Rationale and Design of OPT-RATE AF: A Randomized Clinical Trial of Increased Physiologic Pacing Rates in Heart Failure With Preserved Ejection Fraction

Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. Optimal Pacing Rate for cardiac resynchronization therapy after atrioventricular node ablation in persistent Atrial Fibrillation and heart failure (OPT-RATE AF) is a prospective, randomized crossover study of patients with HFpEF after AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats/min for 3 months and then switched to a rate of 80 beats/min for 3 months and vice versa. The primary end point is the change in exercise capacity assessed using the 6-minute walk test. Notable secondary outcomes will include changes in the Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. Electrocardiogram, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF after AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving quality of life and other important cardiovascular outcomes.