Systolic & diastolic dysfunction in heart failure and preserved ejection fraction

收缩压

• 批准号: 8880898
• 负责人: Amil M Shah
• 金额: $ 13.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8880898
• 关键词: Address; Adverse event; Advisory Committees; Age; Aldosterone Antagonists; Atherosclerosis; Benchmarking; Biological Markers; Blood Vessels; Boston; Cardiac; Cardiology; Cardiovascular system; Cessation of life; Clinical; Clinical Investigator; Clinical Trials; Communities; Coupling; Data; Development; Discrimination; EFRAC; Elderly; Enrollment; Epidemiologist; Faculty; Foundations; Functional disorder; Future; Geometry; Goals; Heart failure; Hospitalization; Hospitals; Image; Impairment; Individual; Injury; Intervention; Investigation; K-Series Research Career Programs; Left; Left Ventricular Ejection Fraction; Left Ventricular Function; Lung; Measures; Mentors; Mentorship; Methodology; Morbidity - disease rate; Myocardial; NT-proBNP; National Heart, Lung, and Blood Institute; Normal Range; Outcome; Participant; Pathologic; Patients; Phenotype; Population; Prevalence; Public Health; Pulmonary Hypertension; Recurrence; Research; Research Design; Research Personnel; Resources; Risk; Risk Assessment; Risk Factors; Risk Marker; Role; Staging; Statistical Methods; Stratification; Stress; Structure; Symptoms; Syndrome; Therapeutic; Therapeutic Intervention; Therapeutic Studies; Therapeutic Trials; Time; Torsion; Training; Troponin T; Ventricular; Woman; adjudicate; adverse outcome; base; cardiovascular risk factor; career; cohort; didactic education; experience; high risk; imaging modality; improved; indexing; insight; interest; member; mortality; novel; novel therapeutic intervention; predictive modeling; pressure; public health relevance; skills

DESCRIPTION (provided by applicant): This is a K08 application for Dr Amil Shah, a cardiology faculty member and early stage investigator at the Brigham and Women's Hospital in Boston, MA. His goal is to become a leading clinical investigator using noninvasive assessments of cardiac structure and function to better understand heart failure risk and progression, and to inform new therapeutic interventions. His near-term goal is to employ novel echocardiographic measures of cardiac function to define the role of previously under-recognized systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). This application presents a comprehensive training plan, including structured mentorship, a well-developed advisory committee, and a tailored didactic curriculum in advanced statistical and imaging methods, which together will provide Dr Shah with the skills necessary to achieve this goal and transition into a successful independent investigator. HFpEF is a well-recognized public health burden. The inability of noninvasive measures of diastolic function to distinguish HFpEF patients from their symptom-free counterparts and to predict adverse events among HFpEF patients, along with the under-appreciation of co-existing systolic dysfunction (detected using novel myocardial deformation imaging) are critical barriers to progress in effectively phenotyping and developing treatments for this heterogeneous syndrome. The main hypothesis of this proposal is that concomitant impairments in systolic and diastolic function occur in parallel with accumulating cardiovascular risk factors and that these impairments are central to the development of HFpEF and subsequent morbidity and mortality. Dr Shah will use state-of-the-art echocardiographic data from two unique, complementary, and well-phenotyped populations with prospectively adjudicated clinical outcomes - the NHLBI TOPCAT clinical trial in HFpEF and the community based NHLBI ARIC cohort - to address the following specific aims: (1) To determine the relationship of novel measures of systolic deformation with clinical and echocardiographic risk markers for incident HF in approximately 8,000 elderly community-dwelling ARIC participants; (2) To determine the extent to which these novel measures of systolic dysfunction associate with risk of developing HFpEF, and risk of CV death or HF hospitalization in prevalent HFpEF; and (3) To improve prognostication by combining novel measures of systolic dysfunction with soluble biomarkers of myocardial stress (NT-pro-BNP) and injury (high sensitivity troponin T) to develop parsimonious risk prediction models for incident HFpEF and for adverse outcomes in patients with prevalent HFpEF. The results of the proposed early career development award will (1) provide key benchmarks for defining pathologic diastolic and systolic dysfunction, (2) clarify the role of these abnormalities in HFpEF to help inform tailored interventions, (3) improve risk assessment to inform future preventative and therapeutic studies, and (4) serve as an ideal vehicle for Dr Shah to transition to an independent investigator.

描述（由申请人提供）：这是一个K 08申请博士阿米尔沙阿，心脏病学教员和早期研究员在布里格姆妇女医院在波士顿，马萨诸塞州。他的目标是成为一名领先的临床研究者，使用心脏结构和功能的非侵入性评估来更好地了解心力衰竭的风险和进展，并为新的治疗干预提供信息。他的近期目标是采用新的超声心动图测量心脏功能，以确定以前认识不足的收缩功能障碍在射血分数保留性心力衰竭（HFpEF）中的作用。该应用程序提供了一个全面的培训计划，包括结构化的指导，一个完善的咨询委员会，以及先进的统计和成像方法的量身定制的教学课程，这些都将为Shah博士提供实现这一目标所需的技能，并过渡到一个成功的独立调查员。 HFpEF是公认的公共卫生负担。舒张功能的无创测量无法区分HFpEF患者与无心肌梗死患者，也无法预测HFpEF患者的不良事件，沿着对共存的收缩功能障碍的认识不足（使用新型心肌变形成像检测），这是有效分型和开发这种异质性综合征治疗方法的关键障碍。该建议的主要假设是，伴随的收缩和舒张功能障碍与心血管风险因素的累积平行发生，并且这些障碍是HFpEF发展以及随后发病率和死亡率的核心。Shah博士将使用来自两个独特、互补和表型良好的人群的最先进的超声心动图数据，这些人群具有前瞻性裁定的临床结局-HFpEF中的NHLBI TOPCAT临床试验和基于社区的NHLBI ARIC队列-以解决以下具体目标：（一）为了确定收缩期变形的新指标与约8例新发HF的临床和超声心动图风险标志物之间的关系，（2）确定这些收缩功能障碍的新指标与HFpEF发生风险以及流行性HFpEF中CV死亡或HF住院风险的相关程度;（3）通过将收缩功能障碍的新指标与心肌应激的可溶性生物标志物相结合来改善测量（NT-pro-BNP）和损伤（高灵敏度肌钙蛋白T），以开发针对偶发HFpEF和流行HFpEF患者不良结局的简约风险预测模型。 建议的早期职业发展奖的结果将（1）提供定义病理性舒张和收缩功能障碍的关键基准，（2）阐明这些异常在HFpEF中的作用 有助于为定制的干预措施提供信息，（3）改善风险评估，为未来的预防和治疗研究提供信息，以及（4）作为Shah博士过渡到独立研究者的理想工具。