ORIGINAL ARTICLE – ADULT CARDIAC
Interactive CardioVascular and Thoracic Surgery 19 (2014) 218–222 doi:10.1093/icvts/ivu128 Advance Access publication 5 May 2014
Preoperative atrial fibrillation predicts mortality and morbidity after aortic valve replacement Tom Kai Ming Wanga,*, Tharumenthiran Ramanathana, David Hyun-Min Choia, Greg Gambleb and Peter Ruygroka,b a b
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand Department of Medicine, University of Auckland, Auckland, New Zealand
* Corresponding author. Auckland City Hospital, 2 Grafton Road, Grafton, Auckland 1023, New Zealand. Tel: +64-9-3670000; fax: +64-9-3074950; e-mail: [email protected] (T.K. Ming Wang). Received 21 January 2014; received in revised form 18 March 2014; accepted 28 March 2014
Abstract OBJECTIVES: Atrial fibrillation (AF) is the commonest cardiac arrhythmia, becoming increasingly prevalent as the population ages. There is conflicting information around whether AF is associated with adverse outcomes after aortic valve replacement (AVR) from the few studies that have investigated this. We compared the characteristics and outcomes of patients undergoing AVR with their history of AF. METHODS: Isolated AVR patients at Auckland City Hospital 2005–2012 were divided into those with and without preoperative AF for comparative analyses. RESULTS: Of 620 consecutive patients, 19.2% (119) had permanent or paroxysmal AF preoperatively. Patients with AF were significantly older (70.5 vs 63.4 years, P < 0.001) and were more likely to be New Zealand European (82.4 vs 68.1%, P = 0.004). They also had higher prevalence of NYHA class III–IV (55.4 vs 37.4%, P = 0.004), inpatient operation (62.1 vs 48.3%, P = 0.008), history of stroke (10.9 vs 5.0%, P = 0.031), lower creatinine clearance (73 vs 82, P = 0.001) and higher EuroSCORE II (5.2 vs 3.4%, P < 0.001). Operative mortality (6.7 vs 2.0%, P = 0.012) and composite morbidity (27.7 vs 16.5%, P = 0.006) were also higher in patients with AF. After adjusting for significant variables, preoperative AF remained an independent predictor of operative mortality with an odds ratio of 3.44 (95% confidence interval 1.29–9.13), composite morbidity of 1.79 (1.05–3.04) and a mortality during follow-up hazards ratio of 2.36 (1.44–3.87). CONCLUSIONS: AF was associated with several cardiovascular and cardiac surgery risk factors, but remained independently associated with short- and long-term mortality. AF should be incorporated into cardiac surgery risk models and surgical AF ablation may be considered with AVR. Keywords: Aortic valve replacement • Aortic stenosis • Atrial fibrillation • Arrhythmia • Cardiac surgery
INTRODUCTION
MATERIALS AND METHODS
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is commonly associated with other cardiovascular diseases and higher mortality [1, 2]. Cardiac surgery offers the opportunity of surgical ablation of AF; however, over half these patients remain untreated [3]. Several recent studies have found patients with AF to have worse outcomes after cardiac surgery [4–10], and evidence strengthening this link would further support performing a concurrent surgical AF ablation procedure. Aortic valve replacement (AVR) is the most commonly performed valvular surgery and the recommended treatment for severe symptomatic aortic stenosis and regurgitation [11]. We evaluated whether preoperative AF was independently associated with increased incidence of adverse outcomes, both short and long term, after AVR.
All patients who underwent isolated AVR without concurrent AF ablation or other cardiac surgery during January 2005 to December 2012 at Auckland City Hospital were studied. Clinical characteristics and outcomes were extracted from a prospectively collected database. Patients were divided into those with a preoperative diagnosis of AF and those without. The Canadian Cardiovascular Society Classification and the NYHA were used to grade angina and dyspnoea, respectively. Comorbidities were defined as per EuroSCORE II parameters. At least moderate severity of valvular stenosis or regurgitation had to be present to be counted. The estimated glomerular filtration rate was calculated using the Modification of Diet and Renal Disease equation as an estimate of renal function. The EuroSCORE [12], EuroSCORE II [13] and STS score [14] were retrospectively
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
T.K.M. Wang et al. / Interactive CardioVascular and Thoracic Surgery
RESULTS A total of 19.2% (119) patients undergoing isolated AVR had AF preoperatively. Baseline characteristics are shown in Table 1. Patients with AF were significantly older (70.5 vs 63.4 years, P < 0.001) and were more likely to be New Zealand European (82.4 vs 68.1%, P = 0.004). They also had higher prevalence of NYHA class III–IV (55.4 vs 37.4%, P = 0.004), inpatient operation (62.1 vs 48.3%, P = 0.008), history of stroke (10.9 vs 5.0%, P = 0.031) and lower creatinine clearance (73 vs 82, P = 0.001). As a result, patients with AF also had a higher EuroSCORE, EuroSCORE II and STS score (P < 0.001 for all 3). By multivariate analysis, 4 baseline variables were independently associated with preoperative AF: age (OR 1.04, 95% CI 1.02– 1.05, P < 0.001); history of congestive heart failure (OR 2.07, 95% CI 1.21–3.52, P = 0.007); cerebrovascular accident (OR 2.62, 95% CI 1.23–5.59, P = 0.013); and tricuspid regurgitation (OR 2.41, 95% CI 1.05–5.51, P = 0.037). Table 2 displays the operative variables and postoperative outcomes. There were no differences in operative variables. In terms of in-hospital outcomes, patients with AF had significantly higher incidence of operative mortality (6.7 vs 2.0%, P = 0.012), composite morbidity (27.7 vs 16.5%, P = 0.006) and prolonged ventilation >24 h (19.3 vs 9.2%, P = 0.003). The observed to expected ratios for operative mortality suggested that EuroSCORE overestimated, whereas the other 2 scores underestimated, operative mortality in those with AF. In those without AF, all scores overestimated operative mortality but the STS score did so to the smallest extent. Figure 1 illustrates the survival of the 2 groups over mean follow-up of 3.8 ± 2.4 years, with patients with AF having higher mortality during follow-up with a HR of 4.85, 95% CI 2.72–8.64, P < 0.001. One-, 3- and 5-year survival rates of patients with AF were 88.2, 74.2 and 64.3%, and in non-AF patients 95.6, 92.4 and 86.7%, respectively. Results of multivariate analyses of outcomes are presented in Table 3. Preoperative AF was an independent predictor of operative mortality (OR 3.38, 95% CI 1.18–9.69, P = 0.023); mortality during follow-up (HR 2.36, 95% CI 1.44–3.87, P = 0.001); composite
morbidity (OR 1.78, 95% CI 1.05–3.04, P = 0.031); and ventilation >24 h (OR 2.48, 95% CI 1.32–4.69, P = 0.005).
DISCUSSION AF is the commonest cardiac rhythm disturbance, present in 19% of our AVR cohort preoperatively, compared with 1.0–35.0% reported in other cardiac surgery studies, indicating the heterogeneity of prevalence across different demographic groups and cardiovascular diseases [4, 7, 9, 10, 15–18]. We found preoperative AF to be associated with many cardiovascular risk factors; however, even upon adjusting for these factors, AF was independently associated with both mortality and morbidity after AVR. Our results have implications for the prognostication and management of this condition. As in other studies, patients with AF in our cohort were found to be older [7, 9, 10, 15, 16, 18] with higher NYHA class scores [4, 5, 7, 9, 10, 15, 16], higher prevalence of congestive heart failure [5, 7, 9, 16, 18], impaired ejection fraction [7, 9, 10, 15, 16, 18], previous stroke [7, 9, 10, 16, 18], tricuspid regurgitation [4, 5], urgent operation [4, 7, 9] and worse renal function [4, 9, 15, 16]. They also had higher EuroSCOREs [9, 10] and STS scores. Other risk factors reported to be associated with preoperative AF in cardiac surgery candidates include hypertension [7, 9, 15, 16, 18], diabetes [6, 7, 9, 15, 16, 18], dyslipidaemia [7, 9, 10, 15], previous myocardial infarction [5, 7, 9, 16, 18], peripheral vascular disease [7, 9, 15, 16], chronic respiratory disease [7, 9, 18], smoking [7, 15, 18] and longer cardiopulmonary bypass time [5, 9]. These findings confirm the links between AF and other cardiovascular diseases and comorbidities and, given that most are established risk factors of cardiac surgery, partly explain the reason why patients with AF have worse surgical outcomes. Only 2 previous studies have identified AF as a predictor of operative mortality by multivariate analysis. One study was the analysis of the large STS database with over 280 000 patients [7], and the other in a small cohort of 83 patients all with impaired ejection fraction of 24 h after AVR. Other studies provide mixed results regarding this: a few found that preoperative AF was not associated with any postoperative morbidities [9, 10, 17], some only found AF to be associated with slightly longer length of hospital stay [4, 6, 15], whereas the remainder reported a higher rate of perioperative renal failure, inotrope or intra-aortic balloon pump support, prolonged ventilation, pacemaker implantation and/or longer length of stay in patients with AF [5, 16, 18]. The STS risk models incorporated AF as a parameter for predicting new stroke, renal failure, prolonged ventilation >24 h, reoperation and longer length of hospital stay [7, 14]. In contrast to operative mortality, most studies, including our cohort, found AF to be independently associated with worse longterm survival after cardiac surgery, with other predictors such as older age, renal impairment, history of diabetes, chronic respiratory
ORIGINAL ARTICLE
calculated. Mortality data were checked against the national registry of New Zealand up till 30 June 2013. Operative mortality (in-hospital or within 30 days), mortality during follow-up and composite morbidity (5 postoperative complications defined by the STS score) were analysed. Univariate analyses were performed using the Mann–Whitney U-test for continuous variables (presented as mean ± standard deviation) and Fisher’s exact test for categorical variables [presented as percentages (frequency)]. Kaplan–Meier curves and the log-rank (Mantel–Cox) test were used for univariate survival analyses. Multivariate analyses were performed with logistic regression to calculate odds ratios (OR) or Cox proportional hazards regression was used to calculate hazards ratios (HR) with their 95% confidence intervals (95% CIs), incorporating variables with P < 0.10 in univariate analyses into these models. Careful relevant variable selection was used in these models so that the number of variables did not significantly exceed the number of adverse events divided by 10. All tests were two-tailed, and P < 0.05 was deemed statistically significant. Analyses were performed with SPSS (Version 17.0, SPSS, Inc., Chicago, IL, USA) and Prism (Version 5, GraphPad Software, San Diego, CA, USA) software. Appropriate ethical approval was obtained before starting the study.
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T.K.M. Wang et al. / Interactive CardioVascular and Thoracic Surgery
Table 1: Baseline characteristics
Demographics Age (years) Female Ethnicity New Zealand European Maori or Pacific Other Body mass index (kg/m2) Body surface area (m2) Presentation NYHA class 1 2 3 4 Unstable angina class IV Syncope Critical preoperative state Inpatient urgent operation Past medical history Previous cardiac surgery Valve surgery Coronary artery bypass grafting Other cardiac operation Congestive heart failure Myocardial infarction Recent myocardial infarction in previous 90 days Diabetes Diabetes, on insulin Hypertension Hypercholesterolaemia Current smoker Active infective endocarditis Cerebrovascular accident Extracardiac arteriopathy Chronic pulmonary disease Dialysis Investigations Ejection fraction Normal (>50%) Mild/moderate impairment (30–50%) Severe impairment (
Interactive CardioVascular and Thoracic Surgery 19 (2014) 218–222 doi:10.1093/icvts/ivu128 Advance Access publication 5 May 2014
Preoperative atrial fibrillation predicts mortality and morbidity after aortic valve replacement Tom Kai Ming Wanga,*, Tharumenthiran Ramanathana, David Hyun-Min Choia, Greg Gambleb and Peter Ruygroka,b a b
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand Department of Medicine, University of Auckland, Auckland, New Zealand
* Corresponding author. Auckland City Hospital, 2 Grafton Road, Grafton, Auckland 1023, New Zealand. Tel: +64-9-3670000; fax: +64-9-3074950; e-mail: [email protected] (T.K. Ming Wang). Received 21 January 2014; received in revised form 18 March 2014; accepted 28 March 2014
Abstract OBJECTIVES: Atrial fibrillation (AF) is the commonest cardiac arrhythmia, becoming increasingly prevalent as the population ages. There is conflicting information around whether AF is associated with adverse outcomes after aortic valve replacement (AVR) from the few studies that have investigated this. We compared the characteristics and outcomes of patients undergoing AVR with their history of AF. METHODS: Isolated AVR patients at Auckland City Hospital 2005–2012 were divided into those with and without preoperative AF for comparative analyses. RESULTS: Of 620 consecutive patients, 19.2% (119) had permanent or paroxysmal AF preoperatively. Patients with AF were significantly older (70.5 vs 63.4 years, P < 0.001) and were more likely to be New Zealand European (82.4 vs 68.1%, P = 0.004). They also had higher prevalence of NYHA class III–IV (55.4 vs 37.4%, P = 0.004), inpatient operation (62.1 vs 48.3%, P = 0.008), history of stroke (10.9 vs 5.0%, P = 0.031), lower creatinine clearance (73 vs 82, P = 0.001) and higher EuroSCORE II (5.2 vs 3.4%, P < 0.001). Operative mortality (6.7 vs 2.0%, P = 0.012) and composite morbidity (27.7 vs 16.5%, P = 0.006) were also higher in patients with AF. After adjusting for significant variables, preoperative AF remained an independent predictor of operative mortality with an odds ratio of 3.44 (95% confidence interval 1.29–9.13), composite morbidity of 1.79 (1.05–3.04) and a mortality during follow-up hazards ratio of 2.36 (1.44–3.87). CONCLUSIONS: AF was associated with several cardiovascular and cardiac surgery risk factors, but remained independently associated with short- and long-term mortality. AF should be incorporated into cardiac surgery risk models and surgical AF ablation may be considered with AVR. Keywords: Aortic valve replacement • Aortic stenosis • Atrial fibrillation • Arrhythmia • Cardiac surgery
INTRODUCTION
MATERIALS AND METHODS
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is commonly associated with other cardiovascular diseases and higher mortality [1, 2]. Cardiac surgery offers the opportunity of surgical ablation of AF; however, over half these patients remain untreated [3]. Several recent studies have found patients with AF to have worse outcomes after cardiac surgery [4–10], and evidence strengthening this link would further support performing a concurrent surgical AF ablation procedure. Aortic valve replacement (AVR) is the most commonly performed valvular surgery and the recommended treatment for severe symptomatic aortic stenosis and regurgitation [11]. We evaluated whether preoperative AF was independently associated with increased incidence of adverse outcomes, both short and long term, after AVR.
All patients who underwent isolated AVR without concurrent AF ablation or other cardiac surgery during January 2005 to December 2012 at Auckland City Hospital were studied. Clinical characteristics and outcomes were extracted from a prospectively collected database. Patients were divided into those with a preoperative diagnosis of AF and those without. The Canadian Cardiovascular Society Classification and the NYHA were used to grade angina and dyspnoea, respectively. Comorbidities were defined as per EuroSCORE II parameters. At least moderate severity of valvular stenosis or regurgitation had to be present to be counted. The estimated glomerular filtration rate was calculated using the Modification of Diet and Renal Disease equation as an estimate of renal function. The EuroSCORE [12], EuroSCORE II [13] and STS score [14] were retrospectively
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
T.K.M. Wang et al. / Interactive CardioVascular and Thoracic Surgery
RESULTS A total of 19.2% (119) patients undergoing isolated AVR had AF preoperatively. Baseline characteristics are shown in Table 1. Patients with AF were significantly older (70.5 vs 63.4 years, P < 0.001) and were more likely to be New Zealand European (82.4 vs 68.1%, P = 0.004). They also had higher prevalence of NYHA class III–IV (55.4 vs 37.4%, P = 0.004), inpatient operation (62.1 vs 48.3%, P = 0.008), history of stroke (10.9 vs 5.0%, P = 0.031) and lower creatinine clearance (73 vs 82, P = 0.001). As a result, patients with AF also had a higher EuroSCORE, EuroSCORE II and STS score (P < 0.001 for all 3). By multivariate analysis, 4 baseline variables were independently associated with preoperative AF: age (OR 1.04, 95% CI 1.02– 1.05, P < 0.001); history of congestive heart failure (OR 2.07, 95% CI 1.21–3.52, P = 0.007); cerebrovascular accident (OR 2.62, 95% CI 1.23–5.59, P = 0.013); and tricuspid regurgitation (OR 2.41, 95% CI 1.05–5.51, P = 0.037). Table 2 displays the operative variables and postoperative outcomes. There were no differences in operative variables. In terms of in-hospital outcomes, patients with AF had significantly higher incidence of operative mortality (6.7 vs 2.0%, P = 0.012), composite morbidity (27.7 vs 16.5%, P = 0.006) and prolonged ventilation >24 h (19.3 vs 9.2%, P = 0.003). The observed to expected ratios for operative mortality suggested that EuroSCORE overestimated, whereas the other 2 scores underestimated, operative mortality in those with AF. In those without AF, all scores overestimated operative mortality but the STS score did so to the smallest extent. Figure 1 illustrates the survival of the 2 groups over mean follow-up of 3.8 ± 2.4 years, with patients with AF having higher mortality during follow-up with a HR of 4.85, 95% CI 2.72–8.64, P < 0.001. One-, 3- and 5-year survival rates of patients with AF were 88.2, 74.2 and 64.3%, and in non-AF patients 95.6, 92.4 and 86.7%, respectively. Results of multivariate analyses of outcomes are presented in Table 3. Preoperative AF was an independent predictor of operative mortality (OR 3.38, 95% CI 1.18–9.69, P = 0.023); mortality during follow-up (HR 2.36, 95% CI 1.44–3.87, P = 0.001); composite
morbidity (OR 1.78, 95% CI 1.05–3.04, P = 0.031); and ventilation >24 h (OR 2.48, 95% CI 1.32–4.69, P = 0.005).
DISCUSSION AF is the commonest cardiac rhythm disturbance, present in 19% of our AVR cohort preoperatively, compared with 1.0–35.0% reported in other cardiac surgery studies, indicating the heterogeneity of prevalence across different demographic groups and cardiovascular diseases [4, 7, 9, 10, 15–18]. We found preoperative AF to be associated with many cardiovascular risk factors; however, even upon adjusting for these factors, AF was independently associated with both mortality and morbidity after AVR. Our results have implications for the prognostication and management of this condition. As in other studies, patients with AF in our cohort were found to be older [7, 9, 10, 15, 16, 18] with higher NYHA class scores [4, 5, 7, 9, 10, 15, 16], higher prevalence of congestive heart failure [5, 7, 9, 16, 18], impaired ejection fraction [7, 9, 10, 15, 16, 18], previous stroke [7, 9, 10, 16, 18], tricuspid regurgitation [4, 5], urgent operation [4, 7, 9] and worse renal function [4, 9, 15, 16]. They also had higher EuroSCOREs [9, 10] and STS scores. Other risk factors reported to be associated with preoperative AF in cardiac surgery candidates include hypertension [7, 9, 15, 16, 18], diabetes [6, 7, 9, 15, 16, 18], dyslipidaemia [7, 9, 10, 15], previous myocardial infarction [5, 7, 9, 16, 18], peripheral vascular disease [7, 9, 15, 16], chronic respiratory disease [7, 9, 18], smoking [7, 15, 18] and longer cardiopulmonary bypass time [5, 9]. These findings confirm the links between AF and other cardiovascular diseases and comorbidities and, given that most are established risk factors of cardiac surgery, partly explain the reason why patients with AF have worse surgical outcomes. Only 2 previous studies have identified AF as a predictor of operative mortality by multivariate analysis. One study was the analysis of the large STS database with over 280 000 patients [7], and the other in a small cohort of 83 patients all with impaired ejection fraction of 24 h after AVR. Other studies provide mixed results regarding this: a few found that preoperative AF was not associated with any postoperative morbidities [9, 10, 17], some only found AF to be associated with slightly longer length of hospital stay [4, 6, 15], whereas the remainder reported a higher rate of perioperative renal failure, inotrope or intra-aortic balloon pump support, prolonged ventilation, pacemaker implantation and/or longer length of stay in patients with AF [5, 16, 18]. The STS risk models incorporated AF as a parameter for predicting new stroke, renal failure, prolonged ventilation >24 h, reoperation and longer length of hospital stay [7, 14]. In contrast to operative mortality, most studies, including our cohort, found AF to be independently associated with worse longterm survival after cardiac surgery, with other predictors such as older age, renal impairment, history of diabetes, chronic respiratory
ORIGINAL ARTICLE
calculated. Mortality data were checked against the national registry of New Zealand up till 30 June 2013. Operative mortality (in-hospital or within 30 days), mortality during follow-up and composite morbidity (5 postoperative complications defined by the STS score) were analysed. Univariate analyses were performed using the Mann–Whitney U-test for continuous variables (presented as mean ± standard deviation) and Fisher’s exact test for categorical variables [presented as percentages (frequency)]. Kaplan–Meier curves and the log-rank (Mantel–Cox) test were used for univariate survival analyses. Multivariate analyses were performed with logistic regression to calculate odds ratios (OR) or Cox proportional hazards regression was used to calculate hazards ratios (HR) with their 95% confidence intervals (95% CIs), incorporating variables with P < 0.10 in univariate analyses into these models. Careful relevant variable selection was used in these models so that the number of variables did not significantly exceed the number of adverse events divided by 10. All tests were two-tailed, and P < 0.05 was deemed statistically significant. Analyses were performed with SPSS (Version 17.0, SPSS, Inc., Chicago, IL, USA) and Prism (Version 5, GraphPad Software, San Diego, CA, USA) software. Appropriate ethical approval was obtained before starting the study.
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T.K.M. Wang et al. / Interactive CardioVascular and Thoracic Surgery
Table 1: Baseline characteristics
Demographics Age (years) Female Ethnicity New Zealand European Maori or Pacific Other Body mass index (kg/m2) Body surface area (m2) Presentation NYHA class 1 2 3 4 Unstable angina class IV Syncope Critical preoperative state Inpatient urgent operation Past medical history Previous cardiac surgery Valve surgery Coronary artery bypass grafting Other cardiac operation Congestive heart failure Myocardial infarction Recent myocardial infarction in previous 90 days Diabetes Diabetes, on insulin Hypertension Hypercholesterolaemia Current smoker Active infective endocarditis Cerebrovascular accident Extracardiac arteriopathy Chronic pulmonary disease Dialysis Investigations Ejection fraction Normal (>50%) Mild/moderate impairment (30–50%) Severe impairment (
