Extracellular matrix turnover biomarkers predict long-term left ventricular remodeling after myocardial infarction: insights from the REVE-2 study

Circ Heart Fail. 2013 Nov;6(6):1199-205. doi: 10.1161/CIRCHEARTFAILURE.113.000403. Epub 2013 Aug 27.


Background: Extracellular matrix turnover plays a key role in wound repair after myocardial infarction (MI). The aim of the study was to evaluate whether biomarkers of myocardial fibrosis measurements 1 month after MI may predict left ventricular (LV) remodeling.

Methods and results: This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Echocardiographic studies were performed at hospital discharge and 12 months after MI. Brain natriuretic peptide as well as biomarkers of myocardial fibrosis (type 1 collagen telopeptide, aminoterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen) were measured 1 month after MI in 218 patients. In multivariate analysis, aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1 (odds ratio [95% confidence interval], 1.86 [1.02-3.39]; P=0.043) 1 month after MI and brain natriuretic peptide >100 pg/mL (2.35 [1.28-4.31]; P=0.006) were associated with a pejorative LV remodeling, whereas LV ejection fraction at discharge (per 5% increment; 0.78 [0.65-0.94]; P=0.01) was independently associated with lower rates of detrimental LV remodeling at 12 months. Patients with high brain natriuretic peptide and aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1, measured 1 month after MI, had the highest risk of developing a primary composite event (cardiovascular death or hospitalization for worsening heart failure; 14 events per 216 patients; P=0.0001) during a 3-year follow-up.

Conclusions: Myocardial fibrosis turnover after MI is associated with LV remodeling. Low aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio (≤1) at 1 month is predictive, in addition to brain natriuretic peptide and LV ejection fraction, of detrimental LV remodeling as well as cardiovascular deaths and hospitalizations for heart failure.

Keywords: collagen type I trimeric cross-linked peptide; myocardial fibrosis; myocardial infarction; procollagen type III-N-terminal peptide; ventricular remodeling.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Disease Progression
  • Echocardiography
  • Electrocardiography
  • Extracellular Matrix Proteins / blood*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / physiopathology
  • Prognosis
  • Prospective Studies
  • Time Factors
  • Ventricular Function, Left / physiology*
  • Ventricular Remodeling / physiology*


  • Biomarkers
  • Extracellular Matrix Proteins