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a Department of Surgical Sciences, Cardiac Surgery Unit, Varese University Hospital, Varese, Italy
b Department of Surgical and Perioperative Sciences, Heart Center, Cardiothoracic Division, Umeå University Hospital, Umeå, Sweden
Accepted for publication July 23, 2009.
* Address correspondence to Dr Mariscalco, Department of Surgical Sciences, Cardiac Surgery Division, Varese University Hospital, University of Insubria, Viale Guicciardini, 7, Varese, I-21100, Italy (Email: giovannimariscalco{at}yahoo.it).
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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Methods: All cardiac surgery patients (n = 9,495) undergoing cardiac surgery between January 1994 and December 2004 were studied. The study population comprised coronary artery bypass graft surgery (CABG [n = 7,621]), valvular surgeries (n = 995), and their combination (n = 879). Patients affected by postoperative AF were identified, and long-term survival was obtained from Swedish population registry and evaluated using Cox proportional hazards methods to adjust for baseline differences.
Results: The overall AF incidence was 26.7%, subdivided into 22.9%, 39.8%, and 45.2% for CABG, valve surgery, and combined procedures, respectively. The median follow-up for the entire study population was 7.9 years (maximum, 13.4). Postoperative AF independently affected long-term survival in CABG patients (hazard ratio 1.22; 95% confidence interval: 1.08 to 1.37). For isolated valvular surgery or combined procedures, AF was not significantly associated with long-term survival (hazard ratio 1.21, 95% confidence interval: 0.92 to 1.58; and hazard ratio 1.15, 95% confidence interval: 0.90 to 1.46, respectively).
Conclusions: Postoperative AF increases late mortality after isolated CABG surgery only. This finding was not statistically confirmed after isolated or combined valvular procedures. Our results draw the attention to possible AF recurrence after hospital discharge, indicating a strict postoperative surveillance.
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Introduction |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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Material and Methods |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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Patient Management and Data Collection
Preoperative management, anesthetic, and surgical techniques were standardized for all patients and have been reported previously [5]. At the end of surgery, patients were transferred to an intensive care unit and managed according to the unit protocols [5, 6]. Atrial fibrillation management and definition were considered as previously described [5]. Briefly, the AF definition included arrhythmia successfully treated as well as that persistent at discharge. The arrhythmia, as defined by physician assessment, was always on the basis of a telemetry strip or from a 12-lead electrocardiogram recording. Patients were monitored by continuous electrocardiography during a minimum period of 48 hours postoperatively. Subsequently, the monitoring was by repeated daily observations by nurses and physicians, at least every 8 hours. In addition, during the study period, specific prophylaxis (beta-blockers, amiodarone, or sotalol) against AF were not adopted. Some of the extracted variables are summarized in the Appendix Table and their definitions have been previously reported and are in accordance with the recent guidelines (Tables 1 and 2)
[5, 6]. Follow-up data on all-cause mortality were collected from the Swedish population registry, using the 10-digit national identification number. Patients of foreign nationality without traceable identity code and survival status were omitted (n = 6). Survival follow-up was closed on May 31, 2007.
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Results |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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The overall incidence of postoperative AF was 26.7%, subdivided into 22.9%, 39.8%, and 45.2% for CABG, valve surgery, and combined procedures, respectively. Patients with AF had a longer hospital stay as compared with patients without the arrhythmia (11.9 ± 5.9 versus 9.8 ± 3.8 days, p < 0.001). For all patients considered collectively, hospital mortality was 0.7%, ranging from 0.5% for CABG patients and 0.4% for valve patients, to 2.0% for patients undergoing combined procedures.
Long-Term Outcome
Follow-up was completed for all 9,432 discharged patients, with a mean follow-up time of 7.9 ± 3.3 years (maximum 13.4). For all three analyzed groups, Kaplan-Meier analysis revealed a reduced survival for patients affected by AF with respect to patients without this complication (Fig 1). In particular for the CABG group, those patients not affected by AF had a 1-, 5-, and 10-year overall survival of 98%, 92%, and 78%, respectively, which compared with 96%, 87%, and 67% for patients with the arrhythmia (p < 0.001). In contrast, for patients exposed to valve procedures, the survival was modestly affected by AF in the early postoperative years (Fig 1). In multivariable analysis, AF independently affected long-term survival in the CABG group only (HR 1.22, 95% CI: 1.08 to 1.37). For isolated valve surgery or combined procedures AF did not have an independent effect on the long-term survival (HR 1.21, 95% CI: 0.92 to 1.58; and HR 1.15, 95% CI: 0.90 to 1.46, respectively). Independent predictors for late mortality in all three groups of surgeries are depicted in Tables 1 and 2. The analysis did not reveal an overall survival differences against time (e.g., the year when the procedure was conducted), and further, possible interactions (AF*age, AF*year of operation, AF and other preoperative variables) were also tested, without significant effects (data not shown).
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Comment |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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Almassi and coworkers [9] first observed a decreased 6-month survival for cardiac surgery patients affected by postoperative AF compared with patients without it (9.4% versus 4.2%, respectively). Similar data were subsequently confirmed by other studies analyzing patients undergoing isolated CABG [3, 8, 10, 12]; postoperative AF was an age-independent predictor for late mortality, with a 20% to 50% increased risk for death for patients affected by this arrhythmia [3, 8, 10, 12]. However, in the study of Mahoney and coworkers [8], AF had no effect on long-term survival (5-year mortality] in patients exposed to valve replacement or combination procedures with CABG. Accordingly, our study confirmed the negative survival AF effect for CABG patients. Of particular interest, in our study, the independent explanatory effect of AF was significant only in the long-term perspective. In the early period, AF was confounded by other factors, which possibly illustrate a dynamic influence on the survival after CABG surgery. However, the association between postoperative AF and late mortality in valve surgery patients was not observed in our study.
The possible mechanisms by which postoperative AF is associated with late mortality are different and complex. Despite attempts to account for confounding mechanisms, it remains distinctly possible that AF is associated with mortality because it occurs in patients with a more severe profile of comorbidities [13]. Many of the independent risk factors of AF also predict long-term mortality [5, 9, 10]. Therefore, distinguishing the intrinsic hazards in response to AF from its coexisting factors of AF etiology is a complex problem [13]. In our series of univariate analyses or with Kaplan-Meier method, AF occurrence in patients exposed to isolated or combined valve procedures revealed significantly increased mortality rates compared with patients without the arrhythmia. It is important to emphasize that this difference developed in the long-term perspective, whereas during the early postoperative years AF had no survival influence at all for patients undergoing isolated valve surgery. However, for valve patients, the survival effect of postoperative AF was not confirmed with multivariable Cox approach, suggesting that AF is a mirror of severe comorbidities exemplified by aging, diabetes mellitus, impaired ventricular function, and renal failure. This effect was in contrast to patients exposed to CABG surgery, among whom the predictive power of AF persisted after statistical adjustment for confounding variables through the Cox multivariable analysis.
Plausible mechanisms supporting a direct effect of postoperative AF include heart failure and the potential AF recurrence with attendant thromboembolic sequelae. Both animal and human studies have demonstrated that AF with rapid ventricular response can predispose to ventricular dilation and cardiac output reduction by the abolished atrial systolic contribution [14]. Moreover, AF promotes impaired hemodynamics from a reduced ventricular filling as well as a circulatory stasis in the left atrium, mechanisms that render patients susceptible to stroke and embolic events [15, 16]. In addition, the reduced cardiac output and impaired cerebral circulation predispose for noncardioembolic stroke [17]. As a matter of fact, recent studies corroborate the association between postoperative AF and late mortality because of stroke and heart failure [3, 12]. Ahlsson and coworkers [12] observed a doubled risk of dying from cerebral ischemia and heart failure among CABG patients affected by AF compared with patients without it (2.6% versus 0.5% and 6.7% versus 2.5%, respectively). A plausible explanation is an AF recurrence in the late period for patients already affected by it postoperatively. Loubani and colleagues [18] observed that 39% of postoperative AF patients had the same arrhythmia after 6 months, and this finding was recently confirmed, with a prevalence of the arrhythmia of 7% in the postoperative AF group [3].
Our data indirectly validate these referred hypotheses. An intriguing assumption might suggest that patients undergoing valve surgeries are subject to a better follow-up by means of echocardiographic examinations and regular clinical visits, compared with coronary surgery patients. Moreover, a subset of patients with mechanical valves are protected from embolic events by their anticoagulation therapy, which certainly must be considered as a mechanism to explain the lack of statistical influence of AF on the late mortality in the valve group of patients. The opposing interpretation implies that AF is a marker of comorbidity, being differently reflected in CABG patients compared with the patients receiving a valve. Hence, possibly, the underlying coronary disease provokes additional AF mechanisms compared with that in valve patients. This tentative theory is supported by the different incidence rates of AF between the groups of patients, and their partly different spectra of underlying AF risk factors [4, 5].
There are several limitations to current study. First, this study is limited by its interpretations from a single center only, and further by its retrospective design, although data were prospectively collected. Second, the study is also limited in statistical terms from the different number of observations among groups. A type II error cannot be surely excluded in view of the more limited numbers of patients in the valve groups, leading to a possible failure to identify postoperative AF as an independent factor for late mortality. However, no studies exist that analyze the impact of AF on postoperative survival in patients undergoing valvular surgery. The only published study describing the AF impact on late mortality was performed by Mahoney and colleagues [8]. However, the follow-up was 5 years only, and no data were provided for the possible univariable/multivariable predictors for late mortality [8]. The statistical role of postoperative AF during follow-up was not studied, aiming the researchers at investigating the cost-effectiveness of amiodarone to prevent AF [8]. Third, the present study does not provide a direct mechanistic explanation for late mortality, a difficulty shared by other researchers into the same topic [2, 4, 8–10].
The association observed between AF and late mortality does not necessarily indicate causation, although studies on the general population affected by chronic AF and studies reporting the outcome of CABG patients affected by postoperative AF revealed a direct AF effect in causing late mortality [3, 12, 15–18]. Cerebrovascular accidents and myocardial infarction because of embolic events are a direct causation of AF [3, 12, 15–18]. Certainly, our study does not provide autopsy details, and only all-cause mortality was considered. Moreover, postdischarge AF recurrence was not documented by our data, being limited to the hospital period only. The demonstrated AF recurrence could have clarified the causative mechanism by which AF after cardiac surgery affect postoperative survival. Because of these limitations, the mechanisms by which mortality is explained by postoperative AF remain at best speculative.
Lastly, another limitation is the lack of follow-up data concerning drug medication at discharge and during follow-up, and also cancer occurrence. The present study did not measure or control for the effect of drug administration at discharge and during follow-up, and the knowledge about the administration of antiarrhythmic medications and the long-term use of anticoagulation therapy during the postoperative period would have strengthened the results. However, similar designs were present in other studies, and our results are in consonance with previous reports [3, 8, 10, 12].
In conclusion, postoperative AF affected the late survival in patients undergoing isolated CABG. This finding was not statistically confirmed among patients operated on for isolated valve surgery or combined procedures, and it possibly indicates a difference between these groups. Although the mechanisms are unclear and the direct AF effect on postoperative survival was not explored by the present study, our data give the perspective on possible arrhythmia recurrence during the postoperative period among CABG patients. Isolated coronary surgery patients affected by AF may benefit from a more strict surveillance and prolonged anticoagulation or AF antiarrhythmic prophylaxis. Follow-up of patients undergoing valvular surgery who are affected by postoperative FA requires further attention and dedicated studies.
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Appendix Table 1 |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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References |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAppendix Table 1References |
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