Singh SN, Tang C, Singh BN, Dorian P, Reda DJ, Harris CL, Fletcher RD, Sharma SC, Atwood JE, Jacobson AK, Lewis D, Lopez B, Raisch DW, Ezekowitz MD

J Am Coll Cardiol. 2006;48:721-730.

Background:

Following the results of the recent AFFIRM trial showing neutral mortality impact of the restoration of sinus rhythm in patients with atrial fibrillation, there has been an increasing focus among the medical community on the control of ventricular rate combined with anticoagulation as an initial treatment approach to atrial fibrillation. However, patients with chronic atrial fibrillation continue to experience disabling symptoms and poor exercise tolerance that may compromise quality of life. Whether restoration of sinus rhythm in patients with atrial fibrillation results in improvement in quality of life (QOL) and exercise performance remains controversial.

Objective:

To determine QOL and exercise performance in patients with persistent atrial fibrillation converted to sinus rhythm compared with those remaining in or reverting to atrial fibrillation.

Methods:

Patients with persistent atrial fibrillation were randomized in a double-blind fashion to amiodarone, sotalol, or placebo after optimal anticoagulation. After 4 weeks of therapy, those not in sinus rhythm were electrically cardioverted. Recurrence of atrial fibrillation was documented by weekly transtelephonic monitoring. Patients were classified into sinus rhythm or atrial fibrillation groups at 8 weeks and 1 year. Patients remaining in sinus rhythm were maintained on their original assigned treatment. Those who remained in or reverted to atrial fibrillation after a second cardioversion were placed on open-label medications. General health-related QOL was evaluated using the Medical Outcomes Study Short Form questionnaire. Disease-specific measures of QOL, including the arrhythmia-related Symptom Checklist, Specific Activity Scale, and the Atrial Fibrillation Severity Scale, were also measured. A modified Naughton treadmill protocol was used to assess exercise performance.

Results:

Six hundred twenty-four patients were followed to 8 weeks (305 in the sinus rhythm group and 319 in the atrial fibrillation group); 557 patients completed the 1-year follow-up. Mean age was 67 years, and 99% were men. Quality-of-life measurements were available for 89% of the patient cohort. Favorable changes were seen in patients in the sinus rhythm (compared with the atrial fibrillation group) at 8 weeks in physical functioning (P < .001), physical role limitation (P = .03), general health (P = .002), and vitality (P < .001); there were also significant improvements in symptom severity (P = .01), functional capacity (P = .003), and atrial fibrillation symptom burden (P < .001). At 1 year, patients in the sinus rhythm had significant improvements in general health (P = .007) and social functioning (P = .02) compared with the atrial fibrillation patients. Symptom frequency and severity were significantly reduced in the sinus rhythm group compared with the atrial fibrillation group (P = .05 and P < .001, respectively). Atrial fibrillation symptom burden also decreased among patients maintained in sinus rhythm (P < .001) at 1 year. These outcomes remained unchanged after adjustment for possible confounders. Although both symptomatic and asymptomatic patients reported improvement in several QOL measurements at 8 weeks, there was no difference in these variables, except for atrial fibrillation symptom burden at 1 year for the asymptomatic subgroup. Exercise performance in the sinus rhythm versus atrial fibrillation groups was greater from baseline to 8 weeks (P = .01) and from baseline to 1 year (P = .02). Exercise performance correlated with physical functioning and functional capacity, except in the atrial fibrillation group at 1 year.

Discussion:

In patients with persistent atrial fibrillation, restoration and maintenance of sinus rhythm were associated with improvement in QOL measures and exercise performance. There was a strong correlation between QOL measure and exercise performance. These data underscore the importance of restoration and maintenance of sinus rhythm in patients with atrial fibrillation in the overall management of the arrhythmia.

Comment:

The results of this study clearly differ from those of the AFFIRM trial; the AFFIRM trial was a study on patients with paroxysmal atrial fibrillation that showed no effect on mortality or on major physical end points with restoration of sinus rhythm. Analysis of these 2 studies shows differences in trial conduct, which may account for the disparate results. As a clinician attempting to make sense of these trials and trying to incorporate the results to everyday practice, these contradictory studies present a challenge. At the end of the day, it is important to look at each individual patient and make clinical decisions based on that one patient rather than the dictates of trials, which are based on patient cohorts.

SL