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

Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure: Implication on Early Remodeling and on the Transition to Heart Failure

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.

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.

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