The Relevance of the Type of Ventricular Arrhythmia in Titin-Related Dilated Cardiomyopathy: A Multicenter Study

Background: Truncating titin variants (TTNtvs) are the most prevalent cause of inherited dilated cardiomyopathy. Occurrence of different ventricular arrhythmia (VA) subtypes, including premature ventricular complexes (PVCs), nonsustained ventricular tachycardia (NSVT), and sustained monomorphic VT (SMVT), has been reported. Objectives: The aim of this study was to analyze the prognostic relevance of distinct VA subtypes among TTNtv carriers and their underlying arrhythmogenic substrates. Methods: Twenty-two TTNtv carriers referred for ablation of SMVT (n = 14) or frequent PVCs (n = 8) from 5 centers were included (mean age 56 ± 11 years; left ventricular ejection fraction 38% ± 13%; 77% male). Detailed phenotyping was performed, including Holter monitoring, cardiac imaging, and electroanatomical mapping. Patients were followed up for a median of 44 months. Results: Demographic characteristics, including age, comorbidities, and left ventricular ejection fraction, were similar. NSVTs were frequent in both groups but faster in patients with SMVT (cycle length: 350 milliseconds [Q1-Q3: 315-403 milliseconds] vs 427 milliseconds [Q1-Q3: 395-469 milliseconds]). Although substrates for SMVT extended in a basal ring–like fashion with septal predominance, PVC sites of origin were limited to the basal anterior left ventricular segment. In the SMVT group, acute complete procedural success was achieved for 36%; during follow-up, 86% had recurrent VT, and 50% died of progressive heart failure. In the PVC group, complete abolition of PVCs was achieved in only 13%; at 3 months, median PVC burden was 1%, and there were no deaths or sustained VT during follow-up. VA subtype and NSVT cycle length were associated with mortality and poor VT-free survival. Conclusions: In TTNtv carriers, SMVTs but not frequent PVCs are associated with high mortality due to heart failure. Occurrence of SMVT may identify a subgroup at risk for rapid, progressive adverse remodeling. The prognostic significance of different VA subtypes needs to be confirmed in a larger cohort.