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Ann Thorac Surg 2006;82:1392-1399
© 2006 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Prognostic Implications of Preoperative Atrial Fibrillation in Patients Undergoing Aortic Valve Replacement: Is There an Argument for Concomitant Arrhythmia Surgery?

^a Division of Cardiovascular Surgery, Mayo Medical Center, Rochester, Minnesota
^b Department of Biostatistics, Mayo Medical Center, Rochester, Minnesota

Accepted for publication April 3, 2006.

^_* Address correspondence to Dr Ngaage, Department of Cardiothoracic Surgery, Cardiac Centre, Morriston Hospital, Swansea SA6 6NL, United Kingdom (Email: dngaage{at}yahoo.com).

Presented at the Poster Session of the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.

	Abstract

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BACKGROUND: The prognostic significance of preoperative atrial fibrillation (AF) at the time of aortic valve replacement is unknown, as is the potential role for concomitant arrhythmia surgery.

METHODS: We performed a cohort comparison of patients with preoperative AF (n = 129) and preoperative sinus rhythm (SR, n = 252) undergoing aortic valve surgery between 1993 and 2002; patients were matched for age, gender, and left ventricular ejection fraction. Follow-up (mean interval, 4.5 years) was 98% complete. Primary endpoints were late cardiac and all-cause mortality, as well as major adverse cardiac or cerebrovascular event.

RESULTS: Patients with preoperative AF presented with more severe congestive heart failure (p = 0.03) and more often had significant tricuspid regurgitation (p = 0.01) preoperatively. They also had worse late survival (risk ratio [RR] for death =1.5, p = 0.03) with 1-, 5-, and 7-year survival rates substantially reduced at 94%, 87%, and 50%, respectively, for those in AF versus 98%, 90%, and 61% for patients in sinus rhythm preoperatively. Individuals in AF had a greater probability of subsequent rhythm-related intervention (RR = 4.7, p = 0.0002), and more frequently developed congestive heart failure (25% vs 10%, p = 0.005) and stroke (16% vs 5%, p = 0.005). By multivariable analysis, preoperative AF was an independent predictor of late adverse cardiac and cerebrovascular events, but not late death.

CONCLUSIONS: Performance of concomitant arrhythmia surgery in patients undergoing aortic valve surgery may reduce late morbidity; however, its potential impact on late mortality in this high-risk subset of patients remains unclear.

	Introduction

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Atrial fibrillation (AF) is the most common abnormal cardiac rhythm [1], frequently accompanying other cardiovascular diseases [2]. Population-based, nonsurgical studies [3–5] have identified AF as a marker of severe cardiac disease and a risk factor for decreased long-term survival. Similarly, excess late mortality has been reported after coronary artery bypass grafting among patients with preexisting AF [6]. There is, therefore, growing enthusiasm for concomitant surgical AF ablation procedures during other cardiac surgical operations. The place of such arrhythmia surgery at the time of aortic valve replacement or repair, however, is undefined.

As a necessary first step in determining the potential value of AF ablation during aortic valve surgery, we examined the impact of preoperative AF on clinical outcomes after aortic valve replacement or repair using a matched cohort comparison design. We compared the early and late clinical outcomes including adverse cardiac and cerebrovascular events, and survival between patients in AF and those in sinus rhythm (SR) preoperatively. We also assessed the impact of the clinical types and duration of preoperative AF on prognosis.

	Patients and Methods

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Study Patients
From January 1993 through December 2002, 1,487 patients underwent isolated aortic valve replacement or repair at our institution, and 145 (10%) of these had preoperative AF. The Institutional Review Board of our institution approved the use of patients' data for this study in May 2004. Patient consent was obtained and those refusing research authorization were excluded. Patient demographics, symptoms, comorbidities, clinical findings, and operative details were obtained through interrogation of the cardiovascular surgery database. This was supplemented by a review of charts, electrocardiographic and echocardiographic reports, operative records, and histopathological notes.

Patients were excluded if they had prior cardiac surgery, prior AF ablation, prior placement of automatic implantable cardioverter defibrillator and/or pacemaker, or other arrhythmia such as atrioventricular block and ventricular tachycardia. Patients with rheumatic valve disease or infective endocarditis were also excluded. The 131 patients with preoperative AF meeting these criteria were matched for age, gender, and left ventricular ejection fraction, to a cohort of 262 patients in normal sinus rhythm using the Greedy method [7] as shown in Figure 1.

View larger version (25K): [in this window] [in a new window]   Fig 1. Algorithm illustrating the patient selection process. (AF = atrial fibrillation; SR = sinus rhythm.)

Definitions
The International Consensus on Nomenclature and Classification [8] groups AF into initial event, paroxysmal, persistent, and permanent types. In this analysis, we have used the simpler schema proposed by Cox [9] and widely utilized in surgical reports; this classifies AF as intermittent or continuous based on clinical presentation: intermittent atrial fibrillation, preoperative AF that is not present at all times; continuous atrial fibrillation, preoperative AF that is present at all times.

Because there are no standard classifications of AF on the basis of duration, we also recorded the duration of AF as the following: short duration atrial fibrillation, preoperative AF that is present for 3 months or less; long duration fibrillation, preoperative AF that is present for more than 3 months.

Statistical Analysis
The primary endpoints of the study were late mortality and(or) major adverse cardiac and cerebrovascular event. Adverse cardiac events included cardiac-related death, myocardial infarction, congestive heart failure, and subsequent rhythm-related intervention. The secondary endpoints of this study were cardiac-related late hospital readmission, and bleeding-thromboembolic complications.

Categoric variables are expressed as percentages and continuous variables are expressed as mean ± SD, unless otherwise stated. Univariate analysis was performed using the ² test for categoric variables, the Wilcoxon rank test for continuous variables, and the Kaplan-Meier method for long-term outcomes. Multivariable analysis was done using Cox proportional hazards models and logistic regression. The stepwise model selection procedure was used to identify risk factors associated with each endpoint of interest. If the primary variable of interest (preoperative AF versus preoperative SR) was selected by the stepwise procedure, then this model is reported in the results section. Otherwise, if the preoperative AF versus preoperative SR grouping variable was not chosen, it was forced into the final model provided by the stepwise procedure. The SAS statistical analysis system (SAS Institute Inc, Cary, NC) was used for data analysis. Statistical significance was defined as p < 0.05 with a 2-tailed test.

	Results

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Patients with AF exhibited a worse preoperative New York Heart Association (NYHA) functional class (p = 0.03) than those in SR (Table 1). They also more frequently exhibited cardiomegaly (p = 0.02) and significant tricuspid regurgitation (p = 0.01), although there was no difference in prevalence of mitral valve regurgitation or in mean pulmonary artery pressures. The prevalence of preoperative renal dysfunction was significantly greater among patients with preoperative AF as well (p = 0.05).

Long-Term Results
As illustrated in Figure 2A, long-term survival was substantially reduced in patients with preoperative AF compared with patients with SR (maximum follow-up 12 years, mean 4.5 years). The risk of late mortality was 50% higher in AF patients as compared with SR patients (respective median survival = 7.1 vs 9.4 years, risk ratio [RR] = 1.5, p = 0.03). The overall 1-, 5-, and 7-year survival rates were 94%, 87%, and 50% for patients with preoperative AF compared with 98%, 90%, and 61% for SR patients, respectively. However, death from cardiac causes were similar between the groups (p = 0.30, Fig 2B).

View larger version (17K): [in this window] [in a new window]   Fig 2. Kaplan-Meier survival curves for patients with preoperative (preop) atrial fibrillation (AF) and those in sinus rhythm (SR) undergoing aortic valve surgery. (A) Over-all survival. (B) Freedom from cardiac death.

View larger version (14K): [in this window] [in a new window]   Fig 3. The rates of subsequent rhythm-related intervention after aortic valve surgery. (AF = atrial fibrillation; SR = sinus rhythm; preop = preoperative.)

Risk Factors for Adverse Clinical Outcome
Prior myocardial infarction (p = 0.006), chronic obstructive pulmonary disease (p = 0.006), concurrent moderate tricuspid valve regurgitation (p <0.0001), and postoperative renal failure (p < 0.0001) were associated with significantly increased length of hospitalization. Preoperative AF was, however, only weakly associated with this outcome (p = 0.07).

The independent determinants of complications late after hospitalization are shown in Table 3. Preoperative AF was associated with a doubling of the risk of adverse cardiac and cerebrovascular events. Other predictors of late events were cardiomegaly, higher NYHA class, and diabetes mellitus.

View larger version (16K): [in this window] [in a new window]   Fig 4. Survival regression model showing risk factors for late death after aortic valve surgery by multivariate analysis. (AF = atrial fibrillation; Ao = aortic; COPD = chronic obstructive pulmonary disease; NYHA = New York Heart Association; preop = preoperative.)

View larger version (16K): [in this window] [in a new window]   Fig 5. Kaplan-Meier survival curves after aortic valve surgery for patients with preoperative AF. (A) Comparison among patients with continuous and intermittent AF. (B) Comparison among patients with AF of 3 months or less and those of more than 3 months duration. (AF = atrial fibrillation; preop = preoperative.)

	Comment

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Prior population-based studies [3–5, 10], including patients with multiple other cardiovascular diseases, have reported increased morbidity among individuals with AF; however, there has not been a focused analysis of patients undergoing aortic valve surgery. Atrial fibrillation predisposes to and aggravates congestive heart failure [11], thus leading to clinical deterioration and increased risk of death [12, 13]. Subsequent rhythm-related interventions such as cardioversions, permanent pacemaker implantation, and AF ablation are often necessary to control symptoms, accounting in part for the findings in our study of more frequent late cardiac-related hospital admissions in patients with preoperative AF. The prevalence of both structural (cardiomegaly) and physiological (AF) substrates for stroke in this group of patients accounts for the increased incidence of cerebrovascular complications among these patients. Interestingly, only 76% of patients with preoperative AF were anticoagulated with Coumadin late postoperatively.

The results of this study also demonstrate an impact of the clinical type of preoperative AF on the long-term outcome. The subset of patients with continuous AF had a higher rate of adverse cardiac and cerebrovascular events after aortic valve surgery compared with those with intermittent AF, and a 9.6-fold increase in risk of late cardiac death. These individuals were less likely to cardiovert to SR in the long term, and had more permanent pacemaker implantations. In addition, patients with AF for longer than 3 months preoperatively had a longer postoperative hospital stay and a greater rate of permanent pacemaker placement after aortic valve surgery compared with those with AF of 3 months duration or less. These findings support early consideration of valve replacement or repair in patients with hemodynamically significant aortic valve disease who first develop AF.

Given the frequency of comorbidities among patients with AF, the rationale for a concomitant arrhythmia procedure during aortic valve surgery must be based on an understanding of the independent influence of the dysrhythmia on outcome. In our study, by univariate analysis, preoperative AF was a predictor of late mortality; however, in multivariate analysis AF was a predictor of adverse cardiac and cerebrovascular events but not death. Other factors associated with AF, such as cardiomegaly and higher NYHA functional class, also escalated the risk of adverse events with cardiomegaly associated with a 2.4-fold increased risk of developing these complications.

Our finding that preoperative AF was not a risk factor for late mortality contrasts with the report of Quader and colleagues [6] that uncorrected preoperative AF is a risk factor for late death after coronary artery bypass grafting. Aortic valve disease and coronary artery disease may have different underlying mechanisms of atrial injury leading to preoperative AF resulting in different structural and functional outcomes [2, 14, 15]. For example, microvascular occlusive disease of the myocardium may play a more crucial role in the pathogenesis of AF in coronary artery disease than in aortic valve disease.

Study Limitations
Despite our efforts to match groups for comparison, patients with AF had a higher prevalence of cardiac morbidity such as cardiomegaly, moderate tricuspid valve regurgitation, and higher NYHA functional class. This makes conclusions about the potential impact of correction of the arrhythmia on late outcomes difficult. Although the "cause and effect" relationship between AF and the associated morphologic and functional cardiac abnormalities is debatable [12, 14, 16–19], their interaction is self-perpetuating [15]. Similarly, the observed outcomes are potentially complicated by the unexpectedly strong impact of prosthesis type on long-term survival. While long-term survival was worse with bioprosthesis (hazard ratio 3.25, 95% confidence interval 1.88 to 5.62, p < 0.0001), patients who received bioprosthesis were more often older, female, had congestive heart failure, cardiomegaly, and moderate mitral regurgitation. This finding demonstrates the importance of adequate multivariate modeling with all appropriate variables.

Finally, this is a retrospective study with the limitations inherent in such a data set. Since preoperative variables were not specifically collected for this study, some details, such as the clinical type and duration of AF, were not available for all the patients. However, these variables were available in a sufficient number of patients to allow comparison among different subgroups of AF patients. In addition, the cardiac rhythm at follow-up was obtained by self-reporting in a survey questionnaire. However, this was confirmed in 15% of patients who were followed locally within one year of the survey. In this subset of patients, self-reporting of late cardiac rhythm was 96% accurate. Nonetheless, silent arrhythmia can be confused with SR by patients. Thus, the rate of cardioversion (percentage of patients in SR at follow-up) among patients with preoperative AF may be overreported. This is a drawback of most studies investigating late cardiac rhythm [20], as electrocardiographic confirmation is not usually feasible.

	Conclusion

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Atrial fibrillation coexists with nonrheumatic aortic valve disease in one-tenth of patients undergoing aortic valve surgery. Patients with preoperative AF have higher rates of congestive heart failure, subsequent rhythm-related intervention and stroke, and a reduction in long-term survival compared with patients in preoperative SR. Preoperative AF is an independent predictor of adverse cardiac events and stroke. Atrial fibrillation present before aortic valve surgery persists postoperatively in the majority of patients, especially those with continuous AF. This subset had a worse outcome compared with those with intermittent AF. Surgical ablation of AF at the time of aortic valve surgery may be beneficial, particularly in regard to reducing late morbidity and stroke. The potential benefit of AF ablation on late mortality after aortic valve replacement is uncertain. This needs further investigation in a prospective randomized study.

	The Society of Thoracic Surgeons: Forty-Third Annual Meeting

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Please mark your calendars for the Forty-Third Annual Meeting of The Society of Thoracic Surgeons, to be held in San Diego, California, from January 29–31, 2007. The program will provide in-depth coverage of thoracic surgical topics selected to enhance and broaden the knowledge of cardiothoracic surgeons. Attendees will benefit from traditional Abstract Presentations, as well as Surgical Forums, Breakfast Sessions, Surgical Motion Pictures, and Town Hall Meetings on specific topics.

Advance registration forms, hotel reservation forms, and details regarding transportation arrangements, as well as the complete meeting program, will be mailed to Society members this fall. Also, complete meeting information will be available on the Society's Web site at www.sts.org. Nonmembers who wish to receive information on the Annual Meeting may contact the Society's secretary, Douglas E. Wood.

Douglas E. Wood, MD

Secretary

The Society of Thoracic Surgeons

633 N. Saint Clair St, Suite 2320

Chicago, IL 60611-3658

Telephone: (312) 202-5800

Fax: (312) 202-5801

e-mail: sts{at}sts.org

website: www.sts.org

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Dumbor L. Ngaage Hartzell V. Schaff Thoralf M. Sundt, III Charles J. Mullany Joseph A. Dearani Richard C. Daly Thomas A. Orszulak Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ngaage, D. L. Articles by Orszulak, T. A. Search for Related Content PubMed PubMed Citation Articles by Ngaage, D. L. Articles by Orszulak, T. A. Related Collections Electrophysiology - arrhythmias