Relation between non-sustained ventricular tachycardia and major arrhythmic events in patients with dilated cardiomyopathy caused by titin truncating variants

Abstract

Abstract Background Truncating titin variants (TTNtv) are the most frequent monogenetic cause of dilated cardiomyopathy (DCM). Current data suggest that nonsustained ventricular arrhythmia is common in patients with TTVtv but its relation to the risk of major arrhythmic events (MAE) is uncertain. Purpose To investigated the relationship between NSVT recorded on Holter ECG or implanted device and MAE in patients with DCM. Methods We retrospectively studied consecutively evaluated patients with DCM (left ventricle ejection fraction (LVEF) below 50%) on echocardiography and a pathogenic TTNtv. Patients with obstructive coronary artery disease, valvular disease, ventricular tachycardia ablation during follow-up time and follow-up less than one month were excluded. Survival was modelled from the initial Holter or device implantation. NSVT was defined as ≥3 consecutive ventricular beats at a rate >120 beats per minute, lasting for <30 s. MAE was defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), sudden cardiac death, implantable cardioverter defibrillator (ICD) treated ventricular arrhythmias (appropriate shock and ATP). The clinical endpoint was MAE (sustained VT, VF, sudden cardiac death, ICD shocks and ATP) and multivariable analysis was performed using Cox proportional hazards models. Event-free survival probabilities were estimated using the Kaplan-Meier method, and comparisons of Kaplan-Meier curves were made using log-rank tests. Results The cohort comprised 58 men and 30 women [mean age 49 ± 15 years; mean follow-up 3.5 ± 1.8 years]. Symptoms were NYHA class I in 56 patients, class II in 25 patients, class III in 7 patients and class IV in none. Holter ECGs were performed in 77 patients, 41 of whom had NSVT. Twenty five patients had pacemaker/ICD in situ; 14 had NSVT. Six patients had MAE; 4 with NSVT. Univariate analysis association between MAE and LVEF ≤35% (hazard ratio (HR), 9.03; 95% confidence interval (CI), 1.49-54.71; P=0.017), prolonged (>8 beats) NSVT (HR, 6.71; 95% CI, 1.22-36.98; P=0.029) and fast (>200 bpm) NSVT (HR, 5.09; 95% CI, 1.02-25.47; P=0.048). Kaplan-Meier showed similar differences in freedom from MAE (LVEF ≤35%; P=0.004, long NSVT; P=0.025, fast NSVT; P=0.031). Conclusion Fast and prolonged NSVT is associated with a higher risk of MAE in patients with TTNtv.Characteristics at the beginningSurvival probability for freedom