Catheter Ablation in Atrial Fibrillation Patients With Heart Failure With Preserved Ejection Fraction: an International, Prospective, Multi-center, Randomized Controlled Study (STABLE-SR IV Trial)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 436
- Locations
- 1
- Primary Endpoint
- Composite endpoint of worsening heart failure requiring unplanned hospitalizations or urgent visits, and cardiovascular death (Time-to-first event analysis)
Study Overview
Brief Summary
To investigate whether RFCA is superior to AADs in AF patients with HFpEF on the basis of optimized anti-heart-failure drug therapy regarding their longterm clinical outcomes.
Detailed Description
Background: Atrial Fibrillation (AF) is a common cardiac rhythm disorder and radiofrequency catheter ablation (RFCA) has become the first-line therapy in the symptomatic AF patients. Heart failure is often the sister disease with AF. Recently, RFCA was found to be superior to antiarrhythmic drugs (AADs) in heart failure patients with AF and reduced ejection fraction (HFrEF), regarding all-cause mortality and hospitalization for worsening heart failure (HF). However, in heart failure patients with AF and preserved ejection fraction (HFpEF), it remains unknown whether RFCA is superior to AADs in an even larger population, despite several nonrandomized retrospective studies. Thus, this prospective, multi-center, randomized controlled trial aims to investigate whether RFCA could better improve the clinical outcome of AF patients with HFpEF than longterm AADs use.
Aim of this study: To investigate whether RFCA is superior to AADs in AF patients with HFpEF on the basis of optimized anti-heart-failure drug therapy regarding their longterm clinical outcomes.
Design: The STABLE-SR-IV trial is an international, prospective, multi-center, randomized controlled trial. In this trial, physical examination, echocardiogram, NT-proBNP and other blood test would be assessed before enrollment. Those who conform to all the inclusion criteria and absent from any exclusion criteria would enter into a run-in period of 5 weeks (±7 days). Anticoagulation and anti-heart-failure therapy for HFpEF must be optimized according to the current guideline. After the run-in period, inclusion and exclusion criteria would be reassessed. Thereafter, all the subjects enrolled would be randomized into RFCA arm and Medical Therapy arm with a 1:1 manner, namely 218 subjects in each arm. Each arm will follow the protocol of RFCA and medical therapy, respectively. Follow-up duration of this study is up to 2~3 years (12 month enrollment).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
The End Point and Adverse Event Committee is constituted of three experts in the field of heart failure and ablation of atrial fibrillation, but independent of the study. The End Point Adverse Event Committee have received blinded data regarding all serious adverse events, all deaths, all hospitalizations, all outpatient or emergency visits, all cerebrovascular accidents, and all first recurrences of atrial fibrillation, from the Contact Research Organization. The End Point and Adverse Event Committee was responsible for the classification of all received events, for the determination of which events fulfill the end point criteria.
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Symptomatic paroxysmal or persistent atrial fibrillation
- •CHADS2-VASc score≥ 2
- •Conform to the diagnosis of HFpEF
- •NYHA II-IV level;
- •Left ventricular ejection fraction (LVEF)≥ 50%;
- •NT-proBNP≥ 300 pg/mL under sinus rhythm or NT-proBNP≥ 600 pg/mL under atrial fibrillation or flutter;
- •Evidence of left ventricular diastolic dysfunction/raised left ventricular filling pressure on echocardiogram.
- •Sign informed consent
Exclusion Criteria
- •A life expectancy below 2 years due to any non-cardiovascular condition
- •Reversible atrial fibrillation, such as hyperthyroidism or hypokalemia-related atrial fibrillation
- •Prior atrial fibrillation ablation
- •Left atrial size≥ 55 mm
- •Heart failure due to any of the following: known genetic hypertrophic cardiomyopathy, infiltrative cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, constrictive pericarditis, active myocarditis, cardiac tamponade, or uncorrected primary valvular disease
- •Previous cardiac transplantation, complex congenital heart disease, rheumatic heart disease
- •Any contraindication for radiofrequency catheter ablation, antiarrhythmic drugs or anticoagulation
- •Acute coronary syndrome, cardiac surgery, angioplasty or cerebrovascular accident within 12 weeks before enrollment
- •Severe hepatic and renal dysfunction
- •Body mass index> 50 kg/m2
- •Female in period of pregnancy or breast-feeding
- •Any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
- •Involved in other studies
- •The inclusion and exclusion criteria would be reassessed after run-in period and the cut-off of NT-proBNP would be set as >125 pg/ml under sinus rhythm or >365 pg/ml under AF/atrial flutter (AFL).
Arms & Interventions
Radiofrequency catheter ablation (RFCA)
Radiofrequency ablation is adopted in the study, instead of cryo ablation, surgical ablation or pulsed field ablation. 3-dimensional model is constructed after transseptal puncture. Circumferential pulmonary vein isolation (CPVI) is performed with irrigated contact force catheter. Previously published STABLE-SR approach is recommended as the ablation strategy beyond CPVI.
Intervention: Radiofrequency catheter ablation (RFCA) (Procedure)
Medical therapy
AADs should be prescribed according to the current guidelines, such as amiodarone, dronedarone, or propafenone. In brief, rhythm control is preferred, including electric cardioversion. However, rate control should be considered if rhythm control is contraindicated, intolerated or unpreferred by patients.
Intervention: Medical Therapy (Drug)
Outcomes
Primary Outcomes
Composite endpoint of worsening heart failure requiring unplanned hospitalizations or urgent visits, and cardiovascular death (Time-to-first event analysis)
Time Frame: From randomization until completion of the planned follow-up, up to 36 months
Secondary Outcomes
- Total number of worsening heart failure events and cardiovascular deaths(From randomization until completion of the planned follow-up, up to 36 months)
- Time to hospitalization or urgent visits for heart failure(From randomization until completion of the planned follow-up, up to 36 months)
- Time to hospitalization for heart failure(From randomization until completion of the planned follow-up, up to 36 months)
- Time to urgent visits for heart failure(From randomization until completion of the planned follow-up, up to 36 months)
- Time to cardiovascular death(From randomization until completion of the planned follow-up, up to 36 months)
- Time to all-cause death(From randomization until completion of the planned follow-up, up to 36 months)
- Time to cardiovascular hospitalization(From randomization until completion of the planned follow-up, up to 36 months)
- Change in quality of life - MLWHFQ(Baseline, 3 months, 12 months)
- Change in 6-minute walk test from baseline to Month 3 and Month 12(Baseline, 3months, 12 months)
- Change in H2FPEF score from baseline to Month 3 and Month 12(Baseline, 3 months, 12 months)
- Change in NYHA class from baseline to Month 3, 6 and 12(Baseline, 3 months, 12 months)
- Time to change of diuretics(From randomization until completion of the planned follow-up, up to 36 months)
- Change in quality of life - KCCQ score(Baseline, 3 months, 12 months)
- Change in atrial fibrillation burden(Baseline, 12 months)
- Time to Atrial Fibrillation recurrence (RFCA arm)(From randomization until completion of the planned follow-up, up to 36 months)
- Change in N-terminal pro-B type natriuretic peptide (NT-proBNP) from baseline to Month 3 and Month 12(Baseline, 3 months, 12 months)
Investigators
Minglong Chen
Director of Heart Center
The First Affiliated Hospital with Nanjing Medical University