Atrial fibrillation is a complicated and vexing disorder, placing patients at high risk for a number of events, particularly stroke. In 2015, results of a new study called LEGACY gave physicians and patients with atrial fibrillation some hope. Findings presented at the American College of Cardiology Scientific Sessions demonstrated that sustained weight loss was associated with reduced burden of atrial fibrillation, improved symptom severity and greater odds of arrhythmia-free survival.
The LEGACY study clarified what some have previously suspected: Weight management is an essential part of treatment for AF. The attention that the study has received since the data were presented and subsequently published in the Journal of the American College of Cardiology may prompt physicians who treat AF to change their practice to place greater emphasis on helping their patients lose weight and maintain weight loss.
“The study is already making its way into clinical guidelines and surely will change current clinical practice,” Prashanthan Sanders, MBBS, PhD, FHRS, Knapman–National Heart Foundation chair of cardiology research at the University of Adelaide, clinical director of cardiac electrophysiology at Royal Adelaide Hospital, Australia, and senior author of the LEGACY study, told Cardiology Today.
Before the spotlight was on the LEGACY study, most physicians were aware that weight loss is beneficial for patients with AF, but they “probably weren’t thinking about it very much,” Peter R. Kowey, MD, FACC, FHRS, professor of medicine and clinical pharmacology at Jefferson Medical College, Philadelphia, and chief of cardiology and William Wilkoff Chair in Cardiovascular Research at Lankenau Heart Institute, Wynnewood, Pennsylvania, said in an interview. “We see a lot of patients with AF, and they have a lot of issues, and they might be obese but we don’t get around to discussing it. Now, doctors will be more aware of it. How much more they will be aware of it, and how much they will intervene, is a big question.”
Current evidence base
In recent years, researchers have explored connections between weight management and the effect on AF.
John D. Day, MD, FHRS, FACC, performs catheter ablation on a patient with atrial fibrillation; he says treating obesity in these patients may have beneficial effects.
Photo courtesy of: Intermountain Medical Center Heart Institute; printed with permission.
For example, Sanders and colleagues in 2013 published study findings in JAMA concluding that weight reduction with intensive risk factor management in 150 patients with obesity and AF reduced AF symptom burden and severity and contributed to beneficial cardiac remodeling. After a median follow-up of 15 months, patients assigned a weight-loss intervention had a greater reduction in weight (14.3 kg vs. 3.6 kg; P < .001), AF symptom burden score (11.8 vs. 2.6; P < .001) and AF symptom severity score (8.4 vs. 1.7; P < .001). Compared with controls, those in the intervention group at 12 months had a greater decrease in mean number of AF episodes and duration of AF based on Holter monitoring (group x time interaction, P < .001).
Sanders and colleagues also conducted the ARREST-AF study of an aggressive risk factor management program focusing on control of weight, BP, lipids, glucose levels, sleep-disordered breathing, smoking and alcohol counseling compared with standard care. Results published in JACC in 2014 highlighted that aggressive management was associated with greater decreases in AF frequency, duration, symptoms and symptom severity and a higher rate of arrhythmia-free survival after AF ablation without the use of medication (P < .001 for all).
The LEGACY study expanded on that research. Sanders and colleagues investigated whether the effect of weight loss on AF is sustained, whether there is a dose effect and whether weight fluctuation influences the effect.
The study included 355 patients with AF and BMI at least 27 kg/m2. All participants were counseled on weight loss and risk factor management, including hypertension, glucose control, sleep apnea, smoking and alcohol use, and offered participation in a physician-led weight management clinic; those who chose not to participate engaged in a self-managed weight-loss program. Patients were stratified by weight loss: 10% or more, 3% to 9% or less than 3%. Patients who lost 10% or more total weight had a greater rate of participation in the physician-led weight management clinic (84% vs. 57% in the 3% to 9% group and 30% in the less than 3% group; P < .001). All three groups averaged approximately 3 years of follow-up, during which weight trends and/or fluctuation were assessed yearly. At least once a year, AF was determined by clinical review, 12-lead ECG and 7-day Holter monitoring.
Patients who lost 10% or more of total weight had a greater decrease in AF burden and symptom severity
(P < .001 for all) compared with lower levels of weight loss. This group also had a greater rate of arrhythmia-free survival with and without rhythm control strategies compared with the other weight-loss groups (P < .001 for comparison with both groups). When Sanders and colleagues conducted multivariate analyses, they found that weight loss and weight fluctuation independently predicted AF-related outcomes (P < .001 for both). Additionally, 10% or more weight loss resulted in sixfold greater probability of arrhythmia-free survival compared with 3% to 9% or less than 3% weight loss.
“Weight loss was also associated with beneficial structural remodeling, including significant reductions in left atrial volume and left ventricular hypertrophy,” Sanders told Cardiology Today.
In other results, the researchers found that weight fluctuation of greater than 5% could renew a patient’s risk for AF. Patients whose weight fluctuated by more than 5% during the study period had a twofold increased risk for arrhythmia recurrence.
“The LEGACY study was a wake-up call for electrophysiologists that AF is not just an electrical phenomenon,” John D. Day, MD, FHRS, FACC, director of heart rhythm services at Intermountain Heart Institute, Murray, Utah, and president of the Heart Rhythm Society, said in an interview. “It may be a manifestation of comorbidities. And we need to treat the underlying causes, or they will just develop new AF circuits.”
The correlation between BMI and AF risk is strong across a wide swath of research, according to a meta-analysis conducted by Sanders and colleagues published in May in JACC: Electrophysiology. The researchers analyzed data from 51 studies covering 626,603 individuals. In cohort studies, there was a 29% (OR = 1.29; 95% CI, 1.23-1.36) increased risk for incident AF for every five-unit increase in BMI, and in case-control studies, there was a 19% (OR = 1.19; 95% CI, 1.13-1.26) increased risk. Similarly, for every five-unit increase in BMI, there was a 10% (OR = 1.1; 95% CI, 1.04-1.17) excess risk for postoperative AF and a 13% (OR = 1.13; 95% CI, 1.06-1.22) excess risk for post-ablation AF, according to the results.