Exercise Intolerance in Heart Failure

Exercise Intolerance in Heart Failure: the Role of Altered Cardiac and Skeletal Muscle Energetics

The investigators are studying whether metabolic abnormalities in cardiac and skeletal muscle in patients with heart failure with preserved ejection fraction (HFpEF) are associated with debilitating exercise intolerance.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Normal Ejection Fraction

Detailed Description

This research is being done to better understand why patients with heart failure have difficulty exercising and performing some activities of daily living. Heart muscle and skeletal muscle (in the legs and arms) depend on normal metabolism (the conversion of foods to chemical fuel) to function properly. Investigators will measure metabolites in the heart and leg muscles, including the levels of high energy phosphates and lipids (fats) using magnetic resonance (MR) techniques. High-energy phosphates serve as a source of energy, which is used by the heart and skeletal muscle for contraction. Magnetic resonance uses magnetic fields to measure the levels of these substances.

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Matthew Kauffman; Phone Number: 443-287-3475; Email: mkauffm7@jhmi.edu
• Study Contact Backup: Name: Tricia Steinberg, RN, MSN; Phone Number: 443-287-3469; Email: asteinb3@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Tricia Steinberg, MSN; Phone Number: 443-287-3469; Email: asteinb3@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

People with and without heart failure will be enrolled.

Description

Inclusion Criteria:

• Patients of either gender who are greater than 21 years of age (no upper age limit),
• Permission of patient's clinical attending physician,
• Previous clinical diagnosis of HF with current New York Heart Association (NYHA) Class II-III symptoms for at least 1 month,
• Left ventricular ejection fraction (EF) >50% by echocardiography, MRI, CT or x-ray or nuclear ventriculography within prior 12 months,
• Stable medical therapy for at least 30 days (no addition or removal or major (>100%) dose change of Renin-Angiotensin-Aldosterone System (RAAS) antagonists, beta-blockers, or calcium channel blockers for hypertension).

Exclusion Criteria:

• Unable to understand the risks, benefits, and alternatives of participation and give meaningful consent,
• Contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips) or indwelling metallic projectiles,
• Significant valvular abnormalities,
• Pregnant women (women of childbearing potential will undergo blood or urine pregnancy testing),
• History of clinical CAD or significant epicardial coronary disease (>50% stenosis) in major coronary artery by x-ray or CT angiography unless (a) the patient underwent prior successful revascularization with percutaneous coronary angioplasty within the prior three years and (b) there are no residual lesions of >50% on the most recent coronary angiographic study.
• History of infiltrative cardiomyopathy or constrictive pericarditis,
• Cor pulmonale,
• Significant pulmonary disease,
• Estimated glomerular filtration rate (eGFR) <20ml/min,
• Any condition other than HF which could limit the ability to perform a 6MW or cardiopulmonary exercise test (CPET) test (e.g., critical peripheral vascular disease, significant orthopedic or neurological conditions),
• Any diseases other than HF which are likely to significantly alter the patient's global perception of status or quality of life over a period of 6 months.
• Significant peripheral vascular disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
HFpEF; Participants with Heart Failure with Preserved Ejection Fraction
HFrEF; Participants with Heart Failure with Reduced Ejection Fraction
Hypertensive Subjects; Participants with Hypertension
Healthy Subjects; Participants without heart failure and without commodities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle mitochondrial function	Maximal oxidative capacity of leg muscle measured by 31P Magnetic Resonance Spectroscopy (MRS)	Baseline
Skeletal muscle energetic decline during exercise	Creatine phosphate rate of decline (umol/g/min) during plantar flexion exercise measured by 31P MRS	Baseline
Cardiac muscle energetics	Cardiac muscle phosphocreatine (PCr)/ adenosine triphosphate (ATP) and creatine kinase(CK) flux (umol/g/s) measured by 31P MRS	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walk test	Six minute walk distance (m)	Six months
Cardiopulmonary exercise testing (CPET)	Peak whole-body oxygen consumption rate during exercise	Six months
Clinical heart failure outcome as assessed by number of hospitalizations		Two years
Clinical heart failure outcome as assessed by time to cardiovascular death		Two years
Clinical heart failure outcome as assessed by overall mortality		Two years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert G Weiss, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure with Preserved Ejection Fraction; HFpEF
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: IRB00129787; R01HL061912 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No