Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF

NCT ID: NCT02589977

Last Updated: 2021-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2020-01-21

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.

Conditions

Heart Failure, Diastolic; Diastolic Heart Failure; Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

regadenoson

Intervention Type: DRUG

evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants

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.

Group Type: OTHER

regadenoson

Intervention Type: DRUG

evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants

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.

Group Type: OTHER

regadenoson

Intervention Type: DRUG

evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants

Interventions

regadenoson

evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants

Intervention Type: DRUG

Other Intervention Names

positron emission tomography; echocardiography; cardiac magnetic resonance imaging

Eligibility Criteria

Inclusion Criteria

• estimated glomerular filtration rate (eGFR) > 60 ml/min
• preserved left ventricular ejection fraction (>= 50%) on echocardiography

• normal cardiac structure and function on echocardiography
• BP < 140/90

• history of BP >140/90
• 1 or more antihypertensive medications
• LV ejection fraction (LVEF) at least 50%
• current BP < 160/90

• 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

• 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

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

HYPERTENSIVE

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

HFpEF

• 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma US, Inc.

INDUSTRY

Sponsor Role: collaborator

Marvin W. Kronenberg, M.D.

OTHER

Sponsor Role: lead

Responsible Party

Marvin W. Kronenberg, M.D.

Professor of Medicine and Radiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marvin W Kronenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24331202 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23671819 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

141686

Identifier Type: -

Identifier Source: org_study_id