Semaglutide for Metabolic Intervention and Adipose Loss to Treat Atrial Fibrillation

Obesity and atrial fibrillation (AF) pose a significant burden on healthcare systems worldwide. Obesity is an established independent risk factor for both the development of AF, as well as increased disease severity and adverse outcomes. According to a meta-analysis of 51 studies involving 60,000 individuals, every 5-unit increment in BMI confers an additional 19%-29% risk of incident AF, a 10% risk of post-operative AF, and a 13% risk of post-ablation AF. The estimated prevalence of AF in the United States is approximately 5.2 million, and is expected to increase to 12.1 million by the year 2030, likely explained by mirroring the growth of the obesity epidemic. While many associations have been made, the underlying pathophysiological mechanisms linking obesity and AF are incompletely understood. Two large longitudinal cohort studies demonstrated that obesity contributes to disease progression to persistent or permanent forms of AF. Importantly, significant weight loss achieved by bariatric surgery has been associated with a reduction in the risk of new-onset AF by 29% in the prospective matched cohort Swedish Obese Study. Weight loss achieved with intensive lifestyle modification has also been shown to impact AF burden. However, these studies have not systematically investigated the biological mechanisms underlying weight loss and AF. The novelty of the proposed study is that it will be the first to examine the impact of weight loss with semaglutide 2.4 mg on biological signaling and cardiac remodeling in relation to reductions in AF burden. Additionally, the proposed study will be the first to evaluate the effect of pharmacological weight loss on the risk of arrhythmia recurrence, combined with antiarrhythmic drugs (AAD) and/or catheter ablation (CA), which are the current first-line strategies for rhythm maintenance in patients with obesity. That is relevant as obesity is a chronic and relapsing health condition as demonstrated in multiple large intensive lifestyle modification studies which show a significant weight loss in the short term but minimal weight reduction in the long-term follow up. Pharmacotherapy has been shown to be superior to lifestyle modification to achieve larger and maintained weight loss. Therefore, The investigators propose the first-ever double-blinded placebo controlled randomized clinical study to assess the efficacy and impact of an anti-obesity medication on atrial fibrillation in patients receiving contemporary therapies for atrial fibrillation.