Management and Outcomes of Heart Failure with Preserved Systolic Function

描述(由申请人提供)：本申请涉及广泛的挑战领域(04)临床研究和特定挑战主题，04-HL-105：在保留收缩功能的情况下治疗心力衰竭在药物和设备疗法方面取得了多项进展，以改善心力衰竭和左心室收缩功能下降患者的护理和结果。然而，心力衰竭的流行病学在过去几十年里一直在发生变化，临床公认的心力衰竭综合征的成年人中，有超过一半的人目前“保留”了左心室收缩功能--通常定义为左心室射血分数为&gt；50%，或对正常或保留的收缩功能进行定性评估。尽管有这些不断变化的趋势和不断扩大的心力衰竭负担，但我们对任何降低心力衰竭患者过早死亡或心力衰竭恶化风险并保留收缩功能的治疗方法的见解很少。此外，我们缺乏关于不同人群心力衰竭患者的特征和事件发生率的当代信息，这些信息有助于指导未来在这些患者中进行随机临床试验。为了解决NIH挑战主题05-HL-105中强调的这些主要知识差距，我们建议利用国家心肺血液研究所赞助的心血管研究网络(CVRN)，这是一个多中心的、基于健康计划的研究网络，为全美约1100万名成员提供护理。通过四个参与的CVRN中心的合作，我们建议召集一个大型的、当代的不同的成人队列，这些成年人被诊断为心力衰竭，并证明左心室收缩功能正常，以检查以下三个具体目标：目的1.收集一个大型的、不同的多中心队列的成人心力衰竭患者，并记录在2000-2008年间保留的左心室收缩功能，并以可用的心力衰竭治疗方法表征最近的实践模式。目的2.在总体和目标患者亚组中，确定心力衰竭和收缩功能保留的成年人的死亡率、心力衰竭住院和总资源利用率的当代发生率和预测因素。目的3.考虑到这一人群中有限的随机临床试验证据，对已被证明对心力衰竭和收缩功能降低的患者有益的靶向治疗(即ACE抑制剂、β-受体阻滞剂和醛固酮受体拮抗剂)的有效性和安全性进行初步评估，并探索与其他治疗慢性心力衰竭的常用治疗方法(如利尿剂、地高辛、硝酸盐和他汀类)相关的结果。慢性心力衰竭给公共卫生造成了沉重的负担--影响了570万美国人--其中大多数人年龄在65岁或以上。超过一半的心力衰竭患者保留了左心室收缩功能，这种情况的预后仍然很差，我们几乎没有随机临床试验数据来指导治疗。这项拟议的研究将提供对当代不良事件发生率和不良结果预测因素的关键和及时的见解，以及改善日益增长的心力衰竭和收缩功能保留患者的护理和结果的潜在方法。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research and specific Challenge Topic, 04-HL- 105: Treatment of Heart Failure with Preserved Systolic Function Multiple advances in pharmacological and device therapies have been made to improve the care and outcomes for patients with heart failure and reduced left ventricular systolic function. However, the epidemiology of heart failure has been changing over the past several decades, with more than half of adults with clinically recognized heart failure syndromes currently having "preserved" left ventricular systolic function-typically defined as having a left ventricular ejection fraction of >50% or qualitative assessment of normal or preserved systolic function. Despite these changing trends and the expanding burden of heart failure, we have very few insights into any therapies that reduce the risk of premature death or heart failure exacerbation for patients with heart failure and preserved systolic function. Furthermore, we lack contemporary information on characteristics and event rates from diverse populations of patients who have heart failure with preserved systolic function that would help guide planning for future randomized clinical trials in these patients. To address these major knowledge gaps highlighted in NIH Challenge Topic 05-HL-105, we propose to leverage the National Heart, Lung and Blood Institute-sponsored Cardiovascular Research Network (CVRN), a multicenter, health plan-based research network that provides care for ~11 million members across the U.S. Through a collaboration of four participating CVRN centers, we propose to assemble a large, contemporary diverse cohort of adults with diagnosed heart failure and documented preserved left ventricular systolic function to examine the following three Specific Aims: Aim 1. To assemble a large, diverse multicenter cohort of adults with heart failure and documented preserved left ventricular systolic function between 2000-2008 and characterize recent practice patterns with available heart failure therapies. Aim 2. To determine contemporary rates and predictors of death, hospitalization for heart failure, and total resource utilization among adults with heart failure and preserved systolic function, overall and in targeted patient subgroups. Aim 3. Given the limited randomized clinical trial evidence in this population, to provide a preliminary evaluation of the effectiveness and safety of targeted therapies (i.e., ACE inhibitors, beta-blockers, and aldosterone receptor antagonists) that have been proven to be beneficial for patients with heart failure and reduced systolic function as well as exploring the outcomes associated with other commonly used therapies in chronic heart failure (e.g., diuretics, digoxin, nitrates, and statins). The public health burden for chronic heart failure is substantial-affecting 5.7 million Americans-the majority of whom are aged 65 years or older. More than half of patients with heart failure have preserved left ventricular systolic function, a condition whose prognosis remains poor and for which we have few randomized clinical trial data to guide therapy. The proposed study will provide critical and timely insights into contemporary adverse event rates and predictors of adverse outcomes, as well as into potential ways to improve the care and outcomes of the growing population of patients with heart failure and preserved systolic function.