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By Joshua D. Moss, MD
Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco
Dr. Moss reports he is a consultant for Abbott, Boston Scientific, and Medtronic.
SYNOPSIS: Weight loss management and aggressive risk factor modification associated with slowing or even reversal of atrial fibrillation progression.
SOURCE: Middeldorp ME, Pathak RK, Meredith M, et al. PREVEntion and regReSsive Effect of weight-loss and risk factor modification on Atrial Fibrillation: The REVERSE-AF study. Europace 2018;20:1929-1935.
Atrial fibrillation (AF) is known to be a progressive disease, often starting as paroxysmal episodes that become increasingly frequent and/or sustained, then evolving into persistent, long-standing persistent, and “permanent” forms. Prior research has clearly shown lower AF burden and fewer symptoms with sustained weight loss, as well as fewer episodes of new onset AF after bariatric surgery. Middeldorp et al sought to characterize the impact of weight loss and risk factor management on progression (or regression) of AF.
Data from the previously published LEGACY study cohort1 were analyzed retrospectively. Of 825 patients with symptomatic AF and BMI > 27 kg/m2 referred to a single center in Australia, 355 patients who had not undergone AF ablation and who had at least 24 months of follow-up were included in the final cohort. Other exclusion criteria were terminal cancer, severe medical illness, or permanent AF. Patients participated in a dedicated physician-led clinic focused on weight loss and risk factor modification, with a structured program that included one-on-one individualized counseling. Goals included an initial target of > 10% weight loss, resting home blood pressures < 130/80 mmHg on at least 80% of readings, cholesterol and glucose intolerance management (with lifestyle measures and pharmacotherapy as needed), treatment of sleep apnea, smoking cessation, and alcohol reduction. Patients were seen in a separate dedicated AF clinic for arrhythmia management, with rate and rhythm control tactics at the discretion of the treating physician.
For outcomes analysis, the 355 patients in the final cohort were divided by the extent of weight loss achieved: < 3% (group 1 = 116 patients), 3-9% (group 2 = 104 patients), and ≥ 10% (group 3 = 135 patients). Baseline characteristics of the three groups were similar, with mean BMI around 33 kg/m2, although group 3 patients were slightly older (mean age, 65 years vs. 63 years in group 2 and 61 years in group 1). All groups were followed for a mean of about four years. The type of AF and burden for each patient were assessed with at least annual clinical review, 12-lead ECG, device interrogation, and seven-day Holter monitoring.
After controlling for a multitude of risk factors, the extent of weight loss achieved was significantly associated with AF progression. More than 40% of patients in group 1 (with < 3% weight loss) saw progression of their AF from paroxysmal to persistent. Only 25% were free of AF at final follow-up; most of the remaining patients saw no change. In marked contrast, 36% of patients in group 3 (with ≥ 10% weight loss) showed reversal of AF from persistent to paroxysmal, and 52% were free of AF over the final year of follow-up; only 3% of patients progressed and 9% showed no change. All groups lowered antiarrhythmic drug use rates by the end of follow-up, with the greatest change by far in group 3. Other notable findings associated with greater weight loss in group 3 were a reduction in AF burden (including 85% of patients with paroxysmal episodes lasting two to seven days initially, regressing to ≤ 48-hour episodes) and lower mean systolic blood pressure readings and less use of antihypertensive medications compared to groups 1 and 2.
The importance of focused weight loss efforts and risk factor modification in the prevention of AF has become increasingly clear. These data add dramatic new evidence to support such treatment to prevent disease progression. Eighty-eight percent of overweight patients who achieved ≥ 10% weight loss via a goal-directed, motivational, structured program with one-on-one individualized counseling experienced either a regression of their disease from persistent to paroxysmal or were free of AF at follow-up.
The primary limitation of the study is its observational nature, with all the biases inherent in the absence of randomization and prospective evaluation. Patients who can lose weight more easily also may be less likely to have progressive disease or perhaps had been overweight for a shorter period and had less attendant atrial remodeling. A direct causative effect of weight loss on AF regression cannot be inferred; still, the association is striking. The primary difficulty in applying the results of the study to clinical practice is actually achieving the kind of weight loss results seen in this single center’s dedicated clinic. Busy clinicians are unlikely to have time to provide comparable, individualized weight loss and risk factor management. However, a strong argument could be made in investing in such a dedicated stand-alone clinic, as long-term healthcare costs undoubtedly would be lower. Data on ablation procedures from this study serve as a good example. More patients in group 3 were arrhythmia-free at the time of final follow-up than patients who were arrhythmia-free in groups 1 and 2 combined, and most were without ablation. Arrhythmia-free patients in group 1 most often required multiple ablations, while those in group 2 most often required one ablation.
Clinicians will continue to offer patients all options for management of AF, including rate-control (if appropriate and effective at mitigating symptoms), antiarrhythmic drug therapy, and ablation. Some electrophysiologists defer offering a first ablation procedure until a certain goal weight is achieved, both to minimize procedural risks and maximize chances for long-term success. No matter what route is chosen, aggressive weight loss efforts and risk factor modification for overweight patients undoubtedly should be a principle component of the treatment plan.
Financial Disclosure: Internal Medicine Alert’s Physician Editor Stephen Brunton, MD, is a retained consultant for Abbott, Acadia, Allergan, AstraZeneca, Avadel, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Mylan, and Salix; he serves on the speakers bureau of AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, and Novo Nordisk. Peer Reviewer Gerald Roberts, MD; Editor Jonathan Springston; Executive Editor Leslie Coplin; Accreditations Manager Amy M. Johnson, MSN, RN, CPN; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.