NCT07254455

CASTLE-HFpEF (Catheter Ablation for Atrial Fibrillation Patients With Heart Failure With Mildly Reduced and Preserved Ejection Fraction)

Catheter Ablation Versus Standard Conventional Treatment in Atrial Fibrillation Patients With Heart Failure With Mildly Reduced and Preserved Left Ventricular Ejection Fraction - A Prospective, Randomized, Multi-national Study Using Two Systems for Rhythm Monitoring

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 900 (estimated)
• Sponsor: Tulane University · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

The clinical equipoise in the treatment of Atrial Fibrillation (AF) in patients with Heart Failure with mildly reduced Ejection Fraction/Heart Failure with Preserved Ejection Fraction (HFmrEF/HFpEF) reflects the scarcity of randomized trials on different treatment modalities. By generating high-quality, evidence-based, randomized data on the impact of treatment on hard outcomes, Catheter Ablation Versus Standard Conventional Treatment in Atrial Fibrillation Patients with Heart Failure with Preserved Ejection Fraction (CASTLE-HFpEF) will provide clinical decision-making guidance and help physicians in the management of patients with HFmrEF/HFpEF and AF. The main hypothesis is that Catheter Ablation (CA) for AF is associated with improved clinical outcomes in patients with HFmrEF/HFpEF and AF compared to medical AF treatment strategies on top of optimal medical HF treatment. CASTLE-HFpEF aims to study these hard clinical outcomes in a randomized cohort of patients with AF and HFmrEF/HFpEF.

Detailed description

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and often coexists with atrial fibrillation (AF), but the optimal management strategy for AF in this population remains unclear. The CASTLE-HFpEF (CASTLE-AF II) trial is a prospective, randomized, multicenter study designed to evaluate whether catheter ablation of AF improves clinical outcomes compared with optimized medical therapy in patients with HFpEF. Approximately 4,000 patients with HFpEF will undergo AF screening using an insertable cardiac monitor. Of these, 980 patients with newly diagnosed AF or AF detected during screening and with an AF burden \> 1% will be randomized 1:1 to catheter ablation or guideline-directed medical therapy. All randomized patients will be followed for three years and monitored continuously for AF burden. The primary endpoint is a hierarchical composite including all-cause mortality, stroke or transient ischemic attack, hospitalization for worsening heart failure, and a clinically meaningful reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 12 months. Secondary endpoints include total heart failure events, patient-reported quality-of-life outcomes, AF burden and rhythm control metrics, and echocardiographic measures of cardiac structure and function. This study seeks to determine whether AF ablation improves clinical outcomes and quality of life in patients with HFpEF and AF, and to define the role of rhythm control strategies in this population.

Conditions

• Atrial Fibrillation
• Heart Failure With Preserved Ejection Fraction

Interventions

Type	Name	Description
PROCEDURE	Catheter ablation	A catheter ablation (CA) is a minimally invasive medical procedure for treatment of cardiac arrhythmias. Rhythm control of AF is attempted by pulmonary vein isolation (PVI) and posterior wall isolation (PWI). During the procedure, a catheter is guided to the heart through a blood vessel, which is either the femoral vein or a central vein, in order to ablate abnormal conductive heart tissue that causes the arrhythmias. Ablation is achieved either by thermal (cauterization by radiofrequency (RF) ablation / freezing by cryoballoon) or non-thermal mechanisms (primarily irreversible electroporation (IRE) through pulsed field ablation (PFA)). In case of successful ablation, a normal heart rhythm (sinus rhythm) can be restored.

Timeline

• Start date: 2026-03-01
• Primary completion: 2028-06-01
• Completion: 2030-10-01
• First posted: 2025-11-28
• Last updated: 2025-12-04