Validation de biomarqueurs du remodelage de la matrice extracellulaire chez des patients ayant une insuffisance cardiaque : Données des études EPHESUS et CARE-HF

Abstract : Background-Left ventricular (LV) remodeling is one of the determinants of heart failure (HF).Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac extracellular matrix (ECM) remodeling. This process has not been investigated in patients with congestive HF and LV systolic dysfunction after acute myocardial infarction (AMI) neither the influence of cardiac resynchronisation therapy (CRT) on such biomarkers was. The aim of this work was to evaluate collagen circulating biomarkers as assessment tools of ECM remodeling, in relation with cardiovascular prognosis: In patients from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). This trial evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo in decreasing all cause deaths rate, cardiovascular mortality or cardiovascular hospitalisations, in patients with HF after AMI complicated by LVSD and treated by standard pharmacologic therapy including angiotensin converting-enzyme inhibitors, beta-blockers and diuretics. and In patients with moderate to severe HF with LV dysfunction and cardiac dyssynchrony, already receiving standard pharmacologic therapy including angiotensin converting-enzyme inhibitors, beta-blockers and diuretics. Patients were randomly assigned to treatment with pharmacological therapy alone or with the addition of CRT in the Cardiac Resynchronization in Heart Failure (CARE-HF) trial. Methods : Serum levels of collagen biomarkers: synthesis biomarkers PIIINP and PINP, degradation marker type I collagen telopeptide (ICTP) and metalloproteinase (MMP) inhibitors (TIMP-1), were measured in 476 patients from the EPHESUS study at baseline, 6 and 9 months. Serial measurements of serum levels of PIIINP, PINP, ICTP and MMP-1 were measured in 260 patients enrolled in the CARE-HF trial at baseline, 3 and 18 months. Results : In the EPHESUS study the combination of ICTP and brain natriuretic peptide (BNP) levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization. During follow-up, levels of PINP and PIIINP were found to be consistently lower in the eplerenone group and significantly lower after 6 months. In the CARE-HF study, baseline serum concentrations of PIIINP were strongly associated with long-term mortality independently from NT-ProBNP. Serum PIIINP concentrations were similar in patients assigned to CRT or control during follow-up. Neither NT-ProBNP nor any of the tested collagen biomarkers predicted the response to CRT. Conclusion : Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients in the acute phase of HF after AMI. Eplerenone suppresses post?acute myocardial infarction collagen turnover changes and acts through ECM remodeling. Collagen biomarkers are associated with cardiovascular outcomes in acute and chronic HF settings. Fibrosis degree, as assessed by collagen biomarker circulating levels is not associated with dyssynchrony degree and with beneficial effects of CRT, which is recommended in HF patients with dyssynchrony.
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Wafae Iraqi. Validation de biomarqueurs du remodelage de la matrice extracellulaire chez des patients ayant une insuffisance cardiaque : Données des études EPHESUS et CARE-HF. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10083⟩. ⟨tel-01748321⟩

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