Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF (HFpEF-PRoF)

February 1, 2021 updated by: Marvin W. Kronenberg, M.D.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NON_RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: 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.
Drug: regadenoson
evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants
Other Names:
  • positron emission tomography
  • echocardiography
  • cardiac magnetic resonance imaging
OTHER: 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.
Drug: regadenoson
evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants
Other Names:
  • positron emission tomography
  • echocardiography
  • cardiac magnetic resonance imaging
OTHER: 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.
Drug: regadenoson
evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants
Other Names:
  • positron emission tomography
  • echocardiography
  • cardiac magnetic resonance imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coronary Flow Reserve
Time Frame: 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.
Baseline study visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial Perfusion Reserve by CMR in Each Study Group.
Time Frame: Baseline study visit.
Myocardial perfusion reserve by CMR.
Baseline study visit.
Extracellular Volume (ECV) by CMR in Each Study Group
Time Frame: Baseline study visit
Extracellular volume (ECV) by CMR.
Baseline study visit
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.
Time Frame: Baseline study visit
Oxidative metabolism (Kmono/rate pressure product) by PET.
Baseline study visit
E/e' by Echo in Each Study Group.
Time Frame: 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.
Baseline study visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Marvin W. Kronenberg, M.D.

Collaborators

Astellas Pharma US, Inc.

Investigators

  • Principal Investigator: Marvin W Kronenberg, MD, Vanderbilt University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (ACTUAL)

January 21, 2020

Study Completion (ACTUAL)

January 21, 2020

Study Registration Dates

First Submitted

August 24, 2015

First Submitted That Met QC Criteria

October 27, 2015

First Posted (ESTIMATE)

October 28, 2015

Study Record Updates

Last Update Posted (ACTUAL)

February 2, 2021

Last Update Submitted That Met QC Criteria

February 1, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 141686 (Other Grant/Funding Number: Department of Defense Congressionally Directed Medical Research Program)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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