protective monocytes and macrophages to limit decompensation and heart damaging

Conditions: Left Ventricular Hypertrophy

Summary: the working hypothesis is that cardiac macrophages specific for the compensated cardiac hypertrophic phase limit the progression toward the decompensated state of heart failure by promoting an inflammatory environment favouring cardiomyocyte survival and preservation of the pump function. the investigators will perform studies in human plasma and monos, cardiac tissues and macrophages to validate this hypothesis.

left ventricular hypertrophy (lvh) occurs following acute and chronic phases of ischemic heart disease as well as during pressure and/or volume overload (arterial hypertension, valvular heart disease). persistence of the pathological stimuli, i.e. pressure and/or volume overload, will ultimately lead to the decompensation of cardiac function described as heart failure (hf). hf is worldwide one of the major healthcare concerns both in terms of the loss of human life and economic burden due to the expanding costs of care for patients with this condition (ambrosy 2014). hf is associated with cardiomyocyte death, exacerbated inflammatory reaction with ensuing fibrosis and alteration of local angiogenesis. a better understanding of the mechanisms involved in the maintenance of the compensated state and in the transition to heart failure will promote the conception of new pharmacological interventions to prevent or even to reverse the transition to heart failure. based on preclinical studies, the aim of this study is to advance our knowledge of relevant mechanisms involved in this process. in an experimental setting in mice, the protective role of macrophages presenting an anti-inflammatory polarization in the progression of isuprel-induced left ventricular hypertrophy to irreversible heart failure has been recently demonstrated (keck et al., submitted). these findings in the experimental model encourage their confirmation in the clinical setting. in the latter case, new therapeutic strategies can be projected to prevent or even to reverse the transition of compensated cardiac hypertrophy to heart failure. to this purpose, the investigators will study cardiac tissue and blood sample of patients presenting compensated cardiac hypertrophy compared to those with end-stage heart failure. patients undergoing aortic valve replacement associated with septal myomectomy for aortic valve stenosis and asymmetric septal hypertrophy as well as patients with hypertrophic obstructive cardiomyopathy (hocm) undergoing septal myomectomy are included in the group of compensated cardiac hypertrophy. patients undergoing heart transplantation or implantation of mechanical life supporting system are included in the group of end-stage heart failure.

Eligibility criteria:
inclusion criteria: * older than 18 years * patients affiliated to a social security regimen * informed signed consent group 1 : compensated • symptomatic patients with severe aortic valve stenosis associated with asymmetric septal hypertrophy or patients with hypertrophic obstructive cardiomyopathy (hocm), with echocardiographic transvalvular gradient ≥ 40 mmhg associated with echocardiographic septal/posterior wall thickness ≥ 1.3 ejection fraction ≥ 50%, planned for aortic valve replacement with septal myomectomy or septal myomectomy for hocm group 2 : transition • symptomatic patients with severe aortic valve stenosis associated with asymmetric septal hypertrophy or patients with hypertrophic obstructive cardiomyopathy (hocm), with echocardiographic transvalvular gradient ≥ 40 mmhg associated with echocardiographic septal/posterior wall thickness ≥ 1.3 ejection fraction \< 50%, planned for aortic valve replacement with septal myomectomy or septal myomectomy for hocm group 3 : decompensated • end-stage heart failure on the waiting list for cardiac transplantation or undergoing ventricular assist device implantation as a bridge to transplantation exclusion criteria: * combined aortic valve replacement and coronary artery bypass grafting or mitral/tricuspid surgery * emergency operation * acute endocarditis * patient unable to give his consent * patient deprived of freedom or under legal protection (guardianship or curatorship) * pregnant or breastfeeding woman

Keywords: left ventricular hypertrophy cardiac macrophages