His-Bundle Corrective Pacing in Heart Failure PI: Valentina Kutyifa, MD, PhD, Roderick Tung, MD University of Rochester Medical Center, Rochester, NY, and University of Chicago, Chicago, IL Heart failure (HF) is a significant chronic health issue with the most prevalent cause of preventable hospitalizations, linked to insurmountable health care costs. Cardiac resynchronization therapy with a defibrillator (BIV-CRT) has been shown to improve outcomes of HF patients with severely reduced left ventricular function, however it was shown to be less beneficial in a subset of patients with right bundle branch block (RBBB) ECG morphology. His-bundle corrective pacing for cardiac resynchronization (His-BIV) is an emerging technology that could be especially helpful in patients with RBBB ECG pattern in whom BIV-CRT is less optimal. However, data are limited on the efficacy and on the mechanism of action of His-CRT as compared to BIV-CRT. Therefore, we propose a randomized mechanistic clinical trial to prospectively evaluate the efficacy and mechanisms of His-CRT vs. BIV-CRT on electrical and mechanical resynchronization in 120 HF patients with severely reduced left ventricular function, wide QRS, and RBBB ECG morphology. The primary aim of this trial is to prospectively evaluate whether His-CRT is more effective improving LV ejection fraction (LVEF) at 6 months than BIV-CRT in HF patients with RBBB. Our secondary aim includes assessing the mechanism of benefit with His-CRT vs. BIV-CRT by evaluating changes in ECG biomarkers, serum biomarkers, and echocardiography biomarkers. Our tertiary aim is to evaluate the temporal development of the biological processes of electrical and mechanical resynchronization with His-CRT vs. BIV-CRT, including temporal changes of ECG biomarkers, NT-proBNP levels, and improvement in functional status and quality of life at 6, 12, and 24 months following device implantation with His-CRT as compared to BIV-CRT. Safety assessment will include serious adverse events, implant procedure-related complications, and evaluation of device and implanted lead parameters during follow-up. Study population will include 120 HF patients with RBBB randomized to His-CRT vs. BIV-CRT in a 1:1 ratio. We will be collecting echocardiography data at baseline and 6-month, and serial ECG data at 6, 12, and 24 months, analyzed by central core laboratories. High-volume, experienced centers with implanted device track records and research infrastructure will participate, with implantation of His-CRT and BIV-CRT performed according to standard of care.