Decio Cavalet Soares AbuchaimI; Carla TanamatiII; Marcelo Biscegli JateneIII; Miguel Lorenzo Barbero MarcialIV; Vera Demarchi AielloV
INTRODUCTION: Although hypoplastic left heart syndrome (HLHS) be extensively studied, this disease still has a high mortality rate compared to other diseases treated as univentricular physiology. In this way, morphological differences between phenotypes within the spectrum of HLHS may be risk factors and their identification can assist in choosing treatment between subgroups.
OBJECTIVE: To identify the most prevalent form of coronary artery dominance in hearts with HLHS groups with mitral atresia (MA) and mitral stenosis (MS).
METHODS: Analysis of coronary anatomy according to the distribution of epicardial branches and the pattern of dominance, classified as right, left or balanced. The control group was composed of nine pieces of morphologically normal hearts, the HLHS group consisted of 9 pieces with MA and 24 pieces with MS. For statistical analysis we used the x2 test.
RESULTS: There were significant differences between the two groups in relation to coronary artery dominance (x2 = 9.298, P = 0.01). Left dominance was present in 75% of cases of MS, and balanced one was only observed in pieces with MS. The control group had right dominance in all cases (P <0.01).
CONCLUSIONS: Left dominance is more common in HLHS than in the control group of normal hearts and, in HLHS, the left coronary dominance is more frequent in the subgroup with MS.
INTRODUÇÃO: Apesar de a síndrome do coração esquerdo hipoplásico (SCEH) ser extensamente estudada, esta doença ainda apresenta mortalidade elevada se comparada a outras doenças tratadas como fisiologia univentricular. Assim, diferenças morfológicas entre fenótipos dentro do espectro da SCEH podem ser fatores de risco e sua identificação pode auxiliar na escolha terapêutica entre os subgrupos anatômicos.
OBJETIVOS: Determinar a forma mais frequente de dominância coronariana em corações com SCEH nos subgrupos com atresia (AM) e estenose mitral (EM).
MÉTODOS: Análise da anatomia coronariana de acordo com a distribuição dos ramos epicárdicos e o padrão de dominância, classificadas em direita, esquerda ou balanceada. O grupo controle foi composto por nove peças de corações morfologicamente normais. O grupo SCEH constituiu-se de nove peças com AM e 24 peças com EM. Para análise estatística foi utilizado o teste do qui-quadrado.
RESULTADOS: Houve diferença significativa entre os dois grupos em relação à dominância coronariana (x2= 9,298; P=0,01). A dominância esquerda esteve presente em 75% dos casos de EM, e a balanceada só foi observada na EM. No grupo controle, observou-se dominância direita em todos os casos (P<0,01).
CONCLUSÕES: A dominância esquerda é mais frequente na SCEH que no grupo controle de corações normais e, na SCEH, a dominância coronariana esquerda é mais frequente no subgrupo com EM.
The hypoplastic left heart syndrome (HLHS) is a spectrum of cardiac malformations characterized by severe underdevelopment of the left heart complex and aorta. It includes both the left ventricular cavity and mass. At one end of the spectrum is the mitral and aortic atresia with absent/not detectable left ventricular cavity. At the other end are the cases with varying degrees of hypoplasia of the mitral and aortic valves and ventricular hypoplasia , leading to the impossibility of maintaining cardiac output and systemic perfusion by the left heart. In anatomic series, there is a predominance of the phenotype with a patent mitral valve (67%) .
Although the HLHS is extensively studied, the surgical treatment performed by the Norwood-type palliative surgery [3-4] or by the so-called hybrid procedures [5-6] has satisfactory results in many centers [7-8]. Nevertheless, this disease still has a high mortality rate between the first and second stage, when compared to other diseases treated as univentricular physiology. There has also been a lot of controversy over whether the subgroup patients with mitral stenosis and aortic atresia present a higher risk of death after the first stage of palliative surgery [9-11] due to factors related to myocardial perfusion or histological changes.
Although mortality from postoperative coronary heart disease is commonly caused by technical factors related to the aortic arch reconstruction , it can also be caused by intrinsic coronary abnormalities such as hypoplasia of the epicardial branches. In addition, the steal phenomenon of epicardial coronary flow by fistula is further considered an intrinsic coronary abnormality, particularly if it is associated with myocardial hypertrophy, as observed in the subgroup with mitral stenosis, which compromises myocardial perfusion . These coronary fistulas usually arise from the left coronary artery branches .
In this context, morphological differences between phenotypes within the spectrum of HLHS may come to be recognized as limiting factors for a favorable postoperative course. Thus, their identification can possibly contribute to the therapeutic choice between the anatomical subgroups in near future.
To determine the most common form of coronary artery dominance in HLSH hearts in groups with mitral atresia and mitral stenosis.
This study was approved by the Research and Ethics Committee of InCor-HCFMUSP. It received the protocol number 0786/09, and represents the partial result of the author's doctorate dissertation.
Selection of Anatomic Specimens
Anatomic specimens selection was carried out at the Museum of the Laboratory of Pathology; Heart Institute (InCor), University of São Paulo Medical School (InCor-HCFMUSP) according to the following criteria:
Anatomic specimens of HLHS obtained from deceased patients of both sexes under the age of 30 days.
- Anatomic specimens in which surgical procedures or the state of preservation prevented proper morphology identification.
- Age over 30 days.
- Other congenital anomalies with hypoplastic left ventricle but not with all criteria for HLHS.
Anatomic specimens were classified according to their morphological diagnosis as follows:
I - group with mitral atresia (MA) associated with either atresia or stenosis of the aortic valve.
II - group with mitral stenosis (MS) associated with either atresia or stenosis of the aortic valve.
The gross examination of the epicardial coronary artery anatomy was done under a magnifying glass. The distribution of the major epicardial branches and the pattern of dominance were determined.
Coronary dominance was defined as the main artery (the right or the left) that supplies the posterior interventricular artery. Thus, it was classified as right, left or balanced (co-dominant) .
Control group consisted of nine specimens of morphologically normal hearts with from patients who died in the neonatal period due to non-cardiac causes.
HLHS group consisted of nine specimens with MA and 24 specimens with MS.
We used the Chi-square test for statistical analysis and P values less than 0.05 were considered statistically significant.
The numbers of hearts with HLHS in each morphological subgroup are shown in Table 1.
We found significant differences between the two groups in relation to coronary dominance (χ2 = 9.298; P = 0.01). Left dominance was present in 75% of MS cases. The balanced dominance (co-dominance) was observed in MS only. The distribution of data is shown in Table 2.
Comparisons with the control group
We did Chi-square tests including the controls. There was a statistically significant difference in the pattern of coronary dominance(P<0.01), once the right dominance was only be observed in the control group.
The right coronary dominance is the most prevalent dominance pattern observed in normal humans [16,17], occurring in 72% of individuals . In HLHS, the dominance has hardly been studied , and most studies analyzed their morphological and histological changes only [19-22].
In HLHS, the spatial distribution of the epicardial coronary vessels is similar to that of normal hearts . The presence of coronary-cavitary fistulas, anomalous origin and tortuosity of the coronary arteries are related to complications and higher mortality .
The finding of coronary fistulas prevails in the hearts with mitral stenosis associated with aortic atresia . Sauer et al.  showed that in hearts with mitral stenosis and aortic atresia, there is an association of 42% of coronary anomalies, such as thickening and tortuosity of the proximal left coronary artery in cases presenting associated endocardial fibroelastosis. The preoperative identification of such anomalies can avoid a direct injury or damage to the underlying areas in a surgery that involves the reconstruction of the aortic root .
Vida et al.  proposed that the patients' subgroup with mitral stenosis and aortic atresia should undergo preoperative cineangiocoronariography to define the magnitude of coronary-cavitary fistulas due to the greater surgical risk, suggesting heart transplantation or hybrid procedures as therapeutic options. Based on the study of their series of cases, the hospital mortality rate was significantly higher (29% vs 7.9%; P=0.002) in this subgroup compared to others. Coronary-cavitary communications were also associated with increased mortality (50% vs 6%; P=0.004).
Glatz et al.  conducted a retrospective study of 72 patients undergoing the Norwood procedure. They observed that the interstage mortality was higher in patients with aortic atresia and mitral stenosis. Thus, they correlated it to possible coronary abnormalities, such as thickening of the tunica media and ventricular-coronary connections. The abnormalities could predispose to ischemia and ventricular dysfunction, and also to potentially life-threatening arrhythmias. These authors consider the possibility that the Tuguo-Sano surgery, which interposes the tube between the right ventricle and the pulmonary trunk, if performed in the subgroup of patients with fistulas, could limit the flow steal during diastole to the pulmonary arteries to the detriment of the potentially vulnerable coronary arteries.
Considering the Brazilian experience, da Silva et al.  revealed no differences between the Norwood and Sano procedures. Some authors presume that the best results with the Sano technique would be more related to the increased experience of the groups than to hemodynamic peculiarities.
Sathanandam et al.,  analyzing the 30-day survival in 100 patients undergoing Norwood-type surgery have obtained a 90%-success rate in the whole group and 89.9% in the subgroup with mitral stenosis and aortic atresia. At 60 days, they obtained 70% 70.4%, respectively without a significant difference. For these authors, the presence of coronary-cavitary fistulas had no effect on mortality.
Following the neonatal period, patients with HLHS have a similar outcome to other patients with single ventricle physiology .
Based on our present study, the left dominance was prevalent in HLHS. Hansel et al. , in an angiographic study also found that the left dominance had been more frequent in HLHS than in the normal population, although in the series studied the right dominance has prevailed. In that sample, the right dominance occurred in 51.2% of the patients, left dominance on 36.9%, and the balanced (co-dominance) in 11.9%. They, however, did not find statistically significant differences between the morphological groups. The left and balanced (co-dominance) dominances were significantly more common in the absence of the left ventricular cavity, in contrast to our findings where the left dominance was significantly higher in cases with mitral stenosis and detectable ventricular cavity.
The main clinical implication of our study is that patients with HLHS should be treated individually, considering the anatomical peculiarities. It is possible that patients with fistulas and left dominance have different prognosis and progression compared to those with fistulas but right dominance. However, the limitation of our study is to have been conducted using autopsy specimens. Thus, these hearts would presumably represent cases with the most severe morphological changes.
However, we support that it is possible for patients with coronary fistulas and left coronary dominance to have different prognosis and clinical evolution compared with patients with fistula and right coronary dominance. In order to support this statement, the total area of irrigated myocardium, its potential for ischemia, and secondary arrhythmias must be considered. These data will be evaluated in an ongoing histological investigation.
The data presented here, which result from the study of autopsy hearts, allowed us to conclude that the pattern of left dominance is more frequent in HLHS than in the control group with normal hearts, and even more prevalent in the subgroup with mitral stenosis.
1. Tchervenkov CI, Jacobs ML, Tahta SA. Congenital Heart Surgery Nomenclature and Database Project: hypoplastic left heart syndrome. Ann Thorac Surg. 2000;69(4 Suppl):S170-9. [MedLine]
2. Aiello VD, Ho SY, Anderson RH, Thiene G. Morphologic features of the hipoplastic left heart syndrome: a reappraisal. Pediatr Pathol. 1990;10(6):931-43. [MedLine]
3. Stasik CN, Gelehrter S, Goldberg CS, Bove EL, Devaney EJ, Ohye RG. Current outcomes and risk factors for the Norwood procedure. J Thorac Cardiovasc Surg. 2006;131(2):412-7. [MedLine]
4. Fantini FA, Gontijo Filho B, Martins C, Lopes RM, Heiden E, Vrandecic E, et al. A operação de Norwood modificada para tratamento da síndrome de hipoplasia do coração esquerdo. Rev Bras Cir Cardiovasc. 2004;19(1):42-6. View article
5. Galantowicz M, Cheatham JP, Phillips A, Cua CL, Hoffman TM, Hill SL, et al. Hybrid approach for hypoplastic left heart syndrome: intermediate results after the learning curve. Ann Thorac Surg. 2008;85(6):2063-70.
6. Assad RS, Zamith MM, Silva MF, Thomaz PG, Miana LA, Guerra VC, et al. Nova bandagem ajustável das artérias pulmonares na síndrome de hipoplasia de câmaras esquerdas. Rev Bras Cir Cardiovasc. 2007;22(1):41-8. [MedLine] View article
7. Silva JP, Fonseca L, Baumgratz JF, Castro RM, Franchi SM, Lianza AC, et al. Síndrome do coração esquerdo hipoplásico: estratégia cirúrgica e comparação de resultados com técnicas de Norwood x Sano. Rev Bras Cir Cardiovasc. 2007;22(2):160-8. [MedLine] View article
8. Furlanetto G, Furlanetto BHS, Henriques SS, Kapins CEB, Lopes LM, Olmos MCC, et al. Nova técnica: operação de Norwood com perfusão regional cerebral e coronariana. Rev Bras Cir Cardiovasc. 2009;24(4):447-52. [MedLine] View article
9. Vida VL, Bacha EA, Larrazabal A, Gauvreau K, Dorfman AL, Marx G, et al. Surgical outcome for patients with the mitral stenosis-aortic atresia variant of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 2008;135(2):339-46. [MedLine]
10. Glatz JA, Fedderly RT, Ghanayem NS, Tweddell JS. Impact of mitral stenosis and aortic atresia on survival in hypoplastic left heart syndrome. Ann Thorac Surg. 2008;85(6):2057-62. [MedLine]
11. Sathanandam SK, Polimenakos AC, Roberson DA, elZein CF, Van Bergen A, Husayni TS, et al. Mitral stenosis and aortic atresia in hypoplastic left heart syndrome: survival analysis after stage I palliation. Ann Thorac Surg. 2010;90(5):1599-607.
12. Bartram U, Grunenfelder J, van Praagh R. Causes of death after the modified Norwood procedure: a study of 122 postmortem cases. Ann Thorac Surg. 1997;64(6):1795-802. [MedLine]
13. DeRose JJ Jr, Corda R, Dische MR, Eleazar J, Mosca RS. Isolated left ventricular ischemia after the Norwood procedure. Ann Thorac Surg. 2002;73(2):657-9. [MedLine]
14. O'Connor WN, Cash JB, Cottrill CM, Johnson GL, Noonan JA. Ventriculocoronary connections in hypoplastic left hearts: an autopsy microscopic study. Circulation. 1982;66(5):1078-86. [MedLine]
16. Kato T, Yasue T, Shoji Y, Shimabukuro S, Ito Y, Goto S, et al. Angiographic difference in coronary artery of man, dog, pig and monkey. Acta Pathol Jpn. 1987;37(3):361-73. [MedLine]
17 . Falci Jr . R, Prates NEVB . Anatomia das artérias coronárias . Rev Med . 1994 ; 72 ( 1/4 ): 21-4 .
18. Hansen JH, Uebing A, Scheewee J, Kramer H-H, Fischer G. The coronary arteries in patients with hypoplastic left heart syndrome: an angiographic study and its clinical implications. Cardiol Young. 2011;121(S1):134.
19. Baffa JM, Chen SL, Guttenberg ME, Norwood WI, Weinberg PM. Coronary artery abnormalities and right ventricular histology in hypoplastic left heart syndrome. J Am Coll Cardiol. 1992;20(2):350-8. [MedLine]
20. Freedom RM, Nykanen D. Hypoplastic left heart syndrome: pathologic considerations of aortic atresia and variations on the theme. Prog Pediatr Cardiol. 1996;5(1):3-18.
21. Sauer U, Gittenberger-de Groot AC, Geishauser M, Babic R, Buhlmeyer K. Coronary arteries in the hypoplastic left heart syndrome. Histopathologic and histometrical studies and implications for surgery. Circulation. 1989;80(3 Pt 1):I168-76. [MedLine]
22. Anderson RH, Spicer D. Fistulous communications with the coronary arteries in the setting of hypoplastic ventricles. Cardiol Young. 2010;20(Suppl 3):86-91. [MedLine]
23. Saroli T, Gelehrter S, Gomez-Fifer CA, van der Velde ME, Bove EL, Ensing GJ. Anomalies of left coronary artery origin affecting surgical repair of hypoplastic left heart syndrome and Shone complex. Echocardiography. 2008;25(7):727-31. [MedLine]
24. Souza AH, Fonseca L, Franchi SM, Lianza AC, Baumgratz JF, Silva JP. A síndrome do coração esquerdo hipoplásico não constitui fator de risco para operação de Fontan. Rev Bras Cir Cardiovasc. 2010;25(4):506-9. [MedLine] View article
Article receive on Tuesday, August 2, 2011