Extracellular Cardiac Matrix Biomarkers in Patients With Acute Myocardial Infarction Complicated by Left Ventricular Dysfunction and Heart Failure

Abstract

Background-Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. Methods and Results-In a substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (Pϭ0.039) and 3.03 (Pϭ0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months. Conclusions-Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post-acute myocardial infarction collagen turnover changes.

Features of Cardiac Remodeling, Associated With Blood Pressure and Fibrosis Biomarkers, Are Frequent in Subjects With Abdominal Obesity

“…15 Cardiac remodeling index (CRI), indicating concentric LV remodeling, is represented by the ratio of LV mass/LV end-diastolic volume. 16 LV hypertrophy, assessed by MRI, was defined according to Alfakih 19,20 with interassay variations <9.8%.…”

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

“…[1][2][3] These structural alterations lead to cardiac dysfunction and overt heart failure in patients with AMI, and ventricular remodeling is thought to be one of the markers for late mortality and other serious clinical events after AMI. 4,5 Recently, oxidative stress and inflammation have been shown to contribute to LV remodeling after AMI. 6 -8 Indeed, oxidative stress and inflammation are involved in apoptotic cell death of myocytes and myocardial fibrosis, thus promoting LV remodeling after AMI.…”

Aplicaciones y proyecciones de los antagonistas del receptor de mineralocorticoides en el tratamiento de patologías cardiovasculares

“…Además, se demostró una correlación positiva entre la concentración plasmática de algunos marcadores de dichos procesos y la concentración de aldosterona 15 . Estudios experimentales han señalado que los ARM son capaces de revertir los efectos deletéreos de aldosterona a nivel cardiaco disminuyendo significativamente la generación de especies reactivas de oxígeno, procesos inflamatorios y el remodelamiento de la matriz extracelular [16][17][18] .…”

“…La activación del RM induce hipertrofia y fibrosis miocárdica de forma temprana 17,18 , ambos fenómenos responsables de una disminución de la compliance e incapacidad de relajación ventricular observada en la insuficiencia cardiaca diastólica (ICD). Ensayos clínicos en pacientes con IC y disfunción sistólica muestran mejoras de la función diastólica dentro de sus hallazgos ecocardiográficos 23 .…”