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

Not Applicable
Conditions
Heart Failure
Interventions
Other: Aerobic exercise in treadmill
Other: Local strengthening exercises
Other: Stretching exercises
Registration Number
NCT03084679
Lead Sponsor
University of Campinas, Brazil
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
90
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Supervised Exercise Training - HFrEFAerobic exercise in treadmillHeart 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.
Supervised Exercise Training- HFpEFLocal strengthening exercisesHeart 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.
Supervised Exercise Training - HFrEFLocal strengthening exercisesHeart 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.
Supervised Exercise Training - HFrEFStretching exercisesHeart 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.
Supervised Exercise Training- HFpEFAerobic exercise in treadmillHeart 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.
Supervised Exercise Training- HFpEFStretching exercisesHeart 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.
Primary Outcome Measures
NameTimeMethod
Myocardial remodeling assessed by CMR in rehabilitation vs usual care.4 months

Investigate whether rehabilitation compared to usual care is associated with significant favorable myocardial remodeling assessed by CMR determination of ECV.

Secondary Outcome Measures
NameTimeMethod
Change in left ventricular mass (absolute/index)4 months

Left ventricular mass absolute (g) and index (g/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in quality of life4 months

Quality of life will be evaluated by numerical score of Minnesota Questionnaire.

Patients will performed the Minnesota Questionnaire at baseline and after 4 months of the intervention.

Change in left ventricular diastolic volume (absolute/index)4 months

Left ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in right ventricular systolic volume (absolute/index)4 months

Right ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in left ventricular systolic volume (absolute/index)4 months

Left ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in left ventricular stroke volume (absolute/index)4 months

Left ventricular stroke volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in functional capacity4 months

VO2max will be evaluated by cardiopulmonary test. Patients will performed the cardiopulmonary test at baseline and after 4 months of the intervention.

Change in left ventricular ejection fraction4 months

Left Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in late gadolinium enhancement4 months

Late gadolinium enhancement (LGE) will be determined by cardiac magnetic resonance using a previously describe inversion recovery sequence after 10-15 minutes of a cumulative dose of 0,2 mmol/kg of gadolinium diethylenetriamine pentaacetic acid. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in diastolic dysfunction assessed by transthoracic echocardiogram4 months

Change in parameters of diastolic dysfunction assessed before and after the intervention.

Change in intracellular lifetime of water (τic - a marker of cardiomyocyte hypertrophy)4 months

τic will be determined by cardiac magnetic resonance T1 measurements acquired before and after administration of gadolinium diethylenetriamine pentaacetic acid (0,2mmol/kg), at 2 different time points (baseline and 4-moths after the intervention)

Change in right ventricular ejection fraction4 months

Right Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in right ventricular diastolic volume (absolute/index)4 months

Right ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in right ventricular stroke volume (absolute/index)4 months

Right ventricular stroke volume (absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in cardiac sympathetic function4 months

Change in cardiac sympathetic function assessed by cardiac uptake of metaiodobenzylguanidine (MIBG) labeled with I-123. Patients will performed the MIBG study at baseline and after 4 months of the intervention.

Change in LV mass/volume ratio4 months

LV mass/volume ratio (g/mL) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP)4 months

Change in NT-proBNP with the intervention.

Trial Locations

Locations (1)

University of Campinas

🇧🇷

Campinas, São Paulo, Brazil

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