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Renal Denervation in Heart Failure with Preserved Ejection Fraction

肾去神经术治疗射血分数保留的心力衰竭

基本信息

批准号：
10280590
负责人：
Traci Taylor Goodchild
金额：
$ 64.27万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10280590
关键词：
Acetates Adult Aldosterone Angiotensin I Angiotensin II Animal Model Animals Attenuated Bilateral Biochemical Biological Markers Blood Pressure Monitors Blood Vessels Cardiac Cardiovascular system Catecholamines Catheters Cholesterol Chronic Clinical Congestive Conscious Coronary Coupled Denervation Deoxycorticosterone Development Devices Diabetes Mellitus Diagnosis Diet Disease Progression Down-Regulation EFRAC Endothelium FDA approved Failure Fatty acid glycerol esters Fibrosis Fructose Functional disorder Genomics Harvest Heart Heart failure Histologic Hypertension Implant In Vitro Kidney Lead Left Left ventricular structure Longevity Lung Measures Mediator of activation protein Medical Medicine Metabolic Metabolic syndrome Mineralocorticoids Miniature Swine Morbidity - disease rate Myocardial Myocardial tissue Nerve Norepinephrine Obesity Pathologic Pathology Patients Pharmacotherapy Physiologic intraventricular pressure Physiological Plasma Prevalence Proteomics Public Health Quality of life RNA Sequences Renal Tissue Renin Severities Signal Transduction Skeletal Muscle Sodium Chloride Stains Sympathetic Nervous System System Therapeutic Time Tissues Treadmill Tests Treatment Failure Tyrosine 3-Monooxygenase Ventricular Work aging population base cardioprotection clinically relevant comorbidity density diabetic effective therapy exercise capacity exercise intolerance experimental study follow-up gene panel hemodynamics hypercholesterolemia improved kidney cortex kidney dysfunction metabolomics mortality novel novel therapeutics porcine model pre-clinical preservation prevent protective effect radio frequency renal artery repaired sex therapeutic target vascular injury western diet

项目摘要

PROJECT SUMMARY Heart failure with preserved ejection fraction (HFpEF) has emerged as a significant unmet medical need in cardiovascular medicine and 60% of all new heart failure diagnoses are HFpEF. The increasing prevalence of HFpEF coupled with a complete lack of effective FDA approved treatments further accentuates this critical public health problem. It is well appreciated that chronic over-activation of the sympathetic nervous system promotes left ventricular (LV) hypertrophic remodeling and fibrosis, profound endothelial and vascular injury, and renal dysfunction. The proposed studies will evaluate the beneficial effects of renal denervation (RDN) on left ventricular and vascular function in a novel swine model of HFpEF. HFpEF will be induced in Göttingen mini-swine following chronic treatment with deoxycorticosterone acetate (DOCA) combined with a Western Diet that induces hypertension and metabolic syndrome followed by LV diastolic dysfunction, pulmonary congestion, exercise intolerance, and clinically relevant HFpEF. RDN will be performed following the onset of HFpEF utilizing a clinical RDN catheter system that employs RF energy to destroy the renal sympathetic nerves. The Central Hypothesis of the proposed studies is that RDN therapy will promote myocardial repair and attenuate HFpEF progression via downregulation of pathological signaling in the kidney and heart. Specific Aim 1 is to determine the effects of RDN therapy on heart failure progression and severity in a clinically relevant large animal model of HFpEF. Specific Aim 2 is to identify candidate cardiac and extra-cardiac mediators that underlie the cardioprotective effects of RDN using genomic, metabolomic, and proteomic approaches. These studies will determine if RDN ameliorates the severity and progression of HFpEF and explore the mechanisms by which RDN exerts cardioprotective and vascular protective effects. These studies will involve an array of physiological, biochemical, genomic, metabolomic, and proteomic approaches to assess the potential efficacy of RDN in HFpEF. Results from these studies will significantly extend our current understanding of the pathobiology of HFpEF and provide critical information that helps to guide the development of novel therapies to treat patients that suffer from HFpEF.

项目总结