Cardio-renal phenotype and prognosis in chronic heart failure

慢性心力衰竭的心肾表型和预后

• 批准号: 9069030
• 负责人: JEFFREY M TESTANI
• 金额: $ 19万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9069030
• 关键词: Ablation; Adult; Aldosterone; Angiotensin II; Automobile Driving; Avidity; Biological Markers; Blood Urea Nitrogen; Center for Translational Science Activities; Cessation of life; Clinical; Clinical Research; Cohort Studies; Comorbidity; Complication; Congestive Heart Failure; Creatinine; Diabetes Mellitus; Diet; Disease Progression; Diuretics; Dose; Enrollment; Ensure; Excretory function; Fellowship; Functional disorder; Funding; Future; Glomerular Filtration Rate; Goals; Hand; Heart Transplantation; Heart failure; High Prevalence; Hypertension; Investigation; Kidney; Lead; Light; Liquid substance; Measurement; Measures; Mediating; Mentors; Mentorship; Methodology; Morbidity - disease rate; Nature; Nerve; Neurohormones; Organ; Patients; Pennsylvania; Peripheral; Phenotype; Physiology; Population; Prevalence; Principal Investigator; Proteins; Publications; Renal Blood Flow; Renal function; Renin; Research; Research Infrastructure; Research Personnel; Research Training; Risk; Risk Factors; Secondary to; Series; Sodium; Structure; Supervision; Sympathetic Nervous System; Syndrome; System; Systolic heart failure; Testing; Therapeutic; Training; Training Programs; Translational Research; United States National Institutes of Health; Universities; Urea; Vasopressins; Work; attributable mortality; base; career development; clinical practice; cohort; cost; experience; high risk; hyperkalemia; improved; mortality; outcome forecast; patient oriented; patient oriented research; prognostic; programs; prospective; response; study population

DESCRIPTION (provided by applicant): This proposal describes a five year intensive mentored training program with the goal of developing the Principal Investigator (PI) into an independent and high impact, patient-oriented researcher. The PI is a fully trained adult cardiologist, has obtained formal research training in the Masters in Translational Research program, and is currently completing an advanced heart failure (HF) and cardiac transplantation clinical fellowship at the University of Pennsylvania. His clinical research mentorship to date has been lead by Dr. Stephen Kimmel (Primary Mentor of this proposal) and as evidenced by the PI's 11 first author publications under Dr. Kimmel's supervision, this is a highly effective mentoring relationship. However, successful transition of the PI to research independence will require substantial additional training and intense mentored career development. A comprehensive training proposal is thus proposed to facilitate the above, which will include: 1) Intensive mentoring from a team lead by Dr. Kimmel 2) Advanced didactic coursework 3) Hands on experience in prospective patient-oriented research 4) Scientific advisory by eminent cardio-renal scholars such as Drs. John Burnett and Robert Schrier 5) Structured career development and establishment of a body of scientific work with which the transition to independence will be based. The overall objective of the scientific aspect of this proposal is to better define cardio-renal phenotypes and their prognostic importance in HF. Renal dysfunction (RD) is a common complication of HF and one of the strongest risk factors for death in these patients. Severe HF and its treatment (i.e., loop diuretics) are known to result in progressive neurohormonal activation and peripheral organ dysfunction (i.e., RD). The risk attributable to RD appears to be isolated to patients with an elevated blood urea nitrogen to creatinine ratio (BUN/Cr), which is a surrogate for renal neurohormonal activation. If neurohormonal activation is indeed underlying the above observations, the direct treatment implications are substantial. However, BUN/Cr is influenced by factors external to neurohormonal activation, and these non-neurohormonal factors may also be important in RD- associated mortality. The aims of this proposal are to quantify the degree to which neurohormones are elevated in HF patients with RD and elevated BUN/Cr, investigate the influence of loop diuretics in the genesis of these neurohormonal abnormalities, and establish whether it is the neurohormonally dependent aspects of BUN/Cr that are driving these mortality observations. We will achieve these aims by: 1) Direct characterization of neurohormonal parameters in HF patients with RD and either a high or low BUN/Cr in the Clinical and Translational Research Center, before and after loop diuretic exposure. 2) Determination in a large prospective HF cohort, the Penn Heart Failure Study, if the fractional excretion of urea (which captures the neurohormonally mediated aspect of BUN/Cr) is responsible for the ability of BUN/Cr to differentiate high and low risk forms of RD. The results of this line of investigation will form the basis upon which future interventional trias in these high risk patients can be based. The combination of formal advanced research training and mentored patient-oriented research experience will ensure the PI emerges as a highly successful independent patient-oriented researcher in HF and cardio- renal interactions.

描述（由申请人提供）：该提案描述了一个为期五年的强化指导培训计划，目标是将首席研究员（PI）发展成为一个独立的、高影响力的、以患者为导向的研究人员。PI是一名训练有素的成人心脏病专家，在转化研究硕士项目中获得了正式的研究培训，目前正在宾夕法尼亚大学完成高级心力衰竭（HF）和心脏移植临床奖学金。他的临床研究指导至今