Abstract Background/Introduction Arrhythmogenic right ventricular cardiomyopathy is a heritable heart muscle disease characterized by progressive substitution of the myocardium with fibrous and fatty tissue, which is the substrate for ventricular arrhythmia, systolic dysfunction and heart failure. Determining the optimal time for heart transplantation is challenging and, therefore, finding risk factors for disease progression is needed. Purpose The purpose of the study was to evaluate the role of markers of myocardial fibrosis sST2, Gal-3, MMP-2 and MMP-9, as well as NT-proBNP and hsTnT, in predicting major adverse outcomes in ARVC. Moreover, we aimed to identify other risk factors for developing end-stage heart failure. Methods We included 91 patients with the definite diagnosis of ARVC according to the 2010 Task Force Criteria (59 males, mean age of 47±16 years). Patients were interviewed for their medical history, electrocardiography and echocardiography were performed and plasma levels of selected biomarkers were measured. Thereafter, subjects were followed for the occurrence of the composite endpoint of death or heart transplantation (HTx) and major arrhythmic events defined as ventricular fibrillation, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator intervention. Results During the median follow-up of 36,4 months [29,8–41,2], 13 subjects (14%) reached the composite endpoint of death or HTx and 27 subjects (30%) experienced major arrhythmic event. Among the studied biomarkers, significantly higher levels of sST2, MMP-2, NT-proBNP and hsTnT were found in patients who achieved the composite endpoint. The remaining prognostic factors are shown in Table 1. In the multivariate analysis, three factors turned out to be significant: higher NT-proBNP levels (the cut-off point ≥890.3 pg/m), greater right ventricular end-diastolic area (the cut-off point ≥39.0 cm2) and history of atrial tachycardia. Kaplan-Meyer survival analysis depending on the number of predictors is presented in Figure 1. None of the biomarkers predicted major arrhythmic events. Conclusions NT-proBNP ≥890.3 pg/ml, RV area ≥39.0 cm2 and history of atrial tachycardia are independent risk factors for death or HTx in ARVC. Among the studied biomarkers, higher levels of sST2, MMP-2, NT-proBNP and hsTnT were observed in patients who reached the composite endpoint. Biomarkers had no value in predicting ventricular arrhythmias. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology, Warsaw, Poland