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J Am Coll Cardiol, 2005; 46:1900-1901, doi:10.1016/j.jacc.2005.08.021
(Published online 18 October 2005). © 2005 by the American College of Cardiology Foundation |
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University of Pennsylvania Health System, Philadelphia, Pennsylvania
* Reprint requests and correspondence: Dr. Edward P. Gerstenfeld, Hospital of the University of Pennsylvania, 9 Founders Pavilion, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. (Email: edward.gerstenfeld{at}uphs.upenn.edu).
Several follow-up AFFIRM studies have attempted to address some of these limitations. In a survival substudy by Corley et al. (5), an on-treatment analysis found that maintaining sinus rhythm was an independent predictor of survival. This was the first study to find a survival advantage to maintenance of sinus rhythm, although this analysis was post-hoc, and it is always difficult to exclude the possibility that the maintenance of sinus rhythm is just a marker of improved health. Interestingly, the survival benefit of maintaining sinus rhythm seemed to be offset by an increased mortality risk of antiarrhythmic drug therapy. This supports the concept that the main reason to initiate antiarrhythmic drug therapy in patients with AF is to control symptoms. Some often ask why one should pursue an aggressive therapy to maintain sinus rhythm when AF is not a life-threatening arrhythmia. However, AF can cause a wide range of symptoms in many patients. In one study, the quality of life of patients with AF was similar to a group of patients with chronic heart failure (6). Maintenance of sinus rhythm in these patients can have a large impact on a patient’s functional status and quality of life.
In this issue of the Journal, Chung et al. (7) present a substudy of the AFFIRM trial that addresses an important question—whether use of antiarrhythmic drugs to maintain sinus rhythm affects exercise tolerance or New York Heart Association (NYHA) functional class compared with a rate control strategy. On the basis of previous studies showing a high rate of silent cerebral infarctions in patients with AF (8,9), the investigators also assessed mental status in both groups using a mini-mental status examination. A prospectively defined subgroup of the AFFIRM trial comprising 245 patients underwent a 6-min walk and mini-mental status examination at baseline, two months, and yearly intervals throughout the five-year study. Outcome was analyzed both by an intention-to-treat analysis and according to the presence or absence of AF during follow-up. No differences were found in baseline characteristics of the substudy population in those assigned randomly to a rate control (125 patients) or rhythm control (120 patients) strategy. Most patients were older (mean age, 70 years), had preserved left ventricular function (mean left ventricular ejection fraction, 51%) and were taking warfarin (93%).
At the conclusion of the substudy, 36% of patients in the rate control arm were in sinus rhythm compared with 65% in the rhythm control arm. Although there was no difference in NYHA functional class in the rate control compared with the rhythm control group, the presence of sinus rhythm throughout the study carried a small-but-statistically significant improvement in NYHA functional class. Patients assigned randomly to the rhythm control group were able to walk a mean of 94 feet further on the 6-min walk test compared with those in the rate control group. However, in the on-treatment analysis, the presence of sinus rhythm was not associated with an overall improvement in 6-min walk time despite the finding that the mean heart rate in the AF group was significantly higher both before and after the 6-min walk by approximately 12 beats/min. There was no difference in mental status between groups.
Should we now embrace rhythm control as the preferred strategy in patients with AF and functional limitations? Clearly this study falls short of allowing any definitive recommendation. Although the improvement in NYHA functional class was statistically significant, careful examination of the y-axis in Figure 1B in the paper by Chung et al. (7) reveals that the overall improvement in functional class was only 0.15, an improvement of limited clinical benefit. It would be helpful to know whether a subgroup of patients with severe limitations at baseline would derive a greater benefit from sinus rhythm, but the number of patients in this substudy was not large enough to allow more detailed analysis. As the authors discussed, the improvement in 6-min walk of 94 feet is on par with improvements observed in therapies such as biventricular pacing for congestive heart failure (10,11). However, if the improvement was due to the maintenance of sinus rhythm, one would expect the on-treatment analysis to show an even greater benefit for those patients maintaining sinus rhythm. Yet, no benefit was shown. An early benefit seemed to occur in the first two years in the sinus rhythm group but then waned by the end of the study. The reason for this lack of benefit is unclear; however, the limited symptomatology and lack of structural heart disease in the AFFIRM trial population may have limited the ability to find dramatic differences in functional status between the two groups. Similarly, the high rate of warfarin use may have limited the ability to detect any difference in mental status between the groups.
Another recent study also examined functional status in patients with AF. The Sotalol Amiodrone Atrial Fibrillation Efficacy Trial (SAFE-T) randomized 655 patients with persistent AF to receive amiodarone, sotalol, or placebo (12). Although the primary outcome of the trial was maintenance of sinus rhythm, functional status and quality of life were prespecified secondary end points. After one year of treatment, the patients maintaining sinus rhythm had significant improvements in three of eight quality of life scores measured by the Short Form-36 questionnaire. Patients in sinus rhythm also had a greater improvement in exercise duration at one year compared with patients remaining in AF (77.9 s vs. 14.6 s; p < 0.02).
How do we make use of these findings in clinical practice? In the end, although the rate and rhythm control strategies are often framed as opposing viewpoints (13), the two strategies often are complementary. We learned from the AFFIRM trial that in older, asymptomatic patients with AF, a rate control strategy often is preferable to the side effects and toxicity of antiarrhythmic drug therapy and multiple cardioversions. For patients with severe symptoms while in AF, a rhythm control strategy is mandatory. The data from Chung et al. (7) and the SAFE-T trial support the notion that maintenance of sinus rhythm also may help patients with functional limitations while in AF. The ideal strategy for the young asymptomatic patient or those with mild symptoms remains unclear. Certainly the cumulative lifetime effect of persistent AF on a 35-year-old patient is impossible to ascertain from the five-year follow-up in the AFFIRM study. If a safe, effective method for achieving long-term sinus rhythm maintenance was available widely, most would opt for it. Whether the promise of atrial specific antiarrhythmic drugs (14) or improvements to nonpharmacologic therapies will meet these goals remains to be seen. For now, clinical judgment and further studies like those by Chung et al. (7) are our best tools for guiding treatment of our patients with AF.
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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