Evaluation of Left Bundle Branch Area Pacing As A Rescue Strategy for Cardiac Resynchronization Therapy Non-response in Patients With Heart Failure: A Randomized Controlled Trial

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Overview: I am reapplying for a 5-year Career Development Award (CDA) to support my overarching goal of studying how imaging tools can improving care of heart failure (HF) patients who require device therapy. This will be accomplished through the completion of mentored research activities and formal training designed to provide the skills necessary to become an independent investigator. During the course of my award, I will study an innovative method of cardiac resynchronization therapy (CRT) in patients with HF who have not had an improvement in cardiac function with the standard treatment of care. I also plan to establish the feasibility of cardiac MRI to assess cardiac function over time in patients with heart failure treated with device therapy. Significance: HF is one of the most common conditions cared for by the Veterans Health Administration and has a 15% annual mortality rate in VA patients. Approximately 50% of the hospitalizations for HF occur in patients with reduced ejection fraction (HFrEF). In these patients, a primary treatment goal includes strategies to increase the cardiac fraction, which has been shown to improve symptoms and decrease the risk of sudden cardiac death. In patients who also have a left bundle branch block, the main therapy has involved placing cardiac pacing leads in the right ventricle and in a cardiac vein overlying the left ventricle, referred to as CRT. However, up to 40% patients who undergo CRT fail to experience the expected improvement in cardiac function and symptoms after 6 months and are referred to as “non-responders.” This study aims to improve cardiac function in “non-responders” by pacing the heart from the left bundle branch area, thereby utilizing the heart’s intrinsic electrical system to promote coordinated ventricular contractions. The intervention developed in this CDA proposal has the potential for wide-reaching impact as it could significantly decrease the morbidity and mortality of HFrEF patients and reduce costs and burdens placed on the VA health care system. Career Plan: My primary area of research has focused on improving outcomes for patients with heart failure. To successfully achieve my goals of improving care for heart failure patients that require device therapy, I need further mentored training in implementation science including: quantitative and mixed methods training, expertise in diagnostic imaging training and research (particularly cardiac MRI), further biostatistics training, and cultivating multidisciplinary collaboration and networking skills. I will achieve these objectives through formal coursework, seminars, and mentored research activities under the guidance of primary mentors Selçuk Adabag, MD, MS (MVAHCS) and Chetan Shenoy, MBBS, MS (University of Minnesota Department of Cardiology), and secondary mentors Bradley Bart, MD (MVAHCS) and Sue Duval (University of Minnesota Department of Cardiology). The mentored research training through this grant will lay the groundwork for my long-term goal of becoming a recognized leader and researcher focused on the use of cardiac imaging to improve patient centered and clinical outcomes for patients with heart failure who require device therapy. Research Plan: My primary research objective is to assess a novel method of CRT in patient with HFrEF and LBBB, who have failed to respond to traditional CRT therapy. To execute this goal, I will complete the following: 1) a prospective, randomized-controlled study assessing the effectiveness of left bundle branch area pacing (LBBAP) vs continued CRT (the current gold standard) in improving cardiac function and patient symptoms, 2) assess the accuracy and feasibility of cardiac MRI in measuring cardiac function in patients with device therapy. The proposed training and research will generate preliminary data necessary for development of a future Merit award proposal to be submitted in Year 4. I plan to propose a prospective, multicenter, randomized controlled trial of the intervention evaluated in this study, which will launch my career as an independent VA CSR&D investigator committed to improving Veterans’ cardiac health though improved diagnostic and therapeutic treatment options.