de marca-passo, do Serviço de Cirurgia Cardíaca e Marcapasso da Santa Casa de Misericórdia da cidade de Marília, SP. A coleta de dados ocorreu no período de agosto de 2009 a junho de 2010. O tamanho amostral mínimo foi estimado em n=85, levando-se em conta um nível de significância de 5% (a=0,05), um erro tipo II de 20% (b=0,20) e magnitude de efeito | r | = 0,30 [19]. O estudo foi previamente aprovado pelo comitê de ética da Faculdade de Medicina de Marília (FAMEMA), protocolo: nº442/08, em consoante com a Declaração de Helsinki. Os voluntários assinaram um termo de consentimento livre e esclarecido. Participaram do estudo os indivíduos de ambos os sexos, entre três e 12 meses de implante de marca-passo por doença do sistema de condução, sem doença arterial coronária, estáveis clinicamente e com idade acima de 18 anos. Foram excluídos os indivíduos com idade inferior a 18 anos, que não compreenderam a sequência dos testes, apresentaram limitação na fala, audição e entendimento e os com falta de interesse em participar. Os voluntários foram avaliados por meio de um protocolo que incluiu dados pessoais, perguntas referentes ao marca-passo cardíaco (tempo, motivo, modo de estimulação), patologias associadas, classe funcional e questionários de qualidade de vida. A classe funcional foi avaliada por meio da escala de atividade específica de classificação funcional proposta por Goldman et al. [17], aplicada em forma de entrevista por um único examinador previamente treinado. Essa escala é composta de perguntas simples sobre atividades específicas e cada uma delas relaciona-se com gastos

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previamente treinado e mascarado em relação aos resultados da classe funcional. A somatória dos pontos foi realizada de acordo com o descrito na literatura para cada questionário [3,15].

total e nos três domínios: desconforto no peito, dispneia e arritmia com classe funcional. Em relação à idade não se observou correlação com a qualidade de vida pelo AQUAREL (Tabela 2). Também foram observadas correlações negativas significantes entre o questionário SF-36 em todos os seus domínios e classe funcional. Em relação à idade, verificouse correlação negativa significante com o domínio capacidade funcional (Tabela 3). No estudo da associação entre idade e classe funcional, observou-se correlação positiva significante (r= 0,237; P= 0,014).

Análise estatística Os dados foram resumidos por meio de tabelas, frequência absoluta, porcentagens, média, desvio-padrão; valor máximo e valor mínimo. Para o cálculo dos escores dos três domínios do questionário para medida da qualidade de vida AQUAREL (desconforto no peito: questões 1 a 6, 11 e 12; dispneia: questões 7 a 10, 18 a 20; arritmia: questões 13 a 17) utilizouse a equação (1) de Oliveira [3] (203, p. 46), com a seguinte equivalência entre letras das respostas dos itens de cada uma das 20 questões do questionário AQUAREL e escala likert de cinco pontos: a)=5; b)=4; c)=3; d)=2 e e)=1. Equação = 100 – {[(ΣN - n°N ) / (n°N X 5) – n°N ]} X 100. Onde: ΣN = somatório de pontuação das questões que compõem o escore e n° N = número de questões que compõem o escore. No estudo das correlações entre variáveis quantitativas foi utilizado o teste não-paramétrico de Spearmann (rS). Adotado o nível de significância de 5% de probabilidade para a rejeição da hipótese de nulidade. RESULTADOS Foram avaliados 107 indivíduos, de ambos os sexos (49,5% feminino e 50,5% masculino), com tempo médio de implante de marca-passo 6,36 meses (±2,99 meses) e média de idade 69,3 anos (±12,6 anos). Observou-se 12,1% de doença de Chagas, 64,5% de hipertensão arterial sistêmica; 24,3% diabetes mellitus e 48,6% relataram não tabagismo. Em relação à classe funcional, a maioria com 70% classe I. A Tabela 1 apresenta a caracterização da amostra. Os resultados do estudo evidenciaram correlações negativas significantes entre qualidade de vida e classe funcional. Na análise do questionário AQUAREL observou-se correlação negativa entre qualidade de vida

Tabela 1. Características gerais e clínicas dos 107 pacientes em estudo. Variáveis Sexo Feminino Masculino Escolaridade Analfabeto Fundamental incompleto Médio incompleto Médio completo Superior completo Doença de Chagas Sim Não Indicação do implante Bloqueio atrioventricular Doença do nó sinusal Outros Tipo de estimulação Bicameral Unicameral Tempo de implante (meses) Média (DP) Mínimo – Máximo Classificação funcional Classe I Classe II Classe III Classe IV

% 49,5 50,5 30,8 55,1 1,9 7,5 3,7 12,1 87,8 57,9 28,0 14,1 86,9 13,1 6,36 ± 2,99 1 - 13 70 7 21 2

Tabela 2. Valores médios de qualidade de vida (AQUAREL) e, correlações entre os domínios desse questionário com classe funcional e idade. Dispneia 75,0 ± 21,3

Arritmia 89,0 ± 14,1

AQUAREL total 84,9 ± 13,9

r= -0,197 r= -0,508 P= 0,042* P= 0,000* Idade r= 0,188 r= -0,041 P= 0,052 P= 0,678 * Significante (P <0,05). Teste de correlação de Spearmann

r= -0,271 P= 0,005* r= 0,051 P= 0,600

r= -0,441 P= 0,000* r= 0,028 P= 0,774

Média (DP) Coeficiente de correlação Classe funcional

Desconforto no peito 90,8 ± 14,9

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Tabela 3. Valores médios de qualidade de vida (SF-36) e, correlações entre os domínios desse questionário com classe funcional e idade.

Média (dp) Coeficiente de correlação Classe funcional Idade

Capacidade funcional 69,2 ± 24,9

Aspectos físicos 58,4 ±37,6

r= -0,686 P= 0,000* r= -0,383 P= 0,000*

r= -0,359 P=0,000* r= 0,063 P= 0,520

Dor 63,5 ±27,0

Estado geral saúde 72,4 ±23,6

74,2 ±20,6

Aspectos sociais 89,1 ±21,8

r= -0,356 P=0,000* r= -0,089 P=0,360

r=-0,465 P=0,000* r=-0,089 P=0,360

r= -0,462 P=0,000* r= -0,044 P=0,651

r= -0,194 P=0,045* r= -0,070 P=0,476

Vitalidade

Aspectos Saúde emocionais mental 62,6 ±43,1 74,0 ±23,0 r= -0,336 P=0,000* r= -0,003 P=0,973

r= -0,358 P=0,000* r= 0,093 P=0,340

* Significante (P <0,05). Teste de correlação de Spearmann.

DISCUSSÃO Qualidade de vida x classificação funcional Segundo publicação recente do Registro Brasileiro de Marca-passos, Ressincronizadores e Desfibriladores (RBM), em 2012, ao analisar os implantes de marca-passo cardíaco catalogados, observa-se atualmente o perfil das indicações: 11,4% de pacientes em classe I, 15,9% em classe II, 41,3% em classe III e 31,3% em classe IV [21]. Esses números representam o universo da estimulação cardíaca no Brasil, as indicações são predominantes a pacientes em classes III e IV. Em relação à avaliação da qualidade de vida com os questionários AQUAREL e SF-36, observou-se que, nenhum domínio obteve resultado com valores abaixo de 50, demonstrando que a qualidade de vida dos pacientes após o implante está acima da média, portanto, pode-se considerar de uma maneira geral que a qualidade de vida percebida por esses pacientes foi boa. Analisando os maiores e menores escores dos questionários, no AQUAREL, a qualidade de vida menor na opinião dos pacientes foi no domínio dispneia com 75 e a melhor qualidade em desconforto com 90,8, sendo o fator menos afetado na vida desses pacientes. No SF-36, o domínio com maior percepção de qualidade de vida foi aspectos sociais com 89,1, observou-se que o domínio aspectos físicos (impacto da saúde física no desempenho das atividades diárias e/ou profissionais) apresentou a menor média dos dois questionários de 58,4, sendo o mais afetado na opinião dos pacientes. Esses achados corroboram com estudo de Oliveira [3], que avaliou a qualidade de vida (AQUAREL e SF-36) em 139 pacientes portadores de marca-passo, observaram prejuízo na qualidade de vida pelo AQUAREL em dispneia (75,3) e melhor qualidade em desconforto (85,3). No SF36, a pior qualidade de vida foi em aspectos emocionais (46,7), seguido pelos aspectos físicos (51,4) e melhor qualidade em aspectos sociais (74,3). Cesarino et al. [22] estudaram a qualidade de vida em 50 pacientes portadores de cardioversor desfibrilador

implantável (CDI) por meio do questionário SF-36. O domínio aspectos sociais apresentou o maior escore (80,5) e o pior foi aspectos físicos (40,5), em concordância com este estudo. Observou-se correlação negativa entre todos os domínios da qualidade de vida e classe funcional em pacientes com marca-passo, sugerindo que aqueles indivíduos pertencentes a melhor classe funcional apresentaram maiores escores de QV, e aqueles pertencentes a piores níveis de classe funcional (no presente estudo, classe III e IV) apresentaram os menores escores. Concordando com achados de Cunha et al. [9], em sua pesquisa estudaram classe funcional (Goldman) e qualidade de vida (AQUAREL e SF-36) em 14 pacientes portadores de marca-passo, observaram também correlação significante entre os instrumentos: nos três domínios do AQUAREL com classe funcional; e nos domínios do SF-36, vitalidade, dor e capacidade funcional com classe funcional. No estudo de Stofmeel et al. [6,7], com 74 pacientes portadores de marca-passo observaram correlação negativa dos escores de qualidade de vida (AQUAREL e SF-36) com a classificação funcional de New York Heart Association (NYHA). Segundo Oliveira et al. [8], as correlações observadas entre os escores dos domínios do AQUAREL e instrumentos já reconhecidamente validados, como o questionário SF-36 e a classificação funcional pela escala de Goldman, sugerem que o AQUAREL é um instrumento de avaliação de qualidade de vida capaz de registrar pela variação de seus escores específicos, mudanças nas sensações subjetivas do ponto de vista dos pacientes com marca-passo. Concordando com o presente estudo, também observaram correlações entre classe funcional e qualidade de vida. Oliveira et al. [23] estudaram qualidade de vida em 139 pacientes portadores de marca-passo, identificaram relação entre a pior qualidade de vida relacionada à saúde nos portadores de marca-passo com doença de Chagas, sexo feminino, condição de solteiro e a pior classe funcional. Na análise multivariada, a pior classe funcional destacou51

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se como preditora independente de baixa qualidade de vida relacionada à saúde no componente físico do SF36 e em todos os domínios do AQUAREL. Portanto, o presente estudo também evidenciou relação direta da classe funcional, que reflete o grau de insuficiência cardíaca, com a qualidade de vida nos pacientes com marca-passo, confirmando os relatos de outros autores como Stofmeel et al. [18]; Oliveira et al. [8,23]; Cunha et al. [9].

escores da qualidade de vida e idade: Gomes et al. [25] avaliaram a qualidade de vida (AQUAREL e SF-36) após implante de marca-passo em 23 pacientes e Antônio et al. [11] avaliaram a qualidade de vida (SF-36) de 25 cardiopatas elegíveis à implantação de marca-passo em um hospital. A idade reflete o envelhecimento, que é um fator de risco não modificável, apresentando maior frequência e maior gravidade nas doenças cardiovasculares. Mesmo sabendo que o implante de MP pode propiciar um benefício em relação à qualidade de vida, muitas vezes este não é mensurado em populações mais idosas em função de outras doenças coexistentes e menor expectativa de vida [25]. No presente estudo observou-se correlação positiva significante entre idade e classe funcional, sugerindo que os pacientes mais idosos apresentaram pior classe funcional, acredita-se que esse fato se explique pela própria fisiologia do envelhecimento, pois a escala de Goldman é sensível para detectar a diminuição das atividades que se relaciona com a capacidade de realizar tarefas que exigem um determinado gasto metabólico, discordando dos resultados de Cunha et al. [9], pois não encontraram correlação. Sugere-se que as escalas de classificação funcional podem constituir um dos instrumentos que integram a avaliação e refletem a qualidade de vida em portadores de marca-passo, podendo auxiliar a equipe de saúde na prática clínica.

Idade x qualidade de vida x classificação funcional Segundo citado por Cunha et al. [9], a literatura apresenta resultados controversos no que se refere à correlação entre idade e qualidade de vida em diferentes populações [14,24,25]. Acredita-se que a idade apresente relação, principalmente, com variáveis relativas à condição física dos pacientes [9,24,26]. Neste estudo observou-se correlação negativa entre idade com o domínio capacidade funcional do SF-36, um dos que representa a condição física. Esse domínio indica o quanto as condições de saúde interferem nas atividades cotidianas, sugerindo que os pacientes com o avançar da idade têm maior comprometimento nas atividades físicas e funcionais, portanto com pior qualidade de vida em capacidade funcional. Semelhante a esses achados, Cunha et al. [9] observaram correlação negativa entre idade e SF-36 no domínio capacidade funcional, por outro lado, também encontraram correlação entre idade e aspecto emocional, sustentando a controversa questão da relação entre qualidade de vida e idade. Van Eck et al. [27] estudaram qualidade de vida em pacientes esperando o implante de marca-passo com uma população controle (sem necessidade de marca-passo). Destacaram que os mais importantes preditores de uma melhor qualidade de vida foram: idade, presença de comorbidades cardiológicas e fibrilação atrial. Relataram que a idade está relacionada inversamente com a qualidade de vida, em concordância com os achados deste estudo. Concordando com os resultados de Cunha et al. [9], no presente estudo também não foram encontradas correlações entre qualidade de vida pelo questionário AQUAREL e idade. Explicaram os autores em seu estudo que, possivelmente, essa diferença de associação entre idade e os dois instrumentos de qualidade de vida se deva ao fato de o SF-36 ser um questionário genérico e ter domínios mais amplos, podendo abranger diferentes aspectos susceptíveis à interferência da idade. Entretanto, Cesarino et al. [22], na pesquisa sobre percepção de qualidade de vida (SF-36) em pacientes com CDI, observaram que a qualidade de vida em relação à idade não apresentou diferença estatisticamente significante. Dois trabalhos desenvolvidos em cidades do interior de Goiás também não observaram associação significante entre os 52

CONCLUSÃO No presente estudo, foi encontrada correlação negativa entre todos os domínios da qualidade de vida com classe funcional. A idade apresentou correlação negativa com qualidade de vida e com classe funcional. A idade e a classe funcional têm influência na qualidade de vida, portanto essas variáveis devem ser consideradas nas estratégias para melhora da qualidade de vida em indivíduos com marca-passo.

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16. Alleyne GAO. Health and the quality of life. Rev Panam Salud Publica. 2001;9(1):1-6. 17. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation. 1981;64(6):1227-34. 18. Stofmeel MA, van Stel HF, van Hemel NM, Grobbee DE. The relevance of health related quality of life in paced patients. Int J Cardiol. 2005;102(3):377-82. 19. Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Delineando a pesquisa clínica: uma abordagem epidemiológica. Porto Alegre: Artmed;2003. 20. Servelhere KR, Fernandes YB, Ramina R, Borges G. Aplicação da escala SF-36 em pacientes operados de tumores da base do crânio. Arq Bras Neurocir. 2011;30(2):69-75. 21. Pachón Mateos JC. RBM – Registro Brasileiro de Marcapassos, Ressincronizadores e Desfibriladores. DECA - SBCCV. [s.l.:s.n.] 2012. 35p. 22. Cesarino CB, Beccaria LM, Aroni MM, Rodrigues LCC, Pacheco SS. Qualidade de vida em pacientes com cardioversor desfibrilador implantável: utilização do questionário SF-36. Rev Bras Cir Cardiovasc. 2011;26(2):238-4. 23. Oliveira BG, Velasquez-Melendez G, Rincón LG, Ciconelli RM, Souza LA, Ribeiro AL. Health-related quality of life in Brazilian pacemaker patients. Pacing Clin Electrophysiol. 2008;31(9):1178-83. 24. Santos PR. Relação do sexo e da idade com nível de qualidade de vida em renais crônicos hemodialisados. Rev Assoc Med Bras. 2006;52(5):356-9. 25. Gomes TB, Gomes LS, Antônio IHF, Barroso TL, Cavalcante AMRZ, Stiva MM, et al. Avaliação da qualidade de vida pósimplante de marcapasso cardíaco artificial. Rev Eletr Enf [internet]. 2011;13(4):735-42. Disponível em: www.fen.ufg. br/revista/v13/n4/v13n4a19.htm.

13. Monteiro R, Braile DM, Brandau R, Jatene FB. Qualidade de vida em foco. Rev Bras Cir Cardiovasc. 2010;25(4):568-74.

26. Castro M, Caiuby AVS, Draibe AS, Canziani MEF. Qualidade de vida de pacientes com insuficiência renal crônica em hemodiálise avaliada através do instrumento genérico SF-36. Rev Assoc Med Bras. 2003;49(3):245-9.

14. Favarato MECS, Favarato D, Hueb WA, Aldrighi JM. Qualidade de vida em portadores de doença arterial coronária: comparação entre gêneros. Rev Assoc Med Bras. 2006;52(4):236-4.

27. van Eck JW, van Hemel NM, Kelder JC, van den Bos AA, Taks W, Grobbee DE, et al. Poor health-related quality of life of patients with indication for chronic cardiac pacemaker therapy. Pacing Clin Electrophysiol. 2008;31(4):480-6.

Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the ORIGINAL ARTICLE myocardium after ischemia/reperfusion injury in isolated rat hearts

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Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos

Yong Cao1, Lie Wang2, Hong Chen3, Zhiqian Lv4

DOI: 10.5935/1678-9741.20130009

RBCCV 44205-1442

Abstract Objective: A simple method to reduce the ischemia/ reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. Method: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. Results: Rat hearts with hyperosmotic perfusion showed

higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, P<0.005), a lower reperfusion arrthythmia score (3.2 vs. 5.3, P<0.001), better ventricular function, and less creatine phosphokinase leakage (340.1 vs. 861.9, P<0.001) than normal osmotic controls. Myocardial catalase content and activity were increased significantly (1435 vs. 917 U/g wet weight, P<0.001) in hearts perfused with hyperosmotic solution in comparison to the normal osmotic controls. Conclusion: Pretreatment with hyperosmotic perfusion in normal rat hearts, which is attributed partly to the increased antioxidative activity, could provide beneficial effects from ischemia and reperfusion-induced injury by increasing coronary flow, and decreasing reperfusion arrhythmia.

1. Doctor - No 6th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Participated the experiment and drafted the manuscript. 2. Doctor - Research Institute of General Surgery, General Hospital, Fuzhou Military Area Command of PLA, Shanghai, China. Participated the experiment and drafted the manuscript. 3. Doctor - Department of Pharmacology, Shanghai Jiaotong University School of Medicine, Shanghai, China. Designed the experiment and participated in the experiment. 4. Doctor - No 6th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Provided the research grant and research plan.

The work was carried out at No 6th People's Hospital and Department of Pharmacology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Descriptors: Ischemia. Reperfusion injury. Myocardial infarction.

Correspondence address Zhiqian Lv and Hong Chen Department of Cardiosurgery, No 6th People's Hospital, Shanghai Jiaotong University School of Medicine, 200233, Shanghai, P R. China E-mail: luzhiqian@gmail.com and hchen100@hotmail.com Article received on September 18th, 2012 Article accepted on October 1st, 2012

Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

Abbreviations, acronyms & symbols CPK HR LVEDP LVP NO ROS SDS-PAGE SOD VF-VT

Creatine phosphokinase Heart rate Left ventricular end diastolic pressure Left ventricular pressure Nitric oxide Reactive oxygen species Sodium dodecyl sulfate–polyacrylamide gel electrophoresis Superoxide dismutase Ventricular fibrillation-ventricular tachycardia

Resumo Objetivo: Um método simples para reduzir a lesão de isquemia/reperfusão que pode acompanhar a cirurgia cardíaca teria grande valor clínico. O objetivo deste estudo foi investigar o efeito da perfusão hiperosmótica na isquemia/ reperfusão em corações isolados de ratos perfundidos. Métodos: Quarenta ratos machos Sprague-Dawley foram divididos aleatoriamente e tiveram os seus corações isolados perfundidos com tampão osmótico normal ou tampão hiperosmótico com a adição de glucose. Os corações foram então submetidos a 30 minutos de isquemia, seguida de 30

INTRODUCTION Each year in the United States, approximately 1 million myocardial infarctions occur, and 700,000 patients undergo cardioplegic arrest for various cardiac surgeries. Minimizing ischemic time in these clinical scenarios has appropriately received a great deal of attention because of the long-established relationship between duration of ischemia and extent of myocardial injury. However after coronary flow is restored, the myocardium is susceptible to another form of insult stemming from reperfusion of the previously ischemic tissue. Given that cardiac ischemia is either unpredictable (myocardial infarction) or inevitable (in the operating room), there is great interest in developing strategies to minimize reperfusion-mediated injury. Hyperosmotic saline has been used successfully in haemorrhagic and other types of shock to protect different tissues and organs [1,2]. Hyperosmotic saline perfusion has also been shown to decrease ischemia/reperfusion injury in rat hearts [3]. Elevated blood glucose also

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min de reperfusão. O fluxo coronariano, tempo de parada isquêmica, arritmia de reperfusão e da função ventricular foram registrados. Vazamento creatinofosfoquinase na artéria coronária, o miocárdio e atividade de superóxidodismutase e catalase foram também examinados. Resultados: Crações de ratos com perfusão hiperosmótica apresentaram maior fluxo coronariano, tempo prolongado de parada isquêmica (10,60 vs. 5,63 min, P<0,005), menor pontuação de reperfusão arritmica (3,2 vs. 5,3, P<0,001), melhor função ventricular e menos vazamento de creatina fosfoquinase (340,1 vs. 861,9, P<0,001) do que controles normais osmóticos. Teor de catalase e atividade do miocárdio também tiveram aumento significativo (1435 vs. 917 peso U/g de peso fresco, P<0,001) em corações perfundidos com solução hiperosmótica em comparação com os controles normais osmóticos. Conclusão: O pré-tratamento com perfusão hiperosmótica em corações de ratos normais, o que é atribuído, em parte, ao aumento da atividade antioxidante, pode oferecer efeitos benéficos de isquemia e reperfusão induzida por lesão, aumentando o fluxo coronário e diminuindo a arritmia de reperfusão. Descritores: Isquemia. Traumatismo por reperfusão. Infarto do miocárdio.

increases plasma osmolarity, and resistance to ischemia/ reperfusion injury is increased in hearts from type 1 diabetic rats that have severe hyperglycaemia [4]. Because both hypertonic saline and, in diabetic rats, hyperglycemia are cardioprotective, we sought to determine whether addition of glucose instead of sodium chloride (NaCl) to produce hyperosmolarity would, in hearts from normal rats, provide protection from ischemia/reperfusion injury. If hyperosmotic glucose perfusion were found to be protective, it might, in the future, be able to be used clinically to attenuate ischemia/reperfusion injury during cardiac bypass surgery. The present study investigates the effect of hyperosmotic perfusion pretreatment with glucose on ischemia/reperfusion arrhythmia and ventricular function damage in isolated rat hearts in vitro. Coronary creatine phosphokinase leakage (that is, leakage of this cardiac enzyme from damaged myocardial cells into the perfusate from the coronary artery), and myocardial content and activity of two antioxidant enzymes, superoxide dismutase 55

Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

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and catalase, were also measured in order to assess the effect of hyperosmotic perfusion with glucose on myocardial cell damage and anti-oxidant activity.

Shanghai, China). Premature ventricular beats, ventricular tachycardia and ventricular fibrillation during reperfusion were recorded. The severity of arrhythmias was scored using the Curtis arrhythmia scoring system [6]. This system uses a scale of 0-9, where 0 indicates occasional ectopic beats and 9 indicates ventricular fibrillation occurring during the first 60s of reperfusion. The time from the clamping of the atrial inflow and aortic outflow to the cessation of ventricular contractions was recorded as the time to arrest, and the time from the beginning of reperfusion to the start of ventricular contractions was recorded as the time to recovery. All hearts were allowed to beat spontaneously. After the 10 min normal buffer equilibration perfusion and 20 min pre-treatment normal buffer or hyperosmotic glucose perfusion (the total pre-ischemia period was 30 min), the hearts were subjected to 30 min global ischemia by clamping both atrial inflow and aortic outflow. The heart was thus in contact with hyperosmotic glucose buffer for a total of 50 min. The heart was kept warm during the ischemic period. At the end of this period, the above flow catheters were opened for a 30 min reperfusion period.

METHODS Animals This study was approved by the animal care and use committee of our institution (2011(LW)-13). Forty male Sprague-Dawley rats (originally weighing 220–280 g) were housed under standard conditions with free access to tap water and chow. Rats were randomly divided either to have their isolated hearts perfused with normal Krebs-Henseleit buffer solution (300 mOsm/L) or with Krebs-Henseleit buffer solution made hyperosmotic (360 mOsm/L) by addition of glucose. Isolated heart preparation and ischemia/reperfusion with normal buffer solution Rats were anaesthetized with sodium pentobarbital (60 mg/kg, i.p.), injected with 25 mg/kg heparin, and their hearts excised a few minutes later. The hearts were then placed in a Langendorff apparatus [5] and rapidly connected to the aortic cannula of this apparatus for retrograde perfusion with Krebs–Henseleit buffer containing (in mmol/L): NaCl 118.0; KCl 4.7; CaCl2 2.5; MgSO4 1.2; KH2PO4 1.2; NaHCO3 25.0; glucose 11.0 mM; Na2 -EDTA 0.5. The perfusate was maintained at 37˚C and aerated continuously with 95% O2 and 5% CO2. The left atrium was connected to a cannula and perfused in order to fill the left ventricle, and a catheter was inserted into the left ventricle to record left ventricular pressure (LVP), left ventricular end diastolic pressure (LVEDP), and maximal rate of LVP rise (dp/dtmax) and fall (dp/dtmin), using a data acquisition system (MPA 2000; Alcott Biotech, Shanghai, China). Aortic perfusion pressure was set at 70 mmHg and left atrial pressure at 15 mmHg throughout the experiment. However, cardiac output as it would occur in the living animal cannot be measured with this method. A catheter inserted into a small artery originating in the marginal or oblique branch of the left circumflex coronary artery was used for continuous measurement of coronary flow (calculated from the fluid fractions collected as volume/ time) in pre-ischemia perfusion, ischemia, and reperfusion periods. We used this location for catheter insertion because it enables more precise and clean collection of coronary effluent than effluent collected from other locations. The perfusate collected from the coronary artery was used to assay for creatine phosphokinase. Electrodes were inserted into the myocardium at the base and apex of the heart, and heart rate (HR) and electrocardiogram were recorded continuously with a data-acquisition system (MPA 2000; Alcott Biotech, 56

Hyperosmotic perfusion The procedure for the rat hearts in the hyperosmotic perfusion group was the same as that described above for normally perfused hearts except that the osmolarity of the Krebs–Henseleit buffer was increased to 360 mOsmol/L during the 20 min pre-treatment period by adding 60 mOsmol/L of glucose and thus increasing the glucose concentration to 71 mM. Biochemical determinations and Western blot analysis At the end of the 30 min reperfusion period, the front portions of the left ventricles were freeze-clamped for use in biochemical assays and Western blotting. Creatine phosphokinase (CPK) from the coronary artery, and superoxide dismutase (SOD) and catalase from myocardial tissue homogenate, were determined with assay kits (Jian-Cheng Biomedical Engineering, Nanjing, China) according to the instructions of the manufacturer. For Western blot analysis, the freeze-clamped sections of the left ventricle were homogenized in lysis buffer (pH 7.4) containing (in mmol/L): Tris-HCl 50; sucrose 150; EDTANa2 5; EGTA 2; Na3VO4 1; NaF 50; phenylmethanesulphonyl fluoride 0.1; leupeptin 1 mg/L. Actin was used as the protein standard. Protein samples were loaded onto 8% sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDSPAGE) acrylamide gels and transferred to polyvinylidene difluoride membranes. Blots were incubated with antibodies to either catalase (Calbiochem, San Jose, CA, USA) or SOD (Kagaard & Perry Laboratories). The membranes were then incubated with corresponding horseradish peroxidase-

Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

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conjugated secondary antibody, and immunoreactive bands were visualized using electrochemoluminescence (Pierce; Thermo Fisher Scientific Inc., Rockford, IL, USA). Relative levels of proteins were semi-quantified with densitometry (Leica).

Ventricular function during ischemia and reperfusion Rat hearts perfused with hyperosmotic solution took a longer time (10.6±1.5 vs. 5.6±0.7 min) to stop beating during ischemia and a shorter time (13.0±2.5 vs. 19.2±1.5 sec) to resume beating during reperfusion than control hearts. In other words, hyperosmotic hearts were asystolic about 32 minutes as opposed to 43 minutes for control hearts. The reperfusion arrhythmia score (3.3±1.7) and ventricular tachycardiafibrillation period (15.0±1.2 min) were significantly reduced in hyperosmotic hearts compared to control hearts (5.3±1.2, 24.3±2 min respectively) (Table 1). There were no significant differences in pre-ischemia HR, LVP, LVEDP, dP/dtmax and dP/dtmin between the 2 groups. However, HR, LVP, dP/dtmax and dP/dtmin in both groups significantly decreased during reperfusion (P<0.05, Table 2).

Statistics Normally distributed continuous variables between control and hyperosmotic glucose groups were compared using an independent two sample t test. Differences between ischemia and reperfusion were determined using a paired t test. Repeated measurement of ANOVA was used for coronary flow. Data are presented as means ± SE. All statistical assessments were two-sided and evaluated at the 0.05 level of significant difference. Statistical analyses were performed using SPSS 15.0 statistics software (SPSS Inc, Chicago, IL).

Coronary flow and correlation with hyperosmotic perfusion Compared to normal osmotic perfusion, hyperosmotic glucose perfusion significantly increased pre-ischemia basal coronary flow in isolated rat heart after 5 and 10 minutes of perfusion (Figure 1). After ischemia and reperfusion treatment, coronary flow was also significantly higher with hyperosmotic glucose than normal osmotic perfusion over the 30 minutes of perfusion (Figure 2).

Creatine phosphokinase (CPK) leakage from myocardial tissue and myocardial anti-oxidant enzymes CPK leakage into the coronary artery, an indication of myocardial cell damage, was significantly reduced after reperfusion in hyperosmotic compared to control hearts, as shown by biochemical assays (360±115 vs. 860±124 U/g). Of the two anti-oxidant enzymes measured, hyperosmotic hearts showed a significant increase in myocardial catalase in both biochemical assay and Western blotting (Table 1 and Figure 3A, C). However, myocardial contents of SOD in hyperosmotic hearts were similar to those of normal control hearts in both biochemical assay and Western blotting (Table 1 and Figure 3B, D).

Fig. 1 – The effects of normal and hyperosmotic glucose perfusion on pre-ischemia coronary flow in isolated rat heart . (mean±SE, n=20 in each time point)

Fig. 2 – The effect of reperfusion with normal and hyperosmotic glucose perfusate on post-ischemia coronary flow in isolated rat heart. (mean±SE, n=20 in each time point)

RESULTS

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Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

Table 1. Ischemic arrest time, heartbeat recovery time, arrhythmia score and VT-VF time after ischemia/reperfusion with hyperosmotic glucose. Control 5.62±0.73 19.19±1.99 5.30±0.27 24.46±0.45 861.90±26.36 343±4.7 917±18.9

Ischemic arrest time (min) Heartbeat recovery time (sec) Arrhythmia score VT-VF duration (min) Creatine phosphokinase leakage (U/g ventricular weight) SOD (U/g wet weight) Catalase (U/g wet weight)

P value 0.005 0.056 <0.001 <0.001 <0.001 0.324 <0.001

Hyperosmotic glucose 10.60±1.50 11.24±2.40 3.20±0.33 14.91±0.28 340.10±24.88 354±10.0 1435±17.5

I/R ischemia/reperfusion; SOD, superoxide dismutase; VF, ventricular fibrillation; VT, ventricular tachycardia. Data are displayed as mean ± standard error. n=20

Table 2. Heart rate, contractility and relaxation before and after ischemia/reperfusion. HR (bpm) Pre 30 min LVP (mmHg) Pre 30 min LVEDP (mmHg) Pre 30 min dP/dtmax (mmHg/sec) Pre 30 min dP/dtmin (mmHg/sec) Pre 30 min

Control

Hyperosmotic glucose

P value

241.00±11.84 100.20±27.81a

249.70±15.82 198.50±17.23a

0.665 0.008

88.12±4.77 63.89±5.34a

86.08±3.50 69.92±3.42a

0.734 0.354

5.32±1.88 53.28±3.94a

5.87±1.21 37.16±3.74a

0.807 0.008

2476.5±218.6 345.0±105.8a

2538.0±129.3 1101.8±97.7a

0.811 <0.001

1657.5±137.5 303.0±61.1a

1881.3±121.6 834.0±46.55a

0.287 <0.001

dP/dtmax, maximal rate of left ventricular rise; dP/dtmin, maximal rate of left ventricular pressure fall; HR, heart rate; LVEDP, left ventricular end diastolic pressure; LVP, left ventricular pressure. a Significant difference between ischemia and reperfusion in each group using paired –t test. Data are displayed as mean ± standard error

Fig. 3 – Myocardial myocardial anti-oxidant enzymes in control and hyperosmotic glucose perfused ventricle. A. The myocardial catalase content was increased after hyperosmotic glucose perfusion. Data are the mean±SD (n = 20 in each time point). *P < 0.05 compared with control. B. There was no marked increase in SOD after hyperosmotic glucose perfusion. Data are the mean±SE (n = 20 in each time point). C. Western blot analysis also showed a marked increase in the levels of myocardial catalase after hyperosmotic glucose perfusion. D. No significant difference of SOD between control and hyperosmotic glucose group was found

Cao Y, et al. - Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

DISCUSSION In the current study, hyperosmotic perfusion pretreatment with glucose of rat hearts subjected to global ischemia resulted in better ventricular contractile and electrophysiological function, increased coronary flow, and less myocardial damage than was seen in normal rat hearts. Hyperosmotic perfusion pretreatment also increased levels of catalase, although levels of a second anti-oxidant enzyme, SOD, were similar to those seen in control hearts. Endothelial nitric oxide (NO) production has previously been shown to be responsible for the increase in coronary blood flow seen after bolus injection of hypertonic saline in anaesthetized pigs [7]. This is a possible mechanism for the increased coronary flow seen with hypertonic perfusion pretreatment of glucose in our study, but we did not measure NO production. Previous research by others has shown that an important change responsible for ischemia/reperfusion damage is the increase in intracellular calcium that occurs during ischemia [8]. Anoxia decreases pH, and the increased Na/H exchange used by the cell to bring the pH back to normal affects Na/Ca exchange in a way that increases intracellular calcium [8]. Myocardial perfusion with fluid made hypertonic with either NaCl or sucrose has been shown to decrease intracellular calcium by decreasing the anoxia-induced increase in Na/H exchange [9]. Reactive oxygen species (ROS) have also been implicated in the pathogenesis of ischemia/reperfusion injury [8]. In our study, hyperosmotic hearts showed an increase in the activity of the anti-oxidant enzyme, catalase, but no increase in SOD, the second enzyme studied. A study of diabetic hearts from rats with severe hyperglycaemia also showed an increase in catalase, but not SOD, compared to normal hearts [4]. And a study of hyperosmotic sodium chloride perfusion of normal and stroke-prone spontaneously hypertensive rat hearts also showed increased catalase but not increased SOD, although in this study raising the osmolarity to 400 mOsm/L was able to increase SOD slightly [10]. In our study, levels of catalase were increased 20%, but levels of the marker of myocardial damage, CPK, however, were decreased 60%. It seems doubtful, therefore, that this modest increase in catalase activity could, by itself, cause such a profound lessening of myocardial damage. An unanswered question is whether beneficial effects for heart by solution made hypertonic by the addition of glucose differs in any way from that provided by solution made hypertonic by the addition of NaCl. Hyperosmotic glucose differs from hypertonic saline in that glucose is a substrate for energy metabolism in the myocardium. In normal conditions, myocardium utilizes fatty acids for aerobic metabolism but in anoxic conditions, it uses glucose

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for anaerobic glycolysis. Anaerobic metabolism plays a crucial role in protecting myocardium from death [11]. Hyperosmotic glucose perfusate provides more glucose for the myocardium to produce ATP through glycolysis, an action beneficial for maintaining the activity of Na+-K+ATPase and the ATP-dependent K channel. This action may attenuate myocardium injury. However, because the manner in which the myocardium utilizes metabolic substrates is complex, the possibility that increases in extracellular glucose availability can be beneficial to heart needs further investigation. Chu et al. [12] also that ischemic myocardium in alloxaninduced-diabetic (DM) group displayed higher expression of cell survival proteins including phospho eNOS, heat shock protein 27, NFkB, and mTOR as compared with ischemic myocardium in normoglycemic (ND), whereas in non-ischemic tissue, expression of these proteins was similar or lower in the DM group. The expression of total Erk 1/2 was similar between ND and DM groups, whereas the expression of phospho-Erk 1/2(Thr202/Tyr204) was lower in the DM group as compared to the ND group [12]. The expression of SAPK/JNK was lower in the DM group [12]. The current study shows that normal rat hearts prefused with hyperosmotic glucose can provide beneficial effects to heart, but these beneficial effects could very well be due to the hyperosmolarity itself rather than glucose. In our study, rat hearts prefused with hyperosmotic glucose before ischemia/reperfusion increased coronary artery flow and decreased coronary artery resistance, increased left ventricular function, and increased levels of catalase but not SOD. In Shenâ&#x20AC;&#x2122;s et al. [10] study, prefused with hyperosmolar NaCl gave similar results: increased coronary artery flow and decreased coronary artery resistance, increased left ventricular function, and increased levels of catalase but not SOD. Shen et al. [10] also compared the effects of a 2 hour perfusion of rats hearts with solution made hyperosmolar with 4 different osmolytes (NaCl, glucose, mannitol, and raffinose) and found no significant differences in levels of the cellular constituents measured. They did not, however look at left ventricular function. Our findings and Shenâ&#x20AC;&#x2122;s et al. [10], therefore, may be due entirely to the hyperosmolarity. However, one must also consider the use for which a solution is intended. Studies comparing the success of solutions used to protect hearts used for transplantation have focused on protecting cellular energy metabolism [13,14]. Despite the crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, Lima et al. [14] had also found that a solution may contain the mannitol, instead of glucose, and the concentrations of K+ (15 mmol/L) and Ca2+ (0.25 mmol/L) of solution can contribute to a better performance by promoting the depolarizing arrest without contributing to an overload of intracellular calcium during 59

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the ischemic period. We were investigating hyperosmotic solutions might be beneficial to normal rat heart ex vivo to against ischemia/reperfusion injury during cardiac bypass surgery. In this situation, the physiologic effect of the hyperosmotic fluid used on non-cardiac tissue must be considered, and the use of glucose instead of NaCl as the osmolyte might have advantages. A limitation of this study is that we should compare the use of glucose to mannitol, an osmotically active but metabolically inactive compound, to see whether hyperosmolarity alone was responsible for the beneficial effects of glucose to heart or not. Perfusion with hypertonic mannitol has been shown to increase catalase levels in normal rat hearts [11] but there are no reports to date about its actions on ventricular function and enzymes during ischemia/reperfusion. Other limitations are that NO production, intracellular calcium, and ROS should be measured to elucidate the mechanism behind of these beneficial effects of hyperosmotic perfusion pretreatment. We also like to study the protein profiles of cell survival signaling and mitogen-activated protein kinase signaling to see whether changes in any of these parameters might be involved in beneficial effects of hyperosmotic perfusion pretreatment with glucose to normal rat heart. In summary, the present study had shown that hyperosmotic perfusion pretreatment may provide beneficial effects to heart from ischemia and reperfusion injury, increase coronary flow, and decrease reperfusion arrhythmia. The beneficial effects induced by hyperosmotic perfusion pretreatment with glucose may be attributed partly to the increased antioxidative activity. It is possible that hyperosmotic perfusion pretreatment may be able in the future to be applied during cardiac bypass surgery for its beneficial effects against ischemia/reperfusion injury.

2. Oliveira RP, Velasco I, Soriano FG, Friedman G. Clinical review: hypertonic saline resuscitation in sepsis. Crit Care. 2002;6(5):418-23.

ACKNOWLEDGEMENTS This study was supported by grants from the National Natural Science Foundation of China (No. 31171099, 30971154 and 30770848). CONFLICT OF INTEREST

4. Chen H, Shen WL, Wang XH, Chen HZ, Gu JZ, Fu J, et al. Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role of increased osmolarity. Clin Exp Pharmacol Physiol. 2006;33(10):910-6. 5. Skrzypiec-Spring M, Grotthus B, Szelag A, Schulz R. Isolated heart perfusion according to Langendorff: still viable in the new millennium. J Pharmacol Toxicol Methods. 2007;55(2):113-26. 6. Curtis MJ, Walker MJ. Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia. Cardiovasc Res. 1998;22(9):656-65. 7. Vacca G, Papillo B, Battaglia A, Grossini E, Mary DA, Pelosi G. The effects of hypertonic saline solution on coronary blood flow in anaesthetized pigs. J Physiol. 1996;491( Pt 3):843-51. 8. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008;88(2):581-609. 9. Ho HS, Liu H, Cala PM, Anderson SE. Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium. Am J Physiol Cell Physiol. 2000;278(5):C953-64. 10. Shen WL, Chen LB, Zhao JX, Guo SJ, Chen YC, Wang LP, et al. Effects of hyperosmotic sodium chloride perfusion on ischemia/reperfusion injury in isolated hearts of normal and stroke-prone spontaneously hypertensive rats. J Clin Exper Cardiol. 2011;2(7):146. 11. Gong J, Li LH, Pei WD, Wang HY, Zheng YL, Zhou GY, et al. Glycolytic and fatty acid metabolic enzyme changes early after acute myocardial ischemia. Zhonghua Xin Xue Guan Bing Za Zhi. 2006;34(6):546-50.

No conflict of interest declared.

12. Chu LM, Osipov RM, Robich MP, Feng J, Oyamada S, Bianchi C, et al. Is hyperglycemia bad for the heart during acute ischemia? J Thorac Cardiovasc Surg. 2010;140(6):1345-52.

REFERENCES

13. Silveira Filho LM, Petrucci O Jr, Carmo MR, Oliveira PP, Vilarinho KA, Vieira RW, et al. Trimetazidine as cardioplegia addictive without pre-treatment does not improve myocardial protection: study in a swine working heat model. Rev Bras Cir Cardiovasc. 2008,23(2):224-34.

1. Gurfinkel V, Poggetti RS, Fontes B, Costa Ferreira Novo F, Birolini D. Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary inflammatory response caused by hemorrhagic shock. J Trauma. 2003;54(6):1137-45.

3. Chen LB, Liu T, Wu JX, Chen XF, Wang L, Fan CL, et al. Hypertonic perfusion reduced myocardial injury during subsequent ischemia and reperfusion in normal and hypertensive rats. Acta Pharmacol Sin. 2003;24(11):1077-82.

14. Lima ML, Fiorelli AI, Vassallo DV, Pinheiro BB, Stolf NA, Gomes OM. Comparative experimental study of myocardial protection with crystalloid solutions for heart transplantation. Rev Bras Cir Cardiovasc. 2012;27(1):110-6.

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Pfeifer PM, et al. - Coping strategies after heart transplantation: ORIGINAL ARTICLE psychological implications

Coping strategies after heart transplantation: psychological implications Estratégias de enfrentamento pós-transplante cardíaco: implicações psicológicas

Paula Moraes Pfeifer1, Patricia Pereira Ruschel2, Solange Bordignon3 DOI: 10.5935/1678-9741.20130010

RBCCV 44205-1443

Abstract Objectives: To investigate coping strategies used by patients submitted to heart transplantation and whether they are related to the perception of the disease and transplantation. Methods: Cross-sectional study with quantitative and qualitative analysis. The sample of 32 patients was assessed by the Ways of Coping Scale and socio-demographic questionnaire, and five of them were selected for interviews. The internal consistency of the scale was assessed, the variables and strategies involved were crossed and content analysis of interviews, investigating the existence of a relationship with the speech of the participants. Results: The individuals have used all coping styles, with a predominance of the problem-focused strategy. Psychologically prepared patients showed a statistically significant increase in the use of problem-focused coping and seek for social support. However, a significant increase in the use of emotion-focused coping was observed in patients who were not prepared. Analysis through the method of Bardin showed as categories: disease; reaction to call; transplantation; fantasies; postoperative; team and coping. Conclusion: Patients with a transplanted heart make use of all coping strategies, with a predominance of the problemfocused strategy. Psychologically prepared individuals used more active coping strategies, which highlights the importance of psychological support during the process.

Resumo Objetivos: Verificar as estratégias de enfrentamento utilizadas por indivíduos que tiveram o coração transplantado e suas relações com percepção da doença e do transplante. Métodos: Estudo transversal com análise quantitativa e qualitativa. A amostra de 32 pacientes foi avaliada pela Escala Modos de Enfretamento de Problemas e questionário sociodemográfico; e cinco deles foram sorteados para entrevista. Realizou-se a avaliação da consistência interna da escala, cruzamentos entre as variáveis e os estilos de enfrentamento e a análise de conteúdo das entrevistas, relacionando os resultados ao discurso dos participantes. Resultados: Os indivíduos utilizaram todos os estilos de enfrentamento, predominando o focalizado no problema. Nos participantes que receberam preparo psicológico, houve aumento estatisticamente significativo dos enfrentamentos focalizados no problema e na busca de suporte social. Entretanto, naqueles que não receberam preparo, houve aumento significativo da utilização do enfrentamento focalizado na emoção. Através do método de Bardin, revelaram-se como categorias: doença, reação ao chamado, transplante, fantasias, pós-operatório, equipe e enfrentamento. Conclusões: Os participantes utilizaram todos os estilos de enfrentamento, predominando a estratégia focalizada no problema. Os que receberam preparo psicológico usaram maior número de estratégias de enfrentamento ativas, o que evidencia a importância do acompanhamento psicológico durante o processo.

Descriptors: Heart transplantation. psychological. Sickness impact profile.

Adaptation,

Descritores: Transplante cardíaco. Adaptação psicológica. Perfil de impacto da doença.

1. Psychologist intern at Instituto de Cardiologia; Specialized in Hospital Psychology, Porto Alegre, RS, Brazil. 2. Psychologist Coordinator of the Psychology Service in Instituto de Cardiologia – Fundação Universitária de Cardiologia/ IC-FUC; Coordinator and Preceptor of Integrated Internship in Health: Cardiology – RISC, Porto Alegre, RS, Brazil. 3. Cardiologist at Instituto de Cardiologia - Fundação Universitária de Cardiologia/ IC-FUC, Porto Alegre, RS, Brazil.

Correspondence address: Paula Pfeifer Instituto de Cardiologia – Serviço de Psicologia Av. Princesa Isabel, 395 – Porto Alegre, RS, Brazil – Zip code: 90620-001. E-mail: paulabmpfeifer@gmail.com

Work carried out at Instituto de Cardiologia, Fundação Universitária de Cardiologia/ IC-FUC, Porto Alegre, RS, Brazil.

Article received on July 2nd, 2012 Article accepted on August 30th, 2012

Pfeifer PM, et al. - Coping strategies after heart transplantation: psychological implications

Abbreviations, Acronyms & Symbols HT WOCS

Heart transplantation Ways of Coping Scale

INTRODUCTION Heart transplantation (HT) can be seen as a process, since it does not imply a "cure", according to the popular conception of absence of disease. HT can significantly improve the quality of life, but the patient will have to adapt to multiple limitations and other health problems [1,2]. A heart transplant requires lifestyle changes, so that the individual may cope with the demanding postoperative protocol and side effects of the drugs used [3-5]. The patient is also confronted with feelings that are roused by the constant threat of rejection, uncertainty of long-term prognosis, ambivalent psychological acceptance of the transplanted organ and influence of the cultural symbolism of the heart [3-5]. These particularities can raise the levels of anxiety and stress and trigger depression, which is considered a relevant risk factor for mortality after HT [3,6,7]. The depressive reaction can influence the clinical picture and compromise good results during the rehabilitation phase, since it may combine with anxiety and directly affect treatment adherence [4]. It is thus of fundamental importance that the patient is able to psychologically defend himself, using a range of coping strategies. These strategies include a hierarchy of flexible, purpose-oriented defense mechanisms, ranging from less adaptive to more evolved types of defense. They are defined as a stress response, which may be behavioral or cognitive, with the purpose of decreasing the aversive characteristics [8]. These strategies can be primarily focused on the problem, by modifying the relationship between the person and the environment, or on emotion, adapting the emotional response to the problem. They represent situational responses, influenced by the perception of environmental and personal systems and by the events of life. Evasive, emotive, fatalistic coping strategies are associated with a smaller capacity of personal control over the disease, increasing levels of depression and anxiety and decrease in treatment adherence [8-10]. The present study aims at the investigation of coping strategies used by patients who have had a HT and at analyzing if there is a relationship between the adoption of these strategies and the perception of the disease and transplantation. METHODS In this cross-sectional study with quantitative and qualitative analysis, sample size was calculated based on 62

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the study by Seidl et al. [11]. Thirty-two patients attended at the Transplantation Service of Instituto de Cardiologia do Rio Grande do Sul (Porto Alegre, RS, Brazil), of both genders, aged over 18 years, and submitted to HT at least one month previously, were included. The instruments used in this study included a demographic questionnaire, with basic data of the patient and information concerning the disease, transplantation and quality of life; a semi-structured-interview with thematic analysis for collecting information about the participant's perception in relation to disease and transplantation; the medical record for obtaining complementary data; and the Ways of Coping Scale (WOCS). The WOCS is a Likert type scale which assesses the magnitude of coping strategies used by the individual when confronted by stressors. The scale is composed of 45 items, with answers ranging from 1 (I never do that) to 5 (I do it always), and was adapted for use in Brazil by Gimenes & Queiroz [8,11,12]. This study was approved by the institutional Ethics Committee Research, is in accordance with the Declaration of Helsinki, and follows the Resolution 196, of October 10, 1996 [13]. Patients returning to the health center for consultation were informed about the study and invited to participate. Those who agreed to participate signed an informed consent and answered to a demographic questionnaire and the WOCS. Five of the patients were randomly selected for interviews, which were recorded with the permission of the participants. The data were tabulated and the interviews were fully transcribed. The results were analyzed in two steps. First, the internal consistency of the WOCS factors was assessed using the Cronbach's alpha coefficient, with the statistical software SPSS version 17.0. Categorical variables were described by absolute and relative frequency, and quantitative variables, through the mean and standard deviation or median and interquartile range. Since coping is a situational concept, the variables and strategies involved were crossed. A difference was observed between participants who received or not psychological preparation for HT, and between those with or without psychiatric disorders. The participants were then assigned to groups according to the presence or absence of the analyzed variables, and the coping strategies were compared through Student's t-test for independent samples. P values lower than 0.05 were considered statistically significant. The variables were evaluated through the Pearson and Spearman correlation. The second step addressed the qualitative analysis of interviews, through the content analysis method described by Bardin [14]. The contents of interviews were separated into units of registry, i.e. phrases with specific themes, which reflect an individual perspective. Subsequently, they were grouped into categories and subcategories according to the recurring content in the speech of the participants,

Pfeifer PM, et al. - Coping strategies after heart transplantation: psychological implications

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in order to articulate a group perspective [14]. The results of the two analyses were compared, for determination of the types of coping strategies used and relating the data obtained to the speech of individuals.

adopted (rs = - 0.471; P = 0.006). When the relationship of coping strategies among themselves was investigated, a moderate direct correlation was observed between coping focused on the problem and the search for social support (r = 0.450; P = 0.010). The comparison of coping strategies used between groups of participants who had or not received psychological preparation for HT is presented in Figure 1. The comparison of the strategies among the groups of patients with or without psychiatric disorders is presented in Figure 2.

RESULTS Descriptive results The main demographic and clinical characteristics of the sample are presented in Table 1. Data that indicate quality of life show that 93.8% of the participants have some type of leisure activity and 43.8% live with spouses and children. In relation to sleep, 81.3% of the patients sleep on average 5 to 8 hours per night; 87.5% report having dreams, and for 31.3% of them, dream contents reported are related to death.

Bardin's content analysis The qualitative analysis of the content of the interviews can be seen in Chart 1.

Evaluation of internal consistency WOCS reliability to assess coping strategies was acceptable. The results of the Cronbach alpha analysis of factors was: coping focused on the problem = 0.885; coping focused on emotion = 0.671; coping through religious/fantastic practices = 0.652; and coping aimed at seeking social support = 0.361. Coping strategies Participants used all types of coping strategies, with predominant focus on solving the problem. The coping strategies presented the following averages and standard deviations: (a) focused on the problem 3.78±0.77; (b) focused on emotion 0.54±2.11; (c) coping through religious/fantastic practices 0.86 ± 3.34; and (d) aimed at seeking social support 3.22±0.75. The analysis of variables age, time of HT and schooling showed that only the variable schooling presented a moderate inverse correlation with the coping strategy

Fig. 1 – Comparison of coping strategies among patients receiving or not psychological preparation for hearth transplantation (µ±SD). *P<0.05 significant

Table 1. Characterization of the sample (n=32) Age 58.5 (23-71) Sex-male 23 (71.9) Marital status-steady relationship 27 (84.4) Education – incomplete elementary school 14 (43.8) Professional status-inactive 19 (59.4) Cardiomyopathy-dilated 25 (78.1) Etiology-ischemic 16 (50) Transplant time* 105.5 (2-211) Psychological assessment 25 (78.1) Psychological preparation 21 (65.6) Duration of psychological follow-up 37 (0-243) Presence of psychiatric disorder 9 (28.1) Diagnosis of major depression 7 (21.9) Presence of suicidal ideation 4 (12.5) Data are presented in n(%); median and interquartile range. *Variables presented in months

Fig. 2 – Comparison of coping strategies among patients with or without psychiatric disorders (µ±SD). *P<0.05 significant

Pfeifer PM, et al. - Coping strategies after heart transplantation: psychological implications

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Chart 1. Analysis of the contents of patientsâ&#x20AC;&#x2122; speeches. Categories

Subcategories

Verbalizations

Disease

Invisibility Disabling symptoms Irreversibility

Who met me on the street though that I had nothing. So I couldn't walk well, or work. It was irreversible by the time it was decided for a transplantation.

Ambivalence Decision Coping

It is hard. One keeps thinking: Well, will I come back or not? There was the fear, then after that I started having that feeling that it was going to be all right. Then I must be decided and know that I'm leaving and I don't know if I'll come back. I was determined: take it or leave it. If I do not live I'll die. I'll try to live. The other time, they called me and I didn't got to come. Then when they called me last time, I did.

Reaction to calls

Transplantation

Solution Opportunity Happiness Gratitude Ambivalence Fear

Fantasies

Change of feelings Death of another Fate of the organ

Post-surgery

Fear of pain Happiness Suffering Recovery of autonomy Threat of rejection Adherence

Team

What helped to accept heart transplantation?

Receiving Trust Psychologist Will to live End the suffering Psychological preparation Personal characteristics

Then the doctor suggested entering a queue for transplants. When the transplantation was decided, there was no other solution. I was taking five medications and did not improve, had no perspective on life. I was disillusioned, and when I saw this light at the end of the tunnel I felt a great joy. A joy, a hapiness. How good it is to be alive. I thank you, because if I hadn't done it I would be no longer here. Sometimes, I would rather not have done. The fear that it does not work well. I have this concern that it can return. The wife of a future colleague cried and I asked why, and she replied: Because now, that he have a new heart, I keep thinking that he won't love me as much he did. I thought that someone had to die for me to live. One of my grandchildren asked what they had done with my heart that was taken away, and my wife said: they must have thrown it in the trash. I imagined a terrible pain after the surgery. I did not die. I'm alive. The feeling when I woke up was very good. I went through a lot, after I did the transplant, I heard voices. On the third day I got up, in the room I showered alone. I have take care of many things which need consideration, because if I stop taking cyclosporine or some other medication needed to avoid rejection, it is certain that I will die. The medication I do self medicate, because I already have separate everything, everything is already set. When I was admitted to the hospital, I was treated with great affection. This helped me a lot. When I came to have the transplant, everyone around me was worried. One day I will die. Now, if I'm get in, they will do everything to save my life. I had great faith, was sure that the doctors were going have success with my surgery. At that time, only a doctor worked, there was no follow-up with you as it is now. I changed my mind talking to a psychologist. She explained things to me, telling about what was going to happen, saying that I was not going to kill anyone. The will to live, for sure. I had to stop in the street because they had no more strength, it was bad. So this is what pushed me to go to fight. The psychologist helped a lot, because the first time I was called I didn't come. My way of seeing things. I do first to think later.

Pfeifer PM, et al. - Coping strategies after heart transplantation: psychological implications

DISCUSSION Several studies have examined coping strategies in the context of health. However, very few of them have investigated coping strategies used in the period after a HT, with virtually no research combining quantitative and qualitative designs [15]. Findings of the present study are consistent with previous reports. Early-stage heart disease is not always accompanied by symptoms, approaching the patient silently [5]. Unlike other diseases, such as certain types of cancer that modify the appearance of the individual, it is invisible, as can be inferred from the participant's speech: People who met me on the street thought that I was well. This aspect, coupled with emotional difficulties in dealing with the disease, may influence the delay in looking for treatment and poor adherence to treatment. The evolution of the disease leads to the development of heart failure and crippling symptoms [1]: So I couldn't walk well, or work. Thus, the indication for HT represents the possibility of survival and improvement in the quality of life [2,16]: I was disillusioned, and when I saw this light at the end of the tunnel I felt a great joy. I was taking five medications and did not improve, had no perspective on life. At the same time, it arouses intense anxiety and fantasies: I thought that someone had to die for me to live. There is also a peculiarity in the influence of cultural symbolism of the heart, associated with life and emotions: The wife of a future colleague cried and I asked why, and she replied: Because now, that he have a new heart, I keep thinking that he won't love me as much he did. In addition to the physical suffering imposed by the disease, the patient is exposed to emotional distress by the uncertainty of survival and confrontation with death. Therefore, the reaction involves ambivalent feelings [3]: It is hard. One keeps thinking: Well, will I come back or not? HT requires from the patient a series of adaptive tasks [3]: I have take care of many things which need consideration, because if I stop taking cyclosporine or some other medication needed to avoid rejection, it is certain that I will die. These events may generate high physical and psychosocial impact, because the transplant is seen as a new disease and not a cure: Sometimes, I think I would rather not have gone through this. In the immediate postoperative period, the participants relate a feeling of happiness for having survived: I did not die. I'm alive. The feeling when I woke up was very good. At the same time, it is a highly disorganizing experience:

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I went through a lot, after I had the transplant I heard voices. As in other studies, most of the survivors of a HT were male and were in a stable relationship, which indicates greater social support and is considered a protective factor [15-17]. A high rate of professional inactivity was observed among the participants, which can be associated with the high emotional impact of the transplantation [18]. A high prevalence of ischemic dilated cardiomyopathy was also observed [19]. Considering the psychical elaboration of the HT, most participants remembered dream, which is an important indicator of emotional capacity. It is important to observe that most dreams were related to death, highlighting again the high emotional impact of transplantation and the attempt of elaboration of the traumatic experience. The WOCS evaluates four types of coping strategies: coping focused on the problem, on emotion, in religious/ fantastic practice and in the search of social support. In the present study, the scale showed acceptable reliability to evaluate such strategies. In general, participants made use of all types of coping strategies, with a predominance of the strategy focused on solving the problem and, to a lesser extent, on emotion. The problem-focused strategies correspond to a cognitively active way of dealing with the situation, through behaviors of approaching the stressor in order to solve the problem. They are also related to positive thinking, i.e. a positive perception of the situation: I was determined: take it or leave it. If I do not live I'll die. I'll try to live. Strategies focused on emotion are a passive way of dealing with the situation, through the adoption of evasive and escape behavior in relation to treatment. They are related to negative emotional reactions and fantasy thoughts of selfguilt and or blaming other people [11,15]: The other time, they called me and I didn't got to come. Then when they called me the last time I did it. Since coping strategy is a situational concept, and as such influenced by the individualâ&#x20AC;&#x2122;s internal and external environment, it was necessary to crossover and investigate correlations between variables and coping strategies. In this sample, no correlation was observed between the variables age and coping strategies [11], or between time of HT and coping strategies [15]. Therefore, the variables age and time of transplant did not influence the choice of coping strategy used by the patients. However, the variable schooling correlated inversely with coping by adoption of religious practices [11]. The coping strategy which uses the adoption of religious practices is related to a range of 65

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feelings, from hope and faith (pertinent to the situation) to fantastic thinking, which can justify passive avoidance behaviors and the hope for a miracle (making treatment adherence more difficult). According to the literature, factors that may be responsible for poor treatment adherence include inadequate knowledge of the process, depression, anxiety, low social support, substance abuse, stress, persistence of psychological suffering, difficulty of access to medication and poor relationship with the team [8]. Therefore, a good relationship with the team can be fundamental [20]: When I was admitted to the hospital, I was treated with great affection. This helped me a lot. I had great faith, was sure that the doctors were going have success with my surgery. I changed my mind talking to a psychologist. She explained things to me, telling about what was going to happen, saying that I was not going to kill anyone. In addition, the use of coping strategies focused on the problem and in seeking social support presented direct correlation, i.e. the increase in coping with the problem is accompanied by greater search for support. The search for social support is related to the demand for instrumental and emotional support or information to assist in coping with the situation [11]. Thus, both strategies involve the adoption of an active posture of the patient in relation to treatment, thus favoring adherence, since they influence both the feelings of confidence in the health team, as the adoption of behaviors of search for health aid. Participants who had received psychological preparation used with higher frequency coping strategies focused on problem (P=0.008) and on the search of social support (P=0.01) than those without this preparation. In addition, there was a decrease in the use of emotion-focused coping (P=0.011). The differences were statistically significant. Taking into consideration that most of the participants had ischemic dilated cardiomyopathy before the HT and that the literature suggests that coronary patients have type "A" personality, these data show the relevance of psychological preparation. Individuals with type "A" personality are described as competitive, rigid, self-controlled, committed to the work and, often, unable to rest. They are described as persons who try to show independence, have difficulty in relating with others and in taking a passive and dependent stance. In addition, they have difficulty in identifying and dealing with their feelings, which makes them more fragile when sick [21]. According to these characteristics, individuals who are not well prepared for the transplant would use more frequently the emotion-focused coping strategy, due to

their emotional difficulties. Because of their difficulty in relating with other persons and assuming a dependent role, they would use less frequently a coping strategy that relies on seeking social support. Similar results were observed for patients who did not receive psychological preparation. These behaviors deserve attention, since they can hinder treatment adherence as well as indicate a greater vulnerability of the patient [6,15]. Therefore, the data obtained from the group of patients psychologically prepared for the HT shows the relevance of this intervention. This preparation allows the patient a moment to talk about the transplant, so that he becomes aware of his fantasies and feelings, as well as the personal way of addressing the situation, a fact that enables a change of behavior and favors the adoption of coping modes more active and adapted to the situation, such as the confrontation focused on solving the problem and the search for social support [22]. These coping strategies are fundamental to the survival, since they influence the behavior of adherence to treatment [9,15]. In addition, the psychological treatment relieves feelings of stress, anxiety and depression, facilitating the process [15]. A comparison of strategies among patients with and without the presence of psychiatric disorder found that in seconds there is a predominance of problem-focused coping style (P=0.046) and less frequently the emotionfocused strategy (P=0.08). However, patients with psychiatric disorders showed a non-significantly higher frequency of coping by religious practice (P=0.748), and a significant increase in the use of emotion-focused coping (P=0.352). These results suggest greater use of passive strategies, indicating an inability to deal with the post-transplant period, as pointed by other studies that emphasize the role of major depression as a risk factor in the post-transplantation period [6,7,15,23]. Taking into account these particularities, the role of the psychologist must start in the preoperative period and extend during the post-transplant period, according to the needs of each patient. In the pre-transplant period, the psychologist assesses how the patient processes information about his health, how he receives the indication for transplantation and what is his level of knowledge of the process. Therefore, the use of psychoprophylaxis â&#x20AC;&#x201C; a technique developed by psychoanalyst Arminda Aberastury â&#x20AC;&#x201C; emphasizes the importance of working the anxieties and fantasies related to the surgery. Therefore, it is necessary to explain every detail of the surgery, from the anesthesia to possible indispositions, decreasing in this way the postoperative anxiety and trauma by making it

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possible to elaborate fantasies, suffering and feelings of unsafety associated with transplantation, as well as the incorporation of a new body image [24]. In the period subsequent to the HT, psychological aspects related to the feeling of loss of the heart, acceptance of the new body and adaptation to changes in life habits should be addressed. In addition, the patient’s sense of autonomy, self-efficacy and responsibility for his own health care, as well as the stimulus to return to life activities, should be strengthened in order to increase adherence to the treatment [9,18,25]. One of the possible limitations of the present study is that the results cannot be generalized to the overall population, since the sample is small, despite being representative of the institutional reality – more than 55% of patients undergoing living transplantation – and reflecting clinical data already observed. In addition, the WOCS showed poor reliability in the analysis of coping strategy focused on seeking social support, highlighting the importance of further studies with more representative samples, with patients with psychiatric disorders and the need for a review of items that represent this factor in WOCS.

4. Pérez San Gregorio MA, Martín Rodríguez A, Pérez Bernal J. Psychological differences of patients and relatives according to post-transplantation anxiety. Span J Psychol. 2008;11(1):250-8.

CONCLUSION Individuals who underwent HT make use of all coping strategies, with a predominance of strategies focused on the problem. The use of this active coping strategy implies behaviors more adapted to the process and responsible for greater adherence to treatment. Participants who were psychologically prepared for HT used a greater number of active coping strategies, a fact that highlights the importance of psychological support during the process. These results indicate the relevance of further studies to investigate the influence of preparation in relation to coping strategies adopted in larger samples.

5. Stolf NAG, Sadala MLA. Os significados de ter o coração transplantado: a experiência dos pacientes. Rev Bras Cir Cardiovasc. 2006;21(3):314-23. 6. Burker EJ, Evon DM, Marroquin Losielle M, Finkel JB, Mill MR. Coping predicts depression and disability in heart transplant candidates. J Psychosom Res. 2005;59(4):215-22. 7. Sirri L, Potena L, Masetti M, Tossani E, Magelli C, Grandi S. Psychological predictors of mortality in heart transplanted patients: a prospective, 6-year follow-up study. Transplantation. 2010;89(7):879-86. 8. Savóia MG, Santana PR, Mejias NP. Adaptação do inventário de estratégias de coping de Folkman e Lazarus para o português. Psicologia USP. 1996;7(1/2):183-201. 9. Lisson GL, Rodrigues JR, Reed AI, Nelson DR. A brief psychological intervention to improve adherence following transplantation. Ann Transplant. 2005;10(1):52-7. 10. Telles-Correia D, Inês M, Barbosa A, Barroso E, Monteiro E. Coping nos doentes transplantados. Acta Med Port. 2008;21:141-8. 11. Seidl EMF, Tróccoli BT, Zannon C. Análise fatorial de uma medida de estratégias de enfrentamento. Psicologia: teoria e pesquisa. 2001;17(3):225-34. 12. Gimenes M, Queiroz B. A teoria do enfrentamento e suas implicações para sucessos e insucessos em psiconcologia. In: Gimenes M, Fávero M, eds. A mulher e o câncer. Campinas: Editorial Psi; 1997. p.111-47. 13. Ministério da Saúde B. Resolução nº 196/MS/CNS, de 10 de outubro de 1996. Diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. [cited 2011 30 Ago]. Available from: http://www.anvisa.gov.br/legis/ resol/196_96.htm. 14. Bardin L. Análise de conteúdo. Lisboa: LDA; 1991. 229p.

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15. Kaba E, Thompson DR, Burnard P. Coping after heart transplantation: a descriptive study of heart transplant recipients’ methods of coping. J Adv Nurs. 2000;32(4):930-6. 16. Evangelista LS, Dracup K, Moser DK, Westlake C, Erickson V, Hamilton MA, et al. Two-year follow-up of quality of life in patients referred for heart transplant. Heart Lung. 2005;34(3):187-93. 17. Assef MAS, Valbuena PFM, Neves Jr MT, Correia EB, Vasconcelos M, Manrique R, et al. Transplante cardíaco no Instituto Dante Pazzanese de Cardiologia: análise da sobrevida. Rev Bras Cir Cardiovasc. 2001;16(4):289-304.

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18. Kristen A, Katus H, Dengler T. Return to work after heart transplantation. Versicherungsmedizin. 2010;62(2):67-72.

22. Goetzinger AM, Blumenthal JA, O’Hayer CV, Babyak MA, Hoffman BM, Ong L, et al. Stress and coping in caregivers of patients awaiting solid organ transplantation. Clin Transplant. 2012;26(1):97-104.

19. Albanesi Filho FM. Cardiomiopatias. Arq Bras Cardiol. 1998;71(2):95-107. 20. Goetzmann L, Lieberherr M, Krombholz L, Ambühl P, Boehler A, Noll G, et al. Subjective experiences following organ transplantation: a qualitative study of 120 heart, lung, liver, and kidney recipients. Z Psychosom Med Psychother. 2010;56(3):268-82. 21. Friedman M, Rosenman RH. Association of specific overt behavior pattern with blood and cardiovascular findings; blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. J Am Med Assoc. 1959;169(12):1286-96.

23. Allman E, Berry D, Nasir L. Depression and coping in heart failure patients: a review of the literature. J Cardiovasc Nurs. 2009;24(2):106-17. 24. Aberastury A. História de una técnica: preparación psicoterapéutica en cirugía. El psicoanalisis de niños y sus aplicaciones. 2ª ed. ed. Buenos Aires: Paidós; 1972. p.34-43. 25. Frota Filho JD, Lucchese FA, Sales MC, Lobo RCM, Tanaka N, Correa Junior JM, et al. Mortality after partial left ventriculectomy in relation to contraindications for heart transplantation. Rev Bras Cir Cardiovasc. 2003;18(1):1-8.

Benfatti RA, et al. - Analysis of left ventricular function in patients with ORIGINAL ARTICLE heart failure undergoing cardiac resynchronization

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Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization Análise da função ventricular esquerda de pacientes com insuficiência cardíaca submetidos à ressincronização cardíaca

Ricardo Adala Benfatti1, Felipe Matsushita Manzano2, José Carlos Dorsa Vieira Pontes3, Amaury Edgardo Mont’Serrat Ávila Souza Dias4, João Jackson Duarte5, Guilherme Viotto Rodrigues da Silva6, Jandir Ferreira Gomes Junior7, Neimar Gardenal8

DOI: 10.5935/1678-9741.20130011

RBCCV 44205-1444

Resumo Fundamentos: O tratamento cirúrgico da insuficiência cardíaca padrão-ouro é o transplante cardíaco, porém, em decorrência das dificuldades desse tratamento, outras propostas cirúrgicas têm sido relatadas, entre elas o implante de ressincronizador cardíaco. Objetivo: Analisar a função ventricular esquerda, por meio da ecocardiografia, de pacientes portadores de insuficiência cardíaca avançada com dissincronia interventricular submetidos a implante de ressincronizador cardíaco. Métodos: Entre junho de 2006 a junho de 2012, foram avaliados 24 pacientes com idade média de 61,5 ± 11 anos, portadores de insuficiência cardíaca congestiva avançada em classe funcional III e IV (NYHA), dissincronia interventricular e tratamento medicamentoso otimizado. Esses pacientes foram submetidos ao implante de ressincronizador cardíaco e avaliados ecocardiograficamente no pós-operatório de seis meses.

Resultados: Houve melhora significativa dos parâmetros ecocardiográficos analisados. A média dos diâmetros diastólicos ventriculares esquerdos reduziu de 69,6 ± 9,8 mm para 66,8 ± 8,8 mm, diâmetros sistólicos de 58,6 ± 8,8 mm para 52,7 ± 8,8 mm e a fração de ejeção, média de 31 ± 8% para 40 ± 7% com nível de significância, respectivamente, de 0,019, 0,0004 e 0,0002, estatisticamente significativos com nível de significância de 0,05. Conclusão: Houve melhora da função ventricular esquerda analisada por meio da ecocardiografia, em seis meses, de pacientes portadores de insuficiência cardíaca avançada submetidos a implante de ressincronizador cardíaco.

1. Master of Science, Assistant Professor of Federal University of Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil – Main author. 2. Medical Doctor of UFMS, Campo Grande, MS, Brazil – Data collection. 3. Philosophy Doctor, Full Professor of UFMS, Campo Grande, MS, Brazil – Final review. 4. Assistant Professor of UFMS, Campo Grande, MS, Brazil – Performed surgeries and bibliographic research. 5. Master of Science of UFMS, Campo Grande, MS, Brazil – Performed surgeries and bibliographic research. 6. Resident Doctor of UFMS, Campo Grande, MS, Brazil – Bibliographic research, assistance of surgeries. 7. Master of Science, Campo Grande, MS, Brazil – Performed Surgeries. 8. Master of Science, Campo Grande, MS, Brazil – Co-author in the writing of the scientific text.

Work carried out at Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil.

Descritores: Insuficiência cardíaca. Terapia Ressincronização Cardíaca. Ecocardiografia.

Correspondence address Ricardo Adala Benfatti Av. Senador Filinto Muller, S/N – Hospital Universitário – UTI Cardiológica – Campo Grande, MS, Brazil. E-mail: ricardobenfatti@gmail.com

Article received on September 9th, 2012 Article accepted on December 18th, 2012

Benfatti RA, et al. - Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization

Abbreviations, acronyms & symbols AAS ACE CRT DCM ECG EF HF LBBB LVDD LVEF LVSD NYHA RV SD SUS UFMS

Acetylsalicylic acid Angiotensin converting enzyme Cardiac resynchronization therapy Dilated cardiomyopathy Electrocardiogram Ejection fraction Heart failure Left bundle branch block Left ventricle diastolic diameter Left ventricular ejection fraction Left ventricle systolic diameter New York Heart Association Right ventricle Standard deviation Unified Health System Federal University of Mato Grosso do Sul

Abstract Background: The gold standard surgical treatment for heart failure is cardiac transplantation, however, due to difficulties of this treatment, other surgical proposals have been reported, including the implantation of cardiac resynchronizer.

INTRODUCTION Heart failure (HF) one of the greatest clinical challenges in the current public health, and it is considered an epidemic on progress, diagnosed in 1% to 2% of developed countries population [1,2]. The HF is one of the most prevalent causes of hospital admissions in Brazil, on the Unified Health System (SUS). In 2007, there were 1.156.136 hospital admissions for cardiovascular diseases, representing the third leading cause of hospital admissions on the SUS, and HF is the main one [3]. The HF treatment has the purpose of symptoms improvement, reduction of mortality, hospital costs decreasing and prevention of readmissions. The treatment of heart failure consists of: nonpharmacological steps (diet, exercising, stress management, and others), drug therapy and surgery [3]. Studies show that medical treatment should always include a beta blocker and an inhibitor of the angiotensin converting enzyme (ACE), composing the optimized medical treatment. For symptomatic patients, diuretics and digitalis are added. But if there is a disabling symptoms persistence, it is necessary to introduce aldosterone 70

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Objective: To analyze the left ventricular function by echocardiography in patients with advanced heart failure with interventricular dyssynchrony undergone implantation of cardiac resynchronizer. Methods: Between June 2006 and June 2012, 24 patients with average age of 61.5 ± 11 years were evaluated, carriers of advanced congestive heart failure functional class III and IV (NYHA), interventricular dyssynchrony and optimal drug therapy, and submitted implantation of cardiac resynchronizer and postoperative echocardiographically evaluated in six months. Results: There was significant improvement of the analyzed echocardiography parameters. The average left ventricular diastolic diameter decreased from 69.6 ± 9.8 mm to 66.8 ± 8.8 mm, systolic diameters from 58.6 ± 8.8 mm to 52.7 ± 8.8 mm, and ejection fraction, average of 31 ± 8% to 40 ± 7% with level of significance, respectively, of 0.019, 0.0004 and 0.0002, statistically significant with a significance level of 0.05. Conclusion: There was a significant improvement of left ventricular function analyzed by echocardiography at six months, in patients with advanced heart failure undergone implantation of cardiac resynchronizer. Descriptors: Heart failure. Cardiac resynchronization therapy. Echocardiography.

antagonists (functional class III heart failure by Criteria Committee of the New York Heart Association - NYHA) with strict control of serum potassium and combination of hydralazine + nitrate [3-6]. The search for alternative or complementary methods to drug treatment, which could change the course of the disease, is a major challenge of the researchers [7]. Surgical treatment should be considered for patients resistant to optimized medical treatment. Cardiac transplantation is the main treatment for patients with severe clinical and hemodynamic conditions, which represent significant changes in the prognosis of HF, but there are major obstacles to its achievement, as the low amount of donors, adverse responses to immunosuppressants, unfavorable clinical conditions and surgical risk, and other factors that are against the surgery [8]. Therefore, other alternative surgical techniques to heart transplantation, including surgical intervention of mitral valve in dilated cardiomyopathy [9], left ventricular aneurysmectomy and implanting a pacemaker of cardiac resynchronization [10,11] are given being performed to improve the clinical conditions and reduce morbidity and mortality of HF patients. The cardiac interventricular dyssynchrony is presented

Benfatti RA, et al. - Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization

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as electromechanical regional change, leading to delays in both contraction and relaxation in cardiac muscle. Among the possible mechanisms of biventricular function worsening, the dyssynchronous contraction of the right ventricle stands out, leading to a septal bulging towards the left ventricle. This can unleash a delay in the papillary muscles activation with consequent mitral valve insufficiency [11]. The interventricular dyssynchrony can be analyzed by echocardiography, using the pulsed Doppler, calculating the electromechanical delay between the ventricles by measuring the time interval between the R wave of the electrocardiogram and the beginning of the curve of flow speed and aortic pulmonary flow. In case the difference between the two intervals is greater than 40 milliseconds, it is an indicative of interventricular dyssynchrony [12,13]. A cardiac resynchronization therapy plays an important role in treating patients with severe heart failure with conduction abnormalities and prolongation of the QRS complex, having as the main representative the left bundle branch block (LBBB), found in about 2550% of patients [14]. Among the indications for implantation of cardiac resynchronizer with or without internal defibrillator, patients with dilated cardiomyopathy with depressed left ventricular ejection fraction (LVEF) less than 35% are included, patients with ischemic heart disease without surgical or interventional treatment conditions, irreversible structural changes, functional class III or IV with electrocardiogram (ECG) showing QRS>150 milliseconds or QRS 120 to 150 milliseconds with dyssynchrony [15]. Studies show that biventricular resynchronization therapy provides a significant medical improvement with a reduction in the number of hospital admissions, improvement in functional class and quality of life. The assessment of ventricular function by echocardiography demonstrates improvement in systolic and diastolic function and ejection fraction [16-20]. The echocardiographic analysis, a cost-effective favorable, reproducible and affordable examination reveals itself as a method not only for indication, but also for postoperative evaluation of patients who underwent cardiac resynchronization therapy, evaluating parameters such as ejection fraction, cardiac synchrony, ventricular remodeling, reducing the degree of mitral valve incompetence and reversal of interventricular electromechanical delay [21-24]. Considering the severity of patients with advanced heart failure with optimized medical treatment in need of surgical treatment and wtih electrocardiographic criteria, medical and echocardiographic for implantation of cardiac resynchronizer. The goal of this research is to analyze left ventricular function through of echocardiography

in patients with advanced heart failure who underwent implantation of cardiac resynchronizer. METHODS Casuistry The echocardiographic data of 24 patients with severe congestive heart failure were analyzed, classified as NYHA functional class III and IV according to the Criteria Committee of the NYHA, underwent implantation of transvenous cardiac resynchronizer, by Cardiovascular Surgery Service of the discipline of Cardiothoracic Surgery of the Helio Mandetta Faculty of MedicineFederal University of Mato Grosso do Sul (UFMS), between June 2006 to June 2012, with the approval of the UFMS Ethics Committee in humans in the approval letter - protocol number 2235-CAAE 0354.0.049.000 11, on November 9, 2011. The patients were between 34 and 86 years old, average 61.5 Âą 11.1 years old, eight (33%) were female and sixteen (67%) males, according to Table 1. All patients were on maximum allowable drug therapy. Concerning etiology, idiopathic dilated cardiomyopathy, valvular diseases from mild to severe functional impairment and ischemic cardiomyopathy have been demonstrated. Table 1. General data of patients. Patients 1. E.M.S. 2. E.S.P. 3. H.R.S. 4. J.B.S. 5. J.C.C. 6. M.D.L. 7. M.L.A.T. 8. M.R.M. 9. P.M.L. 10.C.C.N. 11. D.B.K. 12. J.S.R. 13. S.R.O. 14. N.O.S. 15. S.L. 16. E.C.L. 17. B.F.S. 18. I.F.M. 19. E.L.F. 20. A.M. 21. M.A.S. 22. J.G.I. 23. E.A.O.S. 24. U.R.S.

Gender M M F M M F F F M F F M M M M F M M M F M M M M

Age (years) Functional Class 65 III 61 III 60 III 60 III 66 III 57 III 57 IV 54 IV 69 III 81 III 60 IV 69 IV 63 III 56 III 61 IV 74 III 86 IV 56 IV 42 III 69 III 34 IV 63 IV 48 III 66 III 61.5 Âą 11.1 years

M: male; F: female

Benfatti RA, et al. - Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization

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Inclusion Criteria The inclusion criteria were: 1) patients with dilated cardiomyopathy (DCM) and congestive heart failure functional class (NYHA) III or IV refractory to optimized drug therapy; 2) patients with DCM without possibility of surgery (coronary artery bypass grafting, valve replacement, left ventricular aneurysm resection or correction of congenital heart disease); 3) left and right bundle branch block standard interventricular conduction disturbance, associated with anterosuperior or left branch induced right ventricular cardiac pacing exclusive block; 4) interventricular dyssynchrony documented on echocardiography; 5) QRS complex duration higher or equal to 120 ms.

The study used the echocardiographic data with, a maximum of one month before the pacemaker implantation multisite to evaluation before, and after six months for postoperative evaluation, shown respectively on Tables 2 and 3. The following variables were used: Left Ventricular Diastolic Diameter, Left Ventricular Systolic Diameter and Ejection Fraction, in the standardized methods in the literature.

Echocardiographic assessment Echocardiographic evaluation was performed by the same examiner preoperatively and postoperatively with Medson EX 8008 Apparatus, transducers of frequency 2 and 3 MHz in conventional evaluation plans.

Table 2. Preoperative echocardiographic assessment of patients who underwent implantation of cardiac resynchronizer. Patients E.M.S. E.S.P. H.R.S. J.B.S. J.C.C. M.D.L. M.L.A.T. M.R.M. P.M.L. C.C.N. D.B.K. J.S.R. S.R.O. N.O.S. S.L. E.C.L. B.F.S. I.F.M. E.L.F. A.M. M.A.S. J.G.I. E.A.O.S. U.R.S. Mean SD

LVDD (mm) 80 79 63 85 65 65 56 72 81 68 49 80 65 67 77 78 64 70 78 55 86 69 58 72

LVSD (mm) 70 69 53 72 50 51 48 62 64 54 44 70 53 55 62 65 54 64 64 47 74 62 53 61

EF % 26% 23% 30% 31% 45% 43% 28% 29% 48% 43% 25% 24% 37% 33% 33% 34% 20% 20% 36% 30% 29% 22% 19% 31%

69.6 9.8

58.6 8.7

31% 8%

LVDD: left ventricle diastolic diameter; LVSD: left ventricle systolic diameter; EF: ejection fraction; mm: millimeters; SD: standard deviation

Operative technique The operative technique for implantation of cardiac resynchronizer starts with cardiac monitoring and degermation and antisepsis of the anterior chest wall and neck. Local anesthesia is performed with 2% lidocaine in an area located in the middle third of the right infraclavicular fossa, of approximately 4 cm2. An incision of approximately 4 cm at the place above 1 cm below the right clavicle is made, with careful hemostasis. The first electrode was placed in the right ventricle (RV), followed by the right atrium lead, both by puncture of the right subclavian vein in which the guide wires were inserted, and on them, inserting of the sheaths through which the endocavitary electrodes were passed (active fixation). They were placed in traditional sites (atrium into the right auricle and right ventricle at the end of it) or where the initiation of stimulation was obtained, with acceptable sensing and impedance. The last electrode was placed in the coronary sinus for left ventricular pacing. The electrodes used were: Corox OTW 75 DP (Biotronik速). The position obtained by the use of radiological anatomy with fluoroscopy in left anterior oblique, at an angle of 35 degrees in order to position the electrode of passive fixation on the lateral or posterior vein of the left ventricle. Afterwards, electrophysiological tests took place to verify basic viability and stability. The final stimulus generator is connected, and it immediately starts its activity verified by electrocardiogram tracing. Then the closing of plans was held. Postoperative follow-up The days of observation and monitoring varied from November 2006 until June 2012. All patients were medicated in order to maintain the optimization of drug therapy for heart failure. The postoperative evaluation was performed by the Doppler echocardiogram in six months postoperatively. Statistical analysis The analysis of quantitative variables was performed by comparing average (previously checked the normality of distributions), using the Student t test. The level of significance was P <0.05.

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Benfatti RA, et al. - Analysis of left ventricular function in patients with heart failure undergoing cardiac resynchronization

RESULTS The patients were discharged without complications during the perioperative and no death on the early postoperative. According to the needs of each patient, there was drug use in their highest tolerated doses, with frequent use of digoxin, furosemide, carvedilol, acetylsalicylic acid (AAS), amiodarone, enalapril, losartan, warfarin and espironalactona. Regarding postoperative data, according to Table 3, the mean left ventricular diastolic diameters were 66.8 ± 8.8 mm, systolic diameters, 52.7 ± 8.8 mm and ejection fraction 40 ± 7%. Comparing the pre-and postoperatively data, according to Table 4, there was significant reduction in echocardiographic parameters and increase in the analyzed ventricular function. The average left ventricular diastolic diameter decreased from 69.6 ± 9.8 mm to 66.8 ± 8.8 mm, systolic diameters of 58.6 mm ± 8.8 to 52.7 ± 8.8 mm and there was an increase

Table 3. Postoperative echocardiographic assessment of patients who underwent implantation of cardiac resynchronizer Patients E.M.S. E.S.P. H.R.S. J.B.S. J.C.C. M.D.L. M.L.A.T. M.R.M. P.M.L. C.C.N. D.B.K. J.S.R. S.R.O. N.O.S. S.L. E.C.L. B.F.S. I.F.M. E.L.F. A.M. M.A.S. J.G.I. E.A.O.S. U.R.S. Mean SD

LVDD (mm) 87 79 62 77 64 69 66 67 70 65 53 71 58 72 75 78 58 60 73 53 76 61 54 63

LVSD (mm) 70 60 43 64 51 55 52 57 38 49 37 58 45 59 62 65 54 48 58 43 66 47 44 48

EF % 38% 39% 57% 34% 43% 40% 43% 31% 43% 48% 57% 37% 44% 36% 35% 28% 35% 40% 41% 39% 27% 45% 36% 47%

66.8 8.8

52.7 8.8

40% 7%

LVDD: left ventricle diastolic diameter; LVSD: left ventricle systolic diameter; EF: ejection fraction; mm: millimeters; SD: standard deviation

in ejection fraction, an average of 31% ± 8 to 40 ± 7% significance level, respectively, 0.019, 0.0004 and 0.0002, statistically significant with a significance level of 0.05.

Table 4. Preoperative and postoperative echocardiographic assessment of patients who underwent implantation of cardiac resynchronizer. Parameters LVDD LVSD EF%

Preoperative 69.6± 9.8 MM 58,6 ± 8,8 MM 31 ± 8%

Postoperative 66.8 ± 8.8 MM 52,7 ± 8,8 MM 40 ± 7%

SD 0.019 0.0004 0.0002

LVDD: left ventricle diastolic diameter; LVSD: left ventricle systolic diameter; EF: ejection fraction; mm: millimeters; SD: standard deviation

DISCUSSION Heart failure is a serious public health problem, with high annual mortality [25]. In order to decrease the symptoms, complications and increase life expectancy, several forms of treatment are considered, such as pharmacological and nonpharmacological steps with major therapeutic advances in recent decades. However, many patients remain with significant symptoms and a high number of hospital admissions, determining reserved prognosis and expensive treatments [26,27]. Where surgical treatment should be considered. The cardiac resynchronization therapy (CRT) has an important role in the treatment of patients with advanced heart failure with conduction abnormalities and prolongation of the QRS complex, as main representative the left bundle branch block (LBBB), present in approximately 25-50% patients [14,15,28,29]. Studies have shown the medical benefits of CRT. The tests MIRACLE [30] and MUSTIC [31], CONTAK CD [32] showed that CRT determines functional class improvement of HF patients, exercise tolerance (6 minutes walking test peak VO2), reduction in the rate of HF hospitalization and improved quality of life through the Minnesota questionnaire. However, decrease in mortality with CRT and echocardiographic parameters improving were not demonstrated. A meta-analysis of the CARE-HF [33], MUSTIC [31] and MIRACLE [30] studies, comparing biventricular pacing with optimized medical treatment alone showed a significant reduction in hospitalization rates, reducing the risk of death. McAlister et al. [34], in 2007, in 11 months followup, demonstrated the efficacy and safety of biventricular pacing in over 10,000 patients. They concluded that CRT reduced hospitalizations and all causes of mortality. An 73

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increase in ejection fraction was observed, improving quality of life for the Minnesota questionnaire and improvement in functional class. However, some studies have shown that CRT was able to significantly improve as from the third month of followup echocardiographic parameters, such as reduced stroke volume and left ventricular end-diastolic and increasing of ejection fraction [26-28]. In contrast with the controversy in the literature regarding the improvement in echocardiographic parameters, this research has demonstrated an increase in ejection fraction of 31% ± 8 to 40 ± 7%, reducing of diastolic and left ventricular systolic diameter from 69.6 ± 9.8 mm to 66.8 ± 8.8 mm and 58.6 mm ± 8.9 to 52.7 ± 8.8 mm, respectively, all parameters statistically significant. This research may infer that transvenous CRT improves benefits in the biventricular systolic function with significant improvement in echocardiographic parameters such as ejection fraction and reduction of systolic and diastolic diameters.

5. Remme WJ, Swedberg K; European Society of Cardiology. Comprehensive guidelines for the diagnosis and treatment of chronic heart failure. Task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Eur J Heart Fail. 2002;4(1):11-22.

CONCLUSION In the present study, there was improvement in left ventricular function assessed by echocardiography in patients with advanced heart failure who underwent implantation of cardiac resynchronizer.

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26. Auricchio A, Abraham WT. Cardiac resynchronization therapy: current state of the art: cost versus benefit. Circulation. 2004;109(3):300-7.

18. Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001;344(12):873-80. 19. Bakker PF, Meijburg HW, de Vries JW, Mower MM, Thomas AC, Hull ML, et al. Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. J Interv Card Electrophysiol. 2000;4(2):395-404. 20. Soares MJF, Oliveira MAB, Braile DM. Marcapasso multisítio no tratamento da insuficiência cardíaca: evolução e resultados. Reblampa. 2007;20(1):31-5. 21. Kawaguchi M, Murabayashi T, Fetics BJ, Nelson GS, Samejima H, Nevo E, et al. Quantitation of basal dyssynchrony and acute resynchronization from left or biventricular pacing by novel echo-contrast variability imaging. J Am Coll Cardiol. 2002;39(12):2052-8. 22. Breithardt OA, Stellbrink C, Herbots L, Claus P, Sinha AM, Bijnens B, et al. Cardiac resynchronization therapy can reverse abnormal myocardial strain distribution in patients with heart failure and left bundle branch block. J Am Coll Cardiol. 2003;42(3):486-94. 23. Breithardt OA, Stellbrink C, Kramer AP, Sinha AM, Franke A, Salo R, et al. Echocardiographic quantification of left ventricular asynchrony predicts an acute hemodynamic benefit of cardiac resynchronization therapy. J Am Coll Cardiol. 2002;40(3):536-45. 24. Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CP. Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol. 2003;91(6):684-8. 25. McAlister FA, Teo KK, Taher M, Montague TJ, Humen D, Cheung L. Insights into the contemporary epidemiology and outpatient management of congestive heart failure. Am Heart J. 1999;138(1 Pt 1):87-94.

27. Kadish A, Mehra M. Heart failure devices: implantable cardioverter-defibrillators and biventricular pacing therapy. Circulation. 2005;111(24):3327-35. 28. Souza FSO, Braile DM, Vieira RW, Rojas SO, Mortati NL, Rabelo AC, et al. Aspectos técnicos do implante de eletrodo para estimulação ventricular esquerda através do seio coronariano, com a utilização de anatomia radiológica e eletrograma intracavitário, na terapia de ressincronização cardíaca. Rev Bras Cir Cardiovasc. 2005;20(3):301-9. 29. Kalil C, Nery PB, Bartholomay E, Albuquerque LC. Tratamento com cardioversor-desfibrilador implantável e ressincronização cardíaca: isolados ou associados? Rev Bras Cir Cardiovasc. 2006;21(1):85-91. 30. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346(24):1845-53. 31. Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, et al; Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001;344(12):873-80. 32. Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, et al. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002;39(12):2026-33. 33. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140-50. 34. McAlister FA, Ezekowitz J, Hooton N, Vandermeer B, Spooner C, Dryden DM, et al. Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA. 2007;297(22):2502-14.

Almeida RMS, et al. - O uso de recuperador de sangue em cirurgia cardíaca ARTIGO ORIGINAL com circulação extracorpórea

Rev Bras Cir Cardiovasc 2013;28(1):76-82

O uso de recuperador de sangue em cirurgia cardíaca com circulação extracorpórea The use of cell saver system in cardiac surgery with cardiopulmonary bypass

Rui M. S. Almeida1, Luciano Leitão2

DOI: 10.5935/1678-9741.20130012

RBCCV 44205-1445

Resumo Introdução: O uso de recuperador de sangue (RS) em cirurgia cardíaca é proposto para diminuir o uso de unidades de concentrado de hemácias estocadas (UCH), que aumenta morbidade, mortalidade e reações inflamatórias. Objetivo: O objetivo deste estudo é avaliar se o uso do RS diminui o emprego de UCH, é custo/efetivo e traz benefícios ao paciente. Métodos: Estudo prospectivo realizado entre novembro de 2009 e outubro de 2011, em 100 pacientes consecutivos, submetidos à cirurgia cardiovascular com circulação extracorpórea (CEC), hemodiluição mínima e hemofiltração. Os pacientes foram divididos em grupo 1 (sem RS) e 2 (com RS). Os critérios para a reposição de UCH foram instabilidade hemodinâmica e hemoglobina (Hb) <7-8g/ dl. Foram analisados dados demográficos, Hb, hematócrito (Ht), drenagem mediastinal e reposição de UCH, em diversos intervalos, e tempos de CEC, UTI e hospital. Resultados: Nos grupos 1 e 2, a idade média foi de 64,2 e 60,6 anos, com predominância do sexo masculino, o EuroSCORE logístico de 10,3 e 9,6 e a mortalidade de 2% e 4%, não relacionada ao estudo. O grupo 2 apresentou

incidência de reoperações superior (12 x 6%), mas o número de UCH usado (4,31x1,25) e o tempo de internamento hospitalar (10,8x7,4) foram menores. Realizada análise uni e multivariada, que não demonstrou valores estatisticamente significativos, exceto no uso de UCH. A relação entre o custo do RS e das UCH foi custo/efetiva e o tempo de internamento, menor. Conclusão: O uso de RS diminui o número de UCH usadas, não é custo/efetivo e mostrou benefícios ao paciente.

1. Coordenador do Curso de Medicina da Faculdade Assis Gurgacz (FAG); Professor Associado da Universidade Estadual do Oeste do Paraná (UNIOESTE); Professor Adjunto da Universidade Federal do Paraná (UFPr),Presidente do Conselho Deliberativo da SBCCV e Membro do Conselho Editorial da RBCCV, Cascavel, PR, Brasil. Metodologia, coleta de dados, redação e revisão do artigo. 2. Cirurgião Cardiovascular do Instituto de Cirurgia Cardiovascular do Oeste do Paraná, Cascavel, PR, Brasil. Participação nas cirurgias, discussão da metodologia e revisão do artigo.

Trabalho realizado no Instituto de Cirurgia Cardiovascular do Oeste do Paraná, Cascavel, PR, Brasil.

Descritores: Recuperação de sangue operatório. Transfusão de componentes sanguíneos. Separação celular. Abstract Introduction: The use of cell saver (CS) in cardiac surgery is proposed to reduce the use of units of packed red blood cells stored (URBC), which increases morbidity, mortality and causes inflammatory reactions. Objective: The objective is to evaluate whether the use of CS decreases the use URBC, is cost / effective and beneficial to the patient.

Endereço para correspondência: Rui Manuel Sequeira de Almeida Rua Maranhão, 740 – cj 202 – Cascavel, PR - Brasil – CEP: 85806-050. E-mail: ruimsalmeida@iccop.com.br Artigo recebido em 9 de maio de 2012 Artigo aprovado em 26 de dezembro de 2012

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Almeida RMS, et al. - O uso de recuperador de sangue em cirurgia cardíaca com circulação extracorpórea

Abreviações, acrônimos & símbolos ANS CEC CRM Hb Ht IMC PO RS SC UCH UTI

Agência Nacional de Saúde Suplementar Circulação extracorpórea Cirurgia de revascularização do miocárdio Hemoglobina Hematócrito Índice de massa corpórea Pós-operatório Recuperador de sangue Superfície corpórea Unidades de concentrado de hemácias Unidade de terapia intensiva

Methods: In a prospective study, between November 2009 and October 2011, 100 consecutive patients who underwent cardiovascular surgery with CPB, hemodilution and hemofiltration, were enrolled. Patients were divided into group 1 (no CS) and 2 (CS). The criteria for the replacement of RBC were hemodynamic instability and hemoglobin (Hb)

INTRODUÇÃO Com o progresso e maior conhecimento da fisiopatologia da circulação extracorpórea, vários métodos têm sido usados para diminuir o uso de sangue homólogo. Este tem sido um caminho traçado, com maior incidência de uso em pacientes por questões religiosas e entre aqueles que não desejam fazer uso de concentrado de hemácias. Sabe-se que a utilização deste varia, nos diversos serviços e em diversos continentes, entre 15% a 60% [1]. Nos últimos anos, esforços têm sido realizados de modo a diminuir cada vez mais o uso de sangue homólogo, com a recuperação de sangue autólogo no intraoperatório e, algumas vezes, até no pós-operatório [2], aliados a protocolos mais rígidos de hemostasia ao longo dos atos cirúrgicos. Aparelhos recuperadores de sangue (RS) têm sido usados [3] em pacientes adultos com alto risco de sangramento, sabedores também que os mesmos diminuem a resposta inflamatória à circulação extracorpórea. A Society of Thoracic Surgeons e a Society of Cardiovascular Anesthesiologists [4], em suas diretrizes de 2007, consideraram como classe I, o uso de RS. No entanto, vários autores têm demonstrado que o uso de RS não é tão benéfico como se afirmou [5,6], bem como não é custo-efetivo [7-9]. Com o intuito de esclarecer esse aspecto, os autores delinearam este trabalho, que tem como objetivo primário verificar se o uso de RS, em cirurgias cardiovasculares,

<7-8g/dl. Demographic data, as well as Hb and hematocrit, mediastinal drainage, number of URBC and CPB, ICU and hospital time, were analysed. Results: In groups 1 and 2 the average age was 64.1 and 60.6 years; predominantly male; the logistic EuroSCORE 10.3 and 9.4; mortality 2% and 4%. Group 2 had a higher incidence of reoperations (12% versus 6%), but the average of URBC used (4.31 versus 1.25) and mean length of hospital stay (10.8 versus 7.4 days) was lower. Univariate and multivariate analysis, were performed, which showed no statistically significant values, except in the use of URBC. The relationship between the CS and the cost of RBC was not cost / effective and length of stay was shorter. Conclusion: The use of CS decreases the number of used URBC, is not cost / effective but has shown benefits for patients. Descriptors: Operative blood salvage. Blood component transfusion. Cell separation.

com circulação extracorpórea (CEC), é custo-efetivo. Como objetivos secundários, buscou-se identificar a redução do uso de unidades de concentrado de hemácias estocadas (UCH), em pacientes que fizeram uso do RS, e a morbidade decorrente do uso desse protocolo. MÉTODOS Este é um estudo de coorte concorrente, prospectivo, e não randomizado, realizado no Instituto de Cirurgia Cardiovascular do Oeste do Paraná, em um grupo de 100 pacientes operados consecutivamente pelo mesmo cirurgião (RMSA), no período de novembro de 2009 a outubro de 2011. Todos os pacientes submetidos a cirurgia cardiovascular com CEC foram incluídos, não sendo estabelecidos critérios de exclusão. Os pacientes foram divididos em dois grupos de 50 pacientes: Grupo A – sem utilização de RS, Grupo B – com utilização de RS. Ambos os grupos fizeram uso na CEC, de hemodiluição parcial e hemofiltração. O critério estabelecido para emprego de UCH foi de hemoglobina (Hb) abaixo de 7 ou 8 g/100 ml, se houvesse instabilidade hemodinâmica. Não foi levado em consideração o número de unidades de plasma, plaquetas ou crioprecipitados usadas, por não ser objetivo deste estudo. Todos os pacientes foram submetidos à indução anestésica com uso de midazolan e remifentanil e a sua manutenção com servoflurano. Após esternotomia mediana 77

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e confecção das bolsas para canulação, os pacientes foram heparinizados com uma dose de 300 U/kg, de modo a obter tempo de coagulação ativado superior a 400 segundos; controles foram realizados a cada 60 minutos. Em todos os casos, foi usado oxigenador de membrana de adulto (Braile Biomédica®, São José do Rio Preto, SP, Brasil), com volume total de enchimento de 500 ml. A cardioplegia usada foi sanguínea e de infusão anterógrada. No Grupo B, o recuperador de células usado foi o autoLog Autotransfusion System (Medtronic, Minnesota, USA), durante toda a cirurgia, sendo ao final o sangue do sistema de CEC processado pelo sistema do RS. Foram obtidos a Hb e o hematócrito (Ht), no dia de internamento, na chegada à unidade de terapia intensiva (UTI), no primeiro dia de pós-operatório (PO) e no dia da alta hospitalar; o volume aspirado pelo RS e o infundido também foram registrados, bem como a Hb e o Ht do sangue infundido. O número de UCH usados foi registrado. Os dados do valor do pacote de material descartável de RS e de UCH foram obtidos para a compra, por empresa pertencente à Agência Nacional de Saúde Suplementar (ANS). Em valores correntes nacionais, a UCH foi cotada a R$ 400,00 e o pacote de material descartável de RS a R$ 1.650,00. O estudo foi aprovado pelo Comitê de Ética da Faculdade Assis Gurgacz, sob o número de protocolo 154/2012. Estatisticamente, as variáveis contínuas são representadas pela média e seu desvio padrão, mediana, e foram usados os testes de t de Student, de Mann Whitney e de Fisher, para analisar as variáveis deste estudo.

Utilizamos a estatística nas variáveis do pré-operatório (idade, sexo, peso, tipos de cirurgia, tempo de CEC e de pinçamento aórtico, e volume globular), para verificar se a amostra dos dois grupos era comparável ou não. RESULTADOS A idade dos pacientes variou de 26 a 84 anos de idade, sendo a média de idade dos pacientes do Grupo A de 64,15 ± 9,99 anos, e do B de 60,55 ± 12,01 anos. Houve predominância do sexo masculino em ambos os grupos. Os dados demográficos dos pacientes são apresentados na Tabela 1. No Grupo A, 60% dos pacientes foram submetidos à cirurgia de revascularização do miocárdio, enquanto que, no Grupo B, foram 68%; o EuroSCORE logístico nos dois grupos foi semelhante, bem como o aditivo, por subgrupos (Tabela 2). As variáveis idade, peso, sexo, tipo de cirurgia (nos dois subgrupos com maior número de pacientes), tempo de CEC e de pinçamento aórtico, Hb e VG préoperatórios foram estatisticamente analisados, para ver se os dois grupos eram comparáveis. Não houve diferença estatística entre os dois grupos a não ser na variável sexo (Tabela 3). Dois pacientes do Grupo B eram reoperações (4%), sendo uma quinta cirurgia, e um do Grupo A (2%). Os tempos de CEC, pinçamento aórtico e das diversas fases de internamento, estão representados na Tabela 4. A incidência de reoperações por sangramento foi de 6% no Grupo A e 12% no Grupo B.

Tabela 1. Características clínicas dos dois grupos

EuroSCORE

Idade

Média ± DP Mediana

Grupo A 64,15 ± 9,99 65

Grupo B 60,55 ± 12,01 63

Sexo

Masculino

56%

84%

Aditivo

0a2 2a5 >5 Logístico

9 19 22 10,28

10 21 19 9,55

Peso Altura Superfície Corpórea Índice de Massa Corporal

kg cm cm2

75,61 ± 14,85 166,31 ± 9,35 185,86 ± 23,75 27,25 ± 3,86

78,36 ± 16,59 169, 92 ± 8,48 187,48 ± 20,02 26,72 ± 4,26

CEC xAo

min min

73,06 ± 20,97 38,70 ± 13,91

66,62 ± 15,69 37,43 ± 9,73

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Tabela 2. Tipo de cirurgia.

CRM CRM Associada

Troca V.Ao. Troca V.Mi. Plastia V.Ao. Plastia V.Mi. Aneur. Ao. Ascend. Mixoma DSA DSV

Troca V.Ao. Troca V.Mi. Plastia V.Ao. Plastia V.Mi. DSV Mixoma Aneurisma VE

Grupo A 30

Enxertos Arteriais 34

1 1 2

2 1 4 3 1

Saf 67

Prótese Metálica

Prótese Biológica

Grupo B 34

Enxertos Arteriais 43

Saf

3 1

4 1

2 4

1 5

3 3

3 1

1 1

2 1

Prótese Metálica

2 2

Tabela 3. Tabela comparativa das variáveis Com Cell Saver (n=50) 63,72±12,21 79,58±16,43 38/12

Sem Cell Saver (n=50) 60,56±9,90 76,10±15,04 27/23

Valor P P=0,1587 P=0,2722 P=0,0233

(Aórtico/Não-aórtico)

6/44

9/41

P=0,4195

(Coronários x Não-coronarianos)

41/9

36/14

P=0,2476

67,10±20,05 38,28±13,82 13,70±3,67 41,10

73,10±21,23 38,36±13,82 12,80±1,69 38,40

P=0,1517 P=0,9787 P=0,1397 P=0,1397

Variáveis Idade (anos) Peso (kg) Masc./Fem. Tipo de Cirurgia

Tempo CEC (minutos) Tempo Pinçamento (minutos) Hb pré-op. (g/dl) VG pré-op. (%)

A mortalidade hospitalar foi de 2% no Grupo A (paciente de cirurgia de revascularização do miocárdio – CRM – com troca valvar mitral, por falência de múltiplos órgãos) e 4% no Grupo B (paciente de CRM com troca valvar aórtica e aorta em porcelana, por acidente vascular encefálico, e paciente de CRM com defeito do septo ventricular, de falência de múltiplos órgãos). Não houve óbitos no período de seguimento. O sangramento por dia de pós-operatório, bem como o uso de UCH está apresentado na Tabela 3. O volume total médio de líquido aspirado foi de 1657,00 ± 2309,65 ml, sendo aproveitados 474,58 ±

160,66 ml para infusão, com uma Hb e um Ht médios de 18,58 ± 4,51 g/100 ml e 52,31 ± 11,28%, respectivamente. O sangramento médio foi de 642,51 ± 193,30 ml, no Grupo A, e 685,65 ± 210,36 ml, no Grupo B. A superfície corpórea (SC) e o índice de massa corpórea (IMC) foram, respectivamente, 3,46 e 3,66 ml/cm2 e 23,58 e 25,66 ml nos Grupos A e B, não havendo diferença significativa. Um total de 194 UCH foi usado no Grupo A e 62, no Grupo B. A média de uso de UCH no Grupo A, foi de 2,42 ± 1,37, e no B de 0,70 ± 0,93, sendo que no 0°PO foram usadas 123 e 29, no 1° PO, 42 e 19, no 2° PO, 14 e 13, e até a alta 79

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Tabela 4. Tempos de CEC, pinçamento aórtico e diversos tempos Tempo

CEC xAo

min min

73,06 ± 20,97 38,70 ± 13,91

66,62 ± 15,69 37,43 ± 9,73

Tempo

Pré-Op

Média ± DP Mediana Média ± DP Mediana Média ± DP Mediana Média ± DP Mediana

2,98 ± 2,86 2 4,24 ± 5,87 2 10,79 ± 14,70 7 13,77 ± 15,23 9

2,37 ± 1,73 2 3,66 ± 5,36 2 7,43 ± 6,97 6 9,80 ± 7,33 8

UTI Pós-Op Internamento 1° PO

Hb Ht

g/100 ml %

9,41 ± 1,09 28,27 ± 5,33

9,85 ± 1,27 29,64 ± 3,86

Alta

Hb Ht

g/100 ml %

10,10 ± 1,32 30,41 ± 4,16

9,48 ± 1,20 28,71 ± 3,65

Sangramento

0° PO 1° PO 2° PO Após

ml ml ml ml

428,57 ± 214,10 175,51 ± 134,64 25,67 ± 77,33 12,77 ± 133,76

443,20 ± 271,65 231,84 ± 190,47 10,61 ± 64,19 0,00 ± 0,00

UCH

0° PO 1° PO 2° PO Após

n° n° n° n°

2,51 ± 1,20 1,05 ± 1,00 0,37 ± 0,78 0,38 ± 1,07

0,58 ± 1,48 0,39 ± 0,92 0,27 ± 0,63 0,02 ± 0,14

Tabela 5. Tabela de análise das variáveis estatisticamente significantes Variáveis Hb pós CEC (g/dl) Hb 1° pós-op. (g/dl) Hb alta hospitalar (g/dl) Sangramento (ml) Transfusão (ml)

Com Cell Saver (n=50) 10,55±1,80 9,85±1,28 9,47±1,21 443,2±274 174±449

15 e 1 UCH nos Grupos A e B, respectivamente (Tabela 3). Todos os pacientes do Grupo A foram infundidos com pelo menos duas UCH (2 a 13), durante o internamento, enquanto que 28 pacientes do Grupo B não receberam nenhuma UCH, sendo que os restantes usaram 2,81. Na análise das variáveis, entre os dois grupos, observouse que as únicas diferenças que foram estatisticamente significativas, foram a hemoglobina na alta hospitalar e o número de UCH transfundidas (Tabela 5). Em relação ao custo, comparando-se apenas no Grupo A o valor das UCH totais e, no Grupo B, o das UCH adicionadas ao custo do material do sistema RS, pode-se verificar que no primeiro houve um custo/paciente de R$ 1.552,00 e, no segundo, de R$ 1.946,00. 80

Sem Cell Saver (n=50) 10,29±1,48 9,40±1,09 10,09±1,33 431,6±216 526±468

Valor P P=0,4645 P=0,0846 P=0,0247 P=0,8149 P=0,002

DISCUSSÃO Trabalhos têm demonstrado que o uso de sangue homólogo em cirurgia cardiovascular aumenta não só a mortalidade como também a morbidade [10-12] O uso de equipamentos recuperadores de células sanguíneas teve seu início na década de 1970, em função de uma demanda cada vez maior, por parte dos pacientes, para o não uso de sangue. Essas solicitações foram desencadeadas por um grupo religioso, o qual não permitia o uso de sangue estocado para ser infundido em seus fiéis. Segundo as diretrizes usadas pelo National Health Service, o uso de RS, em cirurgia cardiovascular com CEC, deve ser realizado a critério do cirurgião e pode ser custo-efetivo

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[13]. O objetivo maior no uso do RS é o de ter a capacidade de diminuir a utilização de UCH nos pacientes e, com isso, diminuir as reações inflamatórias e a morbimortalidade. Esse cuidado deve ser tomado simultaneamente com uma perfeita hemostasia tanto na diérese inicial como antes da síntese em cirurgias cardiovasculares. Logo no início na década de 1980 do século XX, alguns autores já se posicionavam contra o uso indiscriminado do RS, por não diminuir nem os custos, nem o requerimento de sangue homólogo [14]. No entanto, vários trabalhos têm demonstrado vantagens no uso do RS, como aumento da concentração de hemoglobina e menos tempo de UTI [15], a menor utilização de UCH, desde que se aproveite o sangue desprezado do ato operatório [16], e os maus resultados com Ht baixo em pós-operatório de cirurgia cardiovascular [17]. Os dados do presente trabalho demonstram tempo menor de internamento em UTI, média de um dia a menos, e a menor utilização de UCH durante todo o internamento. Em relação às complicações pós-operatórias, não houve diferença entre os dois grupos, visto que as mesmas não foram relacionadas ao uso de UCH, mas à doença básica e sua forma de tratamento. Uma das principais diferenças deste estudo, em relação ao de Reyes et al. [18], um dos últimos publicados na literatura mundial, é que neste foram considerados pacientes consecutivos, não havendo nenhuma exclusão (estudo real life), e no outro, os autores excluíram pacientes com: cirurgias concomitantes, cirurgias aórticas, reoperações, emergências, altos níveis de creatinina, anemia e pacientes com SC < 1,6 m2, além de pacientes com um EuroSCORE > 10% e com alto risco de sangramento. Este estudo apresentou 21% de pacientes com EuroSCORE acima daquele percentual e, no grupo que se fez uso de RS, 6% dos pacientes foram operados em vigência de uso de clopidogrel e uma paciente estava sendo submetida a uma quarta reoperação (quinto procedimento). Ainda comparando critérios, a associação de procedimentos apresentou-se em 90% dos pacientes (6% no Grupo B), sendo que nestes 55,6% foram submetidos a explorações cirúrgicas por sangramento, que correspondeu a 5% do grupo total. Attaran et al. [19], num grupo de 1871 pacientes que usaram RS, obteve percentual de re-exploração por sangramento que variou com o tipo de cirurgia, semelhante ao apresentado anteriormente. Estes autores também concluíram que o uso regular do RS não traz nenhum benefício ao paciente, sendo que essa decisão deve ser feita individualmente. Em relação ao custo-benefício do uso do RS, podemos

observar, comparando o custo da quantidade de UCH usadas por paciente, no Grupo A, e o valor do material descartável do RS, no Grupo B, que não houve vantagem econômica, sendo o custo superior no Grupo B, em média, de R$ 394,00. Vários autores têm também chegado a essa conclusão [7-9,11] e, com isso, sua indicação tem sido realizada para casos específicos, em que se projeta um sangramento acima do normal [10]. No entanto, há que se levar em consideração que do grupo que usou RS, em 28 não houve infusão de UCH, sendo o total de 1,25 UCH/ paciente/internamento e, no Grupo A, de 4,31. Vários autores têm demonstrado que o não uso de UCH em pósoperatório diminui não só a morbidade, como também a mortalidade trans e pós-operatória [4,5]. Sem dúvida que este equipamento tem a vantagem de diminuir o uso de UCH na cirurgia cardíaca, porém somente em casos selecionados, não sendo, portanto, seu benefício linear para todos os pacientes. Mais estudos devem ser realizados para podermos ter uma resposta em relação a marcadores inflamatórios e vantagens de seu uso na prática diária. CONCLUSÃO Este estudo demonstrou que o uso de RS não é custoefetivo, que houve redução do número de UCH no grupo que usou RS e que não houve morbidade relacionada à aplicação desse protocolo.

REFERÊNCIAS 1. Reyes G, Prieto M, Alvarez P, Orts M, Bustamante J, Santos G, et al. Cell saving systems do not reduce the need of transfusion in low-risk patients undergoing cardiac surgery. Interact Cardiovasc Thorac Surg. 2011;12(2):189-93. 2. Klein AA, Nashef SA, Sharples L, Bottrill F, Dyer M, Armstrong J, et al. A randomized controlled trial of cell salvage in routine cardiac surgery. Anesth Analg. 2008;107(5):148795. 3. Carless PA, Henry DA, Moxey AJ, O’Connell DL, Brown T, Fergusson DA. Cell salvage for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2006;(4):CD001888.

Almeida RMS, et al. - O uso de recuperador de sangue em cirurgia cardíaca com circulação extracorpórea

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4. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, et al; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5 Suppl):S27-86.

12. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-67.

5. Jakobsen CJ, Ryhammer PK, Tang M, Andreasen JJ, Mortensen PE. Transfusion of blood during cardiac surgery is associated with higher long-term mortality in low-risk patients. Eur J Cardiothorac Surg. 2012;42(1):114-20. 6. Scott BH. Blood transfusion in cardiac surgery: is it appropriate? Ann Card Anaesth. 2007;10(2):108-12. 7. Attaran S, McIlroy D, Fabri BM, Pullan MD. The use of cell salvage in routine cardiac surgery is ineffective and not costeffective and should be reserved for selected cases. Interact Cardiovasc Thorac Surg. 2011;12(5):824-6. 8. Klein AA, Nashef SA, Sharples L, Bottrill F, Dyer M, Armstrong J, et al. A randomized controlled trial of cell salvage in routine cardiac surgery. Anesth Analg. 2008;107(5):1487-95. 9. Serrano FJ, Moñux G, Aroca M. Should the cell saver autotransfusion system be routinely used in elective aortic surgery? Ann Vasc Surg. 2000;14(6):663-8.

13. Kelleher AA, Pepper J, Boecoe M, Shuldham C. Policy for the provision of perioperative red cell salvage. Joint Transfusion Committee Royal Brompton & Harefield Hospitals. Disponível em: http://www.transfusionguidelines.org.uk/docs/pdfs/rtcscent_policy_rcs.pdf 14. Winton TL, Charrette EJ, Salerno TA. The cell saver during cardiac surgery: does it save? Ann Thorac Surg. 1982;33(4):379-81. 15. Marcoux J, Rosin M, McNair E, Smith G, Lim H, Mycyk T. A comparison of intra-operative cell-saving strategies upon immediate post-operative outcomes after CPB-assisted cardiac procedures. Perfusion. 2008;23(3):157-64. 16. Wang G, Bainbridge D, Martin J, Cheng D. The efficacy of an intraoperative cell saver during cardiac surgery: a meta-analysis of randomized trials. Anesth Analg. 2009;109(2):320-30. 17. Hannan EL, Samadashvili Z, Lahey SJ, Culliford AT, Higgins RS, Jordan D, et al. Predictors of postoperative hematocrit and association of hematocrit with adverse outcomes for coronary artery bypass graft surgery patients with cardiopulmonary bypass. J Card Surg. 2010;25(6):638-46.

10. Scott BH. Blood transfusion in cardiac surgery: is it appropriate? Ann Card Anaesth. 2007;10(2):108-12.

18. Reyes G, Prieto M, Alvarez P, Orts M, Bustamante J, Santos G, et al. Cell saving systems do not reduce the need of transfusion in low-risk patients undergoing cardiac surgery. Interact Cardiovasc Thorac Surg. 2011;12(2):189-93.

11. Basran S, Frumento RJ, Cohen A, Lee S, Du Y, Nishanian E, et al. The association between duration of storage of transfused red blood cells and morbidity and mortality after reoperative cardiac surgery. Anesth Analg. 2006;103(1):15-20.

19. Attaran S, McIlroy D, Fabri BM, Pullan MD. The use of cell salvage in routine cardiac surgery is ineffective and not costeffective and should be reserved for selected cases. Interact Cardiovasc Thorac Surg. 2011;12(5):824-6.

Sá MPBO, et al. - Five-year outcomes following PCI with DES versus REVIEW ARTICLE CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

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Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and meta-regression of 2914 patients Desfechos de 5 anos do tratamento de lesões de TCE por stents farmacológicos versus CRM: metaanálise e meta-regressão de 2914 pacientes

Michel Pompeu Barros de Oliveira Sá1, Paulo Ernando Ferraz2, Rodrigo Renda Escobar2, Eliobas Oliveira Nunes2, Alexandre Magno Macário Nunes Soares2, Frederico Browne Correia de Araújo e Sá2, Frederico Pires Vasconcelos2, Ricardo Carvalho Lima3

DOI: 10.5935/1678-9741.20130013

RBCCV 44205-1446

Abstract Objective: To compare the safety and efficacy at long-term follow-up of coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) using drug-eluting stents (DES) in patients with unprotected left main coronary artery (ULMCA) disease. Methods: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant articles were searched for clinical studies that reported outcomes at 5-year follow-up after PCI with DES and CABG for the treatment of ULMCA stenosis. Five studies (1 randomized controlled trial and 4 observational studies) were identified and included a total of 2914 patients (1300 for CABG and 1614 for PCI with DES). Results: At 5-year follow-up, there was no significant difference between the CABG and PCI-DES groups in the risk for death (odds ratio [OR] 1.159, P=0.168 for random effect) or the composite endpoint of death, myocardial infarction, or stroke (OR 1.214, P=0.083). The risk for target vessel revascularization (TVR) was significantly lower in the CABG group compared to the PCI-DES group (OR

0.212, P<0.001). The risk of major adverse cardiac and cerebrovascular events (MACCE) was significantly lower in the CABG group compared to the PCI-DES group (OR 0.526, P<0.001). It was observed no publication bias about outcomes and considerably heterogeneity effect about MACCE. Conclusion: CABG surgery remains the best option of treatment for patients with ULMCA disease, with less need of TVR and MACCE rates at long-term follow-up.

1. MD, MSc – Author. 2. MD – Co-author. 3. MD, MSc, PhD, ChM – Co-author.

Correspondence address: Michel Pompeu Barros de Oliveira Sá. Av. Eng. Domingos Ferreira, 4172/405 Recife, PE, Brazil – Zip code: 51021-040. E-mail: michel_pompeu@yahoo.com.br

Work carried out at Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco (PROCAPE), University of Pernambuco (UPE), Recife, PE, Brazil.

Descriptors: Meta-analysis. Myocardial revascularization. Drug-eluting stents. Resumo Objetivo: Comparar segurança e eficácia do seguimento a longo prazo da cirurgia de revascularização miocárdica (CRM) com intervenção coronária percutânea (ICP), utilizando stents farmacológicos (SF) em pacientes com lesão de tronco de coronária esquerda não-protegida (TCE). Métodos: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar e listas de referências de

Article received on September 23rd, 2012 Article accepted on November 13th, 2012

Sá MPBO, et al. - Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

Abbreviations, Acronyms & Symbols CABG CENTRAL/CCTR CI DES EuroSCORE LILACS MACCE MeSH OR PCI PRISMA SciELO TVR ULMCA

Coronary artery bypass graft Cochrane Central Register of Controlled Trials Confidence interval Drug-eluting stents European System for Cardiac Operative Risk Evaluation Literatura Latino-Americana e do Caribe em Ciências da Saúde Major adverse cardiac and cerebrovascular events Medical subject heading Odds ratio Percutaneous coronary intervention Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scientific Electronic Library Online Target vessel revascularization Unprotected left main coronary artery

artigos relevantes foram escaneados para estudos clínicos que relataram resultados em 5 anos de seguimento após ICP-SF e CRM para o tratamento de lesão de TCE. Cinco estudos (um

INTRODUCTION Rationale Current guidelines recommend percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) with stents as a Class IIa or IIb alternative to coronary artery bypass graft (CABG) in patients with conditions that are associated with a low risk of PCI procedural complications and/or increased risk of adverse surgical outcomes [1]. Capodanno et al. [2] recently published a meta-analysis of 4 randomized controlled trials and suggested, boldly, that “based on that study, revision of the guidelines regarding left main PCI is warranted, raising the level of evidence of current recommendations from B to A”. Although recent randomized controlled trials have suggested that PCI with drug-eluting stents (DES) could be a non-inferior strategy that might be used safely [3,4], sample sizes are small (and some conclusions may be affected by this aspect) and observational studies ("realworld" studies) should not be ignored in meta-analyses. Recently, Sá et al. [5] published a new meta-analysis with 16 studies (three randomized and 13 observational) with 1-year follow up results. This one argued against the “non-inferiority” of PCI with DES in comparison 84

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ensaio clínico randomizado e quatro estudos observacionais) foram identificados e incluíram um total de 2914 pacientes (1300 para CRM e 1614 para ICP-SF). Resultados: Aos 5 anos de seguimento, não houve diferença significativa entre os grupos CRM e ICP-SF no risco de morte (odds ratio [OR] 1,159, P=0,168) ou desfecho composto de morte, infarto do miocárdio , ou AVC (OR 1,214, P=0,083). O risco de necessidade de nova revascularização foi significativamente menor no grupo CRM em comparação com o grupo de ICP-SF (OR 0,212, P<0,001). O risco de eventos adversos cardíacos maiores e cerebrovasculares (EACMC) foi significativamente menor no grupo CRM em comparação com o grupo de ICP-SF (OR 0,526, P<0,001). Não foi observado viés de publicação sobre os resultados e considerável heterogeneidade dos efeitos sobre EACMC. Conclusão: CRM continua sendo a melhor opção de tratamento para pacientes com lesão de TCE, com menos necessidade de novas revascularizações e EACMC no seguimento a longo prazo. Descritores: Metanálise. Revascularização miocárdica. Stents farmacológicos.

to CABG surgery and against the idea that PCI could be considered a reasonable choice in elective cases (not mentioning prohibitive risk patients, acute patients and those who reject surgery), given that, although the rates of death between both strategies were not statistically different, the need of new procedures and major adverse cardiac and cerebrovascular events rates were clearly lower in patients treated with CABG surgery. Sá et al. [5] emphasized that the length of follow-up considered for their study may have been too short (1-year) to truly detect differences between the treatment groups, and so was the study of published by Capodanno et al. [2]. Performing a quick search on medical literature, we found no meta-analyses that evaluated the long-term results regarding this topic (PCI with DES versus CABG in ULMCA disease). Taking into considerations all these aspects, it is necessary to evaluate the long-term results of CABG surgery versus PCI with DES in scenario of ULMCA disease, using the highest level of existing evidence. Objective We performed a meta-analysis of randomized controlled trials and observational studies to compare

Sá MPBO, et al. - Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

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CABG to PCI with DES for the treatment of patients with ULMCA disease, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [6].

or exclusion of studies was decided unanimously. When there was disagreement, a third reviewer took the final decision.

METHODS Eligibility Criteria Using PICOS studies were considered if: (1) population comprised patients with ULMCA disease; (2) compared efficacy or effectiveness between CABG and PCI with DES; (3) outcomes studied included myocardial infarction, cerebrovascular events, death, target vessel revascularization (TVR) or combined outcomes (MACCE – major adverse cardiac and cerebrovascular events); (4) presented follow-up of at least 5 years. Information Sources The following databases were used (until July 2012): MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL/CCTR), ClinicalTrials.gov, SciELO (Scientific Electronic Library Online), LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde – The Latin American and Caribbean Health Sciences), Google Schoolar and reference lists of relevant articles. Search We conducted the search using Medical Subject Heading (MeSH) terms “coronary artery bypass graft” OR “coronary artery bypass grafting” OR “coronary artery bypass surgery” OR “coronary bypass surgery” OR “coronary artery bypass graft surgery” OR “coronary artery bypass” OR “coronary bypass” AND “drug-eluting stent” OR “sirolimus-eluting stent” OR “paclitaxeleluting stent” AND “unprotected left main” OR “left main stenting” OR “left main coronary artery disease” OR “left main PCI” OR “unprotected left main coronary artery” OR “left main stenosis” OR “left main coronary artery stenting” OR “unprotected left main stenting”. Study Selection The following steps were done: (1) identification of titles of records through databases searching; (2) removal of duplicates; (3) screening and selection of abstracts; (4) assessment for eligibility through full-text articles; (5) final inclusion in study. One reviewer followed the steps 1 to 3. Two independent reviewers followed step 4 and selected studies. Inclusion

Data Items The primary endpoint was the Odds Ratio (OR) for mortality after PCI or CABG, up to 5 years. Secondary end points were the OR for composite endpoint of death, myocardial infarction or stroke; TVR (target vessel revascularization – repeat revascularization of the treated vessel) after the procedure; and MACCE (major adverse cardiac and cerebrovascular events – composite endpoint of death, myocardial infarction, stroke or TVR). Data Collection Process Two independent reviewers extracted the data. When there was disagreement about data, a third reviewer (the first author) checked the data and took the final decision about it. From each study, we extracted patient characteristics, study design, and outcomes at 5-year after treatment of ULMCA stenosis. When possible, actual probabilities of mortality and death after 5-year following PCI or CABG were used to calculate odds ratios. Alternatively, probabilities of mortality or MACCE were estimated from published Kaplan-Meier survival curves. We also extracted TVR from the total MACCE events and reported this outcome as a separate measure. When MACCE was not reported, we calculated it using the events of death, myocardial infarction, stroke and TVR and reported this outcome as a separate measure. Risk of Bias in Individual Studies Included studies were assessed for the following characteristics: design (prospective or retrospective), randomization (yes or no), multicenter enrollment (yes or no), characteristics of participants and personnel (performance bias), outcome assessment (detection bias), incomplete outcome data addressed (attrition bias) and adequation of multivariate adjustment for possible confounders. Two independent reviewers assessed risk of bias. Agreement between the two reviewers was assessed using kappa statistics for full text screening, and rating of relevance and risk of bias. When there was disagreement about risk of bias, a third reviewer (the first author) checked the data and took the final decision about it. Summary Measures The principal summary measures were OR’s with 85

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95% Confidence Interval (CI) and P values (that will be considered statistically significant when <0.05). The metaanalysis was completed using the software Comprehensive Meta-Analysis version 2 (Biostat Inc., Englewood, New Jersey, USA).

(Kappa=0.84). Agreement for decisions related to study validity was very good (Kappa=0.81). The search strategy can be seen in Figure 1.

Synthesis of Results Forest plots were generated for graphical presentations for clinical outcomes and we performed the I2 test and Chi2 statistics for assessment of heterogeneity across the studies [7]. Each study was summarized by the OR for PCI compared to CABG. The OR’s were combined across studies using DerSimonian-Laird random effects model [8] and with the fixed effects model using the MantelHaenszel model [9]. Both models were weighted by number of events in each study. Risk of Bias Across Studies To assess publication bias, a funnel plot was generated (for each outcome), being statistically assessed by Begg and Mazumdar’s test [10] and Egger’s test [11]. Meta-regression Analysis Meta-regression analyses were performed to determine whether the effects of CABG were modulated by prespecified factors. Meta-regression graphs describe the effect of CABG on the outcome (plotted as a log OR on the y-axis) as a function of a given factor (plotted as a mean or proportion of that factor on the x-axis). Meta-regression coefficients show the estimated increase in log OR per unit increase in the covariate. Since log OR >0 corresponds to OR >1 and log OR <0 corresponds to OR<1, a negative coefficient would indicate that as a given factor increases, the OR decreases. The pre-determined modulating factors for all outcomes to be examined were: sex, age, diabetes and prior PCI. Sex was represented as the proportion of females in the studies. Age was represented as the mean age of the patients participating in the studies. Diabetes was represented as the proportion of diabetics in the studies. Prior PCI was represented as the proportion of patients who underwent PCI before any interventions in the studies.

Study Characteristics Characteristics of each study are shown in Table 1. A total of 2914 patients were studied with 1300 receiving CABG and 1614 receiving PCI with DES. Of the 5 studies, one was randomized controlled trial [14], one matched the treatment cohorts using European System for Cardiac Operative Risk Evaluation (EuroSCORE) [16], two used other propensity scores to guarantee like-to-like comparisons [12,15], Four studies mostly used Cypher stent (sirolimus) or Taxus stent (paclitaxel) and one study did not report which DES was used. The overall internal validity was moderate risk of bias and is illustrated in Table 2. Synthesis of Results The OR of the risk of death in the CABG group compared with the PCI-DES group in each study, at the 5-year time point, is reported in Figure 2. There was no evidence for heterogeneity of treatment effect among the studies for death. The overall OR (95% confidence interval) of mortality showed no difference between CABG and PCIDES at 5-year (fixed effect model: OR 1.159, P=0.168; random effect model: OR 1.159, P=0.168).

RESULTS Study Selection A total of 14.705 citations were identified, of which 31 studies were potentially relevant and retrieved as full-text. Five publications fulfilled our eligibility criteria [12-16]. Interobserver reliability of study relevance was excellent 86

Fig. 1 – Flow diagram of studies included in data search

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Sá MPBO, et al. - Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

Table 1. Study characteristics. Study

PCI (n)

DES

Complete revascularization with PCI (%) NR

CABG (n)

LIMA to LAD (%)

Off-pump (%)

309

Complete revascularization with CABG (%) NR

Chang et al. 2012 [12]

556

Terazawa et al. 2012 [13]

Boudriot et al. 2011 [14]

Unadjusted risk

Method of Adjustment

CABG higher risk clinical profile; EuroSCORE higher risk profile; SYNTAX score higher risk profile

Propensity matched

Cypher (88%) Taxus (12%)

CABG higher risk clinical profile; EuroSCORE higher risk profile

Multivariate logistic regression and multivariable Cox regression

100

Cypher (98%) Taxus (2%)

101

Randomized, same risk

Unneeded

MAINCOMPARE registry 2010 [15]

396

Cypher (79%) Taxus (21%)

396

Propensity score matched

Unneeded

Chieffo et al. 2010 [16]

107

Cypher (51.4%) Taxus (48.2%)

142

CABG higher risk clinical profile

Propensity score adjusted (EuroSCORE)

CABG: coronary artery bypass grafting; DES: drug-eluting stent; LAD: left anterior descending; LIMA: left internal mammary artery; PCI: percutaneous coronary intervention; NR: non-reported Table 2. Analysis of risk of bias – internal validity.

NP, NR, M

Selection bias B

Performance bias B

Attriction bias C

Dettection bias B

Multivariate adjustment for possible confounders Probably adequate

Terazawa et al. 2012 [13]

NP, NR, NM

Probably adequate

Boudriot et al. 2011 [14]

P, R, M

Probably adequate

P, NR, M

Probably adequate

NP, NR, NM

Probably adequate

Study Chang et al. 2012 [12]

MAIN-COMPARE registry 2010 [15] Chieffo et al. 2010 [16]

Study design

This was performed by 2 independent reviewers. The overall bias of the combined studies was considered moderate. A: risk of bias is low; B: risk of bias is moderate; C: risk of bias is high; D: incomplete reporting

Fig. 2 – Odds ratio and conclusions plot of mortality associated with CABG versus DES

Sá MPBO, et al. - Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

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Fig. 3 – Odds ratio and conclusions plot of composite endpoint (death, myocardial infarction or stroke) associated with CABG versus DES

Fig. 4 – Odds ratio and conclusions plot of target vessel revascularization (TVR) associated with CABG versus DES

The OR of the risk of composite endpoint of death, myocardial infarction or stroke in the CABG group compared with the PCI-DES group in each study, at the 5-year time point, is reported in Figure 3. There was evidence of low heterogeneity of treatment effect among the studies for this composite endpoint. The overall OR (95% confidence interval) of composite end point showed no difference between PCI-DES and CABG at 5-year (fixed effect model: OR 1.215, P=0.061; random effect model: OR 1.214, P=0.083). The OR of the risk of TVR in the CABG group compared with the PCI-DES group in each study, at the 5-year time point, is reported in Figure 4. There was no evidence for heterogeneity of treatment effect among the studies for TVR. The overall OR (95% confidence interval) of TVR showed an important difference between CABG and PCIDES at 5-year (fixed effect model: OR 0.212, P<0.001; 88

random effect model: OR 0.212, P<0.001), which favors the CABG strategy. The OR of the risk of MACCE in the CABG group compared with the PCI-DES group in each study, at the 5-year time point, is reported in Figure 5. There was a considerably evidence for heterogeneity of treatment effect among the studies for MACCE. The overall OR (95% confidence interval) of MACCE showed an important difference between CABG and PCI-DES at 5-year (fixed effect model: OR 0.543, P<0.001; random effect model: OR 0.526, P<0.001), which favors the CABG strategy. Risk of Bias Across Studies Funnel plot analysis (Figure 6) disclosed symmetry around the axis for the treatment effect in all outcomes, which means we probably do not have publication bias related to these end points.

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Fig. 5 – Odds ratio and conclusions plot of major adverse cardiac and cerebrovascular events (MACCE) associated with CABG versus DES

Fig. 6 – Publication bias analysis by funnel plot graphic

Meta-regression Analysis We observed a statistically significant coefficient for 2 situations: (1) MACCE and proportion of diabetic patients (coefficient -0.04, 95% CI -0.07 to -0.01, P=0.016); (2) MACCE and proportion of prior PCI (coefficient -0.03, 95% CI -0.05 to -0.01, P=0.010). It

means that the greater the proportion of diabetic patients and prior PCI in a population undergoing CABG, the lower the OR for MACCE in CABG group, i.e., the greater the protective effect of CABG for diabetic patients and/or submitted to prior PCI in relation to the incidence of MACCE (Figure 7). 89

Sá MPBO, et al. - Five-year outcomes following PCI with DES versus CABG for unprotected LM coronary lesions: meta-analysis and metaregression of 2914 patients

Fig. 7 – Meta-regression analysis by representative plots

DISCUSSION Summary of Evidence The results of this meta-analysis demonstrate that CABG remains the best option for ULMCA disease. At 5-year follow-up, although there was no difference in the risk for death and composite endpoint of death, myocardial infarction and stroke, there was a significantly higher risk for TVR and MACCE (this last one under the influence of heterogeneity of the effects) associated with PCI with DES, with no publication bias of the summary measures of all outcomes. Considerations About this Meta-Analysis To our knowledge, this is the first meta-analysis of studies with 5-years follow-up performed to date about PCI-DES versus CABG in ULMCA disease, providing incremental value by demonstrating that CABG reduces the incidence of TVR and MACCE compared with PCIDES. Furthermore, this analysis suggests that PCI-DES does not significantly reduce the incidence of long-term all-cause mortality and composite endpoint of death, myocardial infarction and stroke in comparison with 90

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CABG. The potential benefits of CABG on these outcomes appear to be influenced by diabetes and previous PCI. Diabetes mellitus is a powerful independent predictor of cardiovascular events. It is associated with extensive coronary artery disease, increased mortality regardless of revascularization mode and unfavorable prognosis if treated medically [17]. The SYNTAX trial [18] has shown in the diabetic subset of patients at 1 year, similar death/ infarction/stroke rates between the two revascularization groups, increased risk across all SYNTAX terciles and higher mortality and MACCE in diabetic patients with SYNTAX score ≥33 with PCI over surgery. As we can see by meta-analysis and meta-regression, the total population of patients with ULMCA disease benefit from surgery (in comparison with PCI-DES) and the population of diabetics benefit more, since the presence of diabetes modulate the effect toward the protective effect (lesser odds ratio). In case of prior PCI, the severity of the progression of coronary atherosclerotic disease may justify the greater MACCE in PCI-DES group previously submitted to PCI, making CABG appears to be more protective. Currently, patients undergoing initial PCI with a stent have severe atherosclerotic disease, but not as severe as those undergoing initial surgical treatment; when treatment with stents fails, these patients are referred for surgical revascularization, however the atherosclerotic disease is then more severe and diffuse [19]. At present, the totality of evidence suggests that CABG appears better for the “sicker” patients, i.e., those with multivessel disease or ULMCA disease and characteristics indicative of extensive atheroma burden with or without depressed left ventricle ejection fraction [20]. We should not forget that SYNTAX trial showed the undoubted benefits of surgery (in comparison with PCI-DES) in the group with higher SYNTAX score, i.e., more extensive and complex lesions [4]. Risk of Bias and Limitations Another limitation is the heterogeneity of the strategies across the studies. Among PCI strategies, studies used many combinations of sirolimus-stent and paclitaxelstents (one did not report). Among CABG strategies, there is variability in rates of use of internal thoracic artery (two did not report), use of cardiopulmonary bypass (on-pump versus off-pump CABG; two did not report), etc. And among both studies, an important aspect to consider is the rate of complete revascularization (not reported in four studies), which reflects in outcomes. There are inherent limitations with meta-analyses, including the use of cumulative data from summary

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estimates. Patient data were gathered from published data, not from individual patient follow-up. Access to individual patient data would have enabled us to conduct further subgroup analysis and propensity analysis to account for differences between the treatment groups. This metaanalysis included data from nonrandomized observational studies, which reflects the “real world” but are limited by treatment bias, confounders, and a tendency to overestimate treatment effects. Patient selection alters outcome and thus makes nonrandomized studies less robust. We tried to analyze the influence of surgical risk profile and profile of lesion complexity; however, it was not possible because studies did not report these issues more systematically and broadly; it would be interesting, for example, that studies always evaluate SYNTAX score of groups, as this would allow further analysis of outcomes with respect to this variable, including meta-analyzes on this topic. A final limitation is the absence of adequate published comparative data for the third therapeutic option, medical therapy. PCI with DES has not been compared with medical therapy alone when we consider ULMCA disease, but CABG has been shown to be superior to medical therapy in this set.

surgery and against the idea that PCI can be considered a reasonable choice in elective cases (not mentioning prohibitive risk patients, acute patients and those who reject surgery), given that, although the rates of death and composite endpoint (death, myocardial infarction or stroke) between both strategies were not statistically different, the need of new procedures and MACCE rates were clearly lower in patients treated with CABG surgery. However, careful analysis of the data shows that no definite conclusion can be drawn from the evidence available due to the heterogeneity of studies with respect to some outcomes, heterogeneity of strategies (different drugeluting stents, different ways to perform surgery, etc) and heterogeneity of coronary lesions complexity. Rigorous studies are necessary to define the best way to treat each subset of ULMCA disease. Based on our findings, we conclude that there is not clear evidence that left main PCI presents non-inferiority to CABG surgery and revision of the guidelines regarding left main PCI must be viewed with caution, and we still do not have enough evidences that make the level of evidence of current recommendations raises from B to A”.

Perspectives Ongoing and planned trials (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease - PRECOMBAT 1 and 2; Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization - EXCEL) will further facilitate evidence-based clinical decisions for ULMCA disease. Furthermore, the 5-year SYNTAX results (not published yet) will provide us a valuable extension of the 3-year information and possibly elucidate whether PCI should be further performed even in high-risk, very complex coronary disease by experienced teams in large volume centers. Others important registries (as CUSTOMIZE registry [11]) did not report their 5-year results yet. We hope that with the publication of all these studies, we will have more evidence about the long-term results, which will enable new meta-analyses with larger samples and other meta-regression analyses, in search of other factors that modulate the results. CONCLUSIONS We found evidence that argues against the “noninferiority” of PCI with DES in comparison to CABG

REFERENCES 1. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association Association for Cardio-Thoracic Surgery (EACTS), Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501-55. 2. Capodanno D, Stone GW, Morice MC, Bass TA, Tamburino C. Percutaneous coronary intervention versus coronary artery bypass graft surgery in left main coronary artery disease: a meta-analysis of randomized clinical data. J Am Coll Cardiol. 2011;58(14):1426-32. 3. Park SJ, Kim YH, Park DW, Yun SC, Ahn JM, Song HG, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718-27. 4. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961-72. 5. Sá MP, Soares AM, Lustosa PC, Martins WN, Browne F, Ferraz PE, et al. Meta-analysis of 5674 patients treated with percutaneous coronary intervention and drug-eluting stents for coronary artery bypass graft surgery for unprotected

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left main coronary artery stenosis. Eur J Cardiothorac Surg. 2013;43(1):73-80.

15. Park DW, Seung KB, Kim YH, Lee JY, Kim WJ, Kang SJ, et al. Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol. 2010;56(2):117-24.

6. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9. 7. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60. 8. DerSimonian R, Kacker R. Random-effects model for metaanalysis of clinical trials: an update. Contemp Clin Trials. 2007;28(2):105-14. 9. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127(9):820-6. 10. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088-101. 11. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34. 12. Chang K, Koh YS, Jeong SH, Lee JM, Her SH, Park HJ, et al. Long-term outcomes of percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main coronary bifurcation disease in the drug-eluting stent era. Heart. 2012;98(10):799-805. 13. Terazawa S, Tajima K, Takami Y, Tanaka K, Okada N, Usui A, et al. Early and late outcomes of coronary artery bypass surgery versus percutaneous coronary intervention with drug-eluting stents for dialysis patients. J Card Surg. 2012;27(3):281-7. 14. Boudriot E, Thiele H, Walther T, Liebetrau C, Boeckstegers P, Pohl T, et al. Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol. 2011;57(5):538-45.

16. Chieffo A, Magni V, Latib A, Maisano F, Ielasi A, Montorfano M, et al. 5-year outcomes following percutaneous coronary intervention with drug-eluting stent implantation versus coronary artery bypass graft for unprotected left main coronary artery lesions the Milan experience. JACC Cardiovasc Interv. 2010;3(6):595-601. 17. Flaherty JD, Davidson CJ. Diabetes and coronary revascularization. JAMA. 2005;293(12):1501-8. 18. Banning AP, Westaby S, Morice MC, Kappetein AP, Mohr FW, Berti S, et al. Diabetic and nondiabetic patients with left main and/or 3-vessel coronary artery disease: comparison of outcomes with cardiac surgery and paclitaxel-eluting stents. J Am Coll Cardiol. 2010;55(11):1067-75. 19. Borges JC, Lopes N, Soares PR, G贸is AF, Stolf NA, Oliveira SA, et al. Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery. J Cardiothorac Surg. 2010;5:91. 20. Smith PK, Califf RM, Tuttle RH, Shaw LK, Lee KL, Delong ER, et al. Selection of surgical or percutaneous coronary intervention provides differential longevity benefit. Ann Thorac Surg. 2006;82(4):1420-8. 21. Caggegi A, Capodanno D, Capranzano P, Chisari A, Ministeri M, Mangiameli A, et al. Comparison of one-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients with unprotected left main coronary artery disease and acute coronary syndromes (from the CUSTOMIZE Registry). Am J Cardiol. 2011;108(3):355-9.

Oliveira IM, et al. - Criss-cross heart: Report of two cases, anatomic and REVIEW ARTICLE surgical description and literature review

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Criss-cross heart: report of two cases, anatomic and surgical description and literature review Coração entrecruzado (Criss-cross heart): relato de dois casos, descrição anatomocirúrgica e revisão de literatura

Ítalo Martins de Oliveira1, Vera Demarchi Aiello2, Marcela Maria Aguiar Mindêllo3, Yasmin de Oliveira Martins4, Valdester Cavalcante Pinto Jr5

DOI: 10.5935/1678-9741.20130014

RBCCV 44205-1447

Resumo Coração entrecruzado (criss-cross heart) é uma anomalia extremamente rara, caracterizada por rotação anormal da massa ventricular ao longo do seu eixo maior e pode estar associada com qualquer malformação dos segmentos e das conexões entre as câmaras cardíacas. Devido às alterações estruturais complexas e à raridade da anomalia, essa anomalia de rotação é muitas vezes mal diagnosticada. Neste trabalho são relatados dois casos de coração entrecruzado com ênfase no diagnóstico morfológico e nas técnicas cirúrgicas utilizadas. Foi também realizada revisão da literatura sobre o assunto, que, embora escassa, foi enfatizada quanto à morfologia, diagnóstico, abordagem cirúrgica e possíveis complicações.

Abstract Criss-cross heart is an extremely rare anomaly, characterized by an abnormal rotation of the ventricular mass along its major axis. It may be associated with any malformation of the heart segments and connections. Due to the complex structural changes and rarity of the anomaly, the rotation of ventricular axis is often misdiagnosed. In this paper, two cases of criss-cross heart are reported, with emphasis on diagnostic and surgical techniques used to corrected the main defects. A literature review on the subject is also presented which, although sparse, emphasized on the morphologic, diagnostic and surgical aspects of the anomaly.

Descritores: Anormalidades congênitas. Procedimentos cirúrgicos cardíacos. Coração entrecruzado.

Descriptors: Congenital abnormalities. Cardiac surgical procedures. Crisscross heart.

1. PhD in Cardiology at Faculty of Medicine in the University of São Paulo, Research Coordinator at Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza, Ceará 2. Pathologist-in-chief, Surgical Pathology Section, Laboratory of Pathology at the Heart Institute of Sao Paulo University School of Medicine 3. Physician, graduated at State University of Ceará 4. Medicine Student at Fortaleza University. 5. Master's Degree in Public Politics Assessment at Federal University of Ceará, Head of the Pediatric Cardiac Surgery Service at Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza, Ceará.

Work carried out at: Hospital de Messejana Dr. Carlos Alberto Studart Gomes. Fortleza, CE, Brazil. Correspondence address: Ítalo Martins de Oliveira Av. Frei Cirilo, 3480 – Messejana Fortaleza, CE, Brazil. Zip code: 60846-190 E-mail: italomartins@cardiol.br Article received on May 9th, 2012 Article accepted on December 26th, 2012

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Oliveira IM, et al. - Criss-cross heart: Report of two cases, anatomic and surgical description and literature review

Abbreviations, acronyms & symbols Ao DORV EF HF ICU LV LVOT MeSH MRI PA PDA PVS RV RVOT VSD

aorta double outlet right ventricle ejection fraction heart failure intensive care unit left ventricle left ventricular outflow tract Health Sciences Descriptors magnetic resonance image pulmonary artery patent ductus arteriosus pulmonary valve stenosis right ventricle right ventricular outflow tract ventricular septal defect

most of the mass placed on the left, with transposition of the great vessels. In the other case the right atrium was connected to the morphologically left ventricle, with discordant atrioventricular connection as will be described below. This study was approved by the Research Ethics Committee of the institution, case number 473/07 on 25/09/2007.

INTRODUCTION Congenital heart defects are present in about 8 cases per 1000 newborns at term. This index increases if premature and stillbirths were considered. Criss-cross heart anomaly is extremely rare, accounting for less than 0.1% of all congenital heart defects, not exceeding 8 per 1,000,000 births [1]. The morphological essence of the criss-cross heart is a rotation of the ventricular mass along its major axis [1]. This conformational change may be associated with any malformation described in cardiac segments, resulting in different relationships and connections between the atria, ventricles and great vessels (Figure 1)[2]. Although translated by Health Sciences Descriptors (MeSH) as “criss-cross heart”, there is no fully accepted and standardized translation to Portuguese for this word from the English language, which is why we use it in its original form throughout this study[3]. In French, some authors refer to this anomaly as “coeur croisé” or as “coeur avec ventricules entrecroisés” [4]. Due to the complex structural changes and the rarity of the disease, this anomaly of rotation is often misdiagnosed due to lack of awareness of the medical team, bringing potential harm to appropriate surgical approach [5]. Depending on the associated anomalies, surgical treatment includes from palliative correction to definitive anatomic correction. In this study, we performed a literature review, based on the report of two cases of criss-cross heart where the pulmonary and systemic circulations intersect at the atrioventricular level. Both present situs solitus or usual arrangement of the organs. In one of them the right atrium was morphologically connected to the right ventricle with 94

Fig. 1 - A: Schematic view of the right ventricular chambers with criss-cross, with double outlet right ventricle (VD). The VD is located anterosuperior and to the left to the left. B: Right atrium (AD) connected to the VD through the tricuspid valve. C: Left atrium (AE) connection with the Left ventricle (VE). In D it is represented the VD inlet, crossing anteriorly the VE inlet. Ao = aorta, AP = pulmonary artery. Reproduced with permission of Cavellucci et al. Braz J Echocardiogr Cardiovasc Imag. 2012;25(4):292-7

CASE REPORT Case 1 Clinical data A 12-day-old male newborn presented with progressive dyspnea and acrocyanosis from the first day of life. On examination, he presented severe dyspnea with retraction of sternal notch, subcostal and intercostal indrawing and

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nasal flaring, diaphoresis, cyanosis ++/4+, afebrile, with a heart rate of 140 beats per minute, respiratory rate of 120 breaths per minute. Cardiac auscultation showed systolic murmur ++/6+ at the left sternal edge and accentuated P2 heart sound. His abdomen presented palpable liver two inches below the right costal margin. Peripheral pulses were present and symmetric and the saturation was 85.5% in oxihood (oxygen hood or helmet). Clinical evaluation started from birth at neonatal Intensive Care Unit (ICU).

in the new aorta, associated with correction of septal defects. In the immediate postoperative period, the patient developed systemic inflammatory response syndrome, reversed by standard therapy. During postoperative period he also presented the following complications: respiratory infection associated with prolonged mechanical ventilation and atelectasis of the left upper lobe. He was discharged on the thirty-sixth day postoperatively using furosemide and amiodarone. Discharge echocardiogram showed the criss-cross heart and post-Jatene's correction condition. There was no evidence of dysfunction of the neopulmonary or the neoaorta. It was also observed a foramen ovale with leftright shunt, small perimembranous VSD and preserved contractile function in both ventricles. After six months of correction, another evaluation showed that the patient presented pulmonary branches supravalvular stenosis, confirmed by cardiac catheterization. At the age of one year and ten months, the patient underwent atrioventriculosseptoplastia and expansion of the right ventricular outflow tract using valved tube. Clinical follow-up was performed every six months and the patient remained asymptomatic, without drugs. New hemodynamic study performed at five years of age, indicated supravalvular stenosis in neopulmonary artery with RV- pulmonary artery (PA) gradient of 38 mmHg.

Tests The transthoracic echocardiography showed situs solitus. There were concordant atrioventricular connections and most of the morphologically left ventricle mass stood on the right. There was transposition of great arteries with a left-sided and anterior aorta originating from the morphologically right ventricle. The posterior pulmonary trunk was located at right and posteriorly to the aortic root. There was a significant gradient in the right ventricular outflow tract (RVOT), and at the left ventricular outflow tract (LVOT) we observed the presence of mild posterior deviation of the infundibular portion of the interventricular septum without evidence of LVOT obstruction (subpulmonary). There was no significant atrioventricular valve regurgitation. Presence of muscular ventricular septal defect (VSD) of 3.6 mm with right ventricle (RV) flow to left ventricle (LV) (aortopulmonary), and large atrial septal defect (ASD) of ostium secundum type, measuring about 7mm with flow from left to right (L-R) and arterial channel of 4.5 mm with L-R continuous flow. Biventricular systolic function was qualitatively normal. Diagnosis This is a case of criss-cross heart with concordant atrioventricular connections, ventriculo-arterial discordance, large ASD, VSD and patent ductus arteriosus (PDA) with continuous flow predominantly L-R. Approach The presence of associated malformations and the patient's clinical outcome characterize the severity of the condition. Jatene's surgical technique was indicated due to the patientâ&#x20AC;&#x2122;s age at the time of diagnosis. Surgical procedure The proposed surgery was performed in March 2007. We performed the switch operation, sectioning just above the arterial valves, and thecoronary arteries were reimplanted

Case 2 Clinical data A seven year-and-11-month-old female child, 19kg, with a history of progressive exertional dyspnea and cyanosis of the extremities since the age of three. On physical examination, the patient was afebrile and mildly cyanotic, with systolic murmur ++/6+ in the lower left sternal border and presence of digital clubbing. Tests A transthoracic echocardiogram showed discordant atrioventricular connections, double outlet right ventricle (DORV), large VSD, criss-cross heart, and pulmonary valve stenosis (PVS) with a peak gradient of 96 mmHg. Hemodynamic study was performed which showed double outlet right ventricle with mild infundibular stenosis, discordant atrioventricular connections, perimembranous VSD, and well developed pulmonary branches and right ventricle decreased in size. Oximetry showed blood oxygen saturation in LV of 87%, aorta (Ao) 91% and right ventricle of 100%, 10mmHg RA pressure, LV 107x15mmHg and AO 107x65x81mmHg. 95

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Diagnosis Criss-cross heart with discordant atrioventricular connections, DORV, large VSD and VPS. The presence of associated malformations characterized the severity of the cardiac defect. A Fontan procedure was indicated, obeying the following criteria: age above 2 years, absence of pulmonary stenosis, mean pulmonary artery pressure less than 15 mmHg, pulmonary vascular resistance below 4 Wood units, preserved left atrioventricular valve and ventricular function. The biventricular repair was contraindicated due to the small size of the right ventricle.

Clinical follow-up was performed every six months for 11 years. At the last visit, the patient was asymptomatic, with normal psychomotor development, without changes in physical examination and under no drug therapy. The last echocardiogram showed mild mitral regurgitation, hypertrophy and mild RV dilatation, cavo-pulmonary connections with diameters and normal flows, with an EF of 69%. â&#x20AC;&#x192; DISCUSSION

Surgical procedure The surgical procedure was performed starting the right atriotomy approximately 1 cm above the insertion of the superior vena cava extending to the inferior cava. Thus, it was possible to make the tunnel, suturing the patch to the interatrial septum leaving the coronary sinus to the left and performing tunnel fenestration. After the completion of the tunnel, suture of the anterior patch over this was performed (Figure 2). Postoperatively, the patient presented as complications: heart failure (HF) and right pleural effusion, resolved using increased diuretic use. Later, she remained unchanged, with no other complications. He was discharged by making use of digoxin, furosemide, captopril and spironolactone. A transthoracic echocardiogram 3 months after surgery showed left ventricle with good contractility and venous connections (cavopulmonary) with fair functioning, ejection fraction (EF) of 71%, LV diastolic diameter of 21mm and 13mm systolic.

Fig. 2 - A: Suture of an anterior atrial patch on the IC-SC tunnel. (Adapted from Pinto Jr et al. [78]. B: Making of the inferior tunnel cava â&#x20AC;&#x201C; superior cava

Description and anatomy The criss-cross heart is an extremely rare malformation but well described morphologically. In descriptive report of a collection of 81 hearts with congenital malformations collected over two decades and published in 1999, only one specimen with criss-cross was found, representing only 1.2% of cases [6]. This congenital defect was first described by Lev & Rowlatt [7] in 1961, but it was only in 1974 that Anderson et al. [4] first used the term criss-cross heart. From this publication, about 300 cases of the anomaly have been reported in articles cited in Pubmed to date (2012) [8-43]. The diagnosis of criss-cross heart is based on the intersection of the axes of the ventricular entries. In a normal heart these axes are virtually parallel. This condition is characterized by a spatial change of the ventricular mass that guides or appears to guide, each ventricle in a contralateral position in relation to the corresponding atrium. While the base of the heart remains unchanged in its spatial position, the ventricles appear to have been twisted along their longitudinal axis. This promotes a change in hemodynamics characterized by crossing flows through the atrioventricular valves, resulting in the false impression that each atrium is being directed to the contralateral ventricle [1]. (Figure 1) The criss-cross heart may present with concordant or discordant atrioventricular connections (Figure 3). These connections were demonstrated in 1961 by Lev & Rowlatt [7] through the study of the anatomy of two hearts presenting atria in solitus position communicating with morphologically discordant ventricles in normal position.- a morphologically right atrium draining to the morphologically left ventricle situated to the left. Another case of criss-cross heart was described by Van Praagh in 1962 [43], in which the morphologically right atrium connected to the morphologically right ventricle on the left side, in a case example with concordant atrioventricular connections.

Oliveira IM, et al. - Criss-cross heart: Report of two cases, anatomic and surgical description and literature review

Fig. 3 - Examples of the types of atrioventricular connections in criss-cross hearts: discordant (A) and concordant (B)

There are cases of criss-cross heart described in the literature with discordant atrioventricular connections associated with transposition of the great vessels which results in a corrected physiological circulation, since the presence of â&#x20AC;&#x153;double mismatchâ&#x20AC;? results in the direction of venous blood to the lungs and arterial blood into the systemic circulation. Patients with this type of anomaly, which represents 0.05% of congenital heart diseases [44] may be symptomatic not because of the criss-cross heart, but by the presence of other associated anomalies such as VSD, pulmonary outflow obstruction, tricuspid valve abnormalities [45]. Often the criss-cross heart is associated with other cardiac malformations. A review of the literature revealed no cases of of this anomaly occurring in isolation. Most patients have ventricular septal defects, transposition of the great arteries, double-outlet right ventricle, hypoplastic right ventricle, pulmonary stenosis and tricuspid hypoplasia, the latter present in most patients. Other associated defects, although less frequent, are straddling mitral or tricuspid valve, subaortic stenosis, aortic arch obstruction and mitral stenosis [1,45-47]. Anomalies of the coronary circulation may be present and usually related to the ventricular position, and in these cases, magnetic resonance image (MRI) and angiography are useful tools in the diagnosis and approach [47]. In literature there are some studies linking the Cx43 gene mutation to pathogenesis of the criss-cross heart. Deletion of gene would result in a delay in establishing heart dextroposition, which makes the right ventricle to maintain a craniomedial position, resulting in a 90Â° rotation of the atrioventricular mass [48]. The Cx43 gene is responsible for the production of a type of the protein connexin. These proteins are

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known to compose gap junctions, and the decrease in their expression has been associated with various genetic alterations, with increased cell proliferation and carcinogenesis [49]. Reaume et al. [50] in 1995 reported that animals with deletions in both alleles of Cx43 died shortly after birth, with no major phenotypic differences compared to controls, except for cyanotic appearance. Necropsy revealed cardiac defects, thereby revealing vital importance of this protein in cardiac development during embrionary development. Ya et al. [48] in 1998 reported that, on the 9th day of development, animals with deletion of Cx43 showed delayed development of the ascending looping of the heart tube, causing malformation of the tricuspid valve patch and changes in conformation and cardiac death of animals shortly after birth with cyanotic appearance. Clinical, supplementary and differential diagnosis Due to the complex structural changes, this anomaly is often not recognized. The diagnosis becomes more difficult due to the similarity of the clinical presentation of the different connections abnormalities [51,52]. The anatomic and physiologic diagnosis of this anomaly can be established by echocardiography, along with other diagnostic methods, such as MRI and cardiac catheterization if necessary [53]. The transthoracic echocardiography can be used to identify the position and morphology of all cardiac chambers, AV valves, in addition to the connections between chambers and vessels. The subcostal window will determine the location of the heart apex and assess mainly the ventricles characteristics. The trabeculae morphological features, will determine the morphologic ventricle characteristics [51]. The great arteries connections are better visualized in the paraesternal window [54,55]. MRI, when showing the heart in the axial, coronal and sagital planes makes such additional examination an important tool for diagnosis of complex congenital heart diseases [56]. MRI, when compared to other imaging tests, has the advantage of providing a wide field of vision and the ability to reconstruct the image in 3 dimensions [57]. The images acquired with the MRI show in detail all the heart components and simultaneously clarifies the changes in the AV connections by being able to diagnose abnormalities of heart rotation [58]. The indications for cardiac catheterization are currently limited, since the images obtained with echocardiography and magnetic resonance imaging better delimit the anatomy, 97

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ventricular function and atrioventricular relationships [51]. Cardiac catheterization may be necessary only to obtain pressure and oximetry data and discard additional septal ventricular defects [53]. Some indications for the invasive study were assessment of pulmonary vascular resistance, angiographic analysis of coronary arteries, presence of pulmonary valve atresia or pulmonary anomalous veins [53]. The differential diagnosis of criss-cross heart should include straddling atrioventricular valve, double atrial outlet where an outlet orifice apparently crosses the other valve, and severe forms of Ebstein anomaly on which the tricuspid valve opens to the infundibulum, giving the appearance of crossing the valves [54].

defect, the presence of flow through the ductus arteriosus and the LV outflow tract obstructions can be assessed, in addition to the determination of the ventricles mass [63]. For cases of dTGA and IAC, according to most authors, the primary anatomic correction should be performed until the 15th day of life, and this period may be extended with relative safety until the end of the 1st month [64]. The approach after the neonatal period is controversial and published experiences generally have a small number of patients. Lacourt-Gayet et al. [65] and Lyer et al. [66] advocate for clinical and echocardiographic selection correction in 1 or 2 stages in these cases. Davis et al. [67] and Ducan et al. [68] indicate primary anatomic correction in all patients until the 2nd month of life, based on an aggressive vasodilator therapy and occasional use of ventricular assistance postoperatively. Yacoub et al. [69] in 1980 reported 20 cases who had undergone late staging, with an immediate mortality of three patients, and 14 of them directed to the 2nd stage, when there were four deaths (29%). The main advantage of the ventricular preparation would be related to better LV conditioning, which could provide better long term outcomes. Moreover, the long interval between stages can be a source of problems related to the presence of pulmonary artery banding, such as distortions of the trunk and branches of the pulmonary artery and an increased incidence of late aortic insufficiency and fibroelastosis [63]. The difficulty of proper control after discharge of some patients also contributes to early correction with rapid preparation. Most children who underwent Jatene's operation have normal physical, psychomotor and cardiovascular development. However, some problems can be found in late development. Among these, pulmonary or RVOT stenoses are the most common and can be directly related to surgical technique and patient's age at the time of correction. The incidence of RVOT obstruction varies from 7%-40% [70], and is the main cause of reoperation after discharge [70,71]. The obstructive process may occur in the infundibular or annular region (proximal obstructions) or supravalvular region (distal obstructions). In the first case described here, the patient developed supra-valvular stenosis in neopulmonary and in pulmonary branches after six months postoperatively, being treated with implantation of a valved tube. In the second case, due to right ventricular hypoplasia the choice was for the Fontan procedure which, over the past 40 years, goes through technical enhancements to the optimization of hemodynamic status. Studies show lack of atrial contractility, over time, since it tends to dilation,

Surgical treatment The natural history of patients is unfavorable without surgical treatment, 64% of deaths occurring in childhood, with 50% still in the neonatal period [58,59]. The surgical management of patients with criss-cross heart consists of the repair of major and limiting malformation, not being ventricular rotation itself the reason for the correction. The initial management is determined by the presence or absence of pulmonary stenosis, and its severity. On those where the pulmonary flow is inadequate, early intervention with prostaglandin E1 is indicated for maintaining the patency of the ductus arteriosus. When anatomic correction fails, balance in pulmonary flow can be achieved with the construction of systemic-pulmonary shunt. The corrective surgery is determined by the potential use of both ventricles. Only some patients are candidates for biventricular repair, due to hypoplasia of the tricuspid valve and right ventricle, atrioventricular valve straddling [60-62]. In these cases the Fontan correction is indicated as a palliative repair option. The case studies reflect the size of the treatment of structural abnormalities associated with the criss-cross heart. In the first, the association with transposition of the great arteries, VSD, ASD and PDA, was defined as a surgical option the Jatene's operation. The surgery is usually performed in the neonatal period and may be performed in patients with VSD and maintains left ventricular mass characteristics compatible to support the systemic resistance. Several factors may contribute to the loss of left ventricular mass, and the reduction of pulmonary arteriolar resistance, the most important. Echocardiographic selection is the primary method for defining the surgical treatment. With this assessment, the size of the atrial septal 98

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turning the flow turbulent with consequent arrhythmia and thrombosis [72]. The use of prosthetic material as part of the tunnel excludes pulsatile mobility of the conduit. Several authors [73,74] have shown that TCP anastomosis, because it excludes the right atrium and makes the inferior cava flow occurs through a tunnel, avoids turbulence, thus reducing the risk of thrombosis and arrhythmias. The use of bovine pericardium for the atrial level tunneling is worrisome because retractions with minimal obstructions can cause significant hemodynamic effects. Rossi et al. [75] in 1986 and Arbustini et al. [76] in 1983 showed calcification in this type of graft, with a clear relation with time. In 1997, Pires et al. [77] demonstrated that bovine pericardial tissue implanted in the atrium calcifies, retracts and promotes thrombus formation. The variation proposed by Van De Wal et al, without the use of prosthetic material, using the retail from the own right atrial wall by confection of the tunnel [72], aimed to improve the outcome in the short term, because it keeps the tunnel contraction, allowing improved systemic venous drainage. On the other hand, in the long-term, as a prosthetic material was not used, a proper growth of this conduit was obtained, without calcification, resulting in lower risk of retraction, embolization and anti-coagulation problems [59]. CONCLUSION

caso e revisão de literatura. Rev Bras Ecocardiogr Imagem Cardiovasc. 2012;25(4):292-7.

The study of these two cases and the extensive literature review on the subject show that the rotation anomalies of the ventricular mass are associated with changes in general connections between the cameras and large arteries and that the surgical approach depends on the morphology of the main defect. The presence of crossed ventricles in the reported cases had no impact alone on the surgical intervention.

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58. Fantini FA, Gontijo B, Martins C, et al. Operação de Fontan: uma técnica em evolução. Rev Bras Cir Cardiovasc 2009;24(4):463-9. 59. Carotti A, Iorio FS, Amodeo A, Giamberti A, Marianeschi S, Nava S, et al. Total cavopul-monary direct anastomosis: a logical approach in selected patients. Ann Thorac Surg. 1993;56(4):963-4. 60 Sato K, Ohara S, Tsukaguchi Yyasui K, Nakata T, Tamai M, et al. A criss-cross heart with concordant atrioventriculo-arterial connection. Report of case. Circulation. 1978;57(2):396-400. 61. Danielson GK, Tabry IF, Ritter DG, Fulton RE. Surgical repair of criss-cross heart with straddling atrioventricular valve. J Thorac Cardiovasc Surg. 1979;77(6):847-51. 62. Kashiwagi J, Imai Y, Aoki M, Shin’oka T, Hagino I, Nakazawa M. An arterial switch oper-ation for a concordant crisscross heart with the complete transposition of the great arteries. J Thorac Cardiovasc Surg. 2002;124(1):176-8. 63. Gontijo Filho B, Fantini FA, Martins C, Lopes RM, Pereira RST, Rabelo SM, et al. Estra-tégia cirúrgica na transposição das grandes artérias com septo interventricular intacto após pe-ríodo neonatal. Arq Bras Cardiol. 2005;85(1):39-44. 64. Plaché C, Bruniaux J, Lacour-Gayet F, Kachaner J, Binet JP, Sidi D, et al. Switch operation for transposition of the great arteries in neonates. A study of 120 patients. J Thorac Cardiovasc Surg. 1988;96(3):354-63. 65. Lacourt-Gayet F, Piot D, Zoghbi, Serraf A, Gruber P, Macé L, et al. Surgical management and indication of left ventricular retraining in arterial switch for transposition of the great arteries with intact ventricular septum. Eur J Cardiothoracic Surg. 2001;20(4):824-9. 66. Iyer KS, Sharma R, Kumar K, Bhan A, Kothari SS, Saxena A, et al. Serial echocardiog-raphy for decision making in rapid two-stage arterial switch operation. Ann Thorac Surg. 1995;60(3):658-64. 67. Davis AM, Wilkinson JL, Karl TR, Mee RB. Transposition of the great arteries with intact ventricular septum. Arterial switch repair in patients 21 days of age or older. J Thoracic Cardi-ovasc Surg. 1993;106(1):111-5. 68. Ducan BW, Poirier NC, Mee RB, Drummond-Webb JJ, Qureshi A, Mesia CI, et al. Selec-tive timing for the arterial switch operation. Ann Thorac Surg. 2004;77(5):1691-6. 69. Yacoub MH, Radley-Smith R, Maclaurin R. Two-stage operation for anatomical correction of transposition of the great arteries with intact interventricular septum. Lancet. 1977;1(8025):1275-8.

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Religion, spirituality and cardiovascular disease: research, clinical implications, and opportunities in Brazil Religião, espiritualidade e doença cardiovascular: pesquisa, implicações clínicas e oportunidades no Brasil

Fernando A. Lucchese1, Harold G. Koenig2

DOI: 10.5935/1678-9741.20130015

RBCCV 44205-1448

Abstract In this paper we comprehensively review published quantitative research on the relationship between religion, spirituality (R/S), and cardiovascular (CV) disease, discuss mechanisms that help explain the associations reported, examine the clinical implications of those findings, and explore future research needed in Brazil on this topic. First, we define the terms religion, spirituality, and secular humanism. Next, we review research examining the relationships between R/S and CV risk factors (smoking, alcohol/drug use, physical inactivity, poor diet, cholesterol, obesity, diabetes, blood pressure, and psychosocial stress). We then review research on R/S, cardiovascular functions (CV reactivity, heart rate variability, etc.), and inflammatory markers (IL-6, IFN-γ, CRP, fibrinogen, IL-4, IL-10). Next we examine research on R/S and coronary artery disease, hypertension, stroke, dementia, cardiac surgery outcomes, and mortality (CV mortality in particular). We then discuss mechanisms that help explain these relationships (focusing on psychological,

social, and behavioral pathways) and present a theoretical causal model based on a Western religious perspective. Next we discuss the clinical applications of the research, and make practical suggestions on how cardiologists and cardiac surgeons can sensitively and sensibly address spiritual issues in clinical practice. Finally, we explore opportunities for future research. No research on R/S and cardiovascular disease has yet been published from Brazil, despite the tremendous interest and involvement of the population in R/S, making this an area of almost unlimited possibilities for researchers in Brazil.

1. M.D., F.A.C.C. Director, Hospital São Francisco (Cardiology and Transplants), Professor and Chairman, Cardiovascular Medicine and Surgery; Faculdade Federal de Ciências Medicas, Porto Alegre, RS, Brazil. 2. M.D. Professor of Psychiatry & Behavioral Sciences; Associate Professor of Medicine, Director, Center for Spirituality, Theology and Health Duke University Medical Center, Durham, North Carolina, USA; Distinguished Adjunct Professor - King Abdulaziz University, Jeddah, Saudi Arabia.

Correspondence address: Harold G. Koenig Box 3400 – Duke University Medical Center – Durham, North Carolina, USA – 27710 E-mail: harold.koenig@duke.edu (also, see website: http://www. spiritualityandhealth.duke.edu)

Descriptors: Religion. Spirituality. Cardiovascular diseases. Cardiac surgical procedures. Research. Mortality. Descritores: Religião. Espiritualidade. Doenças cardiovasculares. Procedimentos cirúrgicos cardíacos. Pesquisa. Mortalidade.

Article received on December 5th, 2012 Article accepted on February 12th, 2013

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Abbreviations, acronyms & symbols ABI BAR BP CABG CAC CAD CC-IMT CD CHF CRP CVD HRV LOS LVM MI MM PTSD R/S SES TIA

Ankle brachial index Arterial baroreflex sensitivity Blood pressure Coronary artery bypass graft Coronary artery calcium Coronary artery disease Common carotid intima-media thickness Cerebrovascular disease Congestive heart failure C-reactive protein Cardiovascular disease Heart rate variability Length of stay Left ventricular mass Myocardial infarction Mindfulness meditation Post-traumatic stress disorder Religion and spirituality Socioeconomic status Transient ischemic attack

INTRODUCTION A growing research database documents a link between religion, spirituality and cardiovascular disease (CVD). Given that Brazil is a highly religious country (87% of the population says that religion is important [1]), cardiologists and cardiac surgeons need to know about this research and the clinical applications that might follow. In this paper, we explore (1) definitions of the terms religion and spirituality (R/S) for conducting research and carrying out applications at the bedside; (2) relationships between R/S and CVD risk factors; (3) R/S, cardiovascular functions, and inflammatory markers (cardiovascular reactivity, C-reactive protein, fibrinogen, etc.); (4) R/S and coronary artery disease; (5) R/S and hypertension; (6) R/S and cerebrovascular disease; (7) R/S and cardiac surgery outcomes; (8) R/S and cardiovascular mortality; (9) mechanisms by which R/S might influence cardiovascular outcomes; (10) some clinical implications of this research; and (11) future research in this area that Brazilian researchers are ideally positioned to take the lead on. 1. DEFINITIONS The area of definitions is one of the most controversial areas in R/S and health research. Terms that need defining are religion, spirituality, secular humanism, and religious coping. Many researchers and clinicians have erred by combining all of these terms under "spirituality." We 104

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will argue that the choice of which term to use may be quite different when conducting research (understanding relationships between R/S and CVD and how R/S impact CVD outcomes) compared to when discussing these issues at the bedside in clinical settings. We define religion as "…beliefs, practices, and rituals related to the transcendent, where the transcendent is God, Allah, HaShem, or a Higher Power in Western religious traditions, or Brahman, manifestations of Brahman, Buddha, Dao, or ultimate truth/reality in Eastern traditions. This often involves the mystical or supernatural. Religions usually have specific beliefs about life after death and rules about conduct within a social group. Religion is a multi-dimensional construct that includes beliefs, behaviors, rituals, and ceremonies that may be held or practiced in private or public settings, but are in some way derived from established traditions that developed over time within a community. Religion is also an organized system of beliefs, practices, and symbols designed (a) to facilitate closeness to the transcendent, and (b) to foster an understanding of one's relationship and responsibility to others when living together in a community [2]”. In contrast to religion is secular humanism, which we define as follows: "The secular or secular humanist has no belief in, connection with, or desire to connect to the transcendent, the sacred, God, or the supernatural. The secular involves beliefs, behaviors, and social relationships that have value and importance on their own intrinsic merit that is not connected with anything outside of the human experience or nature. The attitude is, 'this is all we have so let’s make the best of it together.' That which is real can be observed and verified, and anything that cannot be observed and verified does not exist and does not matter. The world is viewed in a rational, logical, scientific manner. Human relationships, moral values, and ethical standards are very important, and forgiveness, altruism, and gratefulness are often emphasized and practiced, all without any transcendent reference. Atheists, agnostics, and secular humanists would fall into this category. If there is any seeking or searching, then it is for purely secular objects or goals. Most would not refer to themselves as religious, and probably not as spiritual either [3]”. Finally, there is the term spirituality. This is the term over which there is the most disagreement and lack of consensus. Spirituality is a popular expression today preferred over religion. Spirituality is considered personal, something individuals define for themselves. It is often free of rules, regulations, and responsibilities associated with religion. One can be spiritual, but not religious. In fact, a “secular spirituality” is often emphasized today in circles where religion is in disfavor. Thus, spirituality is seen as non-divisive and common to all, both religious and secular. This is an excellent term to use when discussing these

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issues with patients (who can define for themselves what the term means). However, trying to measure spirituality has created a real problem for quantitative researchers, who must work with terms that are clear, agreed upon, distinct and non-overlapping. The goals of quantitative research are to measure and quantify a construct and then relate that construct to similarly quantified health outcomes. The ultimate aim is to compare those with the construct (or who have more of the construct) to those without the construct (or who have less of the construct), and if there is a relationship, then develop an intervention that takes advantage of that connection to improve health outcomes. This is not possible with a construct like spirituality, especially when defined in such a nebulous, diffuse manner. The definition of spirituality that we use in this paper is similar to religion, since religion is a distinct construct that can be measured and quantified and examined in relationship to health outcomes. We define spirituality, then, by saying that it "…is distinguished from all other things – humanism, values, morals, and mental health – by its connection to that which is sacred, the transcendent. The transcendent is that which is outside of the self, and yet also within the self – and in Western traditions is called God, Allah, HaShem, or a Higher Power, and in Eastern traditions may be called Brahman, manifestations of Brahman, Buddha, Dao, or ultimate truth/reality. Spirituality is intimately connected to the supernatural, the mystical, and to organized religion, although also extends beyond organized religion (and begins before it). Spirituality includes both a search for the transcendent and the discovery of the transcendent, and so involves traveling along the path that leads from non-consideration to questioning to either staunch non-belief or belief, and if belief, then ultimately to devotion and finally, surrender.” [4]. As can been seen, our definition of spirituality is very similar to our definition of religion. In the studies we will cite in this article, spirituality has been assessed either using (1) measures of religious belief and practice, (2) measures of positive psychological states (i.e., meaning and purpose, deep inner peace, harmony, well-being, social connections), or (3) measures of positive character traits (i.e., being forgiving or altruistic, having high moral standards). Unfortunately, assessing spirituality using positive psychological states or positive character traits creates a situation where the predictor (spirituality) is contaminated by the outcome (mental health), which results in tautological relationships between spirituality and mental health outcomes (and probably physical health outcomes as well, given the mind-body relationship). The result of such research is meaningless, un-interpretable findings. Thus, only when spirituality is measured using measures of religious involvement (a construct that is

distinctive and non-overlapping with mental health) does it provide meaningful results. For a thorough discussion of the issue of measurement overlap and contamination, which is beyond the scope of the present article, see the following cited resources [5-8]. In reviewing the research below, then, we use spirituality and religion synonymously (i.e., R/S). Furthermore, we have distinguished studies that assess spirituality using contaminated measures by assigning quality scores to each of the studies. In the original review of this research, we usually assigned quality scores of 7 or higher (on a 1 to 10 scale) only to studies that measured spirituality or religion using religious variables that were distinct from mental health outcomes and thus avoided measurement tautology [9]. Religious coping is another term that deserves definition, given its importance as a mechanism by which R/S could affect CVD risk (see section "Understanding Mechanisms" below). By religious coping we mean, " the use of religious beliefs or practices as a way of adapting to the physical, psychological, and social challenges caused by medical illness. For example, in Western religious traditions, religious coping may involve praying to God for strength and comfort, wisdom and direction, health or healing, or help for loved ones. It may involve reading inspirational materials, such as the Holy Scriptures (Torah, Christian Bible, or Holy Qur’an) or reading popular books or magazines on religious topics. R/S coping may involve getting together with members of one’s faith tradition for worship services, singing hymns, prayer, or scripture study. It also may involve the practice of religious rituals related to health and healing, such as lighting candles or participating in sacraments, such as the Eucharist or Confession, or the practice of immersion in a Mikveh or wearing of Tefillin. R/S coping may involve asking others to pray for oneself, praying for others, seeking religious counseling, providing religious support to others, or participating in religious rituals focused on healing."[10]. In discussing the research, we will rely heavily on our systematic review of the literature conducted in 2010 that searched the major online databases (PsycINFO, MEDLINE, etc.) using the terms “religion,” “religiosity,” “religiousness,” and “spirituality” to identify original quantitative data-based research on R/S and health. The online database search was supplemented by asking researchers in the field of R/S and health for any published reports of research that they had conducted on this topic. Furthermore, studies that were cited in the reference lists of the reports identified in this manner were tracked down and included in the review. In this way, the systematic review identified over 3,200 studies that reported data on the relationship between R/S and health. Nearly two-thirds of this research was published between the year 2000 and mid-2010 (e.g., more research on this topic was published 105

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during that 10-year period than in the previous 128 years). Each of these studies, particularly those summarized below on R/S and CVD, is described in the appendices of the the two editions of the Handbook of Religion and Health [11,12]. For both positive and negative findings summarized below, we provide the original citations for a sample of the studies included in the review. However, given the very large number of studies, we cite only a few of the higher quality ones that examine relationships between R/S and cardiovascular risk factors (section 2). In contrast, we try to cite all studies that examine relationships between R/S and specific CVD functions or outcomes (sections 3-8). We also cite more recent research that either confirms or contradicts earlier reports identified in the systematic review.

relationship [24]. The results from studies examining R/S and drug use parallel those on R/S and alcohol. Among 185 studies on the relationship between R/S and drug use, 84% (155 studies) found inverse relationships. Only two studies of the 185 found significant relationships with greater drug use. Of the 112 better designed studies (rated 7 or higher in quality), 96 (86%) reported this finding [2527], wherease only one study found a positive relationship [28]. Most of these studies were conducted in younger adults, typically high school or college students, a time when alcohol and drug use habits are just beginning to develop and will affect their cardiovascular systems for the remainder of their lives. 2c. Physical inactivity. A sedentary lifestyle is known to increase the risk of CVD, and regular exercise is known to decrease that risk [29,30]. Research shows that those who are more R/S are more likely to be physically active or more likely to exercise. Of 37 studies that have examined the association between R/S and physical activity, 25 (68%) found greater exercise or physical activity among those who were more R/S. Of the 21 methodologically most rigorous studies, over three-quarters (76% or 16 studies) reported positive relationships [32,33] whereas only two (10%) found negative relationships [34,35]. 2d. Poor diet/nutrition. Numerous studies have linked diets high in saturated fat, low in omega-3 fatty acids, and low in fruits, vegetables, nuts, and whole grains to increased CVD morbidity and mortality [36-38]. By healthy we mean a high intake of fiber, green vegetables, fruit, fish, and a low intake of processed foods and fat. Regular vitamin intake, eating breakfast, and overall better nutrition are also part of a healthy diet. Again, many studies show that persons who are more R/S consume a healthier diet. Our systematic review uncovered 21 studies that examined this relationship. Nearly two-thirds (62% or 13 studies) found a positive link between R/S and a healthier diet, and only one study reported a worse diet [39]. Of the 10 highest quality studies, seven (70%) reported an association between greater R/S and a healthier diet [4042]; no high quality study reported a worse diet among those who were more R/S. 2e. High cholesterol. A healthier diet might also be expected to affect the level of cholesterol in the blood. Serum cholesterol is strongly linked with all types of CVD. For example, a 10% decrease in LDL is associated with a 10% reduction in risk of myocardial infarction [43]. In our systematic review, we identified 23 studies that had examined associations between R/S and serum cholesterol. The majority (12 of 23) reported significantly lower cholesterol among those who were more R/S. Similarly, of the nine highest quality studies, five (56%) found either lower cholesterol in those who were more R/S [44,45] or reported that a R/S intervention lowered cholesterol [46-

2. CARDIOVASCULAR RISK FACTORS Standard modifiable risk factors for CVD are cigarette smoking, excess alcohol, physical inactivity, poor diet/ nutrition, high blood cholesterol, obesity, diabetes mellitus, high blood pressure, and psychosocial stress (including depression, anxiety, and personality traits such as hostility) [13]. Each of these risk factors is related in one way or another to R/S. 2a. Cigarette smoking. The risk factor most strongly related to both CVD and R/S is tobacco use, a habit that contributes to 30% of all coronary heart disease deaths each year in the U.S. [14]. The problem is of similar or greater magnitude in Brazil, where 18% of adults smoke and this contributes to 45% of all deaths from coronary heart disease [15]. We uncovered 137 studies that had examined the relationship between R/S and smoking, and of those, 123 (90%) reported inverse relationships. No studies found positive relationships. When examining the 83 methodologically most rigorous studies (ratings of 7 or higher on a 1 to 10 quality scale), 75 of those (again 90%) reported inverse relationships with R/S involvement [16-18]. If those who are more R/S smoke less, then this should influence their risk for developing CVD. 2b. Alcohol and drug use. Heavy alcohol use is known to affect cardiac function (alcoholic cardiomyopathy, arrhythmias), blood pressure, and increase risk of stroke [19]. A similar relationship has been found with chronic use of illicit drugs [20]. At least 278 studies have now examined relationships between alcohol use, abuse, or dependence and R/S. The vast majority of those (86%, i.e., 240 studies) found inverse relationships with R/S involvement. Only four of 278 (1%) studies reported positive relationships. The higher quality studies are even more likely to report this finding. Of the 145 studies that were rated 7 or higher in quality, 90% (i.e., 131 studies) found inverse relationships [21-23]; only one study reported a positive 106

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48]; one study reported higher cholesterol, but only in a subgroup of the sample (Mexican-American men) [49]. 2f. Obesity. Many studies show that those who are overweight have an increased risk of CVD [50]. The one characteristic of R/S persons that increases their risk of CVD is heavier weight. We located 36 studies examining associations between weight and R/S involvement, of which 14 (39%) found that R/S was associated with greater weight or higher body mass index. In contrast, only seven studies (19%) found that R/S was associated with lower weight. The findings from more rigorouly designed studies support this conclusion. Of the 25 best studies, 11 (44%) reported greater weight [51,52] and five (20%) found lower weight (or less underweight) [53,54] among those who were more R/S. 2g. Diabetes. Two-thirds of diabetics die of CVD, and the risk of coronary artery disease alone is up to four times higher in those with diabetes [55]. Despite their heavier weight, those who are more R/S do not have a greater risk of being diabetic. At least 14 studies conducted between 2000 and 2010 examined this relationship. Of those, five (36%) found less diabetes, lower blood sugar, a lower HgbA1C [56,57], or improvement in response to a R/S intervention [58-60], four (29%) reported more diabetes [61] or higher indicators of diabetes [62-64], and the remaining studies reported mixed findings [65] or no association. Thus, overall, the research finds no consistent relationship between R/S and diabetes. Perhaps a better diet, or perhaps better compliance with treatment, makes up for the heavier weight of those who are more R/S (neutralizing the risk of diabetes that heavier weight confers). 2h. Blood pressure. The majority of studies find that R/S involvement is related to lower blood pressure. See section 5 on hypertension. 2i. Psychosocial stress. High emotional stress, loneliness, and social isolation are associated with atrial and ventricular arrhythmias [66], left ventricular dysfunction, myocardial ischemia [67], recurrent myocardial infarction [68], and increased risk of cardiac death [69], as well as other cardiac abnormalities. Likewise, personality traits such as cynical hostility [70], and emotional states such as depression [71] and anxiety [72], are linked to increased risk of CVD and worse prognosis. Lower risk, however, has been found for optimism, [73] agreeableness, 74 and other positive emotions [75]. Our systematic review identified 75 studies that examined relationships between R/S and stress level. Of those, 46 (61%) reported lower levels of psychological stress in those who were more R/S and 12% reported higher levels of stress. We also identified 74 studies examining R/S and social support, of which 61 (82%) found significant positive relationships and none found negative relationships; of the 29 best studies, 27 (93%)

reported significantly greater social support among those who were more R/S [76-78]. We also identified 27 studies examining R/S and hostility, of which 18 (67%) reported inverse relationships [79-81]. Our review uncovered many studies examining connections between R/S, depression, and anxiety. Of 444 studies assessing relationships between R/S and depression, 272 (61%) reported lower depression among the more R/S, including 119 (67%) of the 178 highest quality studies [82-84]. Of 299 studies examining relationships with anxiety, 147 (49%) reported inverse associations with R/S, and of the 67 highest quality studies, 38 (55%) did so [85-87]. With regard to optimism, at least 32 studies examined relationships with R/S, and of those, 26 (81%) reported significant positive associations [88-90], and none found the opposite. Concerning the personality trait â&#x20AC;&#x153;agreeableness,â&#x20AC;? 30 studies have examined associations with R/S, and of those, 26 (87%) found that R/S was related to greater agreeableness [91-93]. Finally, with regard to well-being and happiness, we identified 326 quantitative studies examining associations with R/S, and of those, 256 (79%) found positive relationships; of the 120 highest quality studies, 98 (82%) reported that those who were more R/S experienced higher well-being, happiness, or life satisfaction [94-96] and only one study found lower well-being [97]. Thus, in the vast majority of studies, greater R/S is related to fewer negative emotions that predict an increased risk of CVD disease and to more positive emotions that predict a reduced risk of CVD. Likewise, other than being heavier in terms of weight and neutral in terms of diabetes, those who are more R/S are less likely to smoke cigarettes, use or abuse alcohol/drugs, be physically inactive, consume a poor diet, have high cholesterol, and have high blood pressure, each of which is related to a greater risk of CVD morbidity and mortality. 3. CARDIOVASCULAR FUNCTIONS AND INFLAMMATORY MARKERS Given the relationship between R/S and the CVD risk factors above, we would predict that those who are more R/S might also have better cardiovascular functions when tested in the laboratory (i.e., lower cardiovascular reactivity, brachial artery vasoreactivity, peripheral resistance) and lower levels of inflammatory markers (proinflammatory cytokines, C-reactive protein, fibrinogen). 3a. Cardiovascular reactivity. Regarding cardiovascular reactivity (a known risk factor for CVD[98]), at least eight studies have examined relationships with R/S, and of those, four (50%) found inverse relationships [99101] or a reduction in cardiovascular reactivity with a R/S intervention [102]. One study reported a positive relationship (in a situation of unresolved justice) [103], 107

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two studies reported mixed findings (significant positive or significant negative relationships, depending on R/S characteristic) [104,105], and one study found that transcendental meditation had no effect on brachial artery vasoreactivity [106]. 3b. Heart rate variability and other cardiovascular functions. Reduced heart rate variability (HRV) is a known risk factor for CVD [107]. At least four studies have examined relationship between R/S and HRV or assessed the effects of a R/S intervention on HRV. Three of these studies reported positive findings (one showing a positive relationship between R/S and HRV [108] and two finding that Eastern forms of meditation increased HRV [109,110]), whereas one study found that transcendental meditation had no effect [111]. Two additional studies have assessed other cardiac functions. One study examined the effects of saying the Ave Maria (rosary prayer) in Latin or a Tibetan Buddhist mantra (in the original language) on arterial baroreflex sensitivity (BAR) [112]. A reduction in BAR is known to predict future coronary artery disease and heart failure. Results indicated an increase in BAR with both forms of meditation. The second study examined relationships between R/S, coronary artery calcium, and left ventricular mass, finding no relationship [113]. 3c. Inflammation. High levels of inflammatory markers in the blood are known to increase the risk of CVD [114117]. The relationship between R/S and inflammatory markers is a complex one, since the mechanism by which R/S affects inflammatory markers is indirect acting through psychological, social, and behavioral pathways. Furthermore, psychological states (and certain mental disorders) may influence inflammatory marker levels in opposite directions; for example, depression is associated with high levels of the pro-inflammatory marker IFN-γ [118], whereas PTSD and acute stress have been associated with low levels of IFN-γ [119]. As a result, treatments for these mental disorders may either decrease or increase IFN-γ in order to normalize levels. With these complexities mind, we review studies that have examined relationships between R/S and inflammatory markers or have assessed the effects of a R/S intervention on pro-inflammatory cytokines such as interluekin-6 (IL6) or interferon gamma (IFN-γ), other pro-inflammatory markers such as C-reactive protein (CRP) and fibrinogen, and the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10). 3c.1. Interleukin-6. At least nine studies have examined relationships between R/S and blood levels of IL-6. Of those, five (56%) reported significant inverse relationships [120,121] or a reduction in IL-6 in response to a R/S intervention [122-124]. In contrast, IL-6 levels appear to be increased in cardiac surgery patients undergoing existential stress related to religious struggles [125] or

may be increased in response to a spiritual intervention [126]. 3c.2. Interferon gamma. As noted above, IFN-γ is increased in major depression [127] and decreases in response to treatment [128]. However, IFN-γ is suppressed by cortisol [129], decreases in response to acute psychological stress [130], and may actually increase in response to treatment in those with low INF-γ levels [131,132]. Three studies have examined the effects of R/S interventions on INF-γ levels in blood. All three found that the R/S intervention significantly increased INF-γ levels [133-135]. 3c.3. C-reactive protein. There is strong evidence that pro-inflammatory CRP plays a role in the development of atherosclerosis and coronary heart disease [136]. Eight studies have now examined relationships with R/S. Of those, four (50%) reported significant inverse relationships [137-139] or a reduction in CRP in response to a R/S intervention [140]; the other four studies found no association. More recent research supports an inverse relationship between R/S and CRP [141]. 3c.4. Fibrinogen. Only one study, to our knowledge, has examined relationships between serum fibrinogen (a key factor in the development of CVD [142]) and R/S. That study examined the relationship between frequency of religious attendance (as part of a two-item social index) and fibrinogen levels, finding a significant inverse relationship after controlling for multiple covariates [143]. 3c.5. Anti-inflammatory cytokines. Anti-inflammatory cytokines such as IL-4 and IL-10 have the opposite effect of pro-inflammatory cytokines on the development of atherosclerotic plaque [144]. At least two studies have now examined the relationship between R/S and antiinflammatory cytokines. In our systematic review, we identified one study that examined the effects of Buddhistbased mindfulness meditation (MM) on IL-4 and IL-10 levels in 66 women recently diagnosed with breast cancer [145]. Those receiving MM experienced a significant reduction in IL-4 and IL-10 levels compared to controls (approximating that of women without breast cancer) during the 8-week follow-up. Note, however, that antiinflammatory cytokines may be increased in situations of acute stress [146]. A more recent study examined cytokine levels in 33 very elderly persons with cardiovascular disease (mean age 87) who participated in weekly 30-minute sermons by chaplains over 20 months [147]. Plasma IL-10 and IL-6 levels were compared to 26 age-matched controls (mean age 85) without the intervention. Results indicated that the IL-10/IL-6 ratio was significantly higher in those listening to the sermons compared to controls (3.96 vs. 1.79, P<0.05). In summary, the majority of studies find that cardiovascular reactivity and other cardiovascular

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responses are healthier (lower risk in terms of CVD) in those who are more R/S or receiving R/S interventions. Likewise, except in situations of acute psychological stress, the majority of studies find that R/S or R/S interventions are associated with lower levels of inflammatory markers known to be involved in CVD pathogenesis.

on this measure of religious orthodoxy) experienced a significantly lower mortality rate from CAD over the 23year follow-up compared to the least religious group (those scoring in the bottom one-fifth on the religious measure). There were 38 deaths from CAD in the most religious group during follow-up, compared to 61 deaths in the least religious group. There were 135 deaths from other causes in the most religious group, compared to 168 deaths in the least religious group. Overall, the risk of dying from CAD in the most religious group was 20% lower than in the least religious group. Controlling for age, systolic blood pressure, cholesterol, smoking, diabetes, body mass index, and baseline CAD could not explain these results. Overall, then, our systematic review identified 19 studies that examined associations between R/S and CAD. Of those, 12 (63%) reported a significant inverse relationship. Of the 13 most rigorously designed studies, nine (69%) reported inverse relationships [150-158] and one found a positive relationship [159]. The latter study was an 8-year follow-up of 92,395 women ages 50-79 participating in the U.S. Women’s Health Initiative Observational Study. R/S was measured with three questions: religious affiliation, attendance at religious services, and strength/comfort derived from religion. Only the uncontrolled analysis was reported. Women who indicated a religious affiliation at baseline (93% of the sample) were more likely than those with no religious affiliation to experience a coronary event during follow-up (2.7% vs. 1.9%, P<0.0001). Those attending religious services weekly or more (44% of the sample) were also more likely than those attending less than weekly to experience a coronary event (2.7%, vs. 2.5%, P=0.03). Finally, those who received “a great deal” of of strength/comfort from religion were more likely than those receiving no strength/comfort from religion to have a coronary event during follow-up (2.8% vs. 2.0%, P<0.0001). Note that these findings, unlike other studies, did not control for race or age. Older women and women from minority groups (African-American or Hispanic) tend to be much more religious (and at greater risk for CVD) than young or white women. Therefore, controlling for these factors may have explained the association.

4. CORONARY ARTERY DISEASE We have been focusing on R/S and risk factors for CVD. We now shift to examine research that has directly measured relationships between R/S and specific cardiovascular disorders, beginning first with coronary artery disease (CAD). One of the first studies demonstrating an association between R/S and CAD was published in 1986. Friedlander et al. compared the religious orthodoxy of 539 patients in Israel experiencing their first myocardial infarction (MI) with a matched control group of 686 patients without heart disease [148]. Among those with MI, 51% of men and 50% of women described themselves as secular (vs. religious) compared with 21% of men and 16% of women controls. Controlling for age, ethnicity, education, smoking, physical exercise, and body mass index, researchers found that secular men were over four times more likely to have MI compared to religious men (OR=4.2, 95% CI 2.6-6.6) and secular women were over seven times more likely than religious women (OR=7.3, 95% CI 2.3-23.0). Even before that report, Comstock et al. had published a study in 1971 that found significantly fewer deaths from atherosclerotic cardiovascular disease in those attending religious services weekly or more compared to those attending less than weekly [149]. During this 3-year follow-up of 378 white males ages 45-64 in Washington county, Maryland (USA), there were 189 deaths due to artherosclerotic or degenerative heart disease. Those who died were matched by age, race, and sex with men who did not die from heart disease. The risk of dying from atherosclerotic heart disease was over twice as great in men attending church less than once per week, compared to those attending services once weekly or more (RR 2.02, P<0.01). Even after controlling for smoking, SES, hard water, and other risk factors, the increased risk for less frequent attendees remained significantly higher. In a 23-year follow-up of 10,000 middle-aged men employed in civic or municipal occupations in Israel (the Israel Ischemic Study), investigators examined the relationship between religious orthodoxy and death rate from myocardial infarction. Religious orthodoxy was measured using a three-item scale: having a religious vs. secular education, self-identified as orthodox, traditional, or secular, and frequency of synagogue attendance. The most religious group (those scoring in the top one-fifth

5. HYPERTENSION Given the relationship between blood pressure (BP) and psychological stress [160] and the influence that R/S has in helping people to cope with stress, we expect R/S and BP to be related. The systematic review identified 63 studies that measured degree of religious involvement and BP or diagnosis of hypertension. Of those, 36 (57%) reported lower BP or less hypertension in those who were more R/S, whereas seven (11%) reported higher BP. When 109

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examining the higher quality studies (those rated 7 or higher on a 1-10 scale), 24 (62%) reported lower BP or less hypertension among those who were more R/S [161-173] or in response to a R/S intervention [174-184] (including two reports from a single study, one reporting results for the overall sample and one for the sample stratified by race). In contrast, seven studies reported higher blood pressure among the more religious, including two lower quality studies [185,186] and five high-quality studies (13%) [187-191]. Why would R/S would be associated with higher blood pressure? Perhaps in some populations, greater religious involvement might be associated with higher stress, anxiety or guilt, which in turn might increase BP. There is another explanation, however. Note that three of the five studies linking R/S to higher BP included a large proportion of African-Americans (36% to 100% of the sample). Research shows that nearly 40% of AfricanAmericans have high blood pressure [192]. Research also shows that African-Americans are very religious (much more religious than white Americans). Efforts to statistically control for such a powerful confound, then, may not always be successful. Thus, the majority of studies find that R/S is related to lower BP and less hypertension. A smaller number of studies including high quality ones, however, find that R/S is related to higher BP, which needs to be better understood.

measured R/S. Four of those (44%) reported a lower risk of stroke among the more religious, and all of these were high quality studies [193-196]. Of the remaining five studies, four found no association and one reported greater carotid artery thickening in those who were more R/S, placing them at higher risk for stroke [197]. In that cross-sectional study (n=5,474), researchers found that those who attended religious services were 12% to 64% more likely (depending on frequency of attendance) than those who never attended to be above the 90th percentile in common carotid intima-media thickness (CC-IMT). Results were controlled for hypertension, diabetes, smoking, hypercholesterolemia, obesity, age, gender, race, education, and income. Frequency of attendance was also positively associated with obesity. Again, note that 30% of the sample were African-American, who also frequently attended religious servies (50% of those who attended religious services daily were African-American). Although race was controlled for, the latter may have influenced the results. Interestingly, no association was found between religious attendance and coronary artery calcium (CAC), left ventricular mass (LVM), or ankle brachial index (ABI). Furthermore, religious attendance was the only R/S characterisic associated with greater CCIMT; neither frequency of prayer/meditation nor frequency of daily spiritual experiences were related to CC-IMT, CAC, LVM, or ABI. Likewise, when participants were followed for three years, none of the religious variables predicted incident CVD events (myocardial infarction, unstable angina, CAD death, stroke, TIA, CHF, or other CVD death). With regard to dementia, which is often the result of multiple strokes, a number of studies have examined associations with R/S. The systematic review uncovered 21 studies examining R/S and dementia or level of cognitive functioning. Nearly half (48% or 10 studies) reported less dementia or better cognitive functioning in those who were more R/S. Of the 14 studies with the most rigorous designs, eight (57%) reported positive relationships with better cognitive function [198-205]. Three studies, however, reported worse cognitive funcitoning in those who were more R/S [206-208]. The latter may be due to the fact that R/S persons tend to live longer than less religious individuals, increasing the likelihood that they will live to an older age when cognitive problems tend to develop. Recent research supports a positive relationship between R/S and better cognitive function in those with dementia [209] and in those of advanced age [210].

6. CEREBROVASCULAR DISEASE Much less attention has been paid to the relationship between R/S and cerebrovascular disease (CD). We know that CAD and hypertension are related to CD, and so there may also be a relationship between R/S and CD. This is particularly likely given that R/S is related to many of the other risk factors for CD (high serum cholesterol, poor diet, physical inactivity, cigarette smoking, heavy alcohol or drug use, and psychological factors such as stress, anxiety and depression). Of course, heavier weight and perhaps emotional excitement during religious services might also increase the risk of CD. Alternatively, an inverse relationship between R/S and CD (particularly in cross-sectional studies) may simply indicate that those disabled with CD are simply less able to engage in R/S activities, particularly when this involves attending religious services. Finally, those who are disabled by CD may also turn to R/S for comfort in order to cope with their disability, increasing the likelihood of a positive correlation between R/S and CD. Thus, numerous factors need to be considered when studying his relationship. Our systematic review identified a number of studies that had examined relationships between R/S and two cerebrovascular disorders: stroke and dementia. With regard to stroke, there are at least nine studies that 110

7. CARDIAC SURGERY OUTCOMES Psychological stress is known to influence the speed of wound healing. Research shows that it can delay healing

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by up to 60% in older animals and humans [211]. Adverse effects of stress on wound closure can also be demonstrated in young [212] and middle-aged adults [213], as well as in persons undergoing surgical operations [214]. Some investigators have explained this phenomenon as being due to changes in pro-inflammatory cytokines IL-1B, IL-6, and TNF-alpha at the wound site, perhaps the result of higher levels of cortisol stimulated by the stress response [215]. If R/S helps to reduce psychological stress and improve coping, it might also influence the speed of wound healing and successful recovery from cardiac surgery. Unfortunately, very little research has examined the relationship between R/S and either speed of wound healing or recovery from surgery. However, several studies have examined relationships between R/S and infection, a factor that strongly influences the speed of wound healing. Our systematic review identified 12 studies that examined relationships between R/S and susceptibility to infection or concentration of infectious agents in blood (viral load). Of those, eight (67%) reported lower infection rates or lower viral load in those who were more R/S, and no study found greater infection or higher viral load. Of the 10 best studies, seven (70%) found significant inverse associations between R/S and infection or viral load [216-222]. There is also a wealth of research linking R/S involvement or interventions to better immune function (14 of 27 studies) [223] and endocrine function (lower cortisol levels in 19 of 29 studies) [224], both of which are known to influence both infection risk and speed of wound healing. Thus, given the impact that psychological stress may have on wound healing by increasing susceptibility to infection and adversely affecting immune/endocrine functions â&#x20AC;&#x201C; and the relationships between R/S and lower psychological stress, lower susceptibility to infection, and better immune and endocrine functions â&#x20AC;&#x201C; there is every reason to predict that R/S involvement might influence the speed of wound healing and surgical outcomes. As noted above, there is little research examining the direct impact of R/S on outcomes from cardiac surgery. However, we located five studies that have examined this relationship (four observational studies and one clinical trial), which we now describe. In the first study, published in 1995, researchers at Dartmouth Medical Center in Lebanon, New Hampshire (USA), examined the effects of religious attendance, importance of religion, and comfort/support from religion on 6-month mortality rates in 232 patients following coronary artery bypass graft (CABG) surgery [225]. Most of participants were either Protestant (63%) or Catholic (25%), and all were age 55 or older. Among those attending religious services at least once every few months, only 5% died; among those who never or rarely attended, 12%

died (P=0.06). Among those who described themselves as deeply religious (n=37), mortality was 0% compared to 11% in other patients (P=0.04). Finally, mortality in those who indicated they obtained strength/comfort from religion was 6%, compared to 16% in those who did not receive strength/comfort from religion (P=0.01). When logistic regression was used to control for other covariates, such as history of previous cardiac surgery, impairments of physical functioning, age, and frequency of group social activity, patients who said they did not receive strength/ comfort from religion were three times more likely to die than those who said they received strength/comfort from religion (OR=3.25, 95% CI 1.09-9.72). There was also an interaction between social participation and receiving strenght/comfort from religion, such that those who said they neither received strength/comfort from religion nor participated in social groups were over 14 times more likely to die (OR=14.32, 95% CI 2.37-86.56), controlling for other risk factors. In a second observational study, researchers from Rutgers University in New Brunswick, New Jersey (USA) followed 142 patients hospitalized for elective cardiac surgery (coronary artery bypass grafting, CABG), examining the relationship between religiosity and post-operative surgical complications [226]. Surgical complications, assessed by medical record review, were determined only during the time the patient was in the hospital. Religiosity was measured by frequency of religious attendance, frequency of prayer or meditation, and a 5-item scale assessing intrinsic religious commitment. After controlling for demographic, biomedical, and psychosocial variables, scores on intrinsic religious commitment were inversely related to complications following surgery (B=-0.32, P<0.01). No effect was found for frequency of religious attendance or prayer/meditation. In a second and separate study by this Rutgers University research group, they examined the relationship between religiosity and length of stay (LOS) in 405 patients undergoing elective CABG [227]. Patients were interviewed an average of 5 days prior to surgery, and LOS was determined by medical record review. Religiosity was assessed using a 6-item devotional activities scale and a 7-item beliefs scale. After controlling for social support and depressive symptoms, neither measure of religiosity predicted LOS (effect on other surgical outcomes and complications were not examined). In a fourth study, a randomized clinical trial, researchers at the University of Nebraska Heart Institute (USA) examined the effects of listening to prayer during surgery [228]. They randomized 78 cardiac surgery patients to one of three groups: (1) patients who listened to a CD that played a generic prayer, (2) patients who 111

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listened to a CD with a standard relaxation technique, or (3) patients who listened to a tape with no sound (placebo). The CD’s were played starting with the beginning of the unconscious anesthetic period prior to surgery and continued throughout the surgical procedure. The prayer was the following: “Dear God, Please come to my aid. Help me to be at peace during this surgery and in my recovery. Strengthen me and help me to remember you are always present, that your healing love and spirit surround me at all times, and that I am held in your tender care. Amen.” Mortality, sepsis, supraventricular tachycardia, and amount of pain medication (assessed in hospital and 30-days post surgery) were compared between the three groups. No significant differences were found on any outcome between groups. Since the tapes were played while patients were under anesthesia, they were not conscious of the tapes’ contents. The mechanism by which R/S is thought to influence health outcomes is through concious cognitive processes that reduce stress levels and improve coping. Thus, we would not expect that a religious intervention during an unconscious period to have an impact on surgical outcomes. If prayer has an effect on cardiac outcomes following surgery, this study suggests that it probably doesn't have its effect through unconscious processes. The last and final study (to our knowledge) is one conducted by researchers at the University of Michigan (UM) that examined the effects of religious involvement on post-operative complications following CABG at the UM Medical Center in Ann Arbor, Michigan (USA) [229]. A total of 177 patients undergoing CABG were assessed two weeks prior to surgery when data were collected on frequency of religious attendance, private prayer, and importance of religion. The 9-item INSPIRIT and a 4-item religious reverence scale were also administered at that time prior to surgery. Cardiac surgery complications were assessed using a standard measure (Thorasic Surgeons Database). Controlling for other significant predictors of post-operative complications, researchers found that patients who prayed frequently prior to surgery were 45% more likely to have no postoperative complications (OR=1.45, 95% CI 1.03-2.06). No other religious variables significantly predicted postoperative complications when frequency of prayer was controlled for in the model. Thus, three of five studies examining outcomes following cardiac surgery found that R/S predicted significantly better health outcomes and two studies found no effect. These results are positive enough to warrant further studies to examine the effects of R/S or R/S interventions on outcomes following cardiac surgery – especially in other countries. To date, no research has been published from countries outside the United States. 112

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8. OVERALL MORTALITY AND CARDIOVASCULAR MORTALITY In our systematic review, we identified 121 studies on R/S and mortality, of which 82 (68%) found that greater R/S predicted significantly greater longevity [230]. Six studies (5%) reported shorter longevity. Considering the 63 methodologically most rigorous studies, 47 (75%) found greater longevity. With regard to CVD mortality in particular, we identified 12 studies that had examined relationships with R/S. Of those, eight (67%) reported significance inverse relationships during periods of follow-up that ranged from 6 months to 31 years [231238]. In addition, two found no association [239,240] (one study with a follow-up of only 19 months), one reported mixed results [241] (CVD as a cause of death was greater among Catholic sister radiology technicians compared to other female radiology technicians, but was significantly lower compared to US females in general), and one reported greater mortality (although uncertain if statistically significant) in women reporting they received comfort/strength from religion [242]. In several of these studies, all cause mortality was the primary focus (not CVD), but when investigators examined the disease in which the inverse relationship between R/S and mortality was strongest, it was CVD [243,244]. Furthermore, in an independent systematic quantitative review of this research, investigators reported the effects of R/S on mortality were greater in CVD than in any other disease (HR=0.72, 95% CI 0.58-0.89) [245]. No studies of cardiovascular morbidity or mortality have been published from Brazil. 9. EXPLANATORY MECHANISMS As emphasized throughout this article, the way that R/S affects the cardiovascular system must be through psychological, social, or behavioral pathways. At least these are the pathways that we can study using the methods of science that researchers have available to them, i.e., through observational studies, experimental studies, and clinical trials. 9.1. Psychological pathways. By decreasing the probability of stressful life events (by influences on behavior), by providing meaning and purpose to stressful life events that do occur, and by providing role models in sacred scriptures of exemplary individuals dealing with adversity, R/S provides psychological resources that facilitate coping and adaptation. The result is the experience of more positive emotions (well-being, happiness, optimism, meaning and purpose) and fewer negative emotions (depression, anxiety, low self-esteem, hopelessness). These psychological benefits of R/S

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are known to affect immune, inflammatory, endocrine, and autonomic functions, which in turn influence cardiovascular health. Based on the amount of variance in health outcomes explained by R/S factors in regression models, we estimate that psychological factors account for about 50% of the effect of R/S on cardiovascular outcomes. 9.2 Social pathways. By encouraging involvement in the faith community, promoting forgiveness, and nurturing pro-social attitudes and activities, R/S provides social resources to build and maintain family, marital, and friendship networks that will be available to facilitate adaptation and coping (thereby positively influencing mental health). Social support of this kind also influences attitudes and behaviors that affect the ability to obtain an education and a job, influence work ethics, and help persons obtain financial stability that will enable them to access health resources. Finally, social contacts from involvement in a faith community will increase the flow of health information, increasing awareness of the latest research findings, disease screening opportunities, and available medical treatments. We estimate that social pathways account for about 15% of the effects of R/S on cardiovascular outcomes (again, based on regression models). 9.3. Behavioral pathways. By doctrines that promote care for the physical body (as the "temple of the Holy Spirit" in the Christian tradition, for example), R/S affects health behaviors such as cigarette smoking, alcohol and drug use, exercise and physical activity, and diet. Likewise, R/S doctrines discouraging sexual activity outside of marriage and delinquent or criminal activities will influence development of sexually transmitted diseases and risk of motor vehicle crashes and other accidents that could lead to the development of CVD. Our systematic review of research in this area revealed that of 95 studies examining relationships between R/S and risky sexual activities, 82 (86%) found inverse relationships. Likewise, of 104 studies examining associations between R/S and delinquency/crime, 82 (79%) reported inverse relationships. Finally, R/S attitudes encourage honesty and accountability, influencing compliance with medical treatments and adherence to disease screening practices (blood pressure monitoring, blood glucose checks, etc.). In the systematic review, we found that 27 studies examined relationships between R/S and compliance with medical treatments; of those, 15 (56%) reported positive associations. Furthermore, of 44 studies that examined relationships with disease screening, 28 (64%) found that those who were more R/S were more likely to engage in disease screening activities. Thus, a major pathway by which R/S may influence cardiovascular functions and risk of CVD is though health behaviors, lifestyle choices, compliance with medical treatments, and participation

in disease screening. We estimate that these pathways account for about 35% of the total effects of R/S on cardiovascular outcomes. 9.4. Supernatural pathways. Some researchers have sought to explain the relationship between R/S and CVD by invoking mechanisms that lie outside of the natural world (i.e., Divine or supernatural pathways). Classic examples are double-blinded intercessory prayer studies conducted in patients undergoing CABG, including the Byrd study [246] at San Francisco General Hospital, the Kansas City Mid-America Heart Institute study [247], and the multi-site Harvard study [248]. In the latter study, Harvard investigators randomized 1800 CABG patients to prayer or no prayer (a study published in the American Heart Journal). To the disappointment of the researchers in the Harvard study, the findings of this multi-million dollar project indicated that being prayed for made no difference in cardiac outcomes and, in fact, if patients were told they were being prayed for, they actually did significantly worse (i.e., they were more likely to have atrial arrhythmias). This resulted in an article published in Newsweek magazine that was titled "Don't pray for me! Please! [249]”. These studies are neither theologically nor scientifically credible, and so we have not discussed them in this paper. Interested readers are referred elsewhere for a thorough treatment of these studies and why they should not be done [250,251]. 9.5 Comprehensive theoretical model. We present here a theoretical causal model (Figure) adapted from a model presented in the Handbook [252]. The ultimate driving "source" of the cardiovascular benefits (and health benefits more generally) from R/S, according to the three major Western monotheistic traditions, is attachment to God. In Judaism, it is the 1st commandment of the 10 commandments ("Thou shalt have no other gods before Me" [Exodus 20:3]) and emphasized by Moses as the core of the Jewish faith ("Thou shalt love the Lord thy G-d with all thy heart, and with all thy soul, and with all thy mind" [Deuteronomy 6:5]). In Islam, it is in the opening stanza of the Qur'an ("You [alone] we worship, You [alone] we ask for help [for each and everything]" [Al-Fatihah 1:5]," and repeated many times elsewhere (e.g., "…those who have attained to faith Love God more than all else" [AlBaqara 2:165], and "…worship God [alone], and do not ascribe divinity, in any way, to aught beside Him" [AnNisa 4:36]). In Christianity, Jesus said (quoting Moses) that it is the first and greatest commandment and necessary to inherit eternal life ("Thou shalt love the Lord thy God with all thy heart, and with all thy soul, and with all thy mind" [Matthew 22:37]; this teaching is repeated twice more in Mark 12:30 and Luke 10:27). There is no debate here. Belief in, attachment to, and relationship with God is at the core of the monotheistic traditions above. 113

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This relationship with God is then manifested in terms of the theological virtues (love of God, faith or trust in God, hope in God). These virtues are taught and nourished within a religious community, although influenced by peers, education, and training. They are manifested in a person's life by public religious practices (attending religious services and other social group related religious activity), private religious activity (prayer or meditation, reading religious scriptures, watching religious TV, listening to religious music), intrinsic religious beliefs or commitments, religious experiences, and religious coping. The latter we call "religion" or "spirituality" (used synonymously in this paper – see earlier discussion). Religion/spirituality is then seen as influencing day-today decisions made at work, in the family, with friends and colleagues, as well as affecting life-style choices and health behaviors, which in turn influence mental and social health. R/S is also viewed as promoting the "human virtues" (as distinct from the theological virtues) that include forgiveness, honesty, courage, self-discipline, altruism (caring for others), humility, gratefulness, patience, and dependability. The human virtues, in turn, enhance social relationships, increase positive emotions, and reduce negative emotions. R/S has both "indirect" and “direct” effects on health

outcomes. This includes the indirect effects through positive emotions (well-being, meaning and purpose, optimism, hope, etc.), through negative emotions (mental disorders such as depression, suicide, anxiety, substance abuse), and through social relationships (social support, marital stability). R/S also indirectly influence mental, social, and physical health outcomes by effects on decisionmaking, lifestyle choices, and health behaviors, as well as through encouraging human virtues. Besides indirect effects, R/S also has "direct" effects on positive emotions, negative emotions, and social relationships. Mental health (positive and negative), social health, and health behaviors (including diet, exercise, smoking, etc.) are seen as the key factors that influence physiological systems on which healthy cardiovascular functions depend (immune/ inflammatory, endocrine, sympathetic/parasympathetic nervous systems), ultimately affecting rates of CVD. Note that R/S has no "direct" influences on cardiovascular functions or on cardiovascular health/disease. Rather, R/S always operates through psychological, social, and behavioral pathways. This entire system, rests on genetic influences, early developmental experiences during childhood and adulthood, and personality influences that result from an interaction of genetics and developmental forces. Note that

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these genetic and environmental factors (and the interaction of genetics and environment) influence the development of human virtues, decision-making and health behaviors, positive emotions (set-point for happiness and wellbeing), negative emotions (tendencies toward depression or anxiety or vulnerability to alcoholism or drug use), social connections (sociability, extroversion, etc.), and of course, physiological systems underlying cardiovascular functions and cardiovascular diseases themselves. Genetic and environmental factors also influence the person's capacity for religious or spiritual experiences, such that it may be "easier" for some individuals to be spiritual or religious because of their genetic makeup, temperament, or environmental experiences (including race, gender, education, economic situation). For example, the presence of genetic polymorphisms of the promoter region of the serotonin transporter gene may convey an emotional sensitivity to life events that makes an individual more likely to have spiritual or religious experiences, or more vulnerable to emotional distress, which in turn causes people to turn to R/S for comfort and emotional regulation. Indeed, there is growing interest in and research now being done on the genetic basis of spirituality. Thus, the relationship between R/S and cardiovascular health and disease is extremely complex, involving decision-making that is under the individualâ&#x20AC;&#x2122;s control as well as genetic and environmental factors over which the individual has no control. Concluding that a person has a cardiovascular disease (myocardial infarction, cardiac arrhythmia, atherosclerosis, high blood pressure, stroke or vascular dementia) because he or she is "not religious enough," then, is not possible because of the huge amount of information that is needed on which to base such a conclusion (including knowledge about the personâ&#x20AC;&#x2122;s genetic makeup).

10.1. Take a spiritual history. Cardiologists and cardiovascular surgeons should consider taking a brief spiritual history on all seriously ill patients whom they admit to the hospital. This also applies to patients seen for the first time in the outpatient setting, particularly those with chronic cardiovascular disorders that challenge ability to cope. The "screening" spiritual history is quite different from the comprehensive assessment that a chaplain would do when evaluating a patient. The screening spiritual history performed by the physician should take no more than 2-3 minutes, and usually consists of asking the patient about (1) his or her religious denomination, (2) R/S beliefs that assist with coping (or that might be causing distress), (3) R/S beliefs that might influence treatment decisions or conflict with medical care, (4) participation in a faith community and whether supportive, and (5) any other spiritual needs that are present and related to the patient's health or healthcare [254,255]. Besides gathering crucial information that will assist in the medical and surgical care of the patient, a spiritual history sends an important message to the patient: that the doctor is open to discussing these issues and will not avoid them or delegate them to others. When the physician takes a spiritual history, this has been shown to enhance the doctor-patient relationship [256]. However, before taking a spiritual history, the physician should prepare the patient by explaining why he or she is asking these questions. The reason for the questions has nothing to do with the severity of the patient's cardiac condition. Rather, the intention is to provide culturally sensitive care that addresses the whole person â&#x20AC;&#x201C; mind, body and spirit. If the doctor fails to provide such an explanation beforehand, the patient may get the wrong impression, i.e., that the reason the doctor is asking these questions is because the end of life is near and their condition is hopeless. 10.2. Value and support. When taking a spiritual history or discussing R/S matters, the doctor should always communicate to patients that he or she values and respects their R/S beliefs, and is supportive of them. This is true when the doctor has different religious beliefs than the patient, and even if the R/S beliefs of the patient conflicts with medical or surgical treatments. In the latter case, respecting and showing support for the patient's R/S beliefs will enhance the doctor-patient relationship and will likely increase the patient's adherence to medical treatments more generally and increase the likelihood that he will either ultimately comply or at least tell the physician if he doesn't comply. Rejecting or arguing with patients about firmly held R/S beliefs that conflict with treatment is usually disastrous, putting a wedge between the doctor and the patient and increasing the likelihood of resistance or subtle non-compliance. 10.3. Refer to chaplain services. If any but the most

10. CLINICAL APPLICATIONS Although scientific exploration on the influences that R/S has on cardiovascular health and disease is only in its infancy, and much further research is needed to better understand these relationships and effects, there is probably enough known already for us to make some suggestions on how to apply this knowledge to clinical practice. Bear in mind that the suggestions we provide here are largely based on common sense and clinical experience caring for patients with CVD, rather than on systematic research. Furthermore, space limitations allow us only to summarize our recommendations here and do so quite briefly. For a more detailed and comprehensive description of clinical recommendations (and limitations/boundaries), the reader is referred elsewhere [253]. In brief, here is what we would suggest:

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simple of R/S needs come up during the spiritual history, the doctor should refer the patient to a chaplain or pastoral counselor for further evaluation. The physician doesn't have the time or the training to address most patients' spiritual needs, and so should refer patients to experts in this area, especially if there are complex issues at stake. For example, a patient may tell the doctor that she feels that God is punishing her or doesn't care about her, or may even feel that she is going to hell. This is something that chaplains are trained to deal with. Doctors are not. Sometimes, however, if the patient refuses to see a chaplain, then the doctor will have to listen to these concerns and try to understand them (not argue about or dismiss them). 10.4. Engage. Should cardiologists or cardiac surgeons engage in religious or spiritual activities with patients? The most likely issue that comes up is praying with patients. Many religious patients (and even some non-religious patients), particularly when serious medical illness is present, would like to pray with their doctors, especially after hearing a bad diagnosis or prior to undergoing cardiac surgery. We believe it is appropriate for cardiologists and cardiac surgeons to pray with their patients â&#x20AC;&#x201C; if this is something they feel comfortable doing. However, the doctor should only do so after taking a spiritual history and if the patient asks them to pray. If the doctor asks patients to pray, this increases the risk of coercion (i.e., the patient may not want to pray with their doctor, but feel forced to do so in order not to offend or disappoint the doctor). Thus, if doctors are open to praying with patients, they should inform patients that they are willing to do so, but tell patients to ask for prayer at a later time if they wish to do so. In this way, the patient is free to either ask the doctor to pray (if the patient really wants prayer) or not, and no coercion will be involved. 10.5. Prescribe. Given the potential health benefits of R/S, should cardiologists or cardiac surgeons prescribe religious beliefs or activities to patients who are not currently engaged in them [257]? The answer is a resounding "no." Prescribing R/S is not appropriate and possibly unethical. When patients are sick and vulnerable, this is not a time to introduce new R/S beliefs or practices. However, in the vast majority of cases, patients will already be religious or spiritual, and no prescription is necessary. Supporting and encouraging the R/S beliefs and practices of the patient, though, may help to boost the effectiveness of those beliefs in helping the patient cope with their illness. 10.6. Limitations and boundaries. There are limitations to what physicians can do and boundaries across which they should not cross. First, as noted above, doctors should not prescribe R/S beliefs or practices to non-religious patients. Second, physicians should not force a spiritual history if the patient is not R/S (instead, switch the topic to

a discussion of what gives life meaning and purpose in the context of their illness and ask how this can be supported). Third, don't coerce patients in any way regarding R/S; this is a very sensitive and important topic to most patients and they need to feel in control. Fourth, do not pray with patients before taking a spiritual history and unless patients ask for prayer. Fifth, the doctor should not try to spiritually counsel patients unless he or she has the training to do so. Finally, the doctor should not do any activity related to R/S that is not patient-centered and patient-directed. Patient-centered medicine is now considered the standard of medical care, and this especially applies to addressing R/S issues. 10.7. Medical education. A recent survey of medical deans at Brazilian medical schools reported that many schools are beginning to address spiritual issues in the medical curriculum [258]. Researchers surveyed 86 of Brazil's 180 medical schools, finding that 5% had a required course dedicated to R/S and health and 6% had an elective course of this type (combined, nine of 86 schools with required or elective dedicated courses). In addition, 14 other medical schools said that they included a lecture on R/S and health at some point in the curriculum, and 12 more schools said that while they did not have a specific course or lecture on R/S and health, the topic was integrated into another course or lecture. Thus, 41% of the schools surveyed (35 of 86) had some type of content on R/S and health in the curriculum, either on a required or elective basis. Furthermore, when medical deans were asked whether their institution considered R/S and health important for their students, 54% said "very important", 36% "somewhat important", 11% "of little importance," and 0% "not important". These findings are similar to a recent survey of 122 medical schools in the U.S. that found that 7% of the 115 schools that responded had a dedicated required course on R/S and health, and 34% said they offered an elective course dedicated to R/S and health [259]. Likewise, about 40% of medical deans said that including R/S and health in the medical curriculum is important. Thus, many medical schools in both Brazil and the U.S. are now exposing students to spirituality and health in their curricula and there is a growing desire among medical school deans to include more such content in the future.

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11. FUTURE RESEARCH NEEDS Because of the influences that psychological, social, and behavioral factors have on cardiovascular health and disease (influences that are stronger than in most other medical conditions), and the influence that R/S has on those psychological, social and behavioral factors, the potential for R/S affecting cardiovascular health and

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disease is more likely than in any other organ system. The possible avenues for research on R/S and cardiovascular disease are almost endless, especially in Brazil where no research on this topic has yet been published in the peerreview literature. Given the religiousness of the population of Brazil and interest in R/S, particularly among those who are sick with CVD who use R/S to cope with illness, there is a huge opportunity to systematically study these relationships in Brazil. This also means opportunity to conduct research on the benefits or harm of physicians addressing R/S issues in the care of patients with CVD. Below are the types of studies that are needed. 11.1. Observational studies. Both cross-sectional and longitudinal cohort studies are needed on the relationship between R/S and all types of CVD. Prospective studies are needed to determine whether R/S involvement influences coronary artery calcification, left ventricular mass, ankle brachial index, carotid artery intima-media thickness, etc., over time, or predicts negative cardiovascular events. A model study is that of Feinstein et al. [260], but the design should follow patients over a longer time period and assess exposure to R/S across the lifespan rather than only R/S activity at baseline. Of particular importance are studies examining the interaction between R/S and pharmaceutical, biological, and surgical treatments for CVD. In other words, do highly R/S patients respond more quickly to treatment and with fewer complications, and maintain their response longer, compared with patients who are less R/S? Such studies are relatively simple and inexpensive to conduct. For example, if an investigator plans to study the effects of either a medication or a surgical procedure on cardiac outcomes, then measures of R/S could be added to the baseline interview and the effects assessed over time in terms of response to the treatment. There would be no additional cost to such a study, other than adding a few questions to the baseline interview. Time and expertise, however, would be needed to conduct the statistical analysis after the project is completed, and then write up the results for publication. The benefits of R/S to treatments for coronary artery disease, valve problems, heart failure, hypertension, peripheral vascular disease, or stroke could all be assessed using this low cost research strategy. 11.2. Experimental studies. Single group experimental studies conducted in the laboratory are also needed to determine whether prior R/S involvement or current R/S spiritual activities influence basic cardiovascular functions (cardiovascular reactivity, heart rate variability, ejection fraction, etc.) in response to an experimentally induced psychological or physical stressor. While a few studies have been done, more of these are needed that involve larger samples, that measure R/S in greater detail, and that more precisely assess cardiovascular functions. 11.3. Randomized clinical trials. Randomized clinical

trials are also needed that examine the effects of a R/S intervention on medical or surgical outcomes. The intervention might involve a religious cognitive-behavioral therapy that influences attitudes toward and coping with CVD, particularly among seriously ill, chronically disabled cardiac patients. Alternatively, an intervention could be designed that involves chaplain or clergy visits before and after cardiac surgery, followed by an examination of shortterm and long-term surgical outcomes (complications, hospital stay, re-admission rates, speed of wound healing, infection rates, need for pain medication, and mortality, for example). Another intervention might involve studying the effects of cardiac surgeons praying with patients (vs. no prayer with surgeon) on patient satisfaction, other psychological and behavioral outcomes, and surgical outcomes described above. A similar randomized clinical trial could examine the effects of medical cardiologists praying with patients, perhaps following a first-time acute myocardial infarction or a re-infarction. We have discussed here a few high priority areas that might be of interest to cardiovascular researchers. For a more comprehensive resource that outlines and ranks in priority the studies that are needed and their likely cost, and exhaustively describes how to conduct research on spirituality and health, the reader is referred to another resource [261]. This resource includes a description of the different research methodologies, R/S measurement tools, ways of conducting statistical analyses, writing up the results, and publishing the findings, as well as ways of funding this type of research. 12. SUMMARY Given the mechanism by which we think religion/ spirituality influences physical health, i.e., through psychosocial and behavioral pathways, and the strong influence that psychosocial and behavioral factors have on risk of developing cardiovascular disease, there is no medical condition that R/S is more likely to influence than CVD. Compared to the massive volume of research on R/S and health overall (over 3,200 quantitative studies), relatively little research has examined the effects of R/S on cardiovascular morbidity or mortality. Thus, there is a wide-open door for cardiovascular researchers in Brazil â&#x20AC;&#x201C; one of the most religious countries in the world â&#x20AC;&#x201C; to conduct groundbreaking research that establishes (or refutes) the effects that R/S may have on CVD. The fact is that in developed countries, cardiovascular diseases are now the most common cause of both death and functional disability [262]. If R/S beliefs and practices have any influence on CVD, no matter how small, then demonstrating this through research may lead to both a higher quality and longer life for millions worldwide. 117

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SPECIAL ARTICLE

Rev Bras Cir Cardiovasc 2013;28(1):129-36

Cardiac surgery: the infinite quest. Part II Cirurgia cardíaca: a busca infinita. Parte II

Rodolfo A. Neirotti1 Publicamos, abaixo, a segunda parte do artigo “Cardiac surgery – the infinte quest”. Apesar de mais complexo que a anterior, este texto vai além das habilidades técnicas e tem conceitos modernos de como lidar com os sistemas complexos da atual prática da nossa profissão e especialidade. Domingo Braile Editor-Chefe/BJCVS/RBCCV

DOI: 10.5935/1678-9741.20130016

Part II Cardiac surgery: issues around and beyond the operating room Ultramini-abstract: In addition to our clinical and technical work, there is a need to cross boundaries searching for collaboration as well as lessons from other complex systems that has identified common solutions for common problems, indicating that the general theory is independent of any particular industry or activity. Cardiac surgery: a complex system Heart surgery has much in common with other high technology systems in which performance and outcomes depend on multifaceted interactions of individual, technical and organizational factors. In addition, our specialty often functions as a chaotic/emergent system since the initial circumstances vary in patients with the same medical condition resulting in uncertainty and lack of predictability [1]. Complexity: The American Heritage Dictionary defines complex and complicated as “things whose parts are so interconnected or interwoven as to make the whole perplexing”. If we add rarity and small numbers to complexity, the results is a distinctiveness that explains many aspects of our profession and specialty such as variability with institutional differences in outcomes; inconsistency of results in treating rare diseases and uncertainty on any inference about results of complex rare lesions [2]. 1. MD, MPA, PhD, FETCS, Honorary Member of the Brazilian Society of Cardiovascular Surgery.

RBCCV 44205-1449

A system is a set of interdependent elements that are interacting, or working together, to accomplish a common goal. All systems, at the “atomic” level, consist of individuals, activities, connections, and pathways with the following characteristics, qualities or peculiarities in complex systems: • Heterogeneity of the parties (diverse nature and multiple); • Cause-and-effect relationships may be nonlinear and obvious only in retrospect; • Richness of interaction between them (including their contradictory character); • Multidimensional and multi-referential; • Many variables commonly present; • Provide information that by itself reveals the extent of its complexity; • Under an apparent simplicity, they often hide the true dynamics of these processes and interactions between its parts • Vulnerability — Are influenced by factors and surprising circumstances that may affect, cause, or facilitate a change in behavior and expected results, altering all or changed significantly “Complex business generates complex services. Regardless of how much effort and brain power go into designing their complex operations (‘system of work’), it is impossible to do it perfectly and to predict how it will behave under every circumstance” [3]. Complex systems are rich in multiple and interdependent Correspondence address: 1199 Beacon St, Unit 2. Brookline MA 02446 USA E-mail: ra_neirotti@ksg06.harvard.edu Article received on January 31st, 2013 Article accepted on February 28th, 2013

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events that usually manifest unforeseen consequences that are nonlinear and often asymmetric — frequently called black swans. Why call big surprises black swans? It goes back to the second century when Roman poet Juvenal said that some events are “as rare as a black swan” [4]. History is shaped by events that seem impossible until they occur changing predictions and planning. Surprises are by definition unexpected and therefore well beyond the limit of our experience, not allowing us to pick the “next disaster”. Why can’t we foresee these events? Blame it on the way humans make sense of the world — most of their experience falls within a tightly bounded range called “the norm”. Focusing on that narrow array carries the risk of preparing us only for events we are familiar with [5]. Rare diseases — rare as Black swans — are a challenge for the Science of Cardiac Surgery because of their infrequency at any single institution, and thus the gaps in knowledge. Because of this, there is little chance that randomized comparison can be accomplished. In this setting, highly variable outcomes are predictable given the scarceness of skill-based, rule-based, and knowledge-based foundations for performance that avoids and compensates for human errors, the inevitable breakdowns due to complexity and uncertainty. Statistics to determine risk are not available; we just do not have them due to their rarity. Complexity thus calls for experimentation. Once patterns become apparent, it is possible to attempt to destabilize undesirable interactions [6]. By contrast, in chaotic situations — highly sensitive to initial conditions — there are no trends to monitor. Sometimes complexity is at the "edge of chaos” without a pattern to differentiate. Clayton Christensen reminds us that “Theory is often associated with the word theoretical, which, among practical people, has a connotation of impracticality. However, a well researched theory is practical because it allow us to know what cause what and why, and to predict the result of an action. The key to developing a theory that is valid internally and externally is to seek anomalies, to find instances in which the explanation of causality does not yield the result that the theory predicts. The scientific method requires to search for instances in which the theory does not work” [6]. “As the circle of science grows larger, it touches paradox at more places” Nietzsche. Managing complexity: Steven Spear aptly describes the problem and manner of managing complexity: “There are high velocity organizations — whom everyone chases but never catches — that manage to stay ahead because 130

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of their endurance, responsiveness, and an exceptionally high velocity in self correction. They see and seize opportunities and, by the time rivals responded, the leaders have raced on to further opportunities — these systems pose both the capacity to retain their viability and the capacity to evolve” [3]. “These organizations — complex adaptive, selfimprovement systems — face a common problem and have identified a common solution, which keeps them performing way ahead of the pack and always getting better — the two go together. The solution has been used successfully by a wide variety of organizations indicating that the general theory is independent of any particular industry or activity” [3,7]. “And this leads to collaborative rationality, of getting better together, which is a different way of knowing and generating, of making and justifying decisions based on diversity, interdependence and authentic dialogue — not always accepted by the chain of command despite of the limitations of acting unilaterally. The agents interact dynamically, exchanging information and the effects of these connections flow through the system. There are many direct and indirect feedback loops; the overall system is open. The behavior of the system is determined by these interactions, not the components; and the behavior of the system cannot be understood by looking only at the components” [7,8]. Diversity: "Diversity implies that a collaboratively rational process must include not only agents who have power but also those who have needed information or could be affected by outcomes of the process". As in direct democracy, their success depends on the amount and quality of the information available to those involved in the decision making process [9,10]. Interdependence: “Agents must depend to a significant degree on other agents, considering that each stakeholder has something that the others want. This condition ensures that participants maintain a level of interest and energy required to engaging each other and pushing for consensus — such interdependence means that players cannot achieve their interests on their own” [10]. Authentic dialogue: “Deliberations must be characterized by direct engagement so that the parties can test to be sure that claims are accurate, comprehensible, and sincere. Deliberations cannot be dominated by those with power outside the process, and everyone involved must have equal access to all the relevant information and an equal ability to speak and be listened to. In authentic dialogue, nothing is off the table” [10].

Neirotti RA, et al. - Cardiac surgery: the infinite quest. Part II

Structure and dynamics of successful high velocity organizations Structure: Managing and integrating the functions as part of the process. Dynamics: “Continually Improving the Parts and the Process, by engaging those closest to the work in the continual improvement, their speed of detecting and problem solving, learning, and discovering better ways of how to produce. Any snapshot will reveal where they are today but not where they are headed determined by their DNA”. “These organizations, share four capabilities that can be adapted to medical situations: a) specifying design to capture existing knowledge and building in tests to reveal problems and improve a process; b) detecting and rapidly solving problems to build new knowledge avoiding memory perishability; c) sharing new knowledge throughout the organization; d) leading by developing the above mentioned capabilities by allowing enough time and resources for staff/team training, turning employees into problem solvers. Operations are designed to continually let them know that it does not know all there is to know. When the operations speak, these organizations listen, learn, improve, and wait for the next lesson. The lesson learned here and now is spread throughout the organization. The high velocity set themselves apart in how they deal with the problem of unknowable unpredictable systems, understanding, learning and recovering from failures” [3]. How complex systems fail: in those systems that fail, their pieces come together through hard work, goodwill, and improvisation. Their components are managed as if they operated independently; in fact they are quite interdependent. Although it could be a "Sisyphean task" some of them fail wisely learning from their mistakes and try again. However, the choices are often both clear and stark: organizations must either modify their forms and structures (reinvent) in ways appropriated to the emergent environment or, over a period of time, cease to exist. Occasionally, disruptive innovations, creating new organizations are necessary rather than transformation of existing outdated institutions. Like in our profession, the first step to treatment is diagnosis. If one considers that a system has an illness — dysfunction — the first step should be to make a diagnosis to uncover its root causes. Often, administrators and managers have a tendency to prescribe treatment without a proper diagnosis that would allow identifying the systemspecific problems. Policies that work in some setting may not be effective in a different context. A chart constructed

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by combining a diagnostic tree with the National Diamond Model allows displaying the components of the system and pinpointing the potential binding constraints affecting performance and growth before implementing reforms. A similar approach, with different factors, can be used in program evaluations [11,12]. There are many factors which contribute to failed or failing institutions [13]. Reasons people fail • Personal weakness — failure to reach a minimum required performance; • Poor people skills — inability to relate to others; • Deviance — violating an agreed process or practice; • Negative attitude — in reacting to adverse circumstances of life; • Bad fit — mismatched abilities required to execute the job, interests, personality, values; • Lack of focus and attention — priorities not well established leading to inadvertent departure from stipulations; • Weak commitment — not giving the task our very best; • Unwillingness to change — major enemy of success; • Shortcut mind-set — take the shorter road to success; • Excessive confidence — it is not beyond my scope or skills. I can do no wrong → Ego; • Relying on talent alone — avoiding hard work to improve it; • Response to poor information — not feeling you need more information; • No goals — lack of a dream with a time limit; • Frustration — not learning from failures; • Anger: according to Aristotle, “Anyone can become angry, that is easy — but to be angry with the right person, in the right degree, at the right time, for the right purpose, and in the right way — that is not easy”. Rationally speaking, it is a very important emotion and a huge driver of human behavior. In some cases it is even welcome; however, those that can control it — i.e., those who have emotional intelligence or are emotionally astute — avoid being an angry decision maker and may have an advantage in their daily life. In sum, showing your anger conveys a toughness that can help you get what you want. But beware: When your counterpart has better information than you do, your anger could work against you [14]. Human behavior and errors: Medical errors cause 90-120,000 preventable deaths per year in the USA — far more than in car crashes — costing the industry somewhere between $9 billion and $15 billion a year. 131

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Furthermore, only 50% of US patients receive adequate quality of care, altogether enough to take the necessary actions to reduce risk the factors. It is a basic principle of systems that every one of them is perfectly designed to achieve the results it attains. Academics, by studying these systems, could contribute to a better understanding of how the components relate to one another in designing a self improving process that prevents mistakes from occurring. In addition, medical schools should consider building up awareness of the importance of prevention of medical errors among students early on their career [6]. The fact that complexity makes errors inevitable should not be an excuse; we should to do our best to avoid them. Human factors research has been a major contributor to safety, enhanced reliability and error avoidance in those complex socio-technical systems such as the aviation industry. Their long used safety check list looks like a simple and helpful tool to reduce errors, complications and deaths in medicine, as well as in other professions [15]. Unfortunately, industry and watchdogs often rely far too much on a patchwork of retroactive rules, with inspectors adding the negative event to their checklist each time a trouble is found in one of the components, decreasing its usefulness, particularly if thereafter the new norm is looked at with the old lenses. Imperfect outcomes are caused not only by lack of knowledge — ignorance — but by imperfect selection of treatment, imperfect performance, and are too often caused by human errors. Mistakes are the result of either the misapplication of good rules — ineptitude — or the application of bad rules. Most mistakes can be traced back not just due to flawed execution but to flawed thinking of people trying to do a good work, and a tendency to make absurd decisions [16]. Team communication, organization, and mutual supervision are crucial to minimize the chance of making a mistake. Technical failure and human error led to the loss of an Air France flight over the Atlantic in June 2009 and the deaths of 228 people, according to the final report of the French air accident investigation agency (Pilot Linked to Air France Atlantic Plunge, BBC News, July 5, 2012). Similarly, the Fukushima nuclear plant was "a profoundly man-made disaster that could and should have been foreseen and prevented" and its effects "mitigated by a more effective human response" according to the report of the Japanese parliamentary panel. The report catalogued serious deficiencies in both the government and plant operator response adding that regulators should "go through an essential transformation process" to ensure 132

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nuclear safety in Japan (Japan panel: Fukushima nuclear disaster 'man-made'. BBC News, July 5, 2012). It is important to recognize that medicine is so complex that no human being can be in control of everything without some sort of compensation for bounded rationality or hyper rationality. Furthermore, over the last decades, science has filled in an enormous amount of knowledge, challenging even more the human mind’s limited capacity to evaluate and process the information available, considering the time constraint to make some decisions. We have to achieve near perfection in the shortest possible time avoiding the “let's-get-home-itis”, a disease in judgment that has negative impacts on a number of surgeons who sing the praise of speed and quick operations. It may be part of human nature to err, but it is also part of human nature to develop solutions, find better alternatives, and meet the challenges ahead. Rather than punishing those that make mistakes, it is more effective to find out why they made the mistakes in order to act on the system to diminish the odds of repetition [17]. Negative events in complex systems Minor Events are subtle, insidious, except to human factors observers, and many of them largely overlooked by the operator and the team members. As a result, no attempt to correct them is made. In isolation, they have little impact, but their multiplicative effect can lead to negative outcomes. Near Misses can cause severe temporary or permanent complications. By paying attention to close calls, it is possible to recognize them, learn and eventually predict and prevent major events. Unfortunately, decision makers have often a tendency to view near-disasters as successes! Major Events, without compensation, are likely to lead to death. Because they are more obvious, they can be recognized, triggering rescue actions to avoid catastrophic consequences. Risk Factors for Complications are more related to patient variables than to structural hospital characteristics. The highest quality, lowest risk hospitals have a higher prevalence of rescue from complications. It is the failure to compensate that leads to a negative outcome [18]. Individual and organizational factors and their interactions Individuals: Exchanges with highly qualified individuals concerning change often involve negotiation and compromise, since they would not comply with the instructions without adequate rationale. It is not a matter

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of who is right or who is wrong; the focus must be on what professionals should care about: the patient. Though silence is associated with many virtues, it can exact a high price on individuals, generating feelings of humiliation, paralysis, anger and resentment, and eventually, if unexpressed, can seriously damage an organization. Silence can also be the result of cultural conventions and a reluctance to question authority. The message throughout the organization should be: STOP! Any question from the team? “If you see something that concerns you please speak up”. It is difficult to manage secrets! This approach thwarts the blame game, helping to build a culture that promotes participation, and encourages detecting, analyzing, and learning from failures [19]. Organizational factors: Team work in which all components of the cardiovascular services — a cluster of people with similar interests, all focused on excellence — contributes to the quality of the final outcome with an integrated approach. Using an orchestra as a paradigm of team work, a conductor — the chief cardiac surgeon in most centers — leading from the front and by example is needed, working out the problems collectively with the individual orchestra members. He does not produce the sound but he can inspire, teach, and persuade. It is about how to play rather than what, an excellent example of the importance of coaching something that surgeons seldom do. After all, “Music fills a gap in life like nothing else — and brings serenity when other things cannot” [20]. Interaction, negotiation and compromise: In an ideal world, after an operation, patients stay in the intensive care unit where the physician on duty must synthesize information from various sources and personnel into a sound plan of care. When another physician, such as the cardiovascular surgeon — when they participate, though often they do not — collaborates with the critical care specialist to manage a patient, the relationship requires mutual respect and cooperation, without patient ownership, in order for optimal patient care to occur. If the dialog starts with someone saying: this is my patient! It is a bad start. Every agreement in the ICU involving two physicians is a negotiation as much as it is collaboration. Each person concerned approaches the interaction with a defined (and possibly different) idea of what he wants to happen, and therefore there is an urgent need to reach agreement on a plan of action. If you approach a negotiation thinking you know everything, you may not make the best decisions. You could be missing out on information, insight and suggestions that may be critical to the outcome. A leader

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who doesn't nurture an atmosphere where ideas are welcome is shortchanging his or her effectiveness. In addition, team members who are discouraged from giving opinions or input will be ineffective players. It is prudent to approach these discussions with a few ground rules in mind. First, there are certain basic principles of care known to be true that should not be compromised. Second, both parties will learn something from the interaction. Third, there is much in medicine that is either uncertain or can be approached in more than one-way. Ultimately, the best plan more often than not results from honest open communication between physicians and the melding of the best of both points of view. If beyond winning, both physicians enter into the negotiation accepting that give and take is essential to the process, then a well reasoned design of care is achieved and the patient benefits greatly. An analogous approach is applicable to the interactions among surgeons, cardiologists, anesthesiologists and perfusionists. It is difficult to have a team unless every member has respect for people who have different skills [21,22]. The power of a positive NO: “No is perhaps the most important and certainly the most powerful word in the language. Every day we find ourselves in situations where we need to say No — to people at work, at home, and in our communities — because No is the word we must use to protect ourselves and to stand up for everything and everyone that matters to us”. “Saying No the right way is crucial. A wrong one, a clear a resounding NO! can also destroy what we most value by angering and alienating people. The secret to saying No, clearly, respectfully, and effectively, without destroying relationships lies in the art of the Positive No, a technique that anyone can learn. The Positive NO can help you to get not just any Yes but to the right yes the one that truly serves your interests” [23]. Quality: “An essential and distinguishing attribute of something or someone” (Word Net Dictionary). It is difficult to define, but you know it when you see it! Quality is measurable and requires appreciation to recognize the quality, its significance or magnitude and appreciation requires knowledge. In medicine as in many other businesses precision equals precise diagnosis plus doing the right thing (effectiveness) plus doing it right the first time (efficiency). Precision in medicine not only improves outcomes but also can dramatically cut costs. In health care, cost is not a proof of high quality and low cost comes from focus. Value added procedures are possible only after a precise definitive diagnosis has been made [6,24]. 133

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Quality comes from correct integration to get the job done. As we improve the technology of medicine, we also need to include the patient’s story in the equation: Quality of care equals technical quality (precise diagnostic, doing the right thing and doing it correctly) plus service quality, both throughout a process that cannot be turned off at five o’clock. Adopting the quality equation is a decision and a commitment one makes every day that never goes away, that needs to be sustained all year long to become a habit. Institutional quality and qualified people are the key to making quality products, with the best possible use of the ordinary distribution of human talent and a permanent awareness of personal and institutional limitations [25]. Service quality: The privilege to assist in preserving and improving life provides us with much professional satisfaction. But, do we have the necessary background to fulfill the humanistic demands of our profession? Often, one recognizes professionals who have mastered scientific facts and surgical techniques but who lack interpersonal skills and respect for the dignity of man, empathy, and humility. Remember that our attitude often trickles down to the entire team! [26]. To achieve this, a combined approach is necessary, inducing change from the top, by influence or persuasion and commitment to education, and encouraging bottomup grassroots involvement and cooperation. Promoting bottom-up chances is an important component of Edwards Deming’s principles of total quality management. Both the top-down and the bottom-up approaches are not mutually exclusive but rather complementary and are what is meant by Total Quality Management. • Total Quality Management (TQM) is a business strategy aimed at embedding awareness of quality in all organizational processes making it the responsibility of all employees. • TQM requires a re-organization of the work process and the workplace by application of principles of “teamwork” and work “teams” that are supposed to involve the workers and give them greater control in their work Quality problems and categories of poor quality: Overuse, underuse and misuse of funds due to: defensive medicine, ignorance, the culture of money, poor attitude, lack of knowledge, resources, or technology, as well as corruption, greed, etc. Reforms such as revisions to the fee-for service reimbursement and the incentive it provides for overuse can result in significant savings [27,28]. In other words, health care providers who ensure quality care, customer satisfaction, cost control, and efficient and appropriate use of resources, are preferred. 134

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Reporting of quality • Lay media: Anecdotal; substantiation not required; short-lived; • Professional literature/media: Scientific process; scrutinized data; longer lasting; • Value of representation in both lay and professional media: Credible evidence-based outcomes, that are recognized in the professional literature and attract the interest of the lay media provides the best of both worlds. Quality of care: Using “network science”, a method of analysis that examines webs of connections in complex systems, it is possible to map the “Product Space” by depicting clusters of capabilities/products grouping them according to their relatedness. The concept of “proximity” formalizes the intuitive idea that the ability of a center to generate an outcome depends on its ability to produce other ones — “structure of production”. When a center with many complex capabilities adds a new capability, it can create a range of new possible products — new complex procedures. Conversely, adding a single new capability in a center that has few to begin with won’t leverage an existing matrix of capabilities in the same way, indeed it might not produce any new products at all [29]. Systems of care, their impact on quality: Although the knowledge and practice of individual clinicians are important for high-quality care, today we realize that no health care professional can deliver high quality alone; therefore, health care professionals prefer to practice within groups — proximity — and systems of care. Systems of Care equal institution plus staff partnership plus product space plus structure of production [29,30]. Institutional variations in hospital mortality associated with inpatient surgery • Rates of death vary across hospitals, from 3.5% in low-mortality hospitals to 6.9% in high-mortality hospitals; • High mortality hospitals have complications rates similar to those of low mortality hospitals (24.6% and 26.9%, respectively) and of major complications (18.2% and 16.2%, respectively); • Mortality in patients with major complications was almost twice as high in hospitals with high mortality than in those with low mortality — high velocity organizations — (21.4% vs. 12.5%, P<0.001). Hospitals with higher mortality rates — the pack — are less effective in rescuing patients from complications; • Timely recognition and effective management of complications are important in reducing deaths after surgery;

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• The value of avoiding complications is obvious. The quality of care once complications have occurred is crucial for reducing mortality [30]. Business intelligence: how are we doing? Business intelligence — the systematic use of information about one’s business — is vital to understand, report on, and to predict different aspects of performance. High quality intelligence capabilities and analytic skills play crucial roles in the most competitive sectors of the global economy because it can avert bad events providing that the dots are properly linked. How are we doing? Due to the current demand for excellence and transparency, hospitals should start collecting and analyzing data — a method to evaluate future improvements — about outcomes calling for quality from their practitioners in preparation for a not too distant future. Implementing an independent measurement and a reporting system — business intelligence — focused on patient safety with a view to eventually making the information available to the public, will have an impact on quality, as well as on consumer and patient satisfaction. An accurate and unbiased statistical analysis of surgical outcomes allows for an intelligent search of the risk factors, continuous improvement through responsiveness of the parts and the course of actions, as well as for a valid comparison with other institutions. The truth is the truth wherever it is found and to dismiss it because it comes from people with different views is a mistake. Undoubtedly, gathering accurate information is vital also because politicians, bureaucrats and company officials are often wary about alarming citizens. The systematic use of information requires good data and commitment of executives to fact-based and analytical decision-making as a way to learn rather that doing it out of gut feeling or intuition — cognitive illusions, illusion of validity [31]. Gathering solid data, working analytically, and leaving emotions aside all help those on the top to reflect critically on their own behavior, and then change how they act to make better decisions. Efforts to develop fact-based decision-making capabilities are likely to fail unless they are closely supported by top management. High performance organizations adapt and thrive by rapidly making choices that others do not by moving the decision making process down, close to the generation of information and around the needs of the user, instead of moving the information up to the executive suite. The people who construct statistics are very often not the same kind of people needed to publicize them. An

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effective leader should be able to comprehend numberladen reports, evaluate the information provided to him, and draw conclusions from data, rather than be dependent on others to interpret for him. Altogether, evidence-based medicine improves patient care using metrics and evaluations as a tool for learning rather than accounting. Two categories: Reporting: Those providing services to the public, needs to report accurately on what is going on in their business. By getting a relatively early warning on their performance they can fix the problems and educate the team members encouraging their participation with a button up plus horizontal approach. Analytics: This is more understanding-oriented in terms of knowing what factors are really driving your business performance, or prediction-oriented, looking forward instead of backward. Inferences • Cardiac Surgery is not immune to the waves of innovations — Kondratieff waves — sweeping the world at large over the past fifty years starting with disruptive new technologies that have tranformed industries, societies and economies beyond recognition. Developing economies have been spared this technological onslaught, but they might soon have this same problem [32]. As President J. F. Kennedy put it, “Great change dominates the world, and unless we move with change, we will become its victims”. • An innovative partnership among the government, the private sector and foundations can led to major advancement of the health system. • Listening to customers is in general a good idea, but it is not the whole story; in order to innovate smart companies should sometimes ignore what the market says it wants today, relying on inspiration and even distorting reality for the genesis of new products. • We should be prepared for changes in the patient population requiring surgery. Conventional surgical procedures are expected to diminish. Hybrid procedures, requiring special facilities and team work with the participation of people with different skills will be more often adopted. ► Part III will be published in the next issue of the RBCCV Pediatric Cardiac Surgery: a discipline on its own Ultramini-abstract: Although there are common grounds with adult cardiac surgery, it is important to 135

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understand the differences in the business plan, paths, manpower, mindset, training, and infrastructure that are essential in those institutions where pediatric cardiac surgery can and should be performed. Time to start thinking, it is not what we can do, but should we do it?

16. Blackstone E. Cleveland Clinic Foundation, personal communication.

18. De Leval MR, Carthey J, Wright DJ, Farewell VT, Reason JT. Human factors and cardiac surgery: a multicenter study. J Thorac Cardiovasc Surg. 2000;119(4 Pt 1):661-72.

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1. Neirotti R. Paediatric cardiac surgery in less privileged parts of the world. Cardiol Young. 2004;14(3):341-6. 2. Blackstone EH. The challenge of rare diseases. Joint Meeting of the Congenital Heart Surgeons Society and the European Congenital Heart Surgeons Association. Montreal, October 2-4, 2004. 3. Spear SJ. Chasing the rabbit. New York: Mc Graw Hill; 2009. 4. Taleb NN. The Black Swan: the impact of the highly improbable. New York: Random House; 2007. 5. Fugate C. Federal Emergency Management Agency in Preparing for the Next Disaster: The future of crisis data The Nonprofit Technology Network Oct 13, 2010 13:17. 6. Christensen CM, Grossman JH, Hwang J. The innovator’s prescription. a disruptive solution for health care. New York: Mc Graw Hill; 2009. 7. Christensen C. Foreword. In: Spear SJ, ed. Chasing the rabbit. New York: Mc Graw Hill; 2009. 8. Susskind's L. blog on Innes JE, Booher DE. February 20, 2010 about the Book Planning with complexity: an introduction to collaborative rationality for public policy. New York: Routledge; 2010. 9. Innes JE, Booher DE. Planning with complexity: an introduction to collaborative rationality for public policy. New York: Routledge; 2010. 10. Democracy in California. The Economist, April 23rd-29th; 2011. 11. Hausmann R, Rodrik D, Velasco A. Competitive advantage of nations growth diagnosis. Boston: Harvard University; 2004. 12. Porter M. Competitive advantage of nations. New York: The Free Press; 1998. 13. Maxwell JC. Failing forward: turning mistakes into stepping stones for success” Thomas Nelson Inc, April 3; 2007. 14. PON Staff. Tempering your temper. the downside of anger. The Negotiation newsletter. Program on Negotiation at Harvard Law School, April 5, 2011. 15. Gawande A. The checklist manifesto. New York: Metropolitan Books; 2010.

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17. Leape L. Medical errors, public health challenges of the 21st century. Health care think tank. Advanced leadership initiative. Boston: Harvard University; 2009.

19. Edmondson A. Strategies for learning from failures. Harvard Business Review 2011;48-55. 20. Newman M. Life trustee. Boston Symphony Orchestra;2011. 21. Neirotti RA. Cardiac surgery: complex individual and organizational factors and their interactions. Concepts and practices. Rev Bras Cir Cardiovasc. 2010;25(1):VI-VII. 22. Hackbarth R. DeVos Children Hospital. Grand Rapids MI, Personal communication; 2006. 23. Ury W. The power of the positive no. New York: Bantam Books;2007. 24. Meeting of the Joint Committee of Primary Care Trusts (JCPCT) United Kingdom, 16th February, 2011. 25. Shore MF. Harvard Medical School, Personal communication, 2007. 26. Castañeda A. Perspectives on Success in Congenital Heart Surgery. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2008; 88-90. 27. Mello MM, Chandra A, Gawande A, Studdert D. National costs of the medical liability system. Health Aff. 2010;29(9):1569-77. 28. Chassin MR, Galvin RW. The urgent need to improve health care quality. Institute of Medicine National Roundtable on Health Care Quality. JAMA. 1998;280(11):1000-5. 29. Hausmann R, Hidalgo C. In: Jonathan Shaw on “Complexity and the wealth of nations” Harvard Magazine. March-April 2010. 30. Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361(14):1368-75. 31. Davenport T. Research sees business intelligence emerging as crucial competitive advantage. Babson College MA; News room release date: 4/12/2005. 32. Šmihula D. Waves of technological innovations and the end of the information revolution. J Economics Int Finance. 2010;2(4):58-67.

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Dallan LAO, et al. - Revascularização miocárdica no século XXI

ARTIGO ESPECIAL

Revascularização miocárdica no século XXI Myocardial revascularization in the XXI century

Luís Alberto Oliveira Dallan1, Fabio Biscegli Jatene2 Sempre preocupada com o resgate histórico da cirurgia cardiovascular, a Revista Brasileira de Cirurgia Cardiovascular (RBCCV) publica o artigo a seguir, escrito pelos Drs. Luis Dallan e Fábio Jatene, respectivamente, Editor Associado e Ex-EditorChefe da RBCCV. Em um texto rico em detalhes, eles discorrem sobre a história da revascularização miocárdica, desde os seus primórdios até as perspectivas desta hoje consagrada técnica e que deve ser de conhecimento de todos os cirurgões cardiovasculares.

DOI: 10.5935/1678-9741.20130017 Descritores: Revascularização miocárdica. Ponte de artéria coronária. Procedimentos Cirúrgicos cardíacos/História. História.

CORAÇÃO: ESSE ÓRGÃO INTOCÁVEL A despeito da aceitação e emprego rotineiro da cirurgia cardíaca nos dias atuais, nem sempre foi assim. No final do século 19 e início do século 20, o tratamento cirúrgico do coração era considerado fora de qualquer questão. Um dos exemplos mais claros dessa opinião foi a declaração de Theodor Billroth no encontro da Sociedade Médica de Vienna de 1881, em que declarou: "No surgeon who wished to preserve the respect of his colleagues would ever attempt to suture a wound of the heart" [1]. Nem mesmo nas primeiras décadas do século 20 a cirurgia cardíaca ganhou grande expressão. Prova disso é a ausência de qualquer menção da mesma no clássico livro "The Century of the Surgeon", publicado em 1957 por Jurgen Thorwald [2]. Entretanto, a partir dos anos 1950, a circulação extracorpórea ganhou grande desenvolvimento

1. Professor Associado da Faculdade de Medicina da Universidade de São Paulo. Diretor da Unidade Cirúrgica de Coronariopatias do Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil. 2. Professor Titular da Disciplina de Cirurgia Cardiovascular da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.

RBCCV 44205-1450 Descriptors: Myocardial revascularization. Coronary artery bypass. Cardiac Surgical Procedures/History. History.

e passou a ser empregada progressivamente na prática clínica. Isso possibilitou o real princípio da cirurgia cardíaca e gerou seu impulso fantástico, que não cessou até os dias de hoje. O PRESTÍGIO DA CIRURGIA CARDÍACA Apesar de um início tímido até a segunda metade do século 20, a partir dos anos 1960 a cirurgia cardíaca ganhou enorme visibilidade. A figura do cirurgião cardiovascular passou a ser celebrada publicamente, com tanto prestígio quanto astronautas. Nomes como Drs. Christiaan Barnard, Denton Cooley, Michael DeBakey e Norman Shumway passaram a ser conhecidos pelo enorme público, especialmente após o advento do transplante cardíaco. No Brasil não foi diferente. Coube a professores como Euryclides Zerbini e Adib Jatene assumir essa liderança [3].

Endereço para correspondência: Luís Alberto Oliveira Dallan Av. Enéas Carvalho Aguiar, 44 – Cerqueira César São Paulo, SP, Brasil – CEP: 05403-000 E-mail: dcidallan@incor.usp.br Artigo recebido em 24 de setembro de 2012 Artigo aprovado em 1 de outubro de 2012

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REVASCULARIZAÇÃO DO MIOCÁRDIO: AVANÇOS ESTABELECIDOS O tratamento cirúrgico da doença arterial coronária provavelmente hoje se constitui no assunto mais estudado dentre todas as especialidades médicas. Esse fato com certeza torna o método mais atrativo e prestigia sobremaneira quem o procede. Por outro lado, também mantém o cirurgião sob questionamento e estresse constantes. Historicamente, a revascularização do miocárdio está envolta numa enorme visibilidade. Além da possibilidade de morte iminente frente aos procedimentos que manipulam as artérias coronárias, as alternativas hoje disponíveis, como a angioplastia, contribuem para a polêmica sobre qual é o melhor procedimento frente à doença coronária. PRIMÓRDIOS DA REVASCULARIZAÇÃO DO MIOCÁRDIO A noção de doença arterial coronária foi trazida ao Royal College of Physicians, em 1768, por William Heberden e publicada, em 1772, no Medical Transactions of the College. Porém, a relação entre essa doença e a angina do peito não estava completamente elucidada e, apenas em 1876 Adam Hammer [4] sugeriu que a angina do peito e o infarto do miocárdio poderiam ser atribuídos à diminuição ou à interrupção do fluxo sanguíneo coronário, quando pelo menos uma das artérias do coração estivesse comprometida. Isso permitiu melhor compreensão da doença arterial coronária, possibilitando a programação de seu tratamento. Os métodos de revascularização do miocárdio não foram estabelecidos do dia para a noite, nem de maneira linear. Procedimentos utilizados num momento inicial foram, em sequência, abandonados, para serem retomados posteriormente e, algumas vezes, considerados ideais. Nas primeiras décadas do século 20 foram utilizados inúmeros procedimentos sobre o coração, visando ao alívio dos sintomas anginosos. Esses métodos foram todos indiretos e ineficazes. Dentre eles, destacamos o proposto por Beck et al. [5] na Cleveland Clinic, em 1935, que buscou a obtenção de circulação colateral com o envolvimento de estruturas como gordura pericárdica, músculo peitoral ou epíplon sobre o epicárdio escarificado. Apenas em 1951 Vineberg et al. [6], após extenso estudo experimental envolvendo o desenvolvimento de circulação colateral, propuseram o implante da artéria torácica interna na musculatura do ventrículo esquerdo. Para tanto, realizavam um túnel em meio à parede ventricular, em cujo interior posicionavam a artéria torácica interna. Os ramos dessa artéria eram mantidos sangrantes, com finalidade de estabelecerem futuras conexões com 138

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as arteríolas miocárdicas isquêmicas. Essa técnica obteve bons resultados e foi um importante tratamento da angina por vários anos. REVASCULARIZAÇÃO DIRETA DO MIOCÁRDIO: UM INÍCIO POLÊMICO Certamente o grande impulso ao desenvolvimento da revascularização do miocárdio foi o advento da cineangiocoronariografia em 1958, atribuído a Sones et al. [7], na Cleveland Clinic. Entretanto, a ideia de revascularizar diretamente o miocárdio encontrou resistência até meados dos anos 1960. Em 2 de maio de 1960, Goetz et al. [8] realizaram a primeira revascularização do miocárdio com sucesso. Anastomosaram a artéria torácica interna direita, empregando sutura mecânica com anel de tantalum, com a artéria coronária direita. A despeito da perviedade ser mantida por 1 ano, foram veementemente criticados por seus colegas clínicos e cirurgiões e o procedimento foi considerado inseguro e de cunho experimental. Goetz nunca mais realizou qualquer revascularização miocárdica [9]. Em 1962, David Sabiston realizou um enxerto com veia safena num paciente que faleceu após três dias de complicações neurológicas. O caso somente foi reportado em 1974. Em 1964, Garrett et al. [10] realizaram no Methodist Hospital, em Houston, a primeira revascularização miocárdica bem sucedida com veia safena, após insucesso na endarterectomia dessa artéria coronária. Uma angiografia realizada após sete anos demonstrou a patência do enxerto e o caso foi relatado em 1973. REVASCULARIZAÇÃO DO MIOCÁRDIO: TÉCNICAS DE EXCELÊNCIA QUE SE PERPETUARAM Artérias torácicas internas Em Leningrado, Rússia, Kolessov [11] realizou, em 25 de fevereiro de 1964, a primeira anastomose da artéria torácica interna esquerda para o ramo interventricular anterior da artéria coronária esquerda. A técnica contou com a toracotomia esquerda, sem o uso da circulação extracorpórea. Na época, o método não teve boa aceitação nos meios internacionais. Um dos motivos era a constatação de que o fluxo imediato da artéria torácica interna esquerda seria inferior ao das pontes de veia safena. A partir de 1967, René Favaloro, trabalhando em consonância com Mason Sones na Cleveland Clinic, popularizou e deu cunho científico às pontes de veia safena no tratamento da insuficiência coronária [12]. Decorrido apenas um ano, em 1968, esse procedimento para a revascularização do miocárdio foi também realizado no Brasil, pelos Drs. Zerbini e Adib Jatene, sendo rapidamente

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reproduzido por inúmeros grupos em todo o país [13,14]. Mais uma vez coube a um estudo realizado na Cleveland Clinic em 1986, por Loop et al. [15], promover forte impacto na história da cirurgia de revascularização do miocárdio. Nele, os autores constataram a superioridade a longo prazo da artéria torácica interna esquerda sobre a veia safena, quando anastomosada ao ramo interventricular anterior da artéria coronária esquerda. Após 10 anos de seguimento, a observação de perviedade superior a 90% elegeu a artéria torácica interna esquerda como o procedimento padrão para revascularizar esse ramo da artéria coronária esquerda. Mais recentemente, Lytle et al. [16] estenderam estudos semelhantes para um período maior. A observação de 90% de enxertos pérvios em 20 anos após a cirurgia conferiu à artéria torácica interna esquerda a condição de terapêutica mais confiável que se conhece no tratamento da doença arterial coronária. A artéria torácica interna direita, quando utilizada para a artéria coronária direita e seus ramos, não mostrou resultados de perviedade semelhantes aos obtidos quando utilizada para o sistema da artéria coronária esquerda. Um grande avanço na revascularização do miocárdio foi seu emprego “in situ”, por via retroaórtica, para ramos da artéria coronária esquerda. Essa técnica foi descrita em nosso meio por Puig et al. [17], em 1984. Essa artéria torácica também passou a ser utilizada para ramos da artéria circunflexa como enxerto arterial composto com a artéria torácica interna esquerda, ou como enxerto livre. Recentemente, diferentes estudos demonstraram a possibilidade do emprego da artéria torácica interna direita “in situ” por via anterógrada para o ramo interventricular anterior da artéria coronária esquerda, com excelentes resultados imediatos [18-21]. ENXERTOS ARTERIAIS ALTERNATIVOS Artérias radial, gastroepiploica, epigástrica inferior e circunflexa lateral femoral Em 1971, Carpentier já havia introduzido a artéria radial como enxerto alternativo para a revascularização coronária, porém, os resultados iniciais foram desapontadores. Atualmente, sua utilização foi restaurada, especialmente após o advento de drogas antiespasmódicas [22]. Isso também motivou o desenvolvimento de propostas alternativas para evitar o seu espasmo [23]. Com sua dissecção, obtém-se um enxerto de 15 a 20 cm, que pode ser utilizado por meio de anastomose proximal na aorta, ou em “Y” com a artéria torácica interna. Sua dissecção pode ser simultânea com a abertura do tórax e, com frequência, está preparada antes do término da dissecção da artéria torácica interna. Essa foi uma das razões que levou ao abandono temporário de sua utilização, pois sua estrutura tecidual sofria danos importantes, quando submetida

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à isquemia prolongada. Hoje é consenso que, após sua dissecção, deve-se mantê-la em seu leito, recoberta com gaze embebida em papaverina para reversão de eventuais espasmos, até o momento de seu emprego. Como alternativa, pode-se retirá-la somente após a administração de heparina sistêmica, imediatamente antes da confecção de sua anastomose proximal. Dessa forma, ela receberá expansão com a pressão sistêmica, sem manipulação e, consequentemente, com menor risco de lesão de suas camadas (principalmente o endotélio), diminuindo a chance de espasmo perioperatório. Hoje se sabe também que, dada sua característica de espasticidade, sua utilização deve ser evitada em artérias coronárias com lesões menores do que 70%, devido ao risco de competição de fluxo, o que poderia eventualmente levar a ocorrência de “string sign” (afilamento difuso de todo enxerto) [24]. A hipótese de que o local da anastomose proximal pudesse interferir no fluxo do enxerto não foi comprovada [25]. Em 1987, Pym et al. [26] descreveram o uso de segmentos de artéria gastroepiploica. Ela origina-se, respectivamente, das artérias hepática, gastroduodenal e pancreatoduodenal. Localiza-se na face anterior da grande curvatura gástrica, sendo responsável pela irrigação dos dois terços inferiores dessa curvatura. Seu emprego em cirurgia cardíaca reserva-se principalmente aos casos em que se busca o uso exclusivo de enxertos arteriais na revascularização do miocárdio. Habitualmente, é utilizada “in situ” para ramos coronários da face inferior do coração, ou em associação com outras artérias, como as torácicas internas e a radial. Nos anos 1990, Puig et al. [27] introduziram a artéria epigástrica inferior. Anatomicamente, origina-se da artéria ilíaca externa, estando situada no terço inferior da parede abdominal, entre o músculo reto abdominal e sua aponeurose posterior. Nessa região, ela penetra no músculo reto abdominal, dividindo-se em vários ramos, que irão se anastomosar com os ramos da artéria epigástrica superior. Está indicada em pacientes jovens, ou pela indisponibilidade dos enxertos habituais, como pacientes safenectomizados ou portadores de varizes em membros inferiores. O ramo descendente da artéria circunflexa lateral femoral também vem sendo estudado nessa linha alternativa. Já em 2003, Fabrocini et al. [28] estudaram por cineangiografia 81 dentre 147 pacientes em que esse enxerto foi empregado. O índice de perviabilidade ao final de 1 e 3 anos foi de, respectivamente, 97% e 93%. Estudo semelhante em nosso meio também revelou elevada patência a curto prazo (92% em 90 dias) e remodelamento positivo do diâmetro luminal [29]. Os autores concluíram que o ramo descendente da artéria circunflexa lateral femoral constitui uma opção promissora de enxerto arterial. 139

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ENXERTOS COM VEIA SAFENA MAGNA O emprego da veia safena magna consagrou a cirurgia de revascularização do miocárdio e até hoje é utilizado em inúmeros centros para complementação na revascularização de determinadas artérias coronárias. Sabe-se que a patência da veia safena humana é inferior à das artérias torácicas internas. Isso se deve, em parte, ao fato que a estrutura da veia safena pode ser afetada por elevadas pressões de distensão, seja no seu preparo ou quando posicionada como enxerto aortocoronário [30,31]. A dissecção da veia safena magna deve ser realizada por pequenas incisões, com aproximadamente 4 cm de extensão, deixando-se uma “ponte” de pele íntegra entre cada incisão. Existem também dispositivos auxiliares que permitem sua retirada de maneira menos invasiva, com mini-incisões de poucos milímetros. Técnicas mais modernas de sua dissecção demonstram que pressões de distensão reduzidas durante a preparação das veias minimizam o risco de lesões endoteliais, melhorando os resultados futuros [32]. Por outro lado, medicamentos que reduzem as taxas sistêmicas de gordura e de adesividade plaquetária têm demonstrado influência na patência a longo prazo desses enxertos. TÉCNICAS MINIMAMENTE INVASIVAS Revascularização sem circulação extracorpórea A busca por procedimentos menos invasivos levou ao desenvolvimento de técnicas de revascularização sem circulação extracorpórea. A possibilidade de se realizar a cirurgia de revascularização do miocárdio sem seu emprego ganhou ênfase nos anos 1990. Buffolo et al. [33] e Benetti et al. [34], assim como outros grupos, passaram a despontar no mundo demonstrando o benefício dessa técnica na redução da morbidade e mortalidade, especialmente pela diminuição de problemas neurológicos. Reservada inicialmente para tratamento de lesões coronárias únicas e localizadas na parede anterior do coração, essa tática foi rapidamente estendida para pacientes com lesão em dois ou mais vasos. Foram desenvolvidos diferentes modelos de estabilizadores cardíacos, que permitiram a diminuição regional do movimento cardíaco. Passouse também a fazer uso de “shunts” intracoronários, que possibilitaram a manutenção da irrigação do leito distal durante a anastomose, evitando isquemia e eventual deterioração hemodinâmica. Isso proporcionou um maior conforto para a confecção das anastomoses nessas cirurgias [35]. O assunto tornou-se polêmico e inúmeros estudos comparativos foram desenvolvidos, com resultados conflitantes. A maioria deles se baseou na menor reação inflamatória que envolve o procedimento. Mas, certamente, o grande benefício do método consiste 140

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em se evitar a manipulação excessiva da aorta ascendente. Dessa maneira, embora seja desejável minimizar o uso da circulação extracorpórea na revascularização miocárdica, ainda é um grande desafio para a moderna cirurgia cardíaca evitá-la em todos os casos. Revascularização do miocárdio por miniacesso Na busca de manter os benefícios do tratamento cirúrgico da insuficiência coronária, com técnicas menos invasivas e com menor trauma cirúrgico, temse procurado realizar a revascularização do miocárdio com a artéria torácica interna por minitoracotomia, evitando-se a circulação extracorpórea e a esternotomia. O primeiro relato de revascularização do miocárdio por esse miniacesso foi descrito por Benetti & Ballester [36], em 1995. Em dois pacientes, os autores lograram dissecar a artéria torácica interna esquerda por minitoracotomia anterior esquerda, com o auxílio do videotoracoscópio e a anastomosaram à artéria coronária interventricular anterior. Subramanian et al. [37] também relataram experiência com revascularização do miocárdio por minitoracotomia, porém com dissecção direta da artéria torácica interna esquerda, sem o uso do toracoscópio. Uma das principais preocupações dessa nova técnica era a qualidade da anastomose da artéria torácica interna com a artéria coronária, na ausência de circulação extracorpórea e por miniacesso. No início da experiência, alguns autores relataram problemas na anastomose coronária e necessidade de reoperação precoce entre 10% e 15% dos pacientes [38,39]. Com o advento de estabilizadores regionais de coronária, a anastomose coronária com o coração batendo passou a ser realizada com maior segurança e a revascularização do miocárdio sem circulação extracorpórea com esternotomia total ou por miniacesso passou a ter maior aceitação por parte dos cirurgiões cardiovasculares [40-42]. CIRURGIA ROBÓTICA NA REVASCULARIZAÇÃO DO MIOCÁRDIO Várias técnicas minimamente invasivas de revascularização do miocárdio têm sido facilitadas pela adequada visão endoscópica durante a dissecção da artéria torácica interna. O emprego dessas técnicas na cirurgia cardiovascular vem proporcionando uma nova alternativa, menos invasiva, para indivíduos com insuficiência coronária. A operação pode ser realizada com melhor estética, possibilitando uma recuperação mais rápida, com menor tempo de internação hospitalar [43]. No Brasil, a dissecção robótica da artéria torácica interna esquerda foi iniciada em 2001, com o emprego de videotoracoscopia guiada por braço robótico (AESOP), integrado ao sistema de movimentação da fibra óptica,

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através de comunicação por voz [44]. É importante lembrar que o aprimoramento e a aplicação dessas técnicas requerem um treinamento em etapas e uma intensiva curva de aprendizado [45,46]. Diversos estudos recentes vêm demonstrando as vantagens desses procedimentos minimamente invasivos. Em nosso meio, Milanez et al. [47] demonstraram a possibilidade da dissecção da artéria torácica interna esquerda por via robótica, com resultados superponíveis aos obtidos por sua dissecção tradicional. O objetivo final seria a factibilidade da revascularização completa do miocárdio, com o auxílio da videotoracoscopia, sem que se realize a abertura do tórax [48-50]. Nesse sentido, o auxílio robótico vem ganhando terreno progressivo na prática clínica, auxiliando na dissecção da artéria torácica interna e na realização da anastomose coronária [51,52]. Cirurgias robóticas de revascularização do miocárdio com o tórax totalmente fechado são uma realidade em alguns centros dos Estados Unidos e Europa, sendo as anastomoses realizadas com o uso de dispositivos mecânicos, sem a utilização de circulação extracorpórea. A despeito de relatos iniciais com resultados favoráveis, o custo elevado desses equipamentos e a grande dificuldade na curva de aprendizado têm limitado esses procedimentos a poucos centros especializados no mundo. Todas essas inovações visam otimizar os resultados já alcançados, com menor agressão ao paciente e com menor morbidade e mortalidade; algumas, porém, ainda necessitam ser incorporadas de forma rotineira na prática clínica diária, tornando os procedimentos mais eficazes, seguros e reproduzíveis. SALA CIRÚRGICA HÍBRIDA O desenvolvimento e mudanças recentes da cirurgia cardíaca e da cardiologia intervencionista têm demonstrado a necessidade da instalação do laboratório de hemodinâmica integrado à sala cirúrgica. Essas salas híbridas ou “high-tech”, como são mais comumente conhecidas, começaram a ser idealizadas a partir do crescimento da cirurgia cardíaca minimamente invasiva e da necessidade da cardiologia intervencionista em realizar procedimentos cada vez mais invasivos e complexos. A sala híbrida, em geral, é localizada dentro do centro cirúrgico e utilizada em cirurgias menos invasivas, videoassistidas ou robóticas, que necessitem de modalidade de imagens mais sofisticadas e complexas. Elas fornecem segurança ao ato operatório e permitem ao cirurgião uma rápida avaliação do resultado cirúrgico. Procedimentos intervencionistas mais invasivos e complexos que necessitem de rápida atuação do cirurgião cardiovascular e de assistência mecânica também são realizados nessa sala. Atualmente, a sala cirúrgica híbrida é uma realidade,

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não só em instituições acadêmicas e de pesquisas, mas também em hospitais gerais. O interesse recente nessas salas tem levantado questões importantes quanto a utilização, padronização, dimensões e organização de material e pessoal nessas unidades. REVASCULARIZAÇÃO DO MIOCÁRDIO: CONSIDERAÇÕES ATUAIS Ainda nos dias de hoje, a revascularização cirúrgica do miocárdio permanece como uma excelente opção terapêutica para tratamento da doença arterial coronária obstrutiva, mesmo em pacientes diabéticos [53,54], em pacientes idosos [55,56] e em pacientes com baixa fração de ejeção de ventrículo esquerdo [57]. Procedimentos alternativos, como o uso de raios laser [58], células-tronco [59] e até variações no emprego da artéria torácica interna [60] vêm sendo descritos, mas fazem parte do tratamento de um grupo especial de pacientes, que certamente não se enquadram na rotina diária. Está bem claro que a cirurgia de revascularização do miocárdio passa por um momento de transformação, como podemos observar: cirurgias utilizando apenas enxertos arteriais, sem o uso da circulação extracorpórea, realizadas de maneira minimamente invasiva, se possível com o auxílio da robótica. Os objetivos dessa cirurgia são basicamente o alívio nos sintomas anginosos, com consequente melhora da qualidade de vida, bem como o aumento da sobrevida. Busca-se, especialmente em pacientes jovens, um tipo de intervenção alternativa ao tratamento medicamentoso ou percutâneo que mantenha resultados a longo prazo, evitando a recorrência da angina ou de eventos cardíacos, minimizando assim a necessidade de reoperações ou reintervenções. Apesar da tendência do emprego do maior número possível de enxertos arteriais na revascularização miocárdica, devido à patência superior das artérias torácicas internas e outros enxertos arteriais, a veia safena continua sendo muito usada por ser de boa extensão e fácil obtenção. Limitações como falência desse enxerto a longo prazo têm sido contornadas pelo seu preparo adequado e tratamento sistêmico do paciente, especialmente com o controle de sua pressão arterial, dos índices glicêmicos e pelo uso de estatinas. Por outro lado, as artérias torácicas internas raramente desenvolvem doença aterosclerótica, seus diâmetros habitualmente são compatíveis com a artéria coronária a ser revascularizada e suas limitações no comprimento podem ser superadas por meio da esqueletização ou emprego como enxerto livre [61]. Entretanto, a utilização de ambas as artérias torácicas internas requer técnica mais apurada e aumenta o tempo cirúrgico. Sendo assim, a utilização das duas artérias 141

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torácicas internas ainda não é feita de forma rotineira em todos os serviços e nos diversos subgrupos de pacientes. Isso faz com que os índices de utilização das artérias torácicas internas variem de 4% a 30%, mesmo em países como Estados Unidos, Japão e alguns da Europa [62,63]. Atualmente se sabe que, a longo prazo, ocorre a remodelação das artérias torácicas internas, que acabam por adequar seu fluxo ao leito miocárdico receptor. Dessa maneira, a artéria torácica interna direita vem sendo preferida como segundo enxerto arterial, quando comparada à artéria radial. Portanto, o uso das artérias torácicas internas esquerda e direita, complementado ou não por enxertos arteriais ou com veia safena, constitui ainda hoje a condição terapêutica mais indicada no tratamento da doença arterial coronária obstrutiva. Em poucas palavras, o que se considera ideal numa cirurgia de revascularização miocárdica será a sua realização a baixo custo e de forma minimamente invasiva (videoassistida ou robótica), sem o uso da circulação extracorpórea, empregando enxertos arteriais e, se necessário, associada a procedimentos híbridos (cirurgia minimamente invasiva complementada por atuação percutânea).

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34. Benetti FJ, Naselli G, Wood M, Geffner L. Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients. Chest. 1991;100(2):312-6.

24. Dallan LAO, Oliveira SA, Lisboa LA, Platania F, Jatene FB, Iglézias JCR, et al. Revascularização completa do miocárdio com uso exclusivo de enxertos arteriais. Rev Bras Cir Cardiovasc.1998;13(3):187-93. 25. Carneiro LJ, Platania F, Dallan LAP, Dallan LAO, Stolf NAG. Revascularização miocárdica com artéria radial: influência da anastomose proximal na oclusão a médio e longo prazo. Rev Bras Cir Cardiovasc. 2009;24(1):38-43. 26. Pym J, Brown PM, Charrette EJ, Parker JO, West RO. Gastroepiploic-coronary anastomosis. A viable alternative bypass graft. J Thorac Cardiovasc Surg. 1987;94(2):256-9. 27. Puig LB, Ciongolli W, Cividanes GV, Dontos A, Kopel L, Bittencourt D, et al. Inferior epigastric artery as a free graft for myocardial revascularization. J Thorac Cardiovasc Surg.1990;99(2):251-5. 28. Fabbrocini M, Fattouch K, Camporini G, DeMicheli G, Bertucci C, Cioffi P, et al. The descending branch of lateral femoral circumflex artery in arterial CABG: early and midterm results. Ann Thorac Surg. 2003;75(6):1836-41. 29. Gaiotto FA, Vianna CB, Dallan LAO, Senra T, Cesar LAM, Stolf NAG, et al. Ramo descendente da circunflexa lateral femoral na revascularização do miocárdio: avaliação angiotomográfica de curto prazo. 33º Congresso da Sociedade de Cardiologia do Estado de São Paulo. 2012 jun 7-9. São Paulo, SP. 30. Dallan LAO, Miyakawa AA, Lisboa LA, Abreu Filho CA, Campos L, Borin T, et al. Alterações estruturais e moleculares (cDNA) precoces em veias safenas humanas cultivadas sob regime pressórico arterial. Rev Bras Cir Cardiovasc. 2004;19(2):126-35. 31. Dallan LAO, Miyakawa AA, Lisboa LA, Borin TF, Abreu Filho CAC, Campos LC, et al. Ação inibitória da interleucina - 1β sobre a proliferação de células musculares lisas cultivadas a partir de veias safenas humanas. Rev Bras Cir Cardiovasc 2005;20(2):111-6. 32. Souza DS, Dashwood MR, Tsui JC, Filbey D, Bodin L, Johanssonet B, et al. Improved patency in vein grafts harvested with surrounding tissue: results of a randomized study using three harvesting techniques. Ann Thorac Surg. 2002;73(4):1189-95. 33. Buffolo E, Andrade JC, Branco JN, Aguiar LF, Ribeiro EE, Jatene AD. Myocardial revascularization without

35. Jatene FB, Pego-Fernandes PM, Hueb AC, Oliveira PM, Hervoso CM, Dallan LA, et al. Revascularização do miocárdio por técnica minimamente invasiva: o que aprendemos após 3 anos com seu emprego. Rev Bras Cir Cardiovasc. 1999;14(1):6-13. 36. Benetti FJ, Ballester C. Use of thoracoscopy and a minimal thoracotomy, in mammary-coronary bypass to left anterior descending artery, without extracorporeal circulation. Experience in 2 cases. J Cardiovasc Surg (Torino). 1995;36(2):159-61. 37. Subramanian VA, McCabe JC, Geller CM. Minimally invasive direct coronary artery bypass grafting: two-year clinical experience. Ann Thorac Surg. 1997;64(6):1648-53. 38. Alessandrini F, Luciani N, Marchetti C, Guadino M, Possati G. Early results with the minimally invasive thoracotomy for myocardial revascularization. Eur J Cardiothorac Surg. 1997;11(6):1081-5. 39. Pagni S, Qaqish NK, Senior DG, Spence PA. Anastomotic complications in minimally invasive coronary bypass grafting. Ann Thorac Surg. 1997;63(6 Suppl):S64-7. 40. Borst C, Jansen EW, Tulleken CA, Grundeman PF, Mansvelt Beck HJ, van Dongen JW, et al. Coronary artery bypass grafting without cardiopulmonary bypass and without interruption of native coronary flow using a novel anastomosis site restraining device (“Octopus”). J Am Coll Cardiol. 1996;27(6):1356-64. 41. Jansen EW, Grundeman PF, Borst C, Eefting F, Diephuis J, Nierich A, et al. Less invasive off-pump CABG using a suction device for immobilization: the ‘Octopus’ method. Eur J Cardiothorac Surg. 1997;12(3):406-12. 42. Oliveira SA, Lisboa LA, Dallan LA, Rojas SO, Figueiredo LFP. Minimally invasive single-vessel coronary artery bypass with the internal thoracic artery and early postoperative angiography: midterm results of a prospective study in 120 consecutive patients. Ann Thorac Surg. 2002;73(2):505-10. 43. Jatene FB, Fernandes PM, Stolf NA, Kalil R, Hayata AL, Assad R, et al. Minimally invasive myocardial bypass surgery using video-assisted thoracoscopy. Arq Bras Cardiol. 1997;68(2):107-11. 44. Dallan LAO, Lisboa LA, Abreu Filho CA, Platania F, Dallan LAP, Iglézias JC, et al. Assistência robótica para dissecção minimamente invasiva da artéria torácica interna na revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2003;18(1):110.

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45. Bonatti J, Schachner T, Bernecker O, Chevtchik O, Bonaros N, Ott H, et al. Robotic totally endoscopic coronary artery bypass: program development and learning curve issues. J Thorac Cardiovasc Surg. 2004;127(2):504-10.

54. Lev-Ran O, Mohr R, Aviram G, Matsa M, Nesher N, Pevni D, et al. Repeat median sternotomy after prior ante-aortic crossover right internal thoracic artery grafting. J Card Surg. 2004;19(2):151-4.

46. Oehlinger A, Bonaros N, Schachner T, Ruetzler E, Friedrich G, Laufer G, et al. Robotic endoscopic left internal mammary artery harvesting: what have we learned after 100 cases? Ann Thorac Surg. 2007;83(3):1030-4.

55. Guru V, Fremes SE, Tu JV. How many arterial grafts are enough? A population-based study of midterm outcomes. J Thorac Cardiovasc Surg. 2006;131(5):1021-8.

47. Milanez AMM. Revascularização do miocárdio minimamente invasiva com dissecção da artéria torácica interna esquerda por videotoracoscopia robótica e anastomose ao ramo interventricular anterior via minitoracotomia anterior: estudo comparativo com a técnica convencional [Tese de doutorado]. São Paulo: Faculdade de Medicina da Universidade de São Paulo; 2011. 48. Soulez G, Gagner M, Therasse E, Basile F, Prieto I, Pibarot P, et al. Catheter-assisted totally thoracoscopic coronary artery bypass grafting: a feasibility study. Ann Thorac Surg. 1997;64(4):1036-40. 49. Mack MJ, Acuff TE, Casimir-Ahn H, Lönn UJ, Jansen EW. Video-assisted coronary bypass grafting on the beating heart. Ann Thorac Surg. 1997;63(6 Suppl):S100-3. 50. Bonatti J, Schachner T, Bonaros N, Oehlinger A, Wiedemann D, Ruetzler E, et al. Effectiveness and safety of total endoscopic left internal mammary artery bypass graft to the left anterior descending artery. Am J Cardiol. 2009;104(12):1684-8. 51. Loulmet D, Carpentier A, d’Attellis N, Berrebi A, Cardon C, Ponzio O, et al. Endoscopic coronary artery bypass grafting with the aid of robotic assisted. J Thorac Cardiovasc Surg. 1999:118(1):4-10. 52. Reichenspurner H, Damiano RJ, Mack M, Boehm DH, Gulbins H, Detter C, et al. Use of the voice-controlled and computerassisted surgical system ZEUS for endoscopic coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1999;118(1):11-6. 53. Stevens LM, Carrier M, Perrault LP, Hébert Y, Cartier R, Bouchard D, et al. Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg. 2005;27(2):281-8.

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56. Kieser TM, Lewin AM, Graham MM, Martin BJ, Galbraith PD, Rabi DM, et al; APPROACH Investigators. Outcomes associated with bilateral internal thoracic artery grafting: the importance of age. Ann Thorac Surg. 2011;92(4):1269-75. 57. Galbut DL, Kurlansky PA, Traad EA, Dorman MJ, Zucker M, Ebra G. Bilateral internal thoracic artery grafting improves long-term survival in patients with reduced ejection fraction: a propensity-matched study with 30-year follow-up. J Thorac Cardiovasc Surg. 2012;143(4):844-853.e4. 58. Dallan LAO, Gowdak LH, Lisboa LAF, Schettert I, César LAM, Oliveira SA, et al. Terapia celular associada à revascularização transmiocárdica a laser como proposta no tratamento da angina refratária. Rev Bras Cir Cardiovasc. 2008;23(1):46-52. 59. Gowdak LH, Schettert IT, Rochitte CE, Lisboa LA, Dallan LA, Cesar LA, et al. Early increase in myocardial perfusion after stem cell therapy in patients undergoing incomplete coronary artery bypass surgery. J Cardiovasc Transl Res. 2011;4(1):106-13. 60. Dallan LAO, Gowdak LH, Lisboa LAF, Milanez AMM, Platania F, Moreira LFP, et al. Modificação de antigo método (Vineberg) na era das células tronco: nova tática? Arq Bras Cardiol. 2009;93(5):79-81. 61. Lisboa LAF, Dallan LAO, Puig LB, Abreu Filho C, Leca RC, Dallan LAP, et al. Seguimento clínico a médio prazo com uso exclusivo de enxertos arteriais na revascularização completa do miocárdio em pacientes com doença coronária triarterial. Rev Bras Cir Cardiovasc. 2004;19(1):9-16. 62. Kappetein AP. Bilateral mammary artery vs. single mammary artery grafting: promising early results: but will the match finish with enough players? Eur Heart J. 2010;31(20):2444-6. 63. Kinoshita T, Asai T. Bilateral internal thoracic artery grafting: current state of the art. Innovations (Phila). 2011;6(2):77-83.

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Correção endovascular de dissecção de aorta ascendente Endovascular repair of ascending aortic dissection

José Carlos Dorsa Vieira Pontes1, Amaury Mont’Serrat Ávila Souza Dias2, João Jackson Duarte3, Ricardo Adala Benfatti3, Neimar Gardenal4 DOI: 10.5935/1678-9741.20130018

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Resumo Paciente de 84 anos com dissecção de aorta torácica tipo A de Stanford comprometendo todo o arco aórtico e aorta descendente. Proposto e aceito o tratamento endovascular em função da gravidade do quadro clínico. Procedeu-se à dissecção das artérias femorais comum bilateralmente. A aortografia confirmou a exclusão da falsa luz e a patência dos óstios coronarianos.

Abstract Woman, 84 years-old, with Stanford type A thoracic aortic dissection committing aortic arch and descending aorta. Proposed and accepted endovascular treatment according to the severity of the clinical picture. Common femoral artery dissection bilaterally was done. Aortography confirmed the exclusion of the false lumen and patency of the coronary ostia.

Descritores: Aneurisma endovasculares. Stents.

Descriptors: Aneurysm, procedures. Stents.

dissecante.

Procedimentos

INTRODUÇÃO É consenso que o tratamento das dissecções tipo A é cirúrgico e imediato, uma vez que o mesmo impede o óbito decorrente de complicações como tamponamento, rotura, infarto, insuficiência aórtica aguda e complicações neurológicas centrais [1]. Porém, o tratamento cirúrgico convencional apresenta complicações decorrentes do próprio trauma cirúrgico, da exposição do paciente à circulação extracorpórea, da complexidade da lesão aórtica com comprometimento de vasos à distância, da existência das complicações relacionadas à evolução natural da doença, sendo a mortalidade operatória de 10% a 30% [2]. Não obstante a isso, a coexistência de doenças sistêmicas graves, como enfisema, diabetes, insuficiência 1. Doutorado, Diretor Geral do Núcleo do Hospital Universitário – Universidade Federal do Mato Grosso do Sul-UFMS, Campo Grande, MS, Brasil. 2. Especialista em Cirurgia Cardiovascular, Campo Grande, MS, Brasil. 3. Mestre em Cirurgia Cardiovascular, Campo Grande, MS, Brasil. 4. Mestre em Cirurgia Cardiovascular, Cirurgião Cardiovascular, Campo Grande, MS, Brasil.

dissecting.

Endovascular

renal e idade avançada, faz com que o tratamento cirúrgico convencional apresente elevado risco de letalidade. O tratamento endovascular é amplamente empregado para tratamento de doenças da aorta torácica. Na literatura são descritos casos isolados de abordagem endovascular de lesões de aorta ascendente. O presente artigo reporta a correção endovascular de uma paciente com dissecção de aorta ascendente. APRESENTAÇÃO DO CASO CLÍNICO Paciente de 84 anos, procedente de Mato Grosso do Sul, com dor torácica e dispneia, atendida no pronto socorro de um hospital de Campo Grande, MS, em outubro de 2011, ocasião em que foi internada com os seguintes Endereço para correspondência: José Carlos Dorsa Vieira Pontes Hospital Universitário-UFMS Av. Senador Filinto Muller, 355 – Vila Ipiranga Campo Grande, MS, Brasil – CEP: 79080-190 E-mail: carlosdorsa@uol.com.br Artigo recebido em 20 de junho de 2012 Artigo aprovado em 27 de agosto de 2012

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Abreviatuaras, acrônimos e siglas ASD UTI

Angiografia por subtração digital Unidade de terapia intensiva

diagnósticos: doença pulmonar obstrutiva crônica, diabetes mellitus, insuficiência cardíaca congestiva descompensada, pneumonia e insuficiência renal crônica. À radiografia de tórax foi observado alargamento de mediastino. O ecocardiograma realizado à beira de leito demonstrou miocardiopatia dilatada (fração de ejeção de 0,4) além de imagem característica de dissecção de aorta ascendente. Procedeu-se à investigação com angiotomografia coronária, a qual evidenciou dissecção de aorta torácica tipo A de Stanford comprometendo todo o arco aórtico e aorta descendente, porém sem comprometimento dos ramos supra-aórticos, e o início da dissecção a 1 cm do óstio coronariano direito (Figura 1). Não foram observados pontos de reentrada. Em função da gravidade do quadro clínico da paciente, o tratamento cirúrgico convencional mostrava-se não factível, em decorrência das comorbidades e do elevado risco de morte (EuroSCORE 83%). Foi proposto, portanto,

Fig 1 – Dissecção de aorta torácica tipo A de Stanford comprometendo todo o arco aórtico e aorta descendente

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o tratamento endovascular após o esclarecimento e consentimento da paciente e dos seus familiares. Foi solicitada confecção de endoprótese aórtica com diâmetro de 40 mm, com 8 cm de extensão de área recoberta e 2 cm de área não recoberta em sua porção caudal (free flow), o que permite aumento da área de ancoragem, sendo que a área não recoberta iria se fixar no arco aórtico, sem risco de oclusão de seus ramos. Procedeu-se, sob anestesia geral em ambiente de hemodinâmica, à dissecção das artérias femorais comum bilateralmente. Em se tratando de procedimento de exceção e de alto risco, a artéria femoral contralateral foi dissecada preventivamente, em caso de necessidade de instalação de circulação extracorpórea de forma emergencial. A artéria femoral esquerda foi cateterizada para inserção de cateter de aortografia e localização dos óstios coronarianos. A artéria femoral direita foi dissecada e exposta, inserindose fio-guia com sua extremidade ultrapassando a valva

Fig. 2 – Guia rígida posicionada dentro do ventrículo esquerdo

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aórtica e adentrando a cavidade ventricular esquerda. Induzida hipotensão arterial na paciente e posicionado o stent acima dos óstios coronários. Os óstios coronários não foram cateterizados, simplesmente marcados na aortografia, visando ao correto posicionamento da prótese logo acima da origem do óstio direito. Assim sendo, as artérias coronárias não foram seletivadas, apenas contrastadas em modo de aquisição angiografia por subtração digital (ASD), para marcar a distância da artéria coronária direita do orifício de entrada da dissecção. A guia rígida foi posicionada dentro do ventrículo esquerdo, uma vez que a própria ogiva do dispositivo teve que ser posicionada transvalvar (Figura 2). A aortografia realizada nesse momento confirmou a exclusão da falsa luz e a patência dos óstios coronarianos. A paciente foi extubada na sala de cirurgia e encaminhada para a Unidade de Terapia Intensiva (UTI). A evolução foi satisfatória, tendo a paciente recebido alta hospitalar sem realização de exame contrastado, por orientação do Serviço de Nefrologia. No seguimento ambulatorial, com clearance de creatinina abaixo de 25%, e a paciente bem clinicamente, optou-se pela não realização de exame de imagem com contraste apenas para controle e sem indicação clínica precisa, considerando-se a relação custo/benefício.

de dissecção de aorta tipo A, que foi tratado com implante de stent e exclusão da falsa luz. Nosso trabalho demonstra que essa técnica é factível e promissora, e o treinamento da equipe cirúrgica é primordial para sua execução, que quando bem treinada pode abordar lesões aórticas complexas como dessa paciente, com orifício de entrada a 1 cm do óstio coronariano. CONCLUSÃO O resultado cirúrgico não depende somente do treinamento da equipe, atenção particular deve ser dada à endoprótese como a força radial adequada fixação e não deslocamento da mesma, o que comprometeria, nos casos de lesões justaostiais, a oclusão da entrada da falsa luz e poderia obstruir os ramos supra-aórticos. O reparo endovascular de doenças da aorta ascendente ainda é incipiente e não apresenta relevância estatística quanto à mortalidade a médio prazo, requerendo maior período de acompanhamento dos pacientes submetidos a novas técnicas para firmar o seu sucesso.

DISCUSSÃO A utilização de uma endoprótese customizada é objeto de estudo como uma alternativa para a abordagem de lesões em aorta ascendente, portanto, reservando-se aos casos em que os pacientes não apresentem condições de suportar a cirurgia convencional, mas nem por isso necessitem menos a imediata resolução dessa importante doença da aorta. O tratamento endovascular para doenças da aorta é amplamente empregado nas situações de dissecção tipo B de Stanford [1], porém a utilização da mesma para tratamento de aorta ascendente constitui um desafio. O procedimento tem técnica bem particular, exigindo preparo, aprimoramento e domínio apurados. A primeira descrição de utilização de endoprótese para abordagem de dissecção de aorta do tipo A de Stanford foi feita em outubro de 2007 [3]. A utilização de stent em aorta ascendente tem na literatura como exemplo casos isolados com terapia híbrida. Foi relatado em 2007 um implante de stent, porém com paciente em circulação extracorpórea [4]. Casos mais recentes têm abordado a aorta ascendente para tratamento de pseudoaneurismas de forma endovascular [5]. Mais recentemente, em 2012, foi publicado um caso

REFERÊNCIAS 1. Albuquerque LC, Braile DM, Palma JH, Saadi EK, Almeida RMS, Gomes WJ, et al. Diretrizes para o tratamento cirúrgico das doenças da aorta da Sociedade Brasileira de Cirurgia Cardiovascular: atualização 2009. Rev Bras Cir Cardiovasc. 2009;24(2 supl. 1):7-33. 2. Borst HG, Heinemann MK, Stone CD. Surgical treatment of aortic dissection. New York: Churchill Livingstone; 1996. p.357. 3. Senay S, Alhan C, Toraman F, Karabulut H, Dagdelen S, Cagil H. Endovascular stent-graft treatment of type A dissection: case report and review of literature. Eur J Vasc Endovasc Surg. 2007;34(4):457-60. 4. Dias RR, Silva IA, Fiorelli AI, Stolf NAG. Tratamento híbrido com endoprótese não recoberta nas dissecções agudas da aorta tipo A. Rev Bras Cir Cardiovasc. 2007;22(4):495-7. 5. Saadi EK, Moura L, Zago A, Zago A. Endovascular repair of ascending aorta and coronary stent implantation. Rev Bras Cir Cardiovasc. 2011;26(3):477-80.

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Erros em artigos científicos brasileiros são mais conceituais do que de DIVULGAÇÃO CIENTÍFICA expressão

Erros em artigos científicos brasileiros são mais conceituais do que de expressão Mistakes in Brazilian papers are more from concepts than of expression

Elton Alisson

DOI: 10.5935/1678-9741.20130019

Agência FAPESP – A redação científica ainda representa o “calcanhar de Aquiles” de muitos pesquisadores brasileiros. E os erros cometidos ao escrever uma tese ou artigo científico estão muito mais relacionados a problemas de metodologia de pesquisa do que à falta de habilidade com as palavras para apresentar os resultados de forma clara, concisa e interessante. A análise de Gilson Volpato, professor do Departamento de Fisiologia do Instituto de Biociências da Universidade Estadual Paulista (Unesp), campus de Botucatu, está na sexta edição revisada e ampliada do livro Ciência: da filosofia à publicação. Lançada no início de dezembro, a edição acrescenta quatro novos capítulos aos nove da primeira edição, publicada em 1998. Um deles apresenta um breve resumo da história da filosofia para explicar por que a ciência é feita tal como é hoje – aceitando conclusões apenas se forem baseadas em evidências empíricas (comprovadas experimentalmente). A ideia desse capítulo, segundo Volpato, é demonstrar ao leitor o caráter indissociável entre a prática da ciência e questões teóricas e filosóficas, e que só é possível fazer boa ciência e escrever artigos para publicação em revistas de elevado fator de impacto quando se tem uma boa formação filosófica e um entendimento muito preciso dos conceitos científicos. “É necessário ter uma compreensão muito clara sobre o que é fazer ciência para realizar boas pesquisas, que resultem em artigos sólidos para serem publicados em revistas de alto nível. Não dá só para corrigir a ponta desse processo – a redação científica – sem ter uma base bem fundamentada por trás disso”, disse Volpato à Agência FAPESP. Especialista em redação e publicação científica, o autor – que dá cursos na área e já auxiliou pesquisadores brasileiros a reescreverem mais de 250 artigos científicos nas áreas de humanas, exatas e biológicas – avalia que alguns dos artigos publicados por cientistas do país apresentam muitos problemas estruturais. 148

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Entre eles estão introduções que não cumprem essa função, tabelas, gráficos e figuras incompreensíveis, métodos duvidosos e dados que não corroboram as conclusões dos autores mas que, na maioria dos casos, segundo Volpato, apresentam erros inerentes à própria pesquisa. “Se a pesquisa começou errada e é ruim não tem como fazer mágica no artigo. Se o pesquisador estudou uma questão irrelevante, por melhor que sejam os resultados, eles jamais resultarão em artigos científicos que extrapolarão as fronteiras sequer de seu laboratório e que dirá do Brasil”, disse. Um dos principais erros conceituais nos trabalhos publicados por alguns cientistas brasileiros, de acordo com Volpato, é querer fazer ciência para solucionar problemas pontuais e localizados, sem tratar o fenômeno geral, que justamente tem a capacidade de resolver problemas pontuais. Prova disso, de acordo com o especialista, é que no próprio título de alguns trabalhos publicados ainda aparecem o nome da instituição ou da cidade onde a pesquisa foi realizada e os dados foram coletados, reforçando a ideia de que o estudo está circunscrito àquele local. “Para fazer ciência, realmente é preciso de dados que são coletados de algum lugar. Mas o problema é que alguns pesquisadores brasileiros coletam dados de um determinado lugar e só se preocupam com aquele lugar especificamente”, afirmou Volpato. “É muito diferente de pegar os dados de um determinado lugar e construir uma ciência geral, que resolve questões particulares, como pode ser visto em artigos publicados por cientistas estrangeiros em grandes revistas científicas internacionais. Ainda falta esse aprendizado e ousadia científica ao pesquisador brasileiro”, compara. Questões pontuais Segundo Volpato, alguns dos fatores responsáveis pela ausência da ciência geral são a falta de formação filosófica sobre o que é necessário para construir conhecimento e o

Erros em artigos científicos brasileiros são mais conceituais do que de expressão

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fato de que o Brasil ficou por muito tempo fechado para o mundo. Algumas áreas ficaram dissociadas da ciência produzida no exterior. Por outro lado, de acordo com Volpato, outras áreas relacionadas à ciência básica, como imunologia, biologia celular e física, sempre tiveram uma inserção internacional natural que continuou e ganhou maior projeção na década de 1990 com os adventos da globalização e da internet. De acordo com o pesquisador, é preciso rever esse conceito de se fazer ciência sob uma perspectiva estritamente local para que se possa melhorar a qualidade dos artigos científicos publicados por brasileiros e, consequentemente, aumentar a publicação em revistas de alto fator de impacto e citação internacional. “A redação científica é um forte indicador sobre os conceitos científicos dos autores de forma que para melhorá-

la é preciso, primeiramente, corrigir os conceitos dos pesquisadores sobre o que é fazer ciência”, disse. Volpato também é autor dos livros Método lógico para a redação científica, Bases teóricas da redação científica, Publicação científica, Bases teóricas para redação científica, Administração da vida científica, Pérolas da redação científica, Dicas para redação científica, Lógica da redação científica e Estatística sem dor!. O professor também divulga seu trabalho no site www. gilsonvolpato.com.br , que oferece artigos, dicas e reflexões sobre redação científica, educação e ética na ciência. O site dá acesso a aulas on-line do curso “Bases Teóricas para Redação Científica”, apresentado por Volpato na Unesp. Publicado pela Agência Fapesp em 3 de janeiro de 2013. URL: http://agencia.fapesp.br/16655

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DOI: 10.5935/1678-9741.20130020

Impacto na mortalidade precoce e tardia após transfusão de hemáceas em cirurgia de revascularização miocárdica “Lamb’s blood was used for the transfusion, and the man had a violent reaction, the horrible symptoms being chills and fever and black urine.” Jean Baptiste Denis, 1665 Prezado Editor, Li com muito interesse o artigo de Santos et al. [1]: “Impacto na mortalidade precoce e tardia após transfusão de hemácias em cirurgia de revascularização miocárdica”, a ser publicado na Revista Brasileira de Cirurgia Cardiovascular [1]. O assunto é muito relevante, mas algumas considerações importantes valem a pena serem discutidas. A primeira tentativa de transfusão sanguínea para humanos ocorreu na França, em 1665, quando se usou sangue de ovelha para tratamento de uma psicose. O objetivo foi o de restaurar a sanidade ao paciente; no entanto, o que se observou foi a primeira reação à incompatibilidade sanguínea. O primeiro relato de transfusão sanguínea utilizando-se sangue humano ocorreu no ano de 1665, em Londres, por Richard Lower. Os problemas de coagulação, compatibilidade e estocagem de sangue foram resolvidos posteriormente. Durante os conflitos bélicos (principalmente após a II Grande Guerra Mundial), transfusões sanguíneas foram largamente empregadas [2]. A indicação de transfusão de hemocompenentes em pacientes submetidos à cirurgia cardíaca, medidas para limitar a sua utilização (drogas fibrinolíticas, circuitos de extracorpórea recobertos com heparina), reutilização do sangue perdido durante a cirurgia e a não utilização da circulação extracorpórea (CEC), todos contribuíram para a diminuição do número de transfusões [3]. Na verdade, nem sempre é possível a não utilização de hemoderivados. Preocupações existem ao se realizar transfusões: infecções 150

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(virais, bacterianas), incompatibilidade e uma complicação silenciosa, os efeitos imunossupressores [4]. Quando analisam o desfecho mortalidade relacionado à transfusão de hemácias em cirurgia de revascularização do miocárdio, Santos et al. [1] reforçaram as observações quanto ao seu impacto precoce e imediato. Koch et al. [5] analisaram que, na verdade, sangue estocado por mais de 14 dias seria mais relacionado a complicações pós-operatórias. Sangue mais “novo” (menos de 14 dias de conservação) apresenta menor risco relativo (30%) em relação à mortalidade pós-operatória. Em 1 ano, a mortalidade observada foi de 11% para sangue mais “velho” (mais de 14 dias de conservação) [5]. Seria esse dado uma nova limitação ao estudo realizado? Quando analisamos somente transfusão sanguínea e suas influência adversa, não podemos esquecer a eficácia e a segurança no uso da autotransfusão [6]. Se, como observou Koch et al. [5], o sangue estocado apresenta maior risco, então provavelmente o mesmo seria válido para autotransfusão estocada. Mas, se ela for utilizada mais precocemente ou até mesmo no intraoperatório antes da CEC, esse impacto na mortalidade precoce e tardia observado por Santos et al. [1] também ocorreria? O trabalho em questão não nos fornece tais dados. Hélcio Giffhorn Cirurgião cardiovascular, Mestre em Clínica Cirúrgica, Curitiba, PR, Brasil

Cartas ao Editor

3. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5 Suppl):S27-86. 4. Dellinger EP, Anaya DA. Infectious and immunologic consequences of blood transfusion. Crit Care. 2004;8(Suppl 2):S18-23. 5. Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358(12):1229-39. 6. Martin K, Keller E, Gertler R, Tassani P, Wiesner G. Efficiency and safety of preoperative autologous blood donation in cardiac surgery: a matched-pair analysis in 432 patients. Eur J Cardiothorac Surg. 2012;37(6):1396-401.

RESPOSTA Prezado Editor, Inicialmente, gostaríamos de agradecer as observações e comentários feitos pelo Prof. Dr. Hélcio Giffhorn a respeito do artigo “Impacto na mortalidade precoce e tardia após transfusão de hemácias em cirurgia de revascularização miocárdica”[1]. As hemácias estocadas nas bolsas de sangue desenvolvem uma série de alterações estruturais e funcionais com o passar do tempo, conhecidas como “lesão por estocagem” [2]. Uma meta-análise envolvendo 21 estudos: 18 observacionais e três ensaios clínicos randomizados, com predomínio de pacientes de cirurgia cardíaca (6) e trauma (6), concluiu que o uso de sangue estocado por mais tempo foi associado a aumento da mortalidade quando comparado à utilização de sangue estocado por menos tempo [3]. Hajjar et al. [4] publicaram ensaio clínico prospectivo, randomizado e controlado comparando estratégia restritiva versus liberal em 502 pacientes submetidos a cirurgia cardíaca. Independentemente da estratégia transfusional utilizada, a transfusão de apenas uma única unidade de sangue foi associada a aumento significante de morbidade e mortalidade pós-operatória. Não obstante, este estudo empregou apenas bolsas de sangue com pouco tempo de estocagem (inferior a 10 dias de estocagem), com média de apenas 3 dias de estocagem

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em ambos os grupos avaliados. Portanto, a transfusão de sangue “novo” também se encontra associada a maior mortalidade. Uma das possíveis causas de um desfecho clínico adverso mesmo com o uso de sangue “novo” é a queda da bioatividade do óxido nítrico nas hemácias estocadas, que resultaria na diminuição da oferta de oxigênio na microcirculação. Observou-se que essa queda ocorre rapidamente, com apenas algumas horas de estocagem [5,6]. Além disso, outro fator fundamental é o efeito imunomodulador da transfusão, que resulta em redução do número de linfócitos em circulação, modificação nas células T auxiliares e ativação das células imunitárias [7]. Evidentemente, esse efeito depende única e exclusivamente da carga de antígenos transfundidos e não do tempo de estocagem das hemácias. Uma das limitações do nosso estudo, o qual foi retrospectivo, foi a impossibilidade de avaliar o tempo de estocagem de cada uma das 4.936 bolsas de sangue que foram transfundidas. É possível, como sugerido pelo Prof. Dr. Hélcio Giffhorn, que maior tempo de estocagem das bolsas de sangue possa ter influenciado numa maior taxa de mortalidade neste estudo. Atualmente, em grande parte das instituições, é comum que pacientes com indicação de transfusão sanguínea recebam preferencialmente as unidades de sangue de sua tipagem sanguínea que apresentem maior tempo de estocagem. Tal prática visa melhor conservação dos estoques limitados de sangue [3]. De qualquer maneira, o fato de não ter levado em conta o tempo de estocagem das bolsas de sangue transfundidas não invalida a conclusão final deste estudo, que apresentou números muito semelhantes aos encontrados na literatura internacional. Além disso, este estudo exemplifica a conduta transfusional típica empregada por um hospital de grande porte no Brasil. Acreditamos que ter adicionado o tempo de estocagem das bolsas de sangue poderia ter reforçado ainda mais a conclusão final de nosso estudo. Uma das técnicas empregadas para diminuir o uso de sangue alogênico no peri-operatório é a autotransfusão, na qual se realiza doação pré-operatória semanas antes da cirurgia e armazenamento. Tal método teria como vantagens evitar a transmissão de vírus, tais como o HIV e hepatite C, assim como efeitos deletérios causados por fenômenos imunológicos provenientes do uso do sangue alogênico [8]. Uma revisão sistemática de ensaios clínicos randomizados sobre a eficácia da autotransfusão, publicada pela colaboração Cochrane, envolveu 14 ensaios clínicos randomizados e observou redução do risco de receber uma transfusão de sangue alogênica [9]. Contudo, o risco de receber uma transfusão de sangue de qualquer tipo (autóloga ou alogênica) foi maior com o uso da autotransfusão, não sendo possível para os autores estabelecer se os benefícios da autotransfusão foram maiores que seus riscos. Além disso, a autotransfusão na modalidade de doação 151

Cartas ao Editor

pré-operatória e armazenamento não oferece, teoricamente, prevenção quanto ao desenvolvimento da lesão por estocagem. Já a hemodiluição normovolêmica aguda pré-operatória envolve a remoção de sangue do paciente cirúrgico imediatamente antes ou após a indução anestésica e sua simultânea reposição com volumes apropriados de soluções cristaloides ou coloides. O sangue coletado é posteriormente reinfundido para repor as perdas sanguíneas ocorridas durante a cirurgia [10], sem o inconveniente da lesão por estocagem. Goodnough et al. [11] sugerem que a hemodiluição normovolêmica aguda poderia substituir com vantagens o uso da autotransfusão. A recuperação intraoperatória de células é outra técnica utilizada para minimizar o uso de sangue alogênico e consiste em recuperar, filtrar e reinfundir o sangue perdido pelo paciente no intraoperatório, com auxílio de um equipamento específico [12]. Uma revisão sistemática de ensaios clínicos randomizados sobre a eficácia da recuperação intraoperatória de células, publicada pela colaboração Cochrane, incluiu 75 ensaios clínicos e concluiu que a mesma foi eficaz em reduzir o uso de sangue alogênico em pacientes adultos submetidos a cirurgia cardíaca eletiva, sem impactar efeitos clínicos adversos [13]. O presente estudo não avaliou o uso da hemodiluição normovolêmica aguda pré-operatória ou da recuperação intraoperatória de células e seus impactos na morbidade e mortalidade, porém ambas as técnicas constituem excelente perspectiva para a elaboração de estudos futuros. Mais uma vez agradecemos os comentários do Prof. Dr. Hélcio Giffhorn. Dr. Antonio Alceu dos Santos Cardiologista, São Paulo, SP, Brasil

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surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-67. 5. Kor DJ, Van Buskirk CM, Gajic O. Red blood cell storage lesion. Bosn J Basic Med Sci. 2009;9(Suppl 1):21-7. 6. Reynolds JD, Ahearn GS, Angelo M, Zhang J, Cobb F, Stamler JS. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood. Proc Natl Acad Sci U S A. 2007;104(43):17058-62. 7. Blajchman MA. Immunomodulation and blood transfusion. Am J Ther. 2002;9(5):389-95. 8. Martin K, Kaller E, Gertler R, Tassani P, Wiesner G. Efficiency and safety of preoperative autologous blood donation in cardiac surgery: a matched-pair analysis in 432 patients. Eur J Cardiothorac Surg. 2012;37(6):1396-401. 9. Henry DA, Carless PA, Moxey AJ, O'Connell D, Forgie MA, Wells PS, et al. Pre-operative autologous donation for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2002;(2):CD003602. 10. Shander A, Rijhwani TS. Acute normovolemic hemodilution. Transfusion. 2004;44(12 Suppl):26S-34S. 11. Goodnough LT, Monk TG, Brecher ME. Acute normovolemic hemodilution should replace the preoperative donation of autologous blood as a method of autologous-blood procurement. Transfusion. 1998;38(5):473-6. 12. Esper SA, Waters JH. Intra-operative cell salvage: a fresh look at the indications and contraindications. Blood Transfus. 2011;9(2):139-47. 13. Carless PA, Henry DA, Moxey AJ, O'Connell D, Brown T, Fergusson DA. Cell salvage for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2010;(4):CD001888.

REFERÊNCIAS 1. Santos AA, Sousa AG, Thomé HOS, Machado RL, Piotto RF. Impacto na mortalidade precoce e tardia após transfusão de hemácias em cirurgia de revascularização miocárdica. Rev Bras Cir Cardiovasc. 2013;28(1):1-9. 2. Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358(12):1229-39. 3. Wang D, Sun J, Solomon SB, Klein HG, Natanson C. Transfusion of older stored blood and risk of death: a metaanalysis. Transfusion. 2012;52(6):1184-95. 4. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac

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Segunda edição do livro Cardiologia e Cirurgia Cardiovascular Pediátrica está disponível No dia 29 de novembro de 2012, durante o XXII Congresso Brasileiro de Cardiologia Pediátrica, em Foz do Iguaçu, PR, foi lançada oficialmente a segunda edição do livro que celebra o resultado da união entre a Sociedade Brasileira de Cardiologia e a Sociedade Brasileira de Cirurgia Cardiovascular, representada pelos seus respectivos departamentos de cardiologia pediátrica e de cirurgia cardiovascular pediátrica.

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Cartas ao Editor

to integrate so much relevant and important material. I would be interested to know what feedback you get from the readership. And I look forward to the next chapters. All the best, and congratulations. Miles Frederick Shore Cambridge/MA, USA Rodolfo,

(Da esq para a dir.) Maria Del Pilar Payá (gerente editorial da Roca – GEN Grupo Editorial Nacional), Vera Demarchi Aiello (coordenadora de nomenclatura), Sandra da Silva Mattos (coordenadora clínica), Ulisses Alexandre Croti (coordenador geral), Valéria de Melo Moreira (coordenadora de imagens). Valdester Cavalcante Pinto Jr. (coordenador cirúrgico) não aparece na foto porque estava em outro evento no exterior

Essa segunda edição contou com 178 autores que procuraram apresentar o que há de melhor na especialidade. O texto foi ilustrado com 1649 imagens distribuídas em 1240 páginas, o que praticamente o tornou um livro-atlas. Os coordenadores declararam acreditar ser esta obra uma importante contribuição para o desenvolvimento da cardiologia e cirurgia cardiovascular pediátrica no País, além de demonstrar o alto nível de conhecimento, envolvimento e capacidade daqueles que trabalham na área. “Muitos jovens médicos poderão estudar e aprender a maioria dos pontos básicos e importantes nesse livro”, declarou o coordenador geral do livro, Prof. Dr. Ulisses Alexandre Croti. Acompanhando a tendência mundial, o livro também foi apresentado em forma de e-book, o qual pode ser adquirido pelo site http://grupogen.com.br . Neste, também poderão ser acessadas inúmeras figuras e vídeos gratuitamente, confirmando, mais uma vez, um dos principais objetivos do livro de disseminação do conhecimento.

Cardiac surgery: the infinite quest Hi Rodolfo -- I finally got the time to go over your very ambitious paper. I am impressed that a specialty journal would have the leadership to publish such a farreaching piece. And it is also impressive that you are able

I just finished reading part II of " Cardiac Surgery, the Infinite Quest" - it's beautifully written and very provocative. You are on a trajectory to become the "master of missives" in cardiac surgery! All the best, James K. Kirklin Birmingham/AL, USA

100 citações Prezados amigos Recebi nova notificação do Google Acadêmico com a informação que nosso trabalho (Noções básicas de variabilidade da frequência cardíaca e sua aplicabilidade clínica - Luiz Carlos Marques Vanderlei, Carlos Marcelo Pastre, Rosângela Akemi Hoshi, Tatiana Dias de Carvalho e Moacir Fernandes de Godoy, publicado na edição 24.2 da RBCCV) chegou à expressiva marca de 100 citações!!! Parabéns a todos e um agradecimento especial ao Prof. Domingo Braile por ter nos possibilitado essa publicação em uma revista de tão grande expressividade e penetração como a Revista Brasileira de Cirurgia Cardiovascular. Um abraço a todos Moacir Godoy São José do Rio Preto-SP Em visita ao Google Acadêmico, observei o relatado pelo prof Moacir. O artigo foi idealizado por nós a partir de uma estratégia interna dos laboratórios visando à atualização científica sobre VFC e esta ideia foi catalisada nas reuniões em estágio pós-doutoral, incentivada fortemente pelo professor Moacir e, finalmente, iniciou-se a partir da ação do Luiz Carlos. 153

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A partir disso, toda busca referencial e organização dos dados foram feitas pela Rosangela e Tatiana. O desfecho foi, aos meus olhos, extremamente impactante e, pelo jeito, para comunidade acadêmica também. Estou certo de que, não fosse a visão do Prof. Domingo, tais informações não teriam tal circulação e projeção. Reitero a importância da RBCCV neste contexto! Agradeço a todos, "de coração", pelo privilégio de ter trabalhado neste projeto: meu irmão acadêmico Luiz, meus queridos mestres Professores Moacir e Braile e principalmente Memi e Tatiana, que foram incansáveis e pacientes para responder a quaisquer exigências, incluindo as minhas. Valeu a pena e penso estarmos prontos para um novo desafio!!! Um fraternal abraço!!! Marcelo Pastre São José do Rio Preto-SP

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Reflexões de um tradutor na área da Anatomia Humana”, Prezado Sr. Editor, Enviei um artigo “Reflections engendered as a practicing translator concerning the language of Anatomy - Reflexões de um tradutor na área da Anatomia Humana”, que foi publicado na Rev Bras Cir Cardiovasc 2012;27(3):453-6. No presente artigo, por erro meu, foi omitido o nome do coautor: Prof. Dr. Fernando Batigália, M.D. Human Anatomy Tutor; Health Sciences Stricto Sensu Post-Graduate Programme; São José do Rio Preto Medical School (FAMERP). Solicito a emissão de uma errata para corrigir o erro. Sendo só para o momento e contando com a colaboração de V.Sa., despeço-me, Atenciosamente Alexandre Lins Werneck São José do Rio Preto-SP

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DOI: 10.5935/1678-9741.20130021

Errata

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No artigo “Reflections engendered as a practicing translator concerning the language of Anatomy”, publicado na edição 27.3, páginas 453-6, não foi incluído o nome do coautor Fernando Batigália, M.D. Human Anatomy Tutor; Health Sciences Stricto Sensu Post-Graduate Programme; São José do Rio Preto Medical School (FAMERP).

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Revisores RBCCV 28.1

Abaixo, a lista com o nome daqueles que avaliaram os trabalhos publicados nesta edição da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS). A eles, o meu agradecimento.

Domingo Braile Editor-Chefe - RBCCV

Alfredo Inácio Fiorelli

Marcos Rogério Joaquim

Alfredo José Rodrigues

Mauricio de Nassau Machado

Eduardo Keller Saadi Ellen Hettwer Magedanz

Melchior Luiz Lima Neide Micelli Domingos

Guilherme Succi Orlando Petrucci João Galantier José Glauco Lobo Filho Luciana da Fonseca

Paulo Slud Brofman Roberto Gomes de Carvalho

Luiz César Guarita-Souza

Rubens Toffano de Barros

Marcelo N Nakazone

Tomas Salerno

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NORMAS DA RBCCV Revista Brasileira de Cirurgia Cardiovascular/BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Editor Prof. Dr. Domingo M. Braile Av. Juscelino Kubitschek de Oliveira, 1.505 – Jardim Tarraf I 15091-450 – São José do Rio Preto – SP - Brasil E-mail: revista@sbccv.org.br

Informações aos Autores. Os trabalhos enviados para publicação na Revista Brasileira de Cirurgia Cardiovascular – Brazilian Journal of Cardiovascular Surgery – devem versar sobre temas relacionados à cirurgia cardiovascular e áreas afins. Todas as contribuições ci entíficas são revisadas pelo Editor, Editores Associados, Membros do Conselho Editorial e Revisores Convidados e envolvem as seções de Artigos Originais, Editoriais, Revisões, Atualizações, Relatos de Casos, “Como-eu-Faço”, Comunicações Breves, Notas Prévias, Correlação Clínico Cirúrgica, Trabalho Experimental, Multimidia e Cartas ao Editor. A aceitação será feita baseada na originalidade, significância e contribuição científica. Os manuscritos devem ser, obrigatoriamente, submetidos eletronicamente no site www.rbccv.org. br. Caso os autores ainda não tenham se cadastrado, é necessário fazê-lo antes de submeter o trabalho, seguindo as orientações que constam do site. Os textos devem ser editados em Word e as figuras, fotos, tabelas e ilustrações devem estar em arquivos separados. Figuras devem ter extensão jpeg e resolução mínima de 300dpi. Para artigos com Publicação Duplicada, ver tópico específico. Quando o artigo for aprovado, o autor será comunicado pelo e-mail cadastrado no site e deve encaminhar um resumo de até 60 palavras, em português e inglês, do artigo. Eles serão inseridos no mailing eletrônico enviado a todos os sócios quando a RBCCV/BJCVS estiver disponível on-line. Norma. A Revista Brasileira de Cirurgia Cardiovascular – Brazilian Journal of Cardiovascular Surgery adota as Normas de Vancouver - Uniform Requirements for Manuscripts Submitted to Biomedical Journals, organizadas pelo International Committee of Medical Journal Editors – “Vancouver Group” (www.icmje.org). Avaliação pelos pares (peer review). Todos os trabalhos enviados à Revista Brasileira de Cirurgia Cardiovascular serão submetidos à avaliação dos pares (peer review) por pelo menos três revisores selecionados entre os Editores Associados e os membros do Conselho Editorial. Os revisores responderão a um questionário no qual farão a classificação do manuscrito, sua apreciação rigorosa em todos os itens que devem compor um trabalho científico, dando uma nota para cada um dos itens do questionário. Ao final farão comentários gerais sobre o trabalho e informarão se o mesmo deve ser publicado, corrigido segundo as recomendações ou rejeitado definitivamente.

De posse destes dados, o Editor tomará a decisão. Em caso de discrepâncias entre os avaliadores, poderá ser solicitada uma nova opinião para melhor julgamento. Quando forem sugeridas modificações, as mesmas serão encaminhadas ao autor principal e em seguida aos revisores para estes verificarem se as exigências foram satisfeitas. Após a editoração os manuscritos serão enviados ao autor para que este verifique se não há erros. Todo o processo será realizado por via eletrônica e em cada fase serão exigidos prazos rigorosos de execução. Em caso de atraso, um novo avaliador será escolhido, o mesmo acontecendo se algum deles se recusar a analisar o trabalho. Em casos excepcionais, quando o assunto do manuscrito assim o exigir, o Editor poderá solicitar a colaboração de um profissional que não conste da relação os Editores Associados e Conselho Editorial para fazer a avaliação. Idioma. Os artigos devem ser redigidos em português (com a ortografia vigente) e em inglês. Para os trabalhos que não possuírem versão em inglês ou que esta seja julgada inadequada pelo Conselho Editorial, a revista providenciará a tradução com ônus para o(s) autor(es). A versão em inglês será publicada na íntegra no site da Scielo (www.scielo.br) e no da revista (www.rbccv.org.br) permanecendo “online” à disposição da comunidade internacional, com links específicos no site da nossa sociedade, aqui no Brasil e no nosso site, que está hospedado na CTSNET (www.ctsnet. org) nos Estados Unidos da América do Norte. Pesquisa com seres humanos e animais. Os autores precisam citar no item Método que a pesquisa foi aprovada pelo Comissão de Ética em Pesquisa de sua Instituição, em consoante à Declaração de Helsinki – ver endereço eletrônico http://www.ufrgs.br/bioetica/helsin5.htm. Nos trabalhos experimentais envolvendo animais, as normas estabelecidas no “Guide for the Care and Use of Laboratory Animals” (Institute of Laboratory Animal Resources, National Academy of Sciences, Washington, D.C., 1996) e os Princípios éticos na experimentação animal do Colégio Brasileiro de Experimentação Animal (COBEA) devem ser respeitados (www.cobea.org.br/etica.htm). Informações gerais. Os artigos devem ser redigidos em processador de textos Word 97 ou superior (A 4); corpo 12; espaço 1,5; fonte Times News Roman (no caso de símbolos matemáticos, é necessário o uso da fonte “Symbol”); paginados e conter, sucessivamente: Versão em português. a) título em português e inglês; 157

Normas da RBCCV

b) nome completo dos autores; Instituição ou Serviço onde foi realizado o trabalho c) Resumo em português e inglês (máximo de 250 palavras, cada. Cem, cada, nos Relatos de Caso e “Como eu Faço”); d) Introdução; e) Método; f) Resultados; g) Discussão; h) Agradecimentos; i) Referências; j) Legendas das ilustrações k) Tabelas. Seções do Manuscrito Primeira página. Deve conter o título do trabalho de maneira concisa e descritiva, em português e inglês, o nome completo dos autores e o nome e endereço da instituição onde o trabalho foi elaborado. A seguir o nome do autor correspondente, juntamente com o endereço, telefone, fax e e-mail. Se o trabalho foi apresentado em congresso, deve ser mencionado o nome do congresso, local e data da apresentação. Deve ser incluída a contagem de palavras. A contagem eletrônica de palavras deve incluir a página inicial, resumo, abstract, texto, referências e legenda de figuras. Segunda Página - Resumo e Abstract. O resumo deve ser estruturado em quatro seções: Objetivo, Método, Resultados e Conclusão(ões). Devem ser evitadas abreviações. O número máximo de palavras deve seguir as recomendações da tabela. Nos Relatos de Casos e Comoeu-Faço, o resumo deve ser não-estruturado (informativo ou livre). O mesmo vale para o abstract. Correlações clínicocirurgicas e Multimidia não precisam de resumo e abstract. Também devem ser incluídos de três a cinco descritores (palavras-chave), assim como a respectiva tradução para os Keywords (descriptors). Os descritores têm de ser consultados nos endereços eletrônicos: http://decs.bvs.br/, que contém termos em português, espanhol e inglês ou www.nlm.nih. gov/mesh, para termos somente em inglês, ou nos respectivos links no site da revista. Texto. Artigos Originais devem ser divididos em Introdução, Método, Resultados, Discussão e Conclusão. Relatos de Caso em Introdução, Relato do Caso e Discussão. Correlações clínico-cirúrgicas em Dados Clínicos, Eletrocardiograma, Radiograma, Ecocardiograma, Diagnóstico e Operação. Multimidia em Caracterização do Paciente e Descrição da Técnica Empregada. Artigos de Revisão e Atualização, a critério do autor. As referências devem ser citadas numericamente, por ordem de aparecimento no texto, entre colchetes. Se forem citadas mais de duas referências em seqüência, apenas a primeira e a última devem ser digitadas, sendo separadas por um traço (Exemplo: [6-9]). Em caso de citação alternada, todas as referências devem ser digitadas, separadas por vírgula (Exemplo: [6,7,9]).As abreviações devem ser definidas na primeira aparição no texto. Agradecimentos. Devem vir após o texto. Referências. De acordo com as Normas de Vancouver, as referências devem ser numeradas sequencialmente conforme aparição no texto. As referências não podem ter o parágrafo justificado, e sim alinhado à esquerda. 158

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Comunicações pessoais e dados não publicados não devem ser incluídos na lista de referências, mas apenas mencionados no texto e em nota de rodapé na página em que é mencionado. Citar todos os autores da obra se forem seis ou menos ou apenas os seis primeiros seguidos de et al. se forem mais de seis. As abreviações das revistas devem estar em conformidade com o Index Medicus/ MEDLINE. Exemplos: Artigo de Revista 1. Dallan LAO, Gowdak LH, Lisboa LAF, Schettert I, Krieger JE, Cesar LAM, et al. Terapia celular associada à revascularização transmiocárdica a laser como proposta no tratamento da angina refratária. Rev Bras Cir Cardiovasc. 2008;23(1):46-52. Instituição como Autor The Cardiac Society of Australia and New Zealand. Clinical exercise stress testing. Safety and performance guidelines. Med J Aust 1996;116:41-2. Sem indicação de autoria Cancer in South Africa. [editorial]. S Af Med j 1994;84-15. Capítulo de Livro 1. Mylek WY. Endothelium and its properties. In: Clark BL Jr, editor. New frontiers in surgery. New York: McGrawHill; 1998. p.55-64. Livro 1. Nunes EJ, Gomes SC. Cirurgia das cardiopatias congênitas. 2a ed. São Paulo: Sarvier; 1961. p.701. Tese 1. Brasil LA. Uso da metilprednisolona como inibidor da resposta inflamatória sistêmica induzida pela circulação extracorpórea [Tese de doutorado]. São Paulo: Universidade Federal de São Paulo, Escola Paulista de Medicina, 1999. 122p. A EPM virou Universidade em 20 de dezembro 1994, de lá para cá se faz necessário colocar Unifesp e EPM. Eventos Silva JH. Preparo intestinal transoperatório. In: 45° Congresso Brasileiro de Atualização em Coloproctologia; 1995; São Paulo. Anais. São Paulo: Sociedade Brasileira de Coloproctologia; 1995. p.27-9. Material eletrônico Artigo de revista Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis [serial online] 1995 Jan-Mar [cited 1996 Jun 5]; 1(1):[24 screens]. Available from: URL: http://www.cdc.gov/ncidod/EID/eid.htm Livros Tichenor WS. Sinusitis: treatment plan that works for asthma and allergies too [monograph online]. New York: Health On the Net Foundation; 1996. [cited 1999 May 27]. Available from: URL: http://www.sinuses.com Capítulo de livro Tichenor WS. Persistent sinusitis after surgery. In: Tichenor WS. Sinusitis: treatment plan that works for

Rev Bras Cir Cardiovasc 2013;28(1):157-60

Normas da RBCCV

asthma and allergies too [monograph online]. New York: Health On the Net Foundation; 1996. [cited 1999 May 27]. Available from: URL: http://www.sinuses.com/postsurg.htm Tese Lourenço LG. Relação entre a contagem de microdensidade vasal tumoral e o prognóstico do adenocarcinoma gástrico operado [tese online]. São Paulo: Universidade Federal de São Paulo; 1999. [citado 1999 Jun 10]. Disponível em: URL:http://www.epm.br/cirurgia/gastro/laercio Eventos Barata RB. Epidemiologia no século XXI: perspectivas para o Brasil. In: 4° Congresso Brasileiro de Epidemiologia [online].; 1998 Ago 1-5; Rio de Janeiro. Anais eletrônicos. Rio de Janeiro: ABRASCO; 1998. [citado 1999 Jan 17]. Disponível em :URL: http://www.abrasco.com.br/epirio98 Legendas das Figuras. Devem ser formatadas em espaço duplo, em páginas numeradas e separadas, ordenadas após as Referências, uma página para cada legenda. As abreviações usadas nas figuras devem ser explicitadas nas legendas. Tabelas e Figuras. Devem ser numeradas por ordem de aparecimento no texto, conter um título e estar em páginas separadas. As tabelas não devem conter dados redundantes já citados no texto. Devem ser abertas nos lados e com fundo totalmente branco. Abreviações usadas nas tabelas devem ser explicadas na legenda em ordem alfabética . As tabelas e figuras somente serão publicadas em cores se o autor concordar em arcar com os custos de impressão das páginas coloridas. Os manuscritos passam a ser propriedade da Revista Brasileira de Cirurgia Cardiovascular – Brazilian Journal

of Cardiovascular Surgery – não podendo ser reproduzidos sem consentimento por escrito do Editor. Os trabalhos aprovados e publicados na RBCCV não serão devolvidos aos autores. Aqueles não aprovados serão sistematicamente devolvidos. Para a reprodução de qualquer material já previamente publicado ou disponível na mídia eletrônica (incluindo tabelas, ilustrações ou fotografias), deve ser anexada carta com permissão por escrito do Editor ou do detentor do copyright. Artigos Duplicados. A convenção de Vancouver estabelece que artigos duplicados, no mesmo ou outro idioma, especialmente em países diferentes, podem ser justificáveis e mesmo benéficos. Assim, artigos publicados por autores brasileiros em revistas científicas de outros países poderão ser aceitos, se o editor considerar a relevância e a necessidade. Em nota de rodapé na primeira página da segunda versão deverá informar aos leitores, pesquisadores que o artigo foi publicado integralmente ou em parte e apresentar a referência da primeira publicação. A nota deve conter “Este artigo está baseado em estudo previamente publicado em (título da revista com referência completa)”. Limites por tipo de artigo. Visando racionalizar o espaço da revista e permitir maior número de artigos por edição, devem ser observados os critérios abaixo delineados por tipo de publicação. A contagem eletrônica de palavras deve incluir a página inicial, resumo, texto, referências e legenda de figuras. Os títulos têm limite de 100 caracteres (contandose os espaços) para Artigos Originais, Artigos de Revisão e Atualização e Trabalho Experimental e de 80 caracteres (contando-se os espaços) para as demais categorias.

Artigo Original

Editorial

Artigo de Revisão/ Atualização

Relato de Caso

“Como eu faço”

Comunicação Breve/Nota Prévia

Carta ao Editor

Trabalho Experimental

Correlação ClínicoCirúrgica

Multimidia

Nº máximo de autores

Resumo Nº máximo de palavras

250

---

100

Nº máximo de palavras

5.000

1.000

6.500

1.500

2.000

400

5.000

800

Nº máximo de referências

Nº máximo de tabelas + figuras

250 ---

159

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Normas da RBCCV

Exemplo de tabela

Exemplo de figura

Table 1. Lung Cancer Invading the Airway: Site of the Tumor and Number of Treatments Patients

Fig. 1 - Histogram showing effects of transdermal 17ß-estradiol on left internal mammary artery (LIMA) graft cross-sectional area. It increased by 30% (3.45 ± 1. 2 mm2 versus 4.24 ± 1 mm2; P = 0.039).

Trachea

36 (13%)

Carina

28 (10%)

Main bronchi

154 (56%)

195

Bronchus intermedius 29 (11%)

Distal airway

26 (10%)

Total

273

351

Verifique antes de enviar o trabalho - Carta de submissão indicando a categoria do manuscrito - Declaração do autor e co-autores de que concordam com o conteúdo do manuscrito - Pesquisa aprovada pelo Comitê de Ética da Instituição, com o número do processo - Manuscrito redigido em processador de texto Word 97 ou superior (formatado para A 4); corpo 12; espaço 1,5; fonte Time News Roman; paginado; símbolos matemáticos e caracteres gregos utilizando a fonte Symbol - Manuscrito dentro dos limites adotados pela RBCCV para a sua categoria

A versão em inglês das Normas aos Autores da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery está disponível nos sites: http://www.scielo.br/revistas/rbccv/iinstruc.htm ou http://www.rbccv.org.br/page/6

160

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Calendário de Eventos / Meetings Calendar 2013 Abril 4 a 7 - 21st Annual Meeting of the Asian Society for Cardiovascular and Thoracic Surgery. Kobe, Japão. Site: www.ascvts2013.com/ 9 a 12 - Thoracic Surgery Part I. Windsor, Berkshire. Informações: Louise McLeod - EACTS House - Madeira Walk - Windsor, Berkshire, SL4 1EU Fone: 44 1753 832166 E-mail: louise.mcleod@eacts.co.uk ou info@eacts.co.uk 12 a 14 - Southwest Valve Summit. Houston – EUA Informações: Chris Ralls - 6565 Fannin, MGJ9-006Houston, TX 77030 Fone: 1 713 441-4715 / Fax: 1 713 441-0589 E-mail: cralls@tmhs.org Site: www.methodisthealth.com/southwestvalvesummit 18 a 20 – 40º Congresso da Sociedade Brasileira de Cirurgia Cardiovascular. Florianópolis, SC, Brasil. Informações: SBCCV – Rua Beira Rio, 45 – 7º and, conj. 72. São Paulo-SP. CEP 04548-050. Fone: (11) 3849-0341. Fax (11) 5096-0079. Site: /www.sbccv.org.br/40congresso/ 18 e 19 - Aortic Valve Repair: A Step-By-Step Approach. Paris, França. Informações: Emmanuel Lansac - Sabine Ruck, Meeting Manager - Institut Mutualiste Montsouris, Cardiac Pathology Department - 42 Boulevard Dourdan 75014 Paris Fone: 0049 (0)6182 94666 27 E-mail: caviaar@orange.fr ou s.ruck@kelcon.de Site: http://www.caviaar.com 18 e 19 - Applied Basic Sciences: Revision and Viva course for the FRCS (C-Th). Londres, Inglaterra. Fone: 020 7869 6300 E-mail: education@rcseng.ac.uk Site: www.rcseng.ac.uk/courses/course-search/appliedbasic-science-for-cardiothoracic-surgical-trainees 22 a 26 - Minimally Invasive Techniques on Adult Cardiac Surgery (Surgical Training and Manpower Committee (STMP) of European Association of Cardiothoracic Surgery (EACTS). Windsor, Inglaterra. Informações: Louise McLeod - EACTS House - Maderia Walk - Windsor, Berkshire, SL6 6LE, UK Fone: 44 1753 832166/ Fax: 44 1753 620407 E-mail: info@eacts.co.uk Site: www.eacts.org

24 a 26 - Leadership and Management Development for Cardiovascular and Thoracic Surgeons: Part II. Windsor, Inglaterra. Informações: Louise McLeod - EACTS House - Madeira Walk - Windsor, Berkshire, SL4 1EU Fone: 44 1753 832166 E-mail: louise.mcleod@eacts.co.uk ou info@eacts.co.uk 25 e 26 - STS/ACCF Transcatheter Heart Valve (THV) Symposium. Dallas, Estados Unidos. Informações: Michele Chao, Education Manager Fone: 1 312 202-5846 E-mail: mchao@sts.org 26 e 27 - 9th Current Trends in Aortic and Cardiovascular Surgery and Interventions. Houston, Estados Unidos Informações: Elaine Allbritton - Office of Continuing Medical Education - Texas Heart Institute at St. Luke's Episcopal Hospital Fone: 1 713 218-2121/ Fax: 1 713 218-2229 E-mail: eallbritton@heart.thi.tmc.edu Site: www.cme.texasheart.org

Maio 2 e 3 - Mayo Clinic Thoracic Surgery Symposium. Rochester, Estados Unidos. Informações: Mayo School of Continuous Professional Development - 200 First Street SW, Plummer 2-60 - Rochester, MN 55905 Fone: 1 800-323-2688/ Fax: 1 507-538-7234 E-mail: trende.jenna@mayo.edu Site: http://www.mayo.edu/cme 4 a 8 - AATS Annual Meeting 2013. Beverly, Estados Unidos. Informações: The American Association for Thoracic Surgery - 500 Cummings Center - Suite 4550 Beverly, MA 01915 Fone: 1 978-927-8330/Fax: 1 978-524-8890 E-mail: lruggiero@aats.org Site: http://www.aats.org 4 e 5 - Cardiomersion 2013 - Cardiac Emergencies Institute of Cardiac Emergencies Inaugural Symposium. Orlando, Estados Unidos. Informações: Doctor Deepak Puri - Fortis Hospital Mohali, India E-mail: drdeephearts@gmail.com ou drdeepakpuri2@ rediffmail.com Site: http://www.instituteforcardioemergencies.com/ 161

Calendário de Eventos / Meetings Calendar

8 a 11 - 9th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion. Hershey, Estados Unidos. Informações: Heather Stokes - 500 University Drive, SB35 - Hershey, PA 17033 Fone: 1 717-531-5656/Fax: 1 717-531-0486 E-mail: hstokes@hmc.psu.edu Site: http://pennstatehershey.org/web/pedscpb/home 9 a 11 - European Multidisciplinary Conference in Thoracic Oncology. Lugano, Suíça. Informações: Congress Department - Via Luigi Taddei 4 6962 Vignello-Lugano - Switzerland E-mail: emcto@esmo.org Site: http://www.emcto.org 11 a 14 - London Cardiothoracic Surgery Core Review Course. Londres, Inglaterra. Informações: Kamran Baig - 15 Cheriton Close - Barnet, Herts, EN4 9TX E-mail: info@corereview.co.uk Site: www.corereview.co.uk 12 - Pioneering Cardiac Surgeons: Professor Tirone David / Professor Sir Magdi Yacoub / Professor Gibrine El-Khoury. Londres, Inglaterra. Informações: Kamran Baig - 15 Cheriton Close - Barnet, Herts, EN4 9TX E-mail: info@corereview.co.uk Site: http://www.corereview.co.uk 14 e 15 - Intermediate Thoracic Surgery. Londres, Inglaterra. Informações: The Royal College of Surgeons of England - 35-43 Lincoln's Inn Fields - London WC2A 3PE Fone: 020 7869 6300/Fax: 020 7869 6320 E-mail: education@rcseng.ac.uk Site: www.rcseng.ac.uk/courses/course-search/ intermediate-thoracic-surgery 17 a 22 - 2013 American Thoracic Society International Conference. Philadelphia, Estados Unidos. Informações: ATS International Conference Department Fone: 1 212 315-8652 E-mail: conference@thoracic.org Site: http://conference.thoracic.org/2013/ 17 - The Twelfth Yorkshire Chest Imaging Course. Leeds, Inglaterra. E-mail: radiologycourses@hotmail.co.uk 17 a 19 - Baku Heart Days - 3rd International Congress. Baku, Azerbaijan. 162

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Informações: Secretarial Office - Parliament ave. 76 Baku, Azerbaijan Fone: 99450 24599 06/ 9945023393 98/ Fax: (99412) 4921416 E-mail: info@bakuheartdays.az Site: www.bakuheartdays.az 23 e 24 - Arrhythmia Surgery in Patients with Congenital Heart Disease. Orlando, Estados Unidos. Informações: Heather Czujak - 404 Celebration Place Celebration, FL 34747 Fone: 1 407-303-4773/Fax: 1 407-303-4473 E-mail: heather.czujak@flhosp.org Site: www.nicholsoncenter.com 23 e 24 - Postgraduate Course in General Thoracic Surgery. Cambridge, Estados Unidos. Informações: Harvard Medical School-Department of Continuing Education - P.O. Box 417476 - Boston, MA 02241-7476 Fone: 1 617-384-8600/Fax: 1 617-998-1014 E-mail: hms-cme@hms.harvard.edu Site: www.cme.hms.harvard.edu/courses/postgrad 25 a 29 - 21st European Conference on General Thoracic Surgery. Birmingham, Inglaterra. Informações: Sue Hesford – ESTS - 1 The Quadrant, Wonford Road, Exeter - EX2 4LE, UK Fone: 44 1392 430671/Fax: 44 1392 430671 E-mail: sue@ests.org.uk 28 a 31 - Module: Coronary Surgery with Special Focus on Off-Pump Coronary Artery Bypass Surgery. Windsor, Inglaterra. Informações: Louise McLeod - EACTS House - Madeira Walk - Windsor, Berkshire, SL4 1EU Fone: 44 1753 832166 E-mail: louise.mcleod@eacts.co.uk ou info@eacts.co.uk 29 a 31 - Hands-on Cardiac Morphology (Summer Edition). Londres, Inglaterra. Informações: Carina Lim YP - Cardiac Morphology Unit, Brompton Hospital - Sydney Street - London SW3 6NP United Kingdom Fone: 44 (0) 207 351 8751/Fax: 44 (0) 207 351 8230 E-mail: morphology@rbht.nhs.uk Site: www.rbht.nhs.uk/cardiacMorphology/

Junho 3 a 7 - Fundamentals in Cardiac Surgery: Part II. Windsor, Inglaterra.

Calendário de Eventos / Meetings Calendar

Informações: Louise McLeod - EACTS House - Madeira Walk - Windsor, Berkshire, SL4 1EU Fone: 44 1753 832166 E-mail: louise.mcleod@eacts.co.uk ou info@eacts.co.uk 12 a 15 - ASAIO 59th Annual Conference. Chicago, EUA Informações: ASAIO, Inc. - 7700 Congress Avenue, Suite 3107 - Boca Raton, Florida 33487-1356 Fone: 1 561-999-8969/Fax: 1 561-999-8972 E-mail: info@asaio.com Site: www.asaio.com 12 a 15 - 7th Annual The New Orleans Conference: Practices in Cardiac Surgery and Extracorporeal Technologies. Nova Orleans, Estados Unidos. Informações: Gary P. Jones, M.D. Planning committee chair - Joseph Basha, CCP Program Co-Director - Rob Ballantyne, CCP Program Co-Director Fone: 1 318 623-0890/Fax: 1 504 842-3551 E-mail: josephbasha@perfusioninternational.com Site: www.theneworleansconference.com

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13 a 15 - The "Less" Aortic Valves Workshop. Módena, Itália Informações: Noema Srl Unipersonale - Via Orefici, 4 40124 Bologna - Italy Fone: 39 051 230385/Fax: 39 051 221894 E-mail: info@noemacongressi.it Site: www.noemacongressi.it 22 a 25 - 7th Biennial Congress of the SHVD and HVSA. Veneza, Itália. Site: http://meeting.shvd.org/ 25 e 26 - Magna Græcia Aortic Interventional® (MAORI) Symposium - The Third In The Series. Catanzaro, Itália. Informações: Pasquale Mastroroberto M.D., Program Director MAORI Symposium - University Hospital Viale Europa - 88100 Catanzaro, Italy Fone: 39 0961 3695851 E-mail: mastroroberto@unicz.it Site: http://maori.unicz.it/

163

Calendรกrio de Eventos / Meetings Calendar

164

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RBCCV em números

27 anos de circulação ininterrupta Fator de Impacto 1,239 Consultada por leitores de mais de 110 países

www.rbccv.org.br www.scielo.br/rbccv www.bjcvs.org

788.564 acessos no site próprio (www.rbccv.org.br) em 2012 709.180 acessos no site da SciELO (www.scielo.br/rbccv) em 2012 4092 visitantes diariamente 469,65 gigabytes (GB) transferidos, média de 1,28 GB por dia 47.232.073 impressões de páginas em 2012 (requisição do navegador de um visitante para uma página web que possa ser exibida), média diária de 129.049,38. Presente em nas bases de dados EBSCO, Lilacs, Scielo, Latindex, Index Copernicus, Scopus, PubMed, Thomson Scientific (ISI), Google Scholar

Fig.1 – Número de acessos ao site da RBCCV em 2012

Fig. 2 – Transferência de bytes no site da RBCCV durante 2012

Fig. 3 – Número de impressões de páginas da RBCCV em 2012