Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Coronary Flow Reserve
研究概览
简要总结
Unlike heart failure with reduced ejection fraction (HFrEF) where several medicines and devices have been demonstrated to reduce mortality, no such therapies have been identified in HFpEF. This may be in part due to incomplete understanding of the underlying mechanisms of HFpEF.
Recently, impaired myocardial blood flow, reduced myocardial energy utilization, and increased myocardial fibrosis have been postulated to play important pathophysiologic roles in HFpEF. The investigators and others have demonstrated that HFrEF may be associated with altered myocardial energy utilization and "energy starvation." However, there are limited data regarding "energy starvation" in HFpEF and the relationships between myocardial blood flow, energy utilization, and fibrosis in HFpEF are largely unknown. Therefore, the purposes of this study are to use non-invasive cardiac imaging techniques to describe cardiac structure, function, blood flow, energetics, and fibrosis, and the relationships between these in order to better understand underlying mechanisms in HFpEF.
详细描述
The investigators hypothesize that HFpEF is associated with reductions in myocardial blood flow and energy utilization and increased myocardial fibrosis as compared to age and gender matched hypertensive and healthy controls. The investigators will test their hypotheses by comparing measurements of myocardial blood flow, energy utilization, and fibrosis between three subject groups (HFpEF vs hypertension vs healthy). Myocardial blood flow will be quantitated from nitrogen (N)13-Ammonia positron emission tomography (PET) and gadolinium enhanced cardiac magnetic resonance (CMR) imaging, both at rest and stress following coronary vasodilation with regadenoson. Myocardial energy utilization will be quantified with 11C-acetate PET imaging and myocardial fibrosis will be assessed with gadolinium enhanced CMR and alterations in myocardial T1. Echocardiography will be utilized to quantify cardiac diastolic function.
It is anticipated that the results of this proposed study will provide a foundation that will inform future studies aimed at identifying novel preventive or therapeutic agents in HFpEF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •estimated glomerular filtration rate (eGFR) > 60 ml/min
- •preserved left ventricular ejection fraction (>= 50%) on echocardiography
排除标准
- •coronary artery disease
- •diabetes mellitus
- •contraindications to cardiac magnetic resonance imaging (CMR)
- •weight >350 lbs
- •inability to lie flat for imaging
- •contraindications to regadenoson or aminophylline
- •Inclusion criteria:
- •normal cardiac structure and function on echocardiography
- •BP < 140/90
- •Exclusion criteria:
- •known cardiovascular disease, cardiac risk factors or use of cardiac medications
- •HYPERTENSIVE
- •Inclusion criteria:
- •history of BP >140/90
- •1 or more antihypertensive medications
- •LV ejection fraction (LVEF) at least 50%
- •current BP < 160/90
- •Exclusion criteria:
- •known cardiovascular disease or risk factors aside from hypertension or use of cardiac medications
- •Inclusion criteria:
- •physician-confirmed diagnosis of HF
- •symptomatic HF
- •LVEF at least 50%
- •elevated LV filling pressure by catheterization, echocardiographic criteria or B-type-natriuretic peptide > 100
- •current BP < 160/90
- •Exclusion criteria:
- •prior history of LVEF below 50%
- •acute decompensated HF
- •moderate or greater valvular disease
- •significant cardiac arrhythmias
- •pericardial disease
- •congenital heart disease
- •primary pulmonary hypertension
研究组 & 干预措施
normal participants
No cardiovascular abnormalities or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism.
干预措施: regadenoson (Drug)
hypertensive participants
No history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism.
干预措施: regadenoson (Drug)
HFpEF patients
No history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism.
干预措施: regadenoson (Drug)
结局指标
主要结局
Coronary Flow Reserve
时间窗: Baseline study visit
Rest and regadenoson stress coronary flow reserve by ammonia PET. Coronary flow calculated at rest and again at stress with coronary flow reserve calculated as the ratio of stress to rest coronary flow.
次要结局
- Myocardial Perfusion Reserve by CMR in Each Study Group.(Baseline study visit.)
- E/e' by Echo in Each Study Group.(Baseline study visit)
- Extracellular Volume (ECV) by CMR in Each Study Group(Baseline study visit)
- Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.(Baseline study visit)
研究者
Marvin W. Kronenberg, M.D.
Professor of Medicine and Radiology
Vanderbilt University Medical Center