BACKGROUND There is currently no particularly effective strategy for patients with persistent atrial fibrillation accompanying heart failure with preserved ejection fraction (HFpEF), especially with recurrent atrial fibrillation after ablation. In this study, we will evaluate a new treatment strategy for patients with persistent atrial fibrillation who had at least two attempts (≧2 times) of radio-frequency catheter ablation but experienced recurrence, and physiologic conduction was reconstructed after atrioventricular node ablation or drug therapy, to control the patient's ventricular rate to maintain a regular heart rhythm, which is called His-Purkinje conduction system pacing (HPCSP) with atrioventricular node ablation. RESULTS This investigator-initiated, multicenter prospective randomized controlled trial aimed to recruit 296 randomized HFpEF patients with recurrent atrial fibrillation. All the enrolled patients were randomly assigned to the pacing group or the drug treatment group. The primary endpoint is differences in cardiovascular events and clinical composite endpoints (all-cause mortality) between patients in the HPCSP and drug-treated groups. Secondary endpoints included heart failure hospitalization, exercise capacity assessed by cardiopulmonary exercise tests, quality of life, echocardiogram parameters, 6-minute walk distance, NT-ProBNP, daily patient activity levels, and heart failure management report recorded by the CIED. It is planned to compete recruitment by the end of 2023 and report in 2025. CONCLUSIONS The study aims to determine whether His-Purkinje conduction system pacing with atrioventricular node ablation can better improve patients' symptoms and quality of life, postpone the progression of heart failure, and reduce the rate of rehospitalization and mortality of patients with heart failure. BACKGROUND ChiCTR1900027723, URL: http://www.chictr.org.cn/edit.aspx?pid=46128&htm=4.