Therapeutics

In overweight or obese patients with atrial fibrillation, a weight reduction program reduced symptoms

Abed HS, Wittert GA, Leong DP, et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA. 2013;310:2050-60.

Clinical impact ratings: F ★★★★★★✩ C ★★★★★★✩ Question In overweight or obese patients with symptomatic atrial fibrillation (AF), what is the effect of a structured weight reduction program on AF symptoms?

Methods Design: Randomized controlled trial. ANZCTR.org.au ACTRN12610000497000. Allocation: Unclear allocation concealment.* Blinding: Blinded* (study coordinators, treating physicians, and data analysts). Follow-up period: Median 15 months. Setting: Centre for Heart Rhythm Disorders, Adelaide, South Australia, Australia. Patients: 150 patients 21 to 75 years of age (mean age 60 y, 67% men) who had symptomatic paroxysmal or persistent AF, body mass index (BMI) > 27 kg/m2, and waist circumference > 100 cm for men or > 90 cm for women. Exclusion criteria included participation in a weight loss program in the previous 3 months, unstable international normalized ratio, diabetes treated with insulin, or significant cardiac valvular disease. Intervention: Structured weight reduction program (n = 75) or general lifestyle advice and fish oil, 3 g/d (n = 75) (except for patients on dual-platelet therapy or oral anticoagulants). The weight reduction program comprised a modified very-low-calorie diet (800 to 1200 kcal/d) for 8 weeks that was gradually replaced with low-glycemic meals; a written exercise plan (low-intensity exercise, 20 min increasing to 45 min, 3 times/wk); and clinic visits every 3 months. Cardiometabolic risk factors (hypertension, hyperlipidemia, glucose intolerance, sleep apnea, and alcohol and tobacco use) were managed similarly in both groups. Outcomes: Primary outcome was the Atrial Fibrillation Severity Scale (AFSS) and associated subscales (event frequency, duration, and global episode severity). Secondary outcomes included weight, BMI, and waist circumference. Structured weight reduction program vs general lifestyle advice in overweight or obese patients with atrial fibrillation† Outcomes

Mean change from baseline to last completed follow-up‡ Weight reduction Lifestyle advice (CI) program (95% CI)

AFSS symptom burden§

12 (10 to 14)

2.6 (0.8 to 4.3)

Episode frequency score||

3.4 (2.8 to 4.0)

0.7 (0.2 to 1.2)

Episode duration score¶

5.0 (4.3 to 5.7)

0.8 (−0.1 to 1.8)

Global episode severity score||

3.4 (2.6 to 4.2)

1.0 (0.3 to 1.8)

Symptom severity score**

8.4 (5.9 to 11)

1.7 (−0.5 to 3.9)

†CI defined in Glossary. Last completed follow-up > 80% was at 9 mo.

Patient follow-up: 100% at 3 months, 89% at 9 months, and 73% at 12 months (intention-to-treat analysis).

Main results The main results are in the Table. The intervention group had greater reductions in weight, BMI, and waist circumference at all follow-up times than the lifestyle advice group (P < 0.001).

Conclusion In overweight or obese patients with symptomatic atrial fibrillation, a structured weight reduction program reduced atrial fibrillation symptoms. *See Glossary.

Sources of funding: Centre of Heart Rhythm Disorders, University of Adelaide. Prima Health Solutions Pty Ltd provided meal replacements. For correspondence: Dr. P. Sanders, Royal Adelaide Hospital, Adelaide, South Australia, Australia. E-mail [email protected]. ■

Commentary There is already strong evidence of an association between obesity and incident AF, partly due to its relation with such other factors as hypertension, sleep apnea, diabetes, and inflammatory markers. These factors promote atrial and ventricular remodeling (including ventricular hypertrophy), diastolic dysfunction, and left atrial structural remodeling (including fibrosis and enlargement), all of which lead to AF (1). Primary prevention is optimal, but effective secondary interventions would also be beneficial. The study by Abed and colleagues provides the first robust evidence of a weight loss intervention that has a beneficial effect on AF. In this respect, the study should not be dismissed as just another example of the value of weight loss itself. Associated conditions (e.g., hypertension, diabetes, and sleep apnea) were treated similarly in both groups to isolate the effect of the intervention. Of note, the study included blinded assessment of objective outcomes (recurrence and burden of AF, and atrial and ventricular remodeling), which showed a reduction in the number and duration of AF episodes and a trend toward reduced left atrial volume in the weight reduction group. It is possible that the observed effects are secondary to a slightly greater reduction in blood pressure in the weight reduction group than in the lifestyle advice group. Patients were not blinded to treatment, so there is some bias in symptom assessment. Further, symptoms like fatigue and dyspnea may be reduced with weight loss without any effect on AF or its pathophysiology. The rate of follow-up in the study is a concern and a common problem in weight loss programs. Nevertheless, although some improvement was achieved with advice alone, a formal weight reduction intervention achieved a better result. When patients enter such a program and persist with it, there are measurable clinical benefits.

‡Higher numbers signify greater improvements; P < 0.001 for all comparisons.

D. George Wyse, MD, PhD, FACP Libin Cardiovascular Institute of Alberta Calgary, Alberta, Canada

§AFSS = Atrial Fibrillation Severity Scale Score, range 3.25 (single minimally symptomatic episode lasting minutes) to 30 (continuous highly symptomatic episode lasting > 48 h) for symptom burden; score is the sum of frequency, duration, and global severity subscores. ||Score range 1 to 10. ¶Score range 1.25 to 10. **Score range 0 (no symptoms) to 35 (severe symptoms).

Reference 1. Iwasaki YK, Nishida K, Kato T, Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011;124:2264-74.

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18 March 2014 | ACP Journal Club | Volume 160 • Number 6

In overweight or obese patients with atrial fibrillation, a weight reduction program reduced symptoms.

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