Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF

Phase 4

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

HEALTHY

Inclusion criteria:

Exclusion criteria:

known cardiovascular disease, cardiac risk factors or use of cardiac medications

HYPERTENSIVE

Inclusion criteria:

Exclusion criteria:

known cardiovascular disease or risk factors aside from hypertension or use of cardiac medications

HFpEF

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:

Arm && Interventions

Group	Intervention	Description
normal participants	regadenoson	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.
hypertensive participants	regadenoson	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.
HFpEF patients	regadenoson	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.

Primary Outcome Measures

Name	Time	Method
Coronary Flow Reserve	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.

Secondary Outcome Measures

Name	Time	Method
Myocardial Perfusion Reserve by CMR in Each Study Group.	Baseline study visit.	Myocardial perfusion reserve by CMR.
E/e' by Echo in Each Study Group.	Baseline study visit	E/e' by echo. E is the transmitral peak velocity in early diastole. e' is the early diastolic tissue Doppler velocity average between the septal and lateral mitral annulus. E/e' is the ratio of these two values.
Extracellular Volume (ECV) by CMR in Each Study Group	Baseline study visit	Extracellular volume (ECV) by CMR.
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.	Baseline study visit	Oxidative metabolism (Kmono/rate pressure product) by PET.

Locations (1): Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States