Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
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.
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.
ALL

 Inclusion Criteria:

 -  estimated glomerular filtration rate (eGFR) > 60 ml/min

 -  preserved left ventricular ejection fraction (>= 50%) on echocardiography

 Exclusion Criteria:

 -  coronary artery disease

 -  diabetes mellitus

 -  contraindications to cardiac magnetic resonance imaging (CMR)

 -  weight >350 lbs

 -  inability to lie flat for imaging

 -  anemia

 -  contraindications to regadenoson or aminophylline

 HEALTHY

 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

 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:

 -  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