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

概述：我正在重新申请5年职业发展奖(CDA)，以支持我的总体目标 研究成像工具如何改善需要设备治疗的心力衰竭(HF)患者的护理。这 将通过完成有指导的研究活动和旨在 提供成为独立调查员所需的技能。在我获奖期间，我将学习 一种新的心脏再同步治疗方法(CRT)用于尚未接受心脏再同步治疗的心衰患者 心功能的改善与标准治疗的护理。我还计划确定 心脏核磁共振评估心力衰竭患者接受设备治疗后随时间推移的心功能。 意义：心力衰竭是退伍军人健康管理局最常见的疾病之一， VA患者的年死亡率为15%。大约50%的心力衰竭住院病例发生在 射血分数(HFrEF)降低的患者。在这些患者中，主要的治疗目标包括策略 增加心脏分数，这已被证明可以改善症状并降低突发事件的风险 心源性死亡。对于也有左束支传导阻滞的患者，主要的治疗方法是放置 心脏起搏导联位于右心室和位于左心室之上的心脏静脉，称为CRT。 然而，高达40%的接受CRT的患者未能体验到预期的心脏改善 6个月后出现功能和症状，称为“无反应者”。这项研究旨在改进 “无反应者”的心脏功能是通过从左束支区域起搏，从而利用 心脏的内在电系统促进协调的室性收缩。干预措施的发展 在这项CDA提案中，可能会产生广泛的影响，因为它可以显著降低发病率 降低HFrEF患者的死亡率，并降低退伍军人管理局医疗保健系统的成本和负担。 职业生涯规划：我的主要研究领域是改善心力衰竭患者的预后。 为了成功实现改善对需要设备治疗的心力衰竭患者的护理的目标，我需要 实施科学方面的进一步指导培训，包括：量化和混合方法培训， 在诊断成像培训和研究(特别是心脏核磁共振)、进一步的生物统计学培训、 以及培养多学科协作和网络技能。我将通过以下方式实现这些目标 在初级导师Selçuk的指导下，进行正式的课程、研讨会和有指导的研究活动 Adabag，MD，MS(MVAHCS)和Chetan Shenoy，MBBS，MS(明尼苏达大学系) 心脏病)，以及二级导师Bradley Bart，MD(MVAHCS)和Sue Duval(明尼苏达大学 心内科)。通过这笔赠款进行的指导研究培训将为我的 长期目标是成为公认的领导者和研究人员，专注于心脏成像的使用 改善需要设备治疗的心力衰竭患者的以患者为中心的临床结果。 研究计划：我的主要研究目标是评估一种新的CRT方法用于HFrEF患者和 对传统CRT治疗无效的LBBB。为了实现这个目标，我将完成 1)一项评估左束支面积有效性的前瞻性随机对照研究 起搏(LBBAP)与持续CRT(目前的金标准)在改善心功能和患者方面的比较 症状，2)评估心脏MRI测量心脏功能的准确性和可行性 设备疗法。拟议的培训和研究将产生发展所需的初步数据。 未来将在第四年提交的荣誉奖提案。我计划提出一个具有前瞻性的、多中心的、 这项研究中评估的干预措施的随机对照试验，这将开启我作为一名 独立退伍军人CSR&D调查员致力于改善退伍军人的心脏健康 诊断和治疗方案。

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.