Fibrosis, myocardial deformation and biomarkers in hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM) is a rare genetic disease (1), whose phenotypic expression is found in less than 1/1000 people, mainly linked to a mutation of a protein of the sarcomere (14 genes and 400 mutations identified nowadays). HCM occurs in about 50% of cases in young adults under the age of 30 years. Progress in the identification of the responsible mutation does not have allowed significant advances for the clinical management and evaluation of the prognosis of patients with HCM. In fact, the link between genotype and phenotype is poor in the HCM, so that identification of the mutation in approximately 60% of patients does not properly characterize the disease and its evolution. It is therefore necessary to identify new markers to better characterize HCM patients. Myocardial fibrosis could be a severity marker of the HCM but its consequences and determinants are little known or unknown.

The objective of this work is to identify the determinants and consequences of myocardial fibrosis in HCM, particularly the relationship between fibrosis and left ventricular dysfunction assessed by the analysis of myocardial deformation and between fibrosis and heart failure. The study of fibrosis, which concerns 30 to 70% of patients and replace 1 to 70% of the myocardial tissue, is made possible in vivo by analysis of delayed enhancement gadolinium in MRI. This work aims to study the relationship between myocardial fibrosis, heart function assessed by myocardial deformation, heart failure, and biological profile (proteomics) of patients at rest and after exertion.

This study is an observational research. Indeed, all examinations are done as part of usual care patients. Only additional tubes of blood are collected in the initial biological assessment.

Inclusion Criteria:

• Patients with known HCM or recently discovered with a wall thickness greater than or equal to15 mm without family background or> 13 mm in an HCM family context in the absence of other causes found capable of producing such a degree of hypertrophy
• HCM apparently linked to a mutation of a protein of the sarcomere (identified mutation or absence of other causes of hypertrophy found when the mutation search was not performed or was unsuccessful)
• Control subjects will be patients greater than or equal to 18 years without known cardiovascular disease or that may affect their ability to function, addressed to achieve a stress echocardiography for assessment of atypical symptoms, with a low pretest probability of coronary artery disease, and accepting blood sample before and after exercise. They do not realize Holter ECG or cardiac MRI as part of the study.

Exclusion Criteria:

• Refusal of the patient
• Age < 16 years old
• Valvulopathy associated significant (grade 3 or 4 regurgitation, or severe stenosis) other than mitral insufficiency
• Defibrillator, pacemaker, or other cons-indication or intolerance to achieving MRI
• Unable to receive clear information (patient's intellectual default)
• Under protective measure of justice

Patients of both sex over 16 year-old with HCM