Waiting on Atrial Fibrillation Intervention Therapy (WAIT) Study

Atrial fibrillation (AF) is the most common heart rhythm disorder and is associated with symptoms, reduced quality of life, heart failure, stroke, and a high risk of recurrence after catheter ablation. Many patients scheduled for their first ablation are overweight or have obesity, which is one of the strongest predictors of AF recurrence. Weight loss and risk-factor management are known to improve the outcome of ablation, but lifestyle changes are often difficult to achieve in routine care. Semaglutide (Wegovy®) is a GLP-1 receptor agonist approved in the EU for weight management. It has been shown to produce substantial and sustained weight loss and to improve metabolic and cardiovascular risk factors. Whether treatment with semaglutide before AF ablation can improve long-term rhythm outcomes has never been tested in a randomized clinical trial. The WAIT-AF study is a randomized, open-label trial with blinded endpoint assessment. The study includes adults with AF who are scheduled for their first catheter ablation and have a BMI ≥30 kg/m², or ≥27 kg/m² with at least one additional cardiovascular risk factor (such as hypertension, diabetes and dyslipidemia). A total of 200 participants will be enrolled. Participants are randomly assigned in a 1:1 ratio to either standard care or semaglutide (plus lifestyle advice) prior to their scheduled ablation. Semaglutide is administered according to the approved EU label with gradual dose escalation. All participants receive an implantable loop recorder (ILR) before ablation to continuously monitor heart rhythm throughout the study. The primary objective is to determine whether semaglutide improves arrhythmia-free survival 12 months after AF ablation. Recurrence is defined as AF, atrial flutter, or atrial tachycardia lasting ≥30 seconds on continuous ILR monitoring, excluding the standard 3-month blanking period. Secondary outcomes include weight loss, changes in blood pressure, AF symptoms, quality of life, AF burden, need for repeat ablation, hospitalizations for cardiovascular causes, and changes in metabolic risk factors. The study also evaluates safety and tolerability of semaglutide in this patient population. The study aims to determine whether targeted weight management with semaglutide before AF ablation can improve long-term rhythm outcomes and overall cardiovascular health. If successful, this strategy may offer a new approach to optimizing treatment and improving the results of catheter ablation for patients with AF and overweight or obesity

Inclusion Criteria: To be included in the trial, subjects must meet all of the following criteria: 1. Provision of written informed consent prior to participation. 2. Age ≥18 years. 3. Scheduled for first-time catheter ablation for atrial fibrillation using a pulmonary vein isolation (PVI) technique. 4. Body Mass Index (BMI) ≥30 kg/m² (obesity) OR BMI ≥27 kg/m² (overweight) with one or more of the following comorbidities: * prediabetes (defined as HbA1c 39-47 mmol/mol or fasting glucose 5,6-6,9 mmol/L), * known diabetes type 2 * known hypertension (prior diagnosis and/or treatment with antihypertensive medication) * new diagnosis of hypertension (according to ESC GL for hypertension: Systolic BP ≥140 mmHg and/or diastolic BP ≥ 90 mmHg based on two readings on two separate visits, OR Ambulatory BP monitoring (24h average) ≥ 130/80 mmHg) * dyslipidemia defined as either one of the following * Known diagnosis of hyperlipidemia or * Treatment with lipid lowering medication OR either of the following: * LDL \> 3.0 mmol/l * Total cholesterol \> 5 mmol/l * Triglycerides \> 1.7 mmol/l * HDL (\< 1 mmol/l if male, \< 1.2 mmol/l if female) AND/OR * atherosclerotic cardiovascular disease (prior myocardial infarction (MI), stroke, or peripheral arterial disease with claudication and ankle-brachial index \40 kg/m²). * Current use of GLP-1 receptor agonist therapy or dual agonist therapy within 6 months before screening. * Current use of DPP-IV inhibitors. * Diabetes type 1 * Known intolerance or contraindication to semaglutide. * History of pancreatitis or recurrent hypoglycemia. * Uncontrolled diabetic retinopathy * Severe renal failure (estimated glomerular filtration rate \[eGFR\] \