RESEARCH ARTICLE For reprint orders, please contact: [email protected]
Does aortic valve disease etiology predict postoperative atrial fibrillation in patients undergoing aortic valve surgery? Rajesh Dandale*,1, Andrea Rossi2, Francesco Onorati2, Alexander Krapivsky1, Paschalis Kekes1, Aldo Milano2, Francesco Santini2 & Giuseppe Faggian2
ABSTRACT Background: Postoperative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery and is associated with increased mortality and morbidity. Methods: We analyzed 830 patients without prior atrial fibrillation who underwent aortic valve replacement for aortic stenosis and/or aortic regurgitation. Results: The incidence of POAF was 38%. The patients with POAF were older, predominately male and hypertensive. The incidence of POAF was significantly different according to the valve etiology. At multivariate analysis, rheumatic and degenerative aortic valve etiologies were independent predictors of POAF. Conclusion: Aortic valve disease etiology affects the development of POAF. Rheumatic and degenerative etiologies have a higher risk of developing POAF independently of other clinical, functional and hemodynamic variables. Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery [1–5] . Moreover, recent studies have shown that POAF is associated with an increased frequency of stroke [4,6,7] , readmission [6] , perioperative myocardial infarction [6] , ventricular arrhythmia [8] , persistent congestive heart failure [6] , morbidity and an increased use of hospital resources [3] . The incidence of POAF is affected by a multitude of preoperative, intraoperative and postoperative variables [2,9–12] . The array of contributory pathophysiological factors is still under investigation. Recently, there has been increasing interest in the role of inflammation and oxidative stress in the pathophysiology of POAF. In particular, an inflammatory marker – CRP – has been reported to relate to POAF development [13] . Furthermore, changes in cardiac physiology, chronic exposure to inflammation and cardiac remodeling may contribute to POAF development [13–15] . However, no previous studies on aortic valve surgery have compared the impact of valve etiologies on POAF development. The purpose of this study was to investigate the relationship between new-onset POAF and aortic valve etiology in patients undergoing aortic valve replacement surgery.
KEYWORDS
• aortic valve disease • aortic valve replacement • atrial fibrillation • echocardiography
Methods This was a single-center, retrospective, cross-sectional study of patients (all older than 18 years of age) undergoing aortic valve replacement with or without simultaneous coronary artery bypass graft (CABG) and mitral valve surgery between January 2008 and December 2013. The exclusion criteria were history of chronic, paroxysmal atrial fibrillation (AF), other arrhythmic abnormalities and the use of any antiarrhythmic therapy before surgery. The clinical end point of the study was the development of AF during the hospitalization after surgery. POAF was defined according to recent European Society of Cardiology (ESC) guidelines on Department of Cardiology, Evangelisches Krankenhaus, Wertgasse 30, 45468, Mülheim an der Ruhr, Germany Department of Cardiovascular Sciences, University Hospital, Verona, Italy *Author for correspondence: Tel.: +49 208 309 2674; Fax: +49 208 309 2109; [email protected] 1 2
10.2217/FCA.14.57 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(6), 707–715
part of
ISSN 1479-6678
703
Research Article Dandale, Rossi, Onorati et al. AF [16] as any sustained episode of ≥15 s recorded during the postoperative hospital stay. No systematic prophylactic measures were used in order to prevent the development of POAF. As per hospital protocol, a constant telemetry used at least 3 days after the postoperative period in order to detect clinically silent AF episodes. Thereafter, a standard 12-lead ECG was recorded every 12 h. In every patient suspected of an arrhythmic event, a standard 12-lead ECG was performed then monitored with continuous telemetry until 48 h after the resolution of the arrhythmia. The database of the Department of Cardiovascular Sciences (University Hospital Borgo Trento, Verona, Italy) contained detailed information on patient demographics, preoperative risk factors, medication use, details of the procedure and postoperative variables. These data were collected using a standardized dataset and definitions. At our department, the collecting and reporting of patient data are compulsory and mandated by the hospital administration. The aortic valve pathology categorization was delineated as congenital, degenerative, rheumatic, infective, prosthetic malfunction and mixed (difficult to differentiate from each another) on the basis of patient clinical history, echocardiography, direct visualization of the aortic valve during surgery and histopathological examination of the aortic valve. The patients who developed POAF were treated by following the ESC guidelines for the management of AF [16] . Definitions ●●Preoperative variables
Renal dysfunction was defined as serum creatinine >200 mmol/l or a history of dialysis support or functioning renal transplant. Hypertension was defined as a history of blood pressure >140/90 mmHg or lower if treated. Diabetes was defined as a history of diabetes on dietary control, oral hypoglycemic therapy or insulin therapy. BMI was calculated using the standard formula with height and weight. According to BMI, patients were categorized as normal weight (BMI: 30). Acute myocardial infarction was considered when an increase of creatinine kinase of five or more-times the upper limit of normal was measured within 24 h pre- or postsurgery or any new ischemia changes on ECG. As is routine, most of the patients underwent 2D, M-mode and Doppler echocardiographic
704
Future Cardiol. (2014) 10(6)
examinations in the preoperative period (up to 48 h before the operation). Standard right- and left-sided heart catheterization data were available for all patients. Aortic valve gradients were measured routinely in all patients using a 6-Fr double lumen fluidfilled pigtail catheter by the pull-back method. Simultaneously, left ventricular end-diastolic and end-systolic pressure gradients were reported. During right heart catheterization, pulmonary capillary wedge pressure and pulmonary artery systolic and diastolic pressure were measured. ●●Intraoperative & postoperative variables
These data include aortic cross-clamp duration, cardiopulmonary circulation time, other associated surgeries for coronary artery or mitral valve disease, transfusion of red blood cells, hours of ventilation, duration of recovery in intensive care units, postoperative serum creatinine, the highest serum creatinine level in the postoperative period, duration of hospital recovery and in-hospital mortality, which was defined as mortality during hospitalization or within the first 30 postoperative days. It is institutional policy to monitor serum electrolyte levels with acid–base–gas analysis every 2 h for the first 6 h, then every 3 h for the first 24 h and then twice daily for the following 3 postoperative days. Whenever the serum level of potassium was 3.6 mmol/l. ●●Statistical analysis
All statistical analyses were performed using the SPSS statistical program for Windows, version 17.0 (SPSS, Inc., IL, USA). Variables were tested for normal distribution with the Kolmogorov– Smirnov test. Continuous variables are presented as means and standard deviations, and categorical variables are presented as percentages. Patients were divided in two groups according the presence of POAF. Preoperative, intraoperative and postoperative variables were compared between groups. Categorical variables were compared using the χ 2 or Fisher’s exact test. The student’s t-test was used to compare continuous variables, except when the data were skewed; in this case, the Wilcoxon test was used. p < 0.05 was considered to be statistically significant. Variables reaching statistical significance were introduced into the multivariate analysis, which was used in order to identify the independent clinical predictors. In the multivariate model,
future science group
Postoperative atrial fibrillation
Research Article
Table 1. Demographic and clinical characteristics in the postoperative atrial fibrillation present and absent groups. Variable
Present (n = 316)
Postoperative atrial fibrillation Absent (n = 514)
Univariate p-value
Female Age (years) Age >75 years Weight (kg)
147 (46%) 72.3 ± 8.6 127 (40%) 74 ± 14.5
199 (38%) 68.8 ± 12.1 171 (33%) 73.3 ± 13.9
0.02 25) have 1.1 and 1.3 greater odds of POAF development, respectively. Neither concomitant CABG nor mitral valve surgery was associated with POAF (p = 0.98 and 0.58, respectively) on the univariate and multivariate models, as shown in Tables 3 & 4. Although the duration of hospital stay was longer in the POAF group (5.2 ± 39.5 vs 3.6 ± 41 days; p < 0.03), there was no statistically significant difference in terms of in-hospital mortality between the groups (p = 0.81). Discussion We report the results of a retrospective, singlecenter study investigating the effects of aortic valve disease etiology on the development of POAF. The present study provides an important finding that patients with rheumatic aortic valve disease and degenerative aortic valve disease have 2.6 and 2.2 greater odds of developing POAF, respectively.
POAF is a common arrhythmia after cardiac surgery that is reported in 15–40% of patients in the early postoperative period following CABG [1–3] , in 37–50% after valve surgery, in as many as 60% undergoing valve replacement combined with CABG and in 11–24% after cardiac transplantation [4,5] . However, there are few clinical studies based on the impact of aortic valve surgery on POAF [17,18] . Among them, the large study of 4550 patients by Kuduvalli and colleagues found that an age of >70 years, renal dysfunction and heart failure were significant predictors of POAF in patients undergoing aortic valve replacement surgery [17] . Similarly, on the basis of univarient statistical analysis, we found that POAF incidence was higher in patients aged >75 years (p < 0.001), hypertensive patients (p < 0.001) and patients with BMI >25 (p = 0.02). Moreover, the POAF group had prolonged hospital stays after surgery (5.2 ± 39.5 vs 3.7 ± 41 days; p < 0.03) [8–10] . The pathophysiology underlying the development of POAF is unknown; however, most of the evidence suggests it is multifactorial [19] . Ageand hypertension-related structural changes in the atria, the effects of surgical manipulation
Table 4. Results of multivariate logistic regression. Variable
OR (95% CI)
p-value
Rheumatic AVD Degenerative AVD Old patient (>75 years of age) History of hypertension
2.6 (1.2–5.4) 2.2 (1.34–3.55) 1.1 (1.00–1.04) 0.66 (0.46–0.95)
Does aortic valve disease etiology predict postoperative atrial fibrillation in patients undergoing aortic valve surgery? Rajesh Dandale*,1, Andrea Rossi2, Francesco Onorati2, Alexander Krapivsky1, Paschalis Kekes1, Aldo Milano2, Francesco Santini2 & Giuseppe Faggian2
ABSTRACT Background: Postoperative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery and is associated with increased mortality and morbidity. Methods: We analyzed 830 patients without prior atrial fibrillation who underwent aortic valve replacement for aortic stenosis and/or aortic regurgitation. Results: The incidence of POAF was 38%. The patients with POAF were older, predominately male and hypertensive. The incidence of POAF was significantly different according to the valve etiology. At multivariate analysis, rheumatic and degenerative aortic valve etiologies were independent predictors of POAF. Conclusion: Aortic valve disease etiology affects the development of POAF. Rheumatic and degenerative etiologies have a higher risk of developing POAF independently of other clinical, functional and hemodynamic variables. Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery [1–5] . Moreover, recent studies have shown that POAF is associated with an increased frequency of stroke [4,6,7] , readmission [6] , perioperative myocardial infarction [6] , ventricular arrhythmia [8] , persistent congestive heart failure [6] , morbidity and an increased use of hospital resources [3] . The incidence of POAF is affected by a multitude of preoperative, intraoperative and postoperative variables [2,9–12] . The array of contributory pathophysiological factors is still under investigation. Recently, there has been increasing interest in the role of inflammation and oxidative stress in the pathophysiology of POAF. In particular, an inflammatory marker – CRP – has been reported to relate to POAF development [13] . Furthermore, changes in cardiac physiology, chronic exposure to inflammation and cardiac remodeling may contribute to POAF development [13–15] . However, no previous studies on aortic valve surgery have compared the impact of valve etiologies on POAF development. The purpose of this study was to investigate the relationship between new-onset POAF and aortic valve etiology in patients undergoing aortic valve replacement surgery.
KEYWORDS
• aortic valve disease • aortic valve replacement • atrial fibrillation • echocardiography
Methods This was a single-center, retrospective, cross-sectional study of patients (all older than 18 years of age) undergoing aortic valve replacement with or without simultaneous coronary artery bypass graft (CABG) and mitral valve surgery between January 2008 and December 2013. The exclusion criteria were history of chronic, paroxysmal atrial fibrillation (AF), other arrhythmic abnormalities and the use of any antiarrhythmic therapy before surgery. The clinical end point of the study was the development of AF during the hospitalization after surgery. POAF was defined according to recent European Society of Cardiology (ESC) guidelines on Department of Cardiology, Evangelisches Krankenhaus, Wertgasse 30, 45468, Mülheim an der Ruhr, Germany Department of Cardiovascular Sciences, University Hospital, Verona, Italy *Author for correspondence: Tel.: +49 208 309 2674; Fax: +49 208 309 2109; [email protected] 1 2
10.2217/FCA.14.57 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(6), 707–715
part of
ISSN 1479-6678
703
Research Article Dandale, Rossi, Onorati et al. AF [16] as any sustained episode of ≥15 s recorded during the postoperative hospital stay. No systematic prophylactic measures were used in order to prevent the development of POAF. As per hospital protocol, a constant telemetry used at least 3 days after the postoperative period in order to detect clinically silent AF episodes. Thereafter, a standard 12-lead ECG was recorded every 12 h. In every patient suspected of an arrhythmic event, a standard 12-lead ECG was performed then monitored with continuous telemetry until 48 h after the resolution of the arrhythmia. The database of the Department of Cardiovascular Sciences (University Hospital Borgo Trento, Verona, Italy) contained detailed information on patient demographics, preoperative risk factors, medication use, details of the procedure and postoperative variables. These data were collected using a standardized dataset and definitions. At our department, the collecting and reporting of patient data are compulsory and mandated by the hospital administration. The aortic valve pathology categorization was delineated as congenital, degenerative, rheumatic, infective, prosthetic malfunction and mixed (difficult to differentiate from each another) on the basis of patient clinical history, echocardiography, direct visualization of the aortic valve during surgery and histopathological examination of the aortic valve. The patients who developed POAF were treated by following the ESC guidelines for the management of AF [16] . Definitions ●●Preoperative variables
Renal dysfunction was defined as serum creatinine >200 mmol/l or a history of dialysis support or functioning renal transplant. Hypertension was defined as a history of blood pressure >140/90 mmHg or lower if treated. Diabetes was defined as a history of diabetes on dietary control, oral hypoglycemic therapy or insulin therapy. BMI was calculated using the standard formula with height and weight. According to BMI, patients were categorized as normal weight (BMI: 30). Acute myocardial infarction was considered when an increase of creatinine kinase of five or more-times the upper limit of normal was measured within 24 h pre- or postsurgery or any new ischemia changes on ECG. As is routine, most of the patients underwent 2D, M-mode and Doppler echocardiographic
704
Future Cardiol. (2014) 10(6)
examinations in the preoperative period (up to 48 h before the operation). Standard right- and left-sided heart catheterization data were available for all patients. Aortic valve gradients were measured routinely in all patients using a 6-Fr double lumen fluidfilled pigtail catheter by the pull-back method. Simultaneously, left ventricular end-diastolic and end-systolic pressure gradients were reported. During right heart catheterization, pulmonary capillary wedge pressure and pulmonary artery systolic and diastolic pressure were measured. ●●Intraoperative & postoperative variables
These data include aortic cross-clamp duration, cardiopulmonary circulation time, other associated surgeries for coronary artery or mitral valve disease, transfusion of red blood cells, hours of ventilation, duration of recovery in intensive care units, postoperative serum creatinine, the highest serum creatinine level in the postoperative period, duration of hospital recovery and in-hospital mortality, which was defined as mortality during hospitalization or within the first 30 postoperative days. It is institutional policy to monitor serum electrolyte levels with acid–base–gas analysis every 2 h for the first 6 h, then every 3 h for the first 24 h and then twice daily for the following 3 postoperative days. Whenever the serum level of potassium was 3.6 mmol/l. ●●Statistical analysis
All statistical analyses were performed using the SPSS statistical program for Windows, version 17.0 (SPSS, Inc., IL, USA). Variables were tested for normal distribution with the Kolmogorov– Smirnov test. Continuous variables are presented as means and standard deviations, and categorical variables are presented as percentages. Patients were divided in two groups according the presence of POAF. Preoperative, intraoperative and postoperative variables were compared between groups. Categorical variables were compared using the χ 2 or Fisher’s exact test. The student’s t-test was used to compare continuous variables, except when the data were skewed; in this case, the Wilcoxon test was used. p < 0.05 was considered to be statistically significant. Variables reaching statistical significance were introduced into the multivariate analysis, which was used in order to identify the independent clinical predictors. In the multivariate model,
future science group
Postoperative atrial fibrillation
Research Article
Table 1. Demographic and clinical characteristics in the postoperative atrial fibrillation present and absent groups. Variable
Present (n = 316)
Postoperative atrial fibrillation Absent (n = 514)
Univariate p-value
Female Age (years) Age >75 years Weight (kg)
147 (46%) 72.3 ± 8.6 127 (40%) 74 ± 14.5
199 (38%) 68.8 ± 12.1 171 (33%) 73.3 ± 13.9
0.02 25) have 1.1 and 1.3 greater odds of POAF development, respectively. Neither concomitant CABG nor mitral valve surgery was associated with POAF (p = 0.98 and 0.58, respectively) on the univariate and multivariate models, as shown in Tables 3 & 4. Although the duration of hospital stay was longer in the POAF group (5.2 ± 39.5 vs 3.6 ± 41 days; p < 0.03), there was no statistically significant difference in terms of in-hospital mortality between the groups (p = 0.81). Discussion We report the results of a retrospective, singlecenter study investigating the effects of aortic valve disease etiology on the development of POAF. The present study provides an important finding that patients with rheumatic aortic valve disease and degenerative aortic valve disease have 2.6 and 2.2 greater odds of developing POAF, respectively.
POAF is a common arrhythmia after cardiac surgery that is reported in 15–40% of patients in the early postoperative period following CABG [1–3] , in 37–50% after valve surgery, in as many as 60% undergoing valve replacement combined with CABG and in 11–24% after cardiac transplantation [4,5] . However, there are few clinical studies based on the impact of aortic valve surgery on POAF [17,18] . Among them, the large study of 4550 patients by Kuduvalli and colleagues found that an age of >70 years, renal dysfunction and heart failure were significant predictors of POAF in patients undergoing aortic valve replacement surgery [17] . Similarly, on the basis of univarient statistical analysis, we found that POAF incidence was higher in patients aged >75 years (p < 0.001), hypertensive patients (p < 0.001) and patients with BMI >25 (p = 0.02). Moreover, the POAF group had prolonged hospital stays after surgery (5.2 ± 39.5 vs 3.7 ± 41 days; p < 0.03) [8–10] . The pathophysiology underlying the development of POAF is unknown; however, most of the evidence suggests it is multifactorial [19] . Ageand hypertension-related structural changes in the atria, the effects of surgical manipulation
Table 4. Results of multivariate logistic regression. Variable
OR (95% CI)
p-value
Rheumatic AVD Degenerative AVD Old patient (>75 years of age) History of hypertension
2.6 (1.2–5.4) 2.2 (1.34–3.55) 1.1 (1.00–1.04) 0.66 (0.46–0.95)
