Exercise Intolerance in Heart Failure

Recruiting

• Conditions: Heart Failure With Normal Ejection Fraction

• Registration Number: NCT03775577
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

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 Timeline

• Study Start: 2017-04-01
• Study First Submitted: 2018-11-01
• Study First Submitted QC: 2018-12-11
• Study First Posted: 2018-12-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-12
• Primary Completion: 2027-08
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States