Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI in Heart Failure

University of Campinas, Brazil

Status: Unknown

Conditions: Heart Failure

Treatments: Other: Local strengthening exercises; Other: Stretching exercises; Other: Aerobic exercise in treadmill

Study type: Interventional

Funder types: Other

Identifiers

NCT03084679

HF-CMR-53967215800005404

FAPESP 2015/15402-2 (Other Grant/Funding Number)

Details and patient eligibility

About

The investigators hypothesised that novel MRI metrics derived from myocardium post-gadolinium T1 mapping analysis will improve the current knowledge about the role interstitial fibrosis and cardiomyocyte hypertrophy in the development of left ventricular (LV) remodelling and clinical Heart Failure (HF). The investigators believe that these recently described variables will be associated with prognostically important indices in HF development.

Full description

Cardiac hypertrophy is one of the earliest manifestations of myocardial disease, representing a modifiable, prognostic response to hemodynamic stimuli across physiologic (e.g., exercise) and pathologic states (e.g., hypertension, aortic stenosis). The extent of myocardial hypertrophy is determined by a combination of cardiomyocyte size and extracellular volume (ECV) expansion/interstitial fibrosis: while physiologic (exercise-induced) hypertrophy reflects mostly reversible cardiomyocyte hypertrophy, pathologic hypertrophy (e.g., in heart failure) is a combination of both interstitial fibrosis (potentially irreversible) and cardiomyocyte hypertrophy (reversible). Current methods to delineate the potential for LV reverse remodeling (e.g., natriuretic peptides and echocardiographic or clinical markers) detect primarily advanced disease, missing a critical opportunity to intervene and follow patients at an early disease phase where myocardial pathology may be reversible. Therefore, establishing novel, quantitative metrics of myocardial tissue phenotype that define a transition from hypertrophy to fibrosis, and then to irreversible LV remodeling/dysfunction may facilitate targeting therapies at a modifiable stage of disease in HF. The investigator's group has recently extended cardiac T1 mapping MRI techniques to quantify the intracellular lifetime of water (τic) serially as an index of cardiomyocyte diameter, validating this technique histologically in mouse models of pressure overload.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age> 18 years
• Functional limitation (New York Heart Association Class II or worse)
• No contraindication to exercise (American College of Cardiology / American Heart Association criteria)
• Eligibility to take MRI (absence of metallic devices, and glomerular filtration rate > 40ml / min / 1.73m2, etc.)
• Prior diagnosis of Heart Failure (by the Framingham criterion)
• Therapy with diuretic and euvolemia state (evaluated by cardiologist and cardiopulmonary exercise testing)
• Transthoracic echocardiogram

Exclusion criteria

• Severe ischemia in any stress test
• Hypertrophic cardiomyopathy or any infiltrative heart disease
• Chronic obstructive pulmonary disease , pulmonary hypertension (Pulmonary artery pressure> 60mmHg)
• Severe left or right valve disease.
• Pacemaker or implantable cardioverter defibrillator
• Myocardial infarction or revascularization in 3 months
• Anemia (hemoglobin <10 grams / dl) until 1 month before cardiopulmonary exercise testing

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 4 patient groups

Conventional Clinical Care - HFpEF

No Intervention group

Description:

Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.

Supervised Exercise Training- HFpEF

Other group

Description:

Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.

Treatment:

Other: Stretching exercises

Other: Local strengthening exercises

Other: Aerobic exercise in treadmill

Conventional Clinical Care - HFrEF

No Intervention group

Description:

Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.

Supervised Exercise Training - HFrEF

Other group

Description:

Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.

Treatment:

Other: Stretching exercises

Other: Local strengthening exercises

Other: Aerobic exercise in treadmill