New Orleans, LA - An analysis of the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T) has shown that the restoration of sinus rhythm is associated with both short- and long-term improvements in generic quality of life and disease-specific quality of life measures, as well as improved exercise performance.[1] These improvements were even greater in symptomatic atrial-fibrillation patients, report investigators.

"I strongly believe that based on this data, since we don't have mortality data, that we can improve our patients' quality of life with rhythm control," lead investigator Dr Steven Singh (Veterans Affairs Medical Center, Washington, DC) told heartwire. "This is important and one of the reasons why we practice medicine. I believe that every effort should be made to maintain sinus rhythm, at least initially, and if you fail to achieve sinus rhythm, then either pharmacologically or nonpharmacologically there may be a role to keep the patient in atrial fibrillation. But we should at least make an attempt to restore sinus rhythm and maintain it."

The results of the SAFE-T quality-of-life analysis were presented recently during the late-breaking clinical trials session at the Heart Rhythm Society 2005 Scientific Sessions.

In-rhythm analysis

SAFE-T was a double-blind, placebo-controlled study randomizing 665 patients to amiodarone, sotalol, or placebo. The main results showed that both amiodarone and sotalol were equally effective in converting atrial-fibrillation patients to normal sinus rhythm. Amiodarone was superior for maintaining sinus rhythm, however, prolonging the time to first recurrence of atrial fibrillation four to six times longer than sotalol. The results of SAFE-T were recently published in the New England Journal of Medicine and previously reported by heartwire.[2]

In this "in-rhythm" analysis, investigators sought to compare changes in quality of life and exercise performance in patients with persistent atrial fibrillation converted to normal sinus rhythm with patients who reverted back to atrial fibrillation. Patients were classified by their rhythm status at eight weeks and one year and monitored weekly with the use of a transtelephonic ECG monitoring system.

At eight weeks, SF-36 scores for physical functioning, physical limitations, general health, and vitality improved from baseline in the rhythm-control patients. Three more disease-specific measures of quality of life—the symptom checklist (SCL) score, specific activity scale (SAS) score, and atrial fibrillation severity scalescore(AFSS)—were also significantly better in patients with restored sinus rhythm. The benefit of sinus rhythm was maintained at one year, with symptom severity and overall AFSS scores significantly improved in sinus rhythm patients compared with those in atrial fibrillation.

Exercise treadmill times, resting heart rate, and peak heart rate were all significantly improved at eight weeks and one year in patients who maintained sinus rhythm.

Change in exercise test measures from baseline to eight weeks

Exercise test measure	Sinus rhythm group (n=213)	Atrial fibrillation group (n=145)	Mean difference	p
Change in resting heart rate (beats per min)	-24.0	-6.2	-17.8	<0.001
Change in peak heart rate (beats per minute)	-38.2	-14.2	-24.0	<0.001
Change in duration of exercise time (sec)	81.5	33.5	48.0	0.01

Change in exercise test measures from baseline to 52 weeks

Exercise test measure	Sinus rhythm group (n=219)	Atrial fibrillation group (n=113)	Mean difference	p
Change in resting heart rate (beats per min)	-23.1	-4.8	-18.3	<0.001
Change in peak heart rate (beats per minute)	-40.3	-11.4	-28.9	<0.001
Change in duration of exercise time (sec)	74.6	15.2	59.4	0.02

Investigators further stratified patients by symptom status. The patients entering the study with symptomatic disease, those with dizziness, syncope, chest pain, and other symptoms, had greater improvements in the generic quality-of-life and disease-specific quality-of-life scores than those who were asymptomatic.

"In the RACE, PIAF, and AFFIRM studies, there were not any improvements in quality of life with rhythm control," explained Singh. "What was happening in a lot of these rate-control trials was that the patients were classified as being in sinus rhythm, yet many of them were in atrial fibrillation. It is not fair to say that there is no improvement in sinus rhythm when you're not looking at it. The only way, in my opinion, to look at the benefit of rhythm control is an in-rhythm analysis. These data in our study are extremely gratifying to look at in the sense that we know for a fact these patients are in sinus rhythm and are doing better."

Commenting on the quality-of-life perspective for heartwire, Dr Bernard Gersh (Mayo Clinic, Rochester, MN) noted that these previous studies comparing rate-control therapy to rhythm-control therapy enrolled patients who were willing to be randomized to treatment that kept them intentionally out of sinus rhythm, a fact noted by other experts also.

"What those three studies showed was that in this group of patients who tolerated atrial fibrillation well enough to be randomized, rate control was as effective as rhythm control, including in terms of improving quality of life," said Gersh. "But what is not in that group of patients are young people with severe symptoms, patients with severe heart failure, patients with severe left ventricular hypertrophy, who poorly tolerate the rate-control approach. In terms of deciding the right treatment, rate control or rhythm control, I think the key remains to individualize therapy."