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Extracellular Matrix Turnover Biomarkers Predict Long-Term Left Ventricular Remodeling After Myocardial Infarction: Insights From the REVE-2 Study
Study Questions:
What is the predictive ability of biomarkers of myocardial fibrosis measurements 1 month after myocardial infarction (MI) for left ventricular (LV) remodeling?
Methods:
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. B-type natriuretic peptide (BNP) as well as biomarkers of myocardial fibrosis (ICTP: type 1 collagen telopeptide; PINP: aminoterminal propeptide of type I procollagen; PIIINP: aminoterminal propeptide of type III procollagen) were measured 1 month after MI in 218 patients. Factors associated with LV remodeling, defined as an increase >20% of LV end-diastolic volume 12 months after MI, were first identified using univariate (after logarithmic transformation for collagen biomarkers), then by multivariate logistic regression. Event-free survival was illustrated using Kaplan-Meyer curves for clinical outcome.
Results:
In multivariate analysis, PIIINP/ICTP ratio ≤1 (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02-3.39; p = 0.043) 1 month after MI, and BNP >100 pg/ml (OR, 2.35; 95% CI, 1.28-4.31; p = 0.006) were associated with a pejorative LV remodeling, whereas LV ejection fraction at discharge (per 5% increment: OR, 0.78; 95% CI, 0.65-0.94; p = 0.01) was independently associated with lower rates of detrimental LV remodeling at 12 months. Patients with high BNP and PIIINP/ICTP 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/216 patients; p = 0.0001) during a 3-year follow-up.
Conclusions:
The authors concluded that low PIIINP/ICTP ratio (≤1) at 1 month, in addition to BNP and LV ejection fraction, is predictive of detrimental LV remodeling.
Perspective:
The results of the present study suggest that myocardial fibrosis turnover (as assessed by the PIIINP/ICTP ratio) plays an important role in LV remodeling after a first anterior wall MI despite optimal management with initial reperfusion therapy and use of optimal medical treatment at hospital discharge. Low PIIINP/ICTP ratio (≤1), at 1 month, was predictive of detrimental LV remodeling at 12 months and may also predict, along with BNP and LV ejection fraction, cardiovascular deaths and hospitalizations for worsening heart failure at 3 years. While PIIINP/ICTP ratio could be a good marker to detect patients prone to develop LV remodeling after an initial Q-wave anterior MI, additional studies are needed to evaluate early interventions on myocardial fibrosis turnover after MI to prevent LV remodeling.
Keywords: Myocardial Infarction, Extracellular Matrix, Collagen Type I, Biomarkers, Troponin I, Heart Failure, Procollagen, Natriuretic Peptide, Brain
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