OBJECTIVES: We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with non-ischemic dilated cardiomyopathy (NIDC) implanted with an implantable cardioverter defibrillator (ICD) for primary prevention. Extracellular matrix (ECM) alterations in NIDC may provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent SCD. METHODS: Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase (MMP)-1, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were measured as markers of collagen synthesis and degradation in 70 patients with mildly to moderate symptomatic heart failure due to NIDC with LVEF <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. RESULTS: 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. Preimplantation MMP-1 levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (27.7±1.6 ng/ml vs. 24.1±2.5 ng/ml, respectively, p<0.001). The same was true for baseline serum concentrations of TIMP-1 and CITP (89±14 ng/ml vs. 58±18 ng/ml, p=0.008 and 0.46±0.19 ng/ml vs. 0.19±0.07 ng/ml, p<0.001, respectively). CONCLUSIONS: Undoubtedly, ECM alterations play a crucial role in the constitution of an arrhythmogenic substrate in NIDC and, given the availability of therapies to prevent fatal ventricular tachyarrhythmias, the quest for factors that have a very good correlation with appropriate ICD discharges in these patients is logical. Our results confirm the role of serum markers of collagen turnover as predictors of arrhythmic events in ICD recipients and could provide an auxiliary tool in this context.