Exercise Intolerance in Heart Failure

Heart Failure With Normal Ejection Fraction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03775577
• Other study ID #: IRB00129787
• Secondary ID: R01HL061912
• Status: Recruiting
• Start date: April 1, 2017
• Est. completion date: March 2025

Study information

• Verified date: August 2023
• Source: Johns Hopkins University
• Contact: Matthew Kauffman
• Phone: 443-287-3475
• Email: mkauffm7[@]jhmi.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Normal Ejection Fraction

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skeletal muscle mitochondrial function	Maximal oxidative capacity of leg muscle measured by 31P Magnetic Resonance Spectroscopy (MRS)	Baseline
Primary	Skeletal muscle energetic decline during exercise	Creatine phosphate rate of decline (umol/g/min) during plantar flexion exercise measured by 31P MRS	Baseline
Primary	Cardiac muscle energetics	Cardiac muscle phosphocreatine (PCr)/ adenosine triphosphate (ATP) and creatine kinase(CK) flux (umol/g/s) measured by 31P MRS	Baseline
Secondary	Six minute walk test	Six minute walk distance (m)	Six months
Secondary	Cardiopulmonary exercise testing (CPET)	Peak whole-body oxygen consumption rate during exercise	Six months
Secondary	Clinical heart failure outcome as assessed by number of hospitalizations		Two years
Secondary	Clinical heart failure outcome as assessed by time to cardiovascular death		Two years
Secondary	Clinical heart failure outcome as assessed by overall mortality		Two years