Treating Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Ablation or Medication

• Catheter Ablation for Atrial Fibrillation (Procedure): Participants randomized to this arm will undergo catheter ablation within 4 weeks of randomization. Pulmonary vein isolation is required; additional ablation strategies may be applied at investigator discretion. Guideline-directed medical therapy for atrial fibrillation and heart failure will also be provided.
• Rate Control Medications (beta-blockers, calcium channel blockers, digoxin) (Drug): Participants randomized to this arm will receive pharmacologic therapy to achieve guideline-recommended heart rate control (resting HR <80 bpm, <110 bpm with exercise). Therapy may include beta-blockers, non-dihydropyridine calcium channel blockers, or digoxin. If adequate control is not achieved with medication, AV nodal ablation and pacing may be used. Guideline-directed medical therapy for atrial fibrillation and heart failure will also be provided.

Primary outcomes

• Feasibility of Trial Conduct [12 months after randomization]: Recruitment rate (patients recruited per center per month) and crossover rate (percentage of participants switching study arms). Feasibility will be defined as ≥0.7 patients enrolled per center per month and ≤10% crossover.

Secondary outcomes

• Composite of Cardiovascular Mortality and Heart Failure Hospitalization [Up to 12 months post-randomization]: Time to first event of cardiovascular death (due to MI, sudden cardiac death, HF, stroke, CV procedures, CV bleeding, or other CV cause) or hospitalization for heart failure (admission >24h, ED visit, or unscheduled IV diuretic administration).
• All-Cause Mortality [Up to 12 months]: Death from any cause
• Cardiovascular Hospitalizations and ED Visits (Non-HF) [Up to 12 months]: Number of hospitalizations or emergency department visits for other cardiovascular causes, including atrial fibrillation.
• Quality of Life: EQ-5D (Euroquol 5D Questionnaire) [Baseline, 12 months]: EQ5D Will include responses from the Euroquol 5D questionnaire
• Quality of Life: AFEQT (Atrial Fibrillation Effect on Quality of Life) Questionnaire [Baseline, 12 months]: AFEQT- Atrial Fibrillation Effect on Quality of Life Questionnaire (Scored 0-100, 0 is complete disability, 100 is no disability)
• Quality of life- KCCQ-12 (Kansas City Cardiomyopathy Questionnaire-12) [Baseline, 12 months]: KCCQ-12- Kansas City Cardiomyopathy Questionnaire-12 (0-100, 0 is very poor, 100 is excellent)
• Atrial Fibrillation Burden [Baseline, 3, 6, and 12 months]: Proportion of time in atrial fibrillation as measured by Holter monitoring and symptom-triggered ECG recordings
• Change in NT-proBNP levels [Baseline, 12 months]: Change in plasma NT-proBNP levels from baseline to follow-up
• Change in Left Ventricular Ejection Fraction (LVEF) [Baseline, 12 months]: Change in LVEF as measured by echocardiography
• Exercise Capacity (6-Minute Walk Distance) [Baseline, 12 months]: Change in distance walked in 6 minutes from baseline to follow-up
• Recruitment Metrics [Throughout 12-month recruitment]: Recruitment ration of male vs. female participants, refusal rates and reasons.

Other outcomes

• Procedural Complications [Up to 30 days post-ablation procedure]: Symptomatic pulmonary vein stenosis, atrio-esophageal fistula, pericardial effusion requiring pericardiocentesis, major bleeding requiring transfusion.
• Antiarrhythmic Drug Adverse Events [Up to 12 months]: Incidence of drug-related toxicities (e.g., thyroid, hepatic, pulmonary, proarrhythmia)
• All-Cause Death [Up to 12 months]: Number of deaths from any cause

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years
* Diagnosis of atrial fibrillation (documented on Holter, rhythm strip, or ECG)
* New York Heart Association (NYHA) class II-III heart failure
* Left ventricular ejection fraction (LVEF) >40%
* Meet specific NT-proBNP criteria:
* If HF hospitalization within 6 months prior to screening: NT-proBNP >200 pg/ml (if not in AF at screening) or >600 pg/ml (if in AF at screening)
* Otherwise: NT-proBNP >300 pg/ml (if not in AF at screening) or >900 pg/ml (if in AF at screening)
* On stable guideline-directed medical therapy for ≥1 month
* On stable diuretic dose for ≥2 weeks
* Suitable for either ablation-based rhythm control or rate control strategy

Exclusion Criteria:

* Permanent atrial fibrillation diagnosis
* Prior catheter ablation for atrial fibrillation
* NYHA class IV heart failure
* Rheumatic heart disease
* Moderate or severe mitral stenosis
* Mechanical mitral valve
* Severe aortic stenosis or severe aortic/mitral regurgitation
* Renal failure requiring dialysis
* Contraindication to oral anticoagulation
* Infiltrative cardiomyopathies
* Complex congenital heart disease
* Untreated thyroid disease
* Acute coronary syndrome or coronary artery bypass surgery within 12 weeks
* Participation in another clinical trial
* Inability to provide informed consent
* Other serious non-cardiovascular condition with life expectancy ≤1 year
* Age <18 years