Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure

描述（由申请人提供）：心力衰竭（HF）是美国增长最快的心血管疾病，也是老年人住院治疗的最常见原因。许多心衰患者在休息或轻微运动时出现症状，对最佳药物治疗变得难以治愈。在这些晚期心衰患者中，只有不到5%的人有资格进行心脏移植，而且器官捐献极为有限。因此，机械循环支持与心室辅助装置（VAD）已成为晚期心衰的主要治疗方法。VAD植入后的临床结果和生活质量存在显著且无法解释的异质性。此外，我们对生理和心理症状如何与HF潜在发病机制的变化相关，以及症状和致病生物标志物如何解释对VAD植入的不同反应知之甚少。因此，我们的研究目标是：a)表征从晚期心衰到VAD植入后的前6个月期间症状和致病生物标志物变化的共同和独特轨迹；b)将症状和生物标志物随时间的变化与临床事件和生活质量联系起来。我们将收集120名成年晚期HF患者在VAD植入前和植入后6个月的数据。我们的目标是：1)确定生理和心理症状变化的共同轨迹；2)描述心肌应激、全身炎症和内皮功能障碍的血清生物标志物变化的共同轨迹；3)量化接受VAD植入的成人症状和发病机制生物标志物之间的关联。重要的是，我们将编纂临床事件风险和健康相关生活质量方面不同症状和生物标志物轨迹的临床相关性。这项跨学科的临床研究整合并推进了先前的生物学和行为学研究，并以先进的技术治疗一种备受瞩目的心血管疾病为中心。这些研究结果将用于加强患者和提供者关于VAD植入的共同决策，并形成急需的新型干预措施和临床管理策略，以适应VAD植入的不同症状和致病反应。

DESCRIPTION (provided by applicant): Heart failure (HF) is the fastest growing cardiovascular disorder in the U.S., and the most common reason for hospitalization among older adults. Many patients with HF have symptoms at rest or with minimal exertion that become refractory to optimal medical therapy. Fewer than 5% of these advanced HF patients are eligible for heart transplantation, and organ donations are extremely limited. As such, mechanical circulatory support with a ventricular assist device (VAD) has emerged as a primary treatment for advanced HF. There is significant and unexplained heterogeneity in clinical outcomes and quality-of-life after VAD implantation. Moreover, we know very little about how physical and psychological symptoms may relate to changes in underlying HF pathogenesis and how symptoms and pathogenic biomarkers may explain differential responses to VAD implantation. Accordingly, our research goals are to a) characterize common and distinct trajectories of change in symptoms and pathogenic biomarkers during the transition from advanced HF through the first 6 months after VAD implantation, and b) link changes in symptoms and biomarkers over time to clinical events and quality-of-life. We will collect data from a cohort of 120 adults with advanced HF prior to, and for a period of 6 months after VAD implantation. Our aims are to: 1) identify common trajectories of change in physical and psychological symptoms, 2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction, and 3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Importantly, we will codify the clinical relevance of different symptom and biomarker trajectories in terms of clinical-event risk and health-related quality-of-life. This interdisciplinary clinical research integrates and advances prior biological and behavioral research and is centered on an advanced technological treatment of a high profile cardiovascular disorder. These research findings will be used to enhance shared patient and provider decision-making regarding VAD implantation, and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.