DUTCH weight control in atrial fibrillation study (DUTCH-WAIST) : Design and rationale of a randomised controlled trial.

BACKGROUND: Obesity is a well-established and highly prevalent risk factor for atrial fibrillation (AF) and its progression by promoting structural and electrical atrial remodelling, leading to AF recurrence and persistence. Weight loss is expected to reverse atrial remodelling and improve rhythm control. Optimal strategies for weight management are, however, under-explored. OBJECTIVE: To quantify the effect of clinically meaningful weight loss on rhythm control in overweight patients with first detected persistent AF. DESIGN: A multicentre, double-blind, randomised, placebo-controlled trial evaluating semaglutide 2.4 mg once weekly versus placebo, in addition to combined lifestyle intervention (CLI), during a one-year period. PARTICIPANTS: Adults with a BMI > 30 kg/m2, or BMI > 27 kg/m2 with a weight-related comorbidity, and first detected (< 6 months) persistent AF scheduled for electrical cardioversion. INTERVENTION: Weekly subcutaneous injections of semaglutide 2.4 mg or placebo, alongside CLI and standard AF care in both groups. OUTCOMES: The co-primary outcome is (i) a hierarchical assessment of rhythm status at one year, ranking patients by severity from arrhythmic death to sinus rhythm without any additional rhythm control support. (ii) the composite of either persistent atrial fibrillation on ECG, catheter ablation for AF, arrhythmic death, or any serious adverse event due to anti-arrhythmic drugs occurring within 1 year. CONCLUSION: This study investigates whether treatment of overweight with semaglutide, as an adjunct to lifestyle intervention, enhances rhythm control in AF patients with first detected persistent AF and overweight, offering a potential new approach to reducing AF burden and cardiovascular risk in this population.