assessment of the relations between endothelial and venous dysfunctions and left ventricular obstruction in genetic hypertrophic cardiomyopathies

Conditions: Hypertrophic Cardiomyopathy; Endothelial Dysfunction

Summary: left ventricular obstruction is an invalidating complication of hypertrophic cardiomyopathies (hcm), and endothelial dysfunction has also been observed in these pathologies. however, the relation between obstruction and endothelial and venous dysfunctions has not been previously studied. the main objective is to investigate the relations between endothelial and venous dysfunctions and symptomatic left ventricular outflow-tract obstruction in hcm patients.

hypertrophic cardiomyopathies (hcm) secondary to sarcomeric gene mutation or to anderson-fabry disease can be complicated by left ventricular (lv) outflow-tract obstruction responsible of disabling exercise symptoms. lv outflow-tract obstruction is a complex, multifactorial and dynamical phenomenon influenced by the degree of lv hypertrophy but also by mitral valve elongation and hemodynamical components including venous return (lv preload). the clinical and research team of dr réant, responsible of the bordeaux competence center in hereditary or rare cardiomyopathies, has recently demonstrated that lv outflow-tract obstruction can also be influenced by the conditions of realization of exercise echocardiography tests (position: upright versus supine, type: bicycle versus treadmill), and by an abnormal venous return capacity. in parallel, it has also been demonstrated, by other research teams, that hcm can be associated to endothelial and microvascular peripheral dysfunctions. however, to date, the relation between these two elements, and with sudden cardiac death risk, have not been previously studied. the tests which will be performed during normal recommended follow-up of the hcm patients will be: brain natriuretic peptide (bnp) blood sample test, electrocardiogram (ecg), holter ecg, echocardiography at rest and during exercise. the tests realized in addition will be: * air venous plethysmography: non invasive, and non painful test evaluating different parameters of venous filling by inflation of an armband around the leg, upright positioning, flexion-extension of the leg. total duration estimated at 30-45 minutes. * upper member arterial doppler echography with analysis of flow mediated dilatation (fmd) : measurement of the evolution of brachial artery diameter before and after inflation of a armband during 5 minutes. non invasive and non painful test, duration 30 minutes.. * endothelial function biomarkers: blood sample test, 5 minutes. no follow-up is required for this study.

Eligibility criteria:
inclusion criteria: * patients and volunteers: * adults (age ≥18 years), male or female, * for female in age, efficient contraception will be required and a negative pregnancy test will be required, * signed informed consent form will required for each included subject after having read the information note, * affiliated to the national social security system, * patients: .patients diagnosed to have hcm secondary to sarcomeric mutation or to fabry disease, symptomatic (dyspnea on exertion and/or chest pains during exercise), * healthy volunteers: * subjects without known cardiac disease, * no smokers. exclusion criteria: * patients and volunteers: * no cardiac pathology reducing life expectancy to less than 12 months (cancer), * unbalanced arterial hypertension (systolic \>160 mmhg and/or diastolic \>120 mmhg), * pregnancy or breastfeeding, * major obesity \> 140 kg, * impossibility or refusal to give or sign the consent form, * subject in period of exclusion relative to an other protocol, * subject deprived of liberty by judicial or administrative decision, * major protected by the law * patients: * atrial fibrillation at the time of inclusion * valvulopathy with severity greater than moderate.

Keywords: hypertrophic cardiomyopathy endothelial dysfunction venous return left ventricular outflow-tract obstruction sudden cardiac death risk