Serum markers of collagen turnover predict future shocks in implantable cardioverter-defibrillator recipients with dilated cardiomyopathy on optimal treatment.

Abstract

We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy (NIDC) who had received an implantable cardioverter-defibrillator (ICD) for primary prevention. Extracellular matrix alterations in NIDC might provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent sudden cardiac death (SCD). Serum C-terminal propeptide of collagen type-I, C-terminal telopeptide of collagen type-I, matrix metalloproteinase (MMP)-1, and tissue inhibitor of MMP-1 were measured as markers of collagen synthesis and degradation in 70 patients with mild to moderate symptomatic heart failure due to NIDC with left ventricular ejection fraction <35%, who received an ICD for primary prevention of SCD. Patients were evaluated for any appropriate ICD delivered therapy, whether shock or antitachycardia pacing, during a 1-year follow-up period. Appropriate device therapies were delivered in 14 of the 70 patients during the follow-up period, with antitachycardia pacing in 2, antitachycardia pacing with shocks in 4, and shocks in 8. Pre-implantation serum concentrations of C-terminal telopeptide of collagen type-I levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (0.46 +/- 0.19 ng/ml vs. 0.19 +/- 0.07 ng/ml, p < 0.001, respectively). The same was true for baseline MMP-1 and tissue inhibitor of MMP-1 (27.7 +/- 1.6 ng/ml vs. 24.1 +/- 2.5 ng/ml, p < 0.001, and 89 +/- 14 ng/ml vs. 58 +/- 18 ng/ml, p = 0.008, respectively). If the maximum benefit is to be achieved from ICD therapy in NIDC patients for the primary prevention of SCD, a more precise risk stratification is required. As extracellular matrix alterations affect the arrhythmogenic substrate in NIDC, we observed that serum markers of collagen turnover could predict arrhythmic events in ICD recipients.