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

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.