Ziya ApaydinI; Semi OzturkII; Ali Yasar KilincIII; Ahmet Seyfeddin GurbuzIV; Halil Ibrahim BiterI; Ayca GumusdagI
ABSTRACTObjective: To investigate the relationship between aortic stiffness and postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG).
ACE/ARB = Angiotensin converting enzyme inhibitor/angiotensin receptor blocker
ACS = Acute coronary syndrome
AF = Atrial fibrillation
Aix = Augmentation index
AUC = Area under the curve
c = Central
CABG = Coronary artery bypass grafting
CAD = Coronary artery disease
cDBP = Central diastolic blood pressure
CI = Confidence interval
COPD = Chronic obstructive pulmonary disease
CPB = Cardiopulmonary bypass
cPP = Central pulse pressure
CRP = C-reactive protein
cSBP = Central systolic blood pressure
DBP = Diastolic blood pressure
DM = Diabetes mellitus
ECG = Electrocardiogram
eGFR = Estimated glomerular filtration rate
HDL-C = High-density lipoprotein cholestero
HT = Hypertension
LAD = Left atrial diameter
LDL-C = Low-density lipoprotein cholesterol
NI = Not included
OR = Odds ratio
p = Peripheral
pDBP = Peripheral diastolic blood pressure
POAF = Postoperative atrial fibrillation
PP = Pulse pressure
pPP = Peripheral pulse pressure
pSBP = Peripheral systolic blood pressure
PVD = Peripheral vascular disease
PWV = Pulse wave velocity
ROC = Receiver operating characteristic
SBP = Systolic blood pressure
TIA = Transient ischemic attack
Postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) was shown to be associated with long-term mortality. Numerous attempts, including medical and surgical therapies, have been made to prevent POAF. Despite promising results, POAF is still a significant cause of morbidity and mortality, both in hospital stays and during follow-up. Therefore, recognizing patients with relatively higher risk POAF development has crucial importance.
Aortic stiffness was reported to be associated with several cardiovascular outcomes. Brachial pulse pressure (PP) is an indirect evaluation of aortic stiffness and tends to overestimate central hemodynamic. Pulse wave velocity (PWV) is solely dependent on central vascular functions, whereas PP is affected by both vascular and ventricular functions. Therefore, PWV is accepted as the gold standard and recommended by the current guidelines for evaluating cardiovascular risk. Previous studies proposed PP and PWV as predictors of cardiovascular and all-cause mortality[4,5]. Various studies[6,7] showed that PWV and PP may be related to atrial fibrillation (AF) development. We aimed to evaluate the relationship between aortic stiffness parameters and POAF in patients undergoing CABG.
This study is prospective and observational. A total of 110 patients undergoing elective isolated CABG at our institution were included consecutively. Only on-pump CABG procedures were featured. Patients presenting with an acute coronary syndrome (ACS) at index hospitalization were excluded. Patients undergoing concomitant surgeries, such as valve repair/replacement, aneurysmectomy, and emergency procedures were also excluded. Patients with a history of AF (paroxysmal, persistent, permanent) and a history of any arrhythmia implying possible AF were also not considered. The same group of cardiovascular surgeons and anaesthesiologists operated on patients using the same techniques and myocardial protection. Demographic, laboratory, and clinical variables were recorded. All patients provided written informed consent and the study protocol was approved by the local ethics committee (14567952-050/924) following the Declaration of Helsinki and Good Clinical Practice guidelines.
Postoperative Atrial Fibrillation
Patients were routinely followed by a heart rhythm monitor during intensive care unit stay. Daily electrocardiogram (ECG) was taken in the intensive care unit, as well as in the ward. Additional ECG was obtained in case the patient had any complaints such as pain, palpitation, lightheadedness, etc. POAF was defined as an occurrence of any episode of AF lasting > 30 seconds captured on ECG or monitor.
Aortic Pulse Wave Velocity and Augmentation Index Measurement, Mobil-O-Graph® Device
Measurements were performed at index hospitalization one to three days before CABG. Patients were asked to avoid intake of caffeinated beverages, alcoholic beverages, and other stimulants within three hours of measurements. Patients had to rest in the supine position for 10 minutes before measurement at room temperature between 08:00 and 10:00.
Aortic stiffness was measured using a non-invasive oscillometric sphygmomanometer, Mobil-O-Graph® (I.E.M. GmbH, Stolberg, Germany). PWV, augmentation index, peripheral (p), and central (c) systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP were calculated by the software tool. The reliability of the Mobil-O-Graph® in estimating the PWV was demonstrated in previous studies.
Statistical analysis was performed with IBM Corp. Released 2013, IBM SPSS Statistics for Windows, version 22.0, Armonk, NY: IBM Corp. and MedCalc bvba version 16 (Seoul, Korea). The normality of the data was analyzed with the Kolmogorov-Smirnov test. Continuous data were expressed as mean ± standard deviation and categorical data was expressed as percentages. Differences between patient subgroups were tested using Student’s t-test. Categorical variables between groups were assessed with the Chi-square test or Fisher’s exact test, whichever was suitable. Logistic regression analysis was used to identify the independent predictors of POAF. Significant variables in univariate analysis were included in multivariate analysis. Two separate models were constructed. In the first model, age and pPP were excluded due to collinearity, whereas PWV was not included in the second model. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were obtained by plotting the sensitivity against the false-positive rate (1-specificity). ROC curves were compared according to DeLong et al.. The Youden index was used to determine the optimal cutoff values of PWV and pPP for the identification of POAF. A P-value < 0.05 was considered statistically significant.
POAF developed in 32 (29.1%) patients. Patients with POAF were older (63.7±8.6 vs. 58.3±8.4; P=0.014). Chronic obstructive pulmonary disease (COPD) was more common in patients with POAF (11.5% vs. 37.5%; P=0.024), whereas the frequency of hypertension (HT), diabetes mellitus, smoking, and previous coronary artery disease did not differ. C-reactive protein and cholesterol levels were similar between the two groups. Left atrial diameter (LAD) was greater in patients with POAF (35.9±1.6 vs. 36.7±1.7 P<0.039). The use of medications was similar in the two groups. Baseline characteristics are presented in Table 1. p and c SBP and DBP were similar between the two groups, whereas both p and c PP were greater in patients with POAF (pPP: 44.3±11.9 vs. 50.3 ±11.6; P=0.018, cPP: 31.4±8.1 vs. 36.2±8.9; P=0.008). PWV was significantly higher in POAF (8.6±1.3 vs. 9.4±1.3; P=0.006) (Figure 1). Aortic stiffness parameters are presented in Table 1.
|POAF (-)||POAF (±)||P-value|
|Sex (female), n (%)||8(10.3)||3 (9.4)||> 0.999|
|Body mass index (kg/m2)||27.2±3.9||28.1±4.1||0.261|
|Smoking, n (%)||30 (38.5)||15 (46.9)||0.522|
|DM, n (%)||32 (41.0)||20 (39.2)||0.293|
|HT, n (%)||37 (47.4)||16 (50.0)||0.836|
|COPD, n (%)||9 (11.5)||12 (37.5)||0.024|
|PVD, n (%)||9 (11.5)||7 (21.9)||0.232|
|CAD history, n (%)||22 (28.2)||7 (21.9)||0.635|
|Stroke or TlA, n (%)||3 (3.8)||2 (6.3)||0.288|
|Ejection fraction (%)||52.3±10.7||53.4±10.1||0.639|
|Total cholesterol (mg/dl)||268.1 ±91.6||252.6±77.7||0.192|
|HDL-C (mg/dl)||39.9±7.9||39.7 ±8.0||0.944|
|Maximum troponin||0.1 (1.1)||0.1 (1.1)||0.609|
|Cross-clamping time (min)||43.9±19.2||43.2±22.0||0.870|
|CPB time (min)||80.8±33.4||78.6±35.9||0.760|
|Beta-blocker, n (%)||58 (74.4)||19 (59.4)||0.119|
|ACE/ARB inhibitor, n (%)||35 (44.9)||9 (28.1)||0.103|
|Calcium channel blocker, n (%)||10(12.8)||6(18.8)||0.552|
|Diuretic, n (%)||22 (28.2)||8 (25)||0.732|
|Mineralocorticoid antagonist, n (%)||12 (15.4)||3 (9.4)||0.547|
|Statin, n (%)||59 (75.6)||20 (62.5)||0.164|
|Aortic stiffness porometers|
|pDBP (mmHg)||87.8±12.6||89.3 ±10.4||0.575|
ACE/ARB=angiotensin converting enzyme inhibitor/angiotensin receptor blocker; Aix=augmentation index; CAD=coronary artery disease; cDBP=central diastolic blood pressure; COPD=chronic obstructive pulmonary disease; CPB=cardiopulmonary bypass; cPP=central pulse pressure; CRP=C-reactive protein; cSBP=central systolic blood pressure; DM=diabetes mellitus; eGFR=estimated glomerular filtration rate; HDL-C=high density lipoprotein cholesterol; HT=hypertension; LAD=left atrial diameter; LDL-C=low density lipoprotein cholesterol;; pDBP=peripheral diastolic blood pressure; POAF=postoperative atrial fibrillation; pPP=peripheral pulse pressure; pSB-P=peripheral systolic blood pressure; PVD=peripheral vascular disease; PWV=pulse wave velocity; TIA=transient ischemic attack
PWV correlated strongly with age, moderately with pPP, and weakly with LAD. pPP correlated weakly with age and did not correlate with LAD (Table 2).
|P- value||0.025||< 0.001||0.011|
|P-value||< 0.001||0.007||< 0.001|
Predictors of Postoperative Atrial Fibrillation
Age, COPD, LAD, pPP, cPP, and PWV were associated with POAF in univariate logistic regression analysis (Table 3). COPD and PWV were independent predictors of POAF in the first model, whereas COPD and pPP were independent predictors in the second model (Table 4). PWV > 9.5 m/sn had 50% sensitivity and 78.2% specificity (AUC: 0.668, 95% confidence interval [CI] [0.571-0.755], P=0.004), whereas pPP > 41 mmHg had 80.7% sensitivity and 48.7% specificity to predict POAF (AUC: 0.656,95% CI [0.558-0.744], P=0.007]. PWV and pPP had similar accuracy for predicting POAF (difference between AUC: 0,00517; 95% CI [-0,119] - 0,129; z statistic: 0.0818, P=0.94] (Figure 2).
|OR (95% CI)|
|Sex (female)||0.905 (0.224-3.655)||0.899|
|Body mass index||1.063 (0.956-1.181)||0.260|
|CAD history||1.403 (0.531-3.710)||0.495|
|Stroke or TIA||0.600 (0.095-3.773)||0.586|
|Ejection fraction||1.011 (0.967-1.057)||0.635|
|Total cholesterol||0.998 (0.994-1.001)||0.248|
|Graft count||0.988 (0.626-1.560)||0.959|
|Cross-clamping time||0.998 (0.977-1020)||0.868|
|CPB time||0.998 (0.986-1.011)||0.758|
|Maximum troponin||1.021 (0.936-1.115)||0.636|
|ACE/ARB inhibitor||0.854 (0.854-5.068)||0.107|
|Calcium channel blocker||0.637 (0.210-1.931)||0.426|
|Mineralocorticoid antagonist||1.758 (0.461-6.701)||0.409|
ACE/ARB=angiotensin converting enzyme inhibitor/angiotensin receptor blocker; Aix=augmentation index; CAD=coronary artery disease; cDBP=central diastolic blood pressure; CI=confidence interval; COPD=chronic obstructive pulmonary disease; CPB=cardiopulmonary bypass; cPP=central pulse pressure; CRP=C-reactive protein; cSBP=central systolic blood pressure; DM=diabetes mellitus; eGFR=estimated glomerular filtration rate; HDL-C=high density lipoprotein cholesterol; HT=hypertension; LAD=left atrial diameter; LDL-C=low density lipoprotein cholesterol; OR=odds ratio; pDBP=peripheral diastolic blood pressure; POAF=postoperative atrial fibrillation; pPP=peripheral pulse pressure; pSBP=peripheral systolic blood pressure; PVD=peripheral vascular disease; PWV=pulse wave velocity; TIA=transient ischemic attack
|First model||Second model|
|OR (95% CI)||P-value||OR (95% CI)||P-value|
|COPD||4.092 (1.416-11.828)||0.009||4.997 (1.660-15.041)||0.004|
|LAD||1.146 (0.873-1.504)||0.327||1.158 (0.880-1.524)||0.295|
POAF occurred in about one-third of patients in our study, which is compatible with the literature. Although the frequency of POAF varies depending on the description of POAF and research methodology, it seems that POAF is still a significant cause of morbidity. This study showed for the first time that PWV and PP are associated with POAF.
The sensitivity of PP seems better than PWV despite having less specificity. Unfortunately, individual accuracies for predicting AF do not favour one over another. Nevertheless, these parameters may still aid the clinician as a fast bedside preoperative risk assessment. Historically, PP was proposed to be one of the significant determinants of cardiovascular risk. Therefore, PP is one of the most frequently studied parameters related to vascular function, owing to the ease of measurement with a sphygmomanometer. Since PP relies on both aortic and ventricular functions, in our study we had the intention to investigate the effect of vascular function on POAF alone. Currently, PWV is the gold standard of noninvasive assessment of vascular stiffness. Initial methods, arterial catheterization, and tonometry-based methods required more time, effort, and trained staff. Thankfully, the oscillometric method simplified the process, thus PWV is measured in a few minutes and incorporated into daily routine examinations in many clinics.
Mitchell GF et al. showed that increased PP is a significant risk factor for new-onset AF in a large community-based sample. A previous study showed an association between PP and atrial volume; however, we did not find any relationship in our study. PP may be related to subclinical atrial dysfunction in patients with AF, even in patients with normal atrial size. On the other hand, PWV in our study was related to atrial size, compatible with a previous study.
PWV and PP are also associated with left ventricular diastolic dysfunction, which predisposes to AF. Fumagalli S et al. found that vascular stiffness increasing with age is related to altered left ventricular performance, which is evaluated with longitudinal strain in the elderly with preserved ejection fraction. Therefore, subclinical left ventricular remodeling related to vascular stiffness might further cause atrial remodeling and, subsequently, AF. Furthermore, electrocardiographic studies demonstrated that increased P-wave dispersion is associated with altered aortic elasticity, thus increasing the risk for AF in young prehypertensive patients.
COPD is the most consistent predictor of AF and POAF in numerous studies. Despite a strong relationship, the exact pathophysiology remained to be clarified. Hypoxia and hypercapnia were speculated to cause arrhythmia. Oxidative stress and related inflammation might be other causes triggering AF. Additionally, medications such as beta-agonists and anticholinergic drugs frequently used for COPD treatment cause AF. Pulmonary HT in COPD also might induce atrial remodeling. Additional mechanisms, including altered diastolic dysfunction and P-wave dispersion, seem to contribute to occurrences of POAF in COPD.
Central aortic hemodynamics seem more related to afterload owing to the proximity to the heart. However, we opted for pPP since it is easily measured with a simple cuff and strongly correlated with cPR Aortic stiffness is a complex measurement and is not fully understood yet. On the other hand, PWV serves as a holistic measure of aortic stiffness. Although PWV is associated with HT and age, it is less affected by other conventional risk factors. The relationship between aortic stiffness and POAF might be due to the similarity of the remodeling process in the atria and aorta. In conclusion, PP and PWV might be useful for detecting patients with a susceptibility to POAF.
1. El-Chami MF, Kilgo P, Thourani V, Lattouf OM, Delurgio DB, Guyton RA, et al. New-onset atrial fibrillation predicts long-term mortality after coronary artery bypass graft. J Am Coll Cardiol. 2010;55(13):1370-6. doi:10.1016/j.jacc.2009.10.058. [MedLine]
2. Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013; 2013(1 ):CD003611. doi:10.1002/14651858.CD003611 .pub3.
3. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021 -104. Erratum in: Eur Heart J. 2019;40(5):475. doi:10.1093/eurheartj/ehy339. [MedLine]
4. Domanski M, Mitchell G, Pfeffer M, Neaton JD, Norman J, Svendsen K, et al. Pulse pressure and cardiovascular disease-related mortality: follow-up study of the multiple risk factor intervention trial (MRFIT). JAMA. 2002;287(20):2677-83. doi:10.1001/jama.287.20.2677. [MedLine]
5. Zhong Q, Hu MJ, Cui YJ, Liang L, Zhou MM, Yang YW, et al. Carotidfemoral pulse wave velocity in the prediction of cardiovascular events and mortality: an updated systematic review and meta-analysis. Angiology. 2018;69(7):617-29. doi:10.1177/0003319717742544. [MedLine]
6. Roetker NS, Chen LY, Heckbert SR, Nazarian S, Soliman EZ, Bluemke DA, et al. Relation of systolic, diastolic, and pulse pressures and aortic distensibility with atrial fibrillation (from the multi-ethnic study of atherosclerosis). Am J Cardiol. 2014;114(4):587-92. doi:10.1016/j.amjcard.2014.05.041. [MedLine]
7. Chen LY, Foo DC, Wong RC, Seow SC, Gong L, Benditt DG, et al. Increased carotid intima-media thickness and arterial stiffness are associated with lone atrial fibrillation. Int J Cardiol. 2013;168(3):3132-4. doi:10.1016/j.ijcard.2013.04.034. [MedLine]
8. Hametner B, Wassertheurer S, Kropf J, Mayer C, Eber B, Weber T. Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements. Blood Press Monit. 2013; 18(3):173-6. doi:10.1097/MBP.0b013e3283614168. [MedLine]
9. DeLong ER, DeLong DM, Clarke-Pearson DL Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837-45. [MedLine]
10. Filardo G, Damiano RJ Jr, Ailawadi G,Thourani VH, Pollock BD, Sass DM, et al. Epidemiology of new-onset atrial fibrillation following coronary artery bypass graft surgery. Heart. 2018;104(12):985-92. doi:10.1136/heartjnl-2017-312150. [MedLine]
11. Blacher J, Staessen JA, Girerd X, Gasowski J, Thijs L, Liu L, et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med. 2000;160(8):1085-9. doi:10.1001/archinte.160.8.1085. [MedLine]
12. Mitchell GF, Vasan RS, Keyes MJ, Parise H, Wang TJ, Larson MG, et al. Pulse pressure and risk of new-onset atrial fibrillation. JAMA. 2007;297(7):709-15. doi:10.1001/jama.297.7.709. [MedLine]
13. Przewlocka-Kosmala M, Jasic-Szpak E, Rojek A, Kabaj M, Sharman JE, Kosmala W. Association of central blood pressure with left atrial structural and functional abnormalities in hypertensive patients: implications for atrial fibrillation prevention. Eur J Prev Cardiol. 2019;26(10):1018-27. doi:10.1177/2047487319839162. [MedLine]
14. Kilicgedik A, Ç Efe S, Gürbüz AS, Acar E, Yilmaz MF, Erdoğan A, et al. Left atrial mechanical function and aortic stiffness in middle-aged patients with the first episode of atrial fibrillation. Chin Med J (Engl). 2017;130(2):143-8. doi:10.4103/0366-6999.197979. [MedLine]
15. Shi D, Meng Q, Zhou X, Li L, Liu K, He S, et al. Factors influencing the relationship between atrial fibrillation and artery stiffness in elderly Chinese patients with hypertension. Aging Clin Exp Res. 2016;28(4):653-8. doi:10.1007/s40520-015-0455-8. [MedLine]
16. Abhayaratna WP, Barnes ME, O’Rourke MF, Gersh BJ, Seward JB, Miyasaka Y, et al. Relation of arterial stiffness to left ventricular diastolic function and cardiovascular risk prediction in patients > or =65 years of age. Am J Cardiol. 2006;98(10):1387-92. doi:10.1016/j.amjcard.2006.06.035. [MedLine]
17. Fumagalli S, Migliorini M, Pupo S, Marozzi I, Boni S, Scardia A, et al. Arterial stiffness and left ventricular performance in elderly patients with persistent atrial fibrillation. Aging Clin Exp Res. 2018;30(11):1403-8. doi:10.1007/S40520-018-0935-8. [MedLine]
18. Celik T, Yuksel UC, Bugan B, Celik M, Fici F, lyisoy A, et al. P-wave dispersion and its relationship to aortic elasticity in young prehypertensive patients. Am J Hypertens. 2009;22(12):1270-5. doi:10.1038/ajh.2009.157. [MedLine]
19. Terzano C, Romani S, Conti V, Paone G, Oriolo F, Vitareili A. Atrial fibrillation in the acute, hypercapnic exacerbations of COPD. Eur Rev Med Pharmacol Sci. 2014;18(19):2908-17. [MedLine]
20. Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension. 2009;54(6):1328-36. doi:101161/HYPERTENSIONAHA.109.137653. [MedLine]
Authors’Roles & Responsibilities
ZA= Substantial contributions to the design of the work; final approval of the version to be published
SO= Final approval of the version to be published
AYK= Final approval of the version to be published
ASG= Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; final approval of the version to be published
HIB= Drafting the work or revising it critically for important intellectual content; final approval of the version to be published
AG= Drafting the work or revising it critically for important intellectual content; final approval of the version to be published
Article receive on Sunday, January 15, 2023
Article accepted on Sunday, February 12, 2023