Waiting on Atrial Fibrillation Intervention Therapy (WAIT) Study (WAIT)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation (AF); Obesity & Overweight
• Intervention / Treatment: Drug: Semaglutide 2.4 mg; Behavioral: Standard medical treatment

Detailed Description

The WAIT trial evaluates whether metabolic optimization with once-weekly semaglutide prior to catheter ablation can improve rhythm outcomes in patients with atrial fibrillation and overweight/obesity. Excess adiposity and related cardiometabolic risk factors are strongly linked to atrial structural remodeling and higher rates of post-ablation arrhythmia recurrence. Although weight reduction is recommended in guidelines, sustained lifestyle-based weight loss is often difficult to achieve. Semaglutide provides an evidence-based pharmacologic strategy for clinically meaningful weight loss and risk-factor improvement, which may enhance the effectiveness of ablation.

This randomized, open-label study allocates participants 1:1 to semaglutide plus standard of care or standard of care alone for at least three months before undergoing their first AF ablation. All participants receive routine clinical management and continuous rhythm monitoring using an implantable loop recorder for 12 months post-ablation, with blinded adjudication of rhythm outcomes. The study integrates real-world clinical practice, using only routine clinical assessments, registry data, and ILR monitoring without introducing additional invasive procedures.

The trial is designed to determine whether targeted periablation metabolic therapy can increase arrhythmia-free survival, reduce AF burden, improve symptoms and quality of life, and favourably impact cardiovascular risk profiles. Results are expected to inform the role of GLP-1 receptor agonist therapy as part of a structured periablation optimization strategy for patients with AF and overweight or obesity.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Emma Svennberg, MD PhD; Phone Number: +46739584822; Email: emma.svennberg@regionstockholm.se
• Study Contact Backup: Name: Ewa Molaei, RN; Phone Number: +46812381692; Email: ewa.molaei@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital
    • Contact: Emma Svennberg; Phone Number: 0739584822; Email: emma.svennberg@regionstockholm.se
    • Contact: Ewa Molaei; Phone Number: +46812381692; Email: ewa.molaei@regionstockholm.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 <0.85, prior revascularization, or amputation)
     • obstructive sleep apnea.
5. For women of childbearing potential: Inclusion after a highly sensitive negative pregnancy test and agreement to use highly effective contraception during the study period (e.g., hormonal contraception, intrauterine device, or barrier method combined with spermicide).

Exclusion Criteria:

• Morbid obesity (BMI >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] <15 mL/min/1.73 m² or in dialysis)
• Severe hepatic failure (decompensated liver disease Child-Pugh class C)
• Severe cardiac failure (NYHA class IV)
• Life expectancy <12 months.
• Inability to self-administer the investigational medicinal product.
• Prior catheter ablation procedure for atrial fibrillation.
• Pregnancy, breastfeeding, or planned pregnancy during or within two months after the study period.
• Participation in another interventional clinical trial within the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized to Semaglutide; Participants randomized to the active arm receive once-weekly subcutaneous semaglutide (Wegovy®) initiated at 0.25 mg and uptitrated to a target dose of 2.4 mg as tolerated, according to the approved SmPC. Treatment begins ≥3 months before the planned first catheter ablation for atrial fibrillation. Participants receive structured lifestyle and weight-management advice in accordance with routine clinical practice.	Drug: Semaglutide 2.4 mg; The intervention consists of once-weekly subcutaneous semaglutide (Wegovy®), initiated at 0.25 mg and uptitrated to a target dose of 2.4 mg as tolerated, administered for at least three months prior to the participant's first planned atrial fibrillation ablation. Semaglutide is provided in pre-filled pens and used according to the approved SmPC for weight management. This intervention is uniquely characterized by pharmacological weight-loss therapy added on top of standard-of-care management, distinguishing it from the control arm, which receives identical clinical follow-up and lifestyle counselling but no GLP-1 receptor agonist. This allows evaluation of whether targeted metabolic therapy before ablation improves arrhythmia-related outcomes.; Other Names: Standard of care; Behavioral: Standard medical treatment; Participants randomized to the standard-of-care arm receive routine clinical management for atrial fibrillation and weight-related comorbidities without GLP-1 receptor agonist therapy. Usual care may include lifestyle counselling, blood pressure and lipid management, treatment of dysglycaemia, and guideline-directed preparation for first-time catheter ablation. No trial-specific medicinal product is administered.
Active Comparator: Standard of care; Participants randomized to the standard-of-care arm receive routine clinical management for atrial fibrillation and weight-related comorbidities without GLP-1 receptor agonist therapy. Usual care may include lifestyle counselling, blood pressure and lipid management, treatment of dysglycaemia, and guideline-directed preparation for first-time catheter ablation. No trial-specific medicinal product is administered. Pa	Behavioral: Standard medical treatment; Participants randomized to the standard-of-care arm receive routine clinical management for atrial fibrillation and weight-related comorbidities without GLP-1 receptor agonist therapy. Usual care may include lifestyle counselling, blood pressure and lipid management, treatment of dysglycaemia, and guideline-directed preparation for first-time catheter ablation. No trial-specific medicinal product is administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arrhythmia-free survival at 12 months after catheter ablation, excluding the 3-month blanking period, with recurrence defined as any ILR-detected AF, atrial flutter, or atrial tachycardia ≥30 seconds.	Arrhythmia-free survival at 12 months after catheter ablation, excluding the 3-month blanking period, with recurrence defined as any ILR-detected AF, atrial flutter, or atrial tachycardia ≥30 seconds.	12 months post-ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AF burden	trial fibrillation burden measured by continuous implantable loop recorder monitoring, expressed as the percentage of time in AF during predefined assessment windows. AF burden will be evaluated prior to the ablation procedure and again at 12 months post-ablation to compare the effect of the intervention versus standard of care.	At ablation and at 12 months post-ablation.
Per protocol analysis of the primary outcome	Assessment of arrhythmia-free survival at 12 months post-ablation in participants who completed the study without major protocol deviations. Recurrence is defined identically to the primary ITT analysis (ILR-detected AF, atrial flutter, or atrial tachycardia ≥30 seconds after the blanking period). This analysis evaluates the treatment effect under optimal adherence.	12 months post-ablation
Time to first arrhythmia recurrence after the blanking period	Time from the end of the 3-month post-ablation blanking period to the first ILR-detected episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting ≥30 seconds. This endpoint evaluates the durability of rhythm control beyond the blanking period.	From month 3 to month 12 post-ablation.
Number of repeat ablations required to achieve sinus rhythm	Total number of additional catheter ablation procedures performed per participant after the index ablation in order to restore or maintain sinus rhythm. This endpoint compares the need for redo ablations between the intervention and standard-of-care groups.	From index ablation to 12 months post-ablation.
Freedom from symptomatic AF without redo ablation	Proportion of participants who remain free from symptomatic atrial fibrillation, atrial flutter, or atrial tachycardia without requiring a repeat ablation procedure. Symptomatic episodes are defined by patient-reported symptoms corroborated by rhythm documentation. This endpoint evaluates clinically meaningful rhythm control without the need for additional invasive therapy.	From index ablation to 12 months post-ablation.
Symptom burden using questionnaires at baseline, ablation, 12 months	Assessment of atrial fibrillation-related symptom burden and functional impact using the AFEQT and AFSS validated questionnaires. Changes in symptom and quality-of-life scores will be compared between groups to evaluate improvement over time.	At baseline, at the time of ablation, and at 12 months post-ablation
Quality of life changes using RAND-36	Assessment of changes in health-related quality of life using the RAND-36 questionnaire. .A clinically meaningful change is defined as an improvement of approximately 3-5 points in any RAND-36 domain. This endpoint evaluates the impact of the intervention on physical, emotional, and functional well-being over time.	At baseline, at the time of ablation, and at 12 months post-ablation.
Weight loss ≥10% or BMI <27 kg/m² at time of ablation and at 12 months post ablation	Proportion of participants achieving either ≥10% reduction in baseline body weight or a BMI <27 kg/m². This endpoint assesses the metabolic effect of the intervention compared with standard of care.	At the time of ablation and at 12 months post-ablation.
Blood pressure reduction	Change in systolic and diastolic blood pressure compared with baseline, including the proportion of participants achieving >10% systolic blood pressure reduction. Measurements are performed using standardized clinical procedures to evaluate the intervention's impact on blood pressure control.	At baseline, at the time of ablation, and at 12 months post-ablation.
Changes in blood biomarkers including glucose levels, HbA1c, creatinine and NT-proBNP	Evaluation of changes in fasting glucose and/or HbA1c and/or creatinine and/or NT-proBNP among participants with where these have been obtained through routine clinical care. This endpoint assesses whether the intervention influences glycaemic control and renal function l in patients for whom such measurements are already clinically indicated. No additional study-specific blood tests are performed.	At routine clinical assessments nearest to baseline, ablation, and 12 months post-ablation.
Complications during and after the ablation procedure	Incidence of procedure-related complications occurring during the catheter ablation or within the post-procedural follow-up period. Events may include vascular complications, pericardial effusion, tamponade, stroke/TIA, transient arrhythmias, anesthesia-related events, or other clinically relevant adverse outcomes, as documented in medical records. This endpoint compares procedural safety between study groups.	During the ablation procedure and through 12 months post ablation.
Left ventricular ejection fraction (LV-EF) pre- and post-ablation	Assessment of changes in left ventricular ejection fraction from before to after the ablation procedure, based solely on echocardiograms performed as part of routine clinical care. No study-specific imaging is required; data will be included only for participants who undergo a post-ablation echocardiogram in standard practice. This endpoint evaluates whether the intervention influences cardiac function over time.	At routine clinical echocardiography closest to baseline and the post-ablation assessment (up to 12 months).
Prevalence of diabetes, renal failure, and heart failure	Assessment of the proportion of participants with diabetes, renal failure, or heart failure using information from routine clinical care, medical records, and linked registry data. No study-specific testing is performed. This endpoint describes baseline comorbidity burden and identifies new or worsening diagnoses captured through standard care or registries.	At baseline and at 12 months post-ablation (via clinical records and registry data).
Cardiovascular hospitalization	Incidence of hospitalizations due to cardiovascular causes, identified through routine clinical records and national or regional registry data. Events may include admissions for arrhythmias, heart failure, acute coronary syndromes, or other cardiovascular conditions. No study-specific assessments are required.	From index ablation to 12 months post-ablation.
All-cause hospitalization	Incidence of hospital admissions for any cause, identified through routine clinical records and national or regional registry data. This endpoint evaluates the broader healthcare impact of the intervention beyond cardiovascular events. No study-specific assessments are required.	From index ablation to 12 months post-ablation.
Change in antiarrhythmic drug use	Assessment of initiation, discontinuation, or dose changes in antiarrhythmic medications (e.g., class I or III agents, beta-blockers) based on routine clinical records. This endpoint evaluates differences in pharmacologic rhythm control requirements between groups.	From baseline to 12 months post-ablation.
Ablation procedure duration	Total duration of the catheter ablation procedure, extracted from routine procedural reports. This endpoint evaluates whether pre-ablation metabolic optimization influences procedural complexity.	During the index ablation procedure.
Fluoroscopy time and radiation dose	Total fluoroscopy exposure time and radiation dose recorded during the index ablation procedure, as documented in routine procedural logs. This endpoint assesses potential differences in radiation exposure related to patient characteristics or weight loss.	During the index ablation procedure.
Healthcare utilization	Assessment of overall healthcare use, including outpatient cardiology visits, emergency department visits, and telephone/remote consultations. Data will be obtained from routine clinical records and linked regional or national healthcare registries. This endpoint evaluates whether the intervention affects healthcare demand and resource use. No study-specific visits or assessments are required.	From randomization to 12 months post-ablation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Artificial-intelligence based prediction of arrhythmia recurrence from 12-lead ECG	Exploratory assessment of whether artificial intelligence (AI) analysis of standard 12-lead ECGs can predict arrhythmia recurrence after ablation. ECGs obtained through routine clinical care will be analysed using validated AI algorithms to evaluate associations between ECG-derived features and later recurrence captured by ILR monitoring. No study-specific ECGs are required.	ECGs recorded as part of routine care at baseline, at ablation, and during follow-up up to 12 months post-ablation

Collaborators and Investigators

• Sponsor: Emma Svennberg
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Emma Svennberg, MD PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Semaglutide; Ablation; Implantable Loop Recorder; Pulmonary Vein Isolation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Nutrition Disorders; Heart Diseases; Overnutrition; Body Weight; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Atrial Fibrillation; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; semaglutide
• Other Study ID Numbers: WAIT; 2025-524182-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to GDPR and national data protection regulations, the use of identifiable clinical and registry-linked data, and the absence of a fully anonymised IPD-sharing infrastructure. Data will only be accessible to authorised study personnel and regulatory bodies as required. Summary results will be published in accordance with scientific and ethical standards.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No