search
Back to results

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

Primary Purpose

Heart Failure, Diastolic, Diastolic Heart Failure, Hypertension

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
regadenoson
Sponsored by
Marvin W. Kronenberg, M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Heart Failure, Diastolic focused on measuring magnetic resonance imaging, positron-emission tomography, echocardiography, myocardial blood flow, energy metabolism

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

normal participants

hypertensive participants

HFpEF patients

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Coronary Flow Reserve
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

Myocardial Perfusion Reserve by CMR in Each Study Group.
Myocardial perfusion reserve by CMR.
Extracellular Volume (ECV) by CMR in Each Study Group
Extracellular volume (ECV) by CMR.
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.
Oxidative metabolism (Kmono/rate pressure product) by PET.
E/e' by Echo in Each Study Group.
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.

Full Information

First Posted
August 24, 2015
Last Updated
February 1, 2021
Sponsor
Marvin W. Kronenberg, M.D.
Collaborators
Astellas Pharma US, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02589977
Brief Title
Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
Acronym
HFpEF-PRoF
Official Title
Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
January 21, 2020 (Actual)
Study Completion Date
January 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Marvin W. Kronenberg, M.D.
Collaborators
Astellas Pharma US, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Diastolic, Diastolic Heart Failure, Hypertension
Keywords
magnetic resonance imaging, positron-emission tomography, echocardiography, myocardial blood flow, energy metabolism

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
normal participants
Arm Type
Other
Arm Description
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.
Arm Title
hypertensive participants
Arm Type
Other
Arm Description
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.
Arm Title
HFpEF patients
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
regadenoson
Other Intervention Name(s)
positron emission tomography, echocardiography, cardiac magnetic resonance imaging
Intervention Description
evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants
Primary Outcome Measure Information:
Title
Coronary Flow Reserve
Description
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.
Time Frame
Baseline study visit
Secondary Outcome Measure Information:
Title
Myocardial Perfusion Reserve by CMR in Each Study Group.
Description
Myocardial perfusion reserve by CMR.
Time Frame
Baseline study visit.
Title
Extracellular Volume (ECV) by CMR in Each Study Group
Description
Extracellular volume (ECV) by CMR.
Time Frame
Baseline study visit
Title
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.
Description
Oxidative metabolism (Kmono/rate pressure product) by PET.
Time Frame
Baseline study visit
Title
E/e' by Echo in Each Study Group.
Description
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.
Time Frame
Baseline study visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marvin W Kronenberg, MD
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24331202
Citation
Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. J Card Fail. 2013 Dec;19(12):802-10. doi: 10.1016/j.cardfail.2013.10.010. Epub 2013 Oct 29.
Results Reference
result
PubMed Identifier
23671819
Citation
Gupta DK, Shah AM, Castagno D, Takeuchi M, Loehr LR, Fox ER, Butler KR, Mosley TH, Kitzman DW, Solomon SD. Heart failure with preserved ejection fraction in African Americans: The ARIC (Atherosclerosis Risk In Communities) study. JACC Heart Fail. 2013 Apr;1(2):156-63. doi: 10.1016/j.jchf.2013.01.003.
Results Reference
result

Learn more about this trial

Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF

We'll reach out to this number within 24 hrs