Tirzepatide on Atrial Fibrillation Recurrence After Catheter Ablation in Patients With Obesity and HFpEF (TEAR-AF-HFpEF)

Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Patients With Obese and HFpEF: A Randomized Controlled Trial

This multicenter, randomized, open-label, blinded-endpoint trial evaluates whether weekly subcutaneous tirzepatide for 12 months reduces atrial fibrillation (AF) recurrence after catheter ablation in adults with obesity and heart failure with preserved ejection fraction (HFpEF). HFpEF is diagnosed by direct intraprocedural measurement of mean left atrial pressure (mLAP ≥ 15 mmHg at rest) during the ablation procedure, providing a hemodynamically anchored, homogeneous study population free from the diagnostic ambiguities of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and E/e' in AF patients. Approximately 602 participants will be randomized 1:1 to tirzepatide (titrated to a target of 10 mg/week, maximum 15 mg/week) plus standard care, or standard care alone. Both groups receive an identical structured lifestyle intervention. The primary endpoint is the first documented AF/atrial flutter/atrial tachycardia episode lasting ≥ 30 seconds, occurring between day 91 and day 365 after ablation, adjudicated by an independent blinded clinical endpoint committee.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Heart Failure With Preserved Ejection Fraction (HFpEF); Tirzepatide
• Intervention / Treatment: Drug: Tirzepatide; Behavioral: Structured Lifestyle Intervention

Detailed Description

Background and Rationale: Obesity and HFpEF are key drivers of AF onset and recurrence. In patients with both conditions, 12-month AF recurrence after catheter ablation reaches 40-55%. The LEGACY and ARREST-AF cohorts demonstrated that ≥10% weight loss approximately halves AF recurrence. Tirzepatide, a dual GIP/GLP-1 receptor agonist, achieved over 20% weight reduction in SURMOUNT-1 and improved heart failure outcomes in the SUMMIT trial of HFpEF with obesity. Whether tirzepatide reduces post-ablation AF recurrence has not been prospectively tested. TEAR-AF-HFpEF enrolls a population most likely to benefit mechanistically - obesity plus HFpEF - and tests the hypothesis with a hemodynamically defined HFpEF cohort.

Study Design: Multicenter randomized open-label parallel-group blinded-endpoint superiority trial. Eligible patients are randomized 1:1 within 48 hours of ablation, stratified by site, AF type (paroxysmal vs persistent), and BMI.

Intervention:

Tirzepatide arm: weekly subcutaneous tirzepatide starting at 2.5 mg/week with monthly 2.5 mg dose escalation to a target of 10 mg/week, advanced to 15 mg/week if tolerated, for 12 months.

Control arm: standard care without GLP-1 class drugs. Both arms receive identical structured lifestyle intervention (≥150 min/week moderate aerobic activity, sleep apnea screening), and standard-of-care guideline-directed therapies for AF, anticoagulation, and HFpEF.

Sample Size and Statistical Approach: A total of 602 participants (301 per arm) provides 80% power at two-sided α = 0.05, assuming 15% loss to follow-up. The primary analysis is an intention-to-treat Kaplan-Meier comparison with log-rank test and Cox proportional hazards modeling stratified by randomization factors.

• Study Type: Interventional
• Enrollment (Estimated): 602
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Beijing Anzhen Hospital
      • Contact: Email: wang_lili1002@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 to 80 years
• Symptomatic atrial fibrillation (paroxysmal or persistent of ≤ 5 years duration), undergoing first-time catheter ablation

• Body weight criteria (aligned with NMPA-approved tirzepatide indication)，meeting at least one of the following:

  • BMI ≥28.0 kg/m² (obesity threshold per Chinese criteria), OR
  • BMI ≥24.0 kg/m² and <28.0 kg/m² (overweight per Chinese criteria) with at least one weight-related comorbidity: hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM), obstructive sleep apnea syndrome (OSAS), or atherosclerotic cardiovascular disease (ASCVD)
• HFpEF defined by intraprocedural mean left atrial pressure ≥ 15 mmHg at rest
• Left ventricular ejection fraction ≥ 50% on echocardiography within 30 days prior to enrollment
• Provision of written informed consent

Exclusion Criteria:

• Prior use of any GLP-1 receptor agonist or GIP/GLP-1 dual receptor agonist
• Type 1 diabetes mellitus; or type 2 diabetes with HbA1c > 10%
• Personal history of pancreatitis; personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
• Severe gastrointestinal disease, including gastroparesis or active inflammatory bowel disease
• Prior bariatric surgery
• Moderate or severe valvular heart disease, hypertrophic cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, or restrictive cardiomyopathy
• Severe renal impairment (eGFR < 30 mL/min/1.73m²)
• Active malignancy, excluding basal cell carcinoma
• Acute coronary syndrome, stroke, percutaneous coronary intervention, or cardiac surgery within 30 days prior to enrollment
• Pregnancy, lactation, or planned pregnancy within 6 months
• Life expectancy < 12 months
• Concurrent participation in another interventional clinical trial
• Any condition that, in the investigator's judgment, would interfere with participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide + Lifestyle Intervention; Participants receive subcutaneous tirzepatide once weekly for 12 months in addition to guideline-directed lifestyle intervention. Dose escalation: 2.5 mg/week for weeks 1-4; 5 mg/week for weeks 5-8; 7.5 mg/week for weeks 9-12; 10 mg/week from week 13 onward (target); may be escalated to 15 mg/week if tolerated. All participants additionally receive a structured lifestyle intervention identical to the control arm.	Drug: Tirzepatide; Dual GIP and GLP-1 receptor agonist administered as a weekly subcutaneous injection. Titrated from 2.5 mg/week to a target of 10 mg/week (maximum 15 mg/week) over 12 weeks, then maintained at the maximum tolerated dose for the remainder of the 12-month treatment period.; Other Names: Mounjaro; Behavioral: Structured Lifestyle Intervention; Guideline-directed AF management (rate/rhythm control, anticoagulation by CHA2DS2-VASc). Guideline-directed HFpEF therapy (MRA, SGLT2 inhibitor as clinically indicated). Structured lifestyle intervention: monthly dietitian-led counseling targeting a 500 kcal/day caloric deficit; exercise prescription of ≥150 min/week moderate aerobic; smoking cessation and alcohol moderation counseling.
Active Comparator: Lifestyle Intervention; Participants receive guideline-directed standard care for AF, anticoagulation, and HFpEF, without any GLP-1 receptor agonist or GIP/GLP-1 dual agonist. The same structured lifestyle intervention as the experimental arm is delivered, including monthly dietitian-led counseling, exercise prescription, and sleep apnea screening, to ensure equal follow-up intensity.	Behavioral: Structured Lifestyle Intervention; Guideline-directed AF management (rate/rhythm control, anticoagulation by CHA2DS2-VASc). Guideline-directed HFpEF therapy (MRA, SGLT2 inhibitor as clinically indicated). Structured lifestyle intervention: monthly dietitian-led counseling targeting a 500 kcal/day caloric deficit; exercise prescription of ≥150 min/week moderate aerobic; smoking cessation and alcohol moderation counseling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Recurrence of atrial fibrillation, atrial flutter, or atrial tachycardia	Any documented atrial arrhythmia - defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) - lasting ≥30 seconds, in the absence of antiarrhythmic drug (AAD) use	Day 91 through Week 52 after catheter ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Monitoring Time Spent in AF (AF Burden)	Percentage of total monitoring time spent in AF, measured by 7-day ambulatory ECG patch.	At Week 12, Week 26, and Week 52
Change in body weight	Absolute and percentage change in body weight (kg) from baseline to 52 weeks.	Baseline to Week 52
Change in body mass index (BMI)	Change from baseline to 52 weeks in BMI (kg/m²)	Baseline to Week 52
Change in waist circumference	Change from baseline to 52 weeks in waist circumference (cm).	Baseline to Week 52
Change in left atrial volume index (LAVI)	Change in echocardiographic LAVI (mL/m²) from baseline to 52 weeks, measured by core laboratory	Baseline to Week 52
Change in Echocardiographic E/e' Ratio	Change in echocardiographic E/e' from baseline to 52 weeks, measured by core laboratory.	Baseline to Week 52
Time to First Hospitalization for Heart Failure	Time to first hospitalization for heart failure, adjudicated by the CEC.	Day 1 through Week 52
Time to Cardiovascular Death	Time to cardiovascular death	Day 1 through Week 52
Time to Death From Any Cause	Time to death from any cause.	Day 1 through Week 52
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score	Change in KCCQ overall summary score and clinical summary score from baseline to 52 weeks. Both scores range from 0 to 100, with higher scores indicating better health status (fewer symptoms, less physical limitation, and better quality of life).	Baseline to Week 52
Change in Serum NT-proBNP Concentration	Change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline to 52 weeks, measured by central laboratory.	Baseline to Week 52
Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration	Change in serum hs-CRP concentration from baseline to 52 weeks, measured by central laboratory.	Baseline to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in epicardial adipose tissue volume	Change in epicardial adipose tissue volume measured by cardiac CT from baseline to 12 months.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Yunlong Wang
• Collaborators: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Yunlong Wang, PHD, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Atrial Fibrillation; HFpEF; Tirzepatide; GIP/GLP-1 receptor agonist
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Nutrition Disorders; Heart Diseases; Overnutrition; Body Weight; Arrhythmias, Cardiac; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Atrial Fibrillation; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: TEAR-AF-HFpEF_V1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual de-identified participant data underlying the published results, together with the study protocol, statistical analysis plan, and data dictionary, will be made available upon reasonable request after publication of the primary results.
• IPD Sharing Time Frame: Beginning 12 months after publication of the primary results, ending 5 years thereafter.
• IPD Sharing Access Criteria: Requests reviewed by the trial steering committee. Investigators must submit a methodologically sound proposal, have approval from an independent review committee, and sign a data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No