NCT02589977

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
55

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Nov 2015

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

October 28, 2015

Completed
4 days until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 21, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 21, 2020

Completed
1 year until next milestone

Results Posted

Study results publicly available

February 2, 2021

Completed
Last Updated

February 2, 2021

Status Verified

February 1, 2021

Enrollment Period

4.2 years

First QC Date

August 24, 2015

Results QC Date

December 23, 2020

Last Update Submit

February 1, 2021

Conditions

Heart Failure, DiastolicDiastolic Heart FailureHypertension

Keywords

magnetic resonance imagingpositron-emission tomographyechocardiographymyocardial blood flowenergy metabolism

Outcome Measures

Primary Outcomes (1)

  • 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.

    Baseline study visit

Secondary Outcomes (4)

  • Myocardial Perfusion Reserve by CMR in Each Study Group.

    Baseline study visit.

  • Extracellular Volume (ECV) by CMR in Each Study Group

    Baseline study visit

  • Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.

    Baseline study visit

  • E/e' by Echo in Each Study Group.

    Baseline study visit

Study Arms (3)

normal participants

OTHER

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

hypertensive participants

OTHER

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

HFpEF patients

OTHER

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

Interventions

regadenosonDRUG

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

Also known as: positron emission tomography, echocardiography, cardiac magnetic resonance imaging
HFpEF patientshypertensive participantsnormal participants

Eligibility Criteria

Age50 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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
  • normal cardiac structure and function on echocardiography
  • BP \< 140/90
  • known cardiovascular disease, cardiac risk factors or use of cardiac medications
  • HYPERTENSIVE
  • history of BP \>140/90
  • or more antihypertensive medications
  • LV ejection fraction (LVEF) at least 50%
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

  • 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.

    PMID: 24331202RESULT

  • 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.

    PMID: 23671819RESULT

MeSH Terms

Conditions

Heart Failure, DiastolicHypertension

Interventions

regadenosonMagnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Heart FailureHeart DiseasesCardiovascular DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

Spectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Results Point of Contact

Title
Marvin Kronenberg, MD
Organization
Vanderbilt University Medical Center
marvin.w.kronenberg@vumc.org
615-322-2318

Study Officials

  • Marvin W Kronenberg, MD

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Medicine and Radiology

Study Record Dates

First Submitted

August 24, 2015

First Posted

October 28, 2015

Study Start

November 1, 2015

Primary Completion

January 21, 2020

Study Completion

January 21, 2020

Last Updated

February 2, 2021

Results First Posted

February 2, 2021

Record last verified: 2021-02

Locations

US(1)