This Article Full Text Full Text (PDF) All Versions of this Article: 119/18/2471    most recent CIRCULATIONAHA.108.809194v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Iraqi, W. Articles by Zannad, F. Search for Related Content PubMed PubMed Citation Articles by Iraqi, W. Articles by Zannad, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Attack Heart Failure Hazardous Substances DB SPIRONOLACTONE Related Collections Other myocardial biology Congestive Cardiovascular Pharmacology Acute myocardial infarction Related Article

(Circulation. 2009;119:2471-2479.)
© 2009 American Heart Association, Inc.

Heart Failure

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

Insights From the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) Study

Wafae Iraqi, PharmD; Patrick Rossignol, MD, PhD; Michael Angioi, MD; Renaud Fay, PharmD; Josette Nuée, PhD; Jean Marie Ketelslegers, MD, PhD; John Vincent, MD; Bertram Pitt, MD; Faiez Zannad, MD, PhD

From CHU de Nancy, Hôpital Jeanne d’Arc, Dommartin-lès-Toul, France (W.I., P.R., R.F., J.N., F.Z.); Inserm, Centre d’Investigation Clinique de Nancy CIC-P 9501, Dommartin-lès-Toul, France (W.I., P.R., M.A., R.F., J.N., F.Z.); Nancy-Université, Faculté de Médecine, Vandoeuvre-les-Nancy, France (W.I., P.R., M.A., R.F., J.N., F.Z.); Inserm U684, Nancy Université, Nancy, France (W.I., P.R., F.Z.); Cliniques Universitaires St-Luc, Department of Internal Medicine, School of Medicine, Brussels, Belgium (J.M.K.); Pfizer Inc, New York, NY (J.V.); Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor (B.P.); and Department of Cardiology, Heart Failure and Hypertension Unit, CHU Nancy, Vandoeuvre les Nancy, France (M.A., F.Z.).

Correspondence to Faiez Zannad, CIC Inserm-CHU, Hôpital Jeanne d’Arc, 54200 Dommartin les Toul, France. E-mail f.zannad{at}chu-nancy.fr

Received July 29, 2008; accepted March 11, 2009.

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 (P=0.039) and 3.03 (P=0.002), 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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 119: 2417-2419. [Extract] [Full Text]