Background: Titin (TTN) variants are the most prevalent inherited causes of dilated cardiomyopathy (DCM). Different ventricular arrhythmia (VA) subtypes have been reported during the course of the disease that may require catheter ablation (CA).

Objective: We aimed to analyze the long-term outcomes of patients with TTN variants referred for catheter ablation of VAs and to study the prognostic relevance of the type of VA at presentation. 

Methods: Twenty-two consecutive patients with (likely) pathogenic TTN variants referred for CA of VAs from 4 centers were included (mean age 56±11years, ejection fraction 38±13%, 77% male). Detailed phenotyping was performed in all patients including Holter monitoring, cardiac imaging, and electroanatomical voltage mapping. Patients with premature ventricular contractions (PVCs)/non-sustained ventricular tachycardias (nsVTs), defined as ≥3 consecutive ventricular beats >100bpm lasting ≤30sec, were compared to patients with sustained monomorphic VTs (SMVTs). Complete procedural success was defined as non-inducibility of any VT or reduction of PVC-burden ≥80% after CA. Patients were followed for VT-free survival.

Results: Eight patients were referred for CA of PVCs/nsVTs and 14 for CA of SMVTs. Patients with SMVTs were more often male (13/14 [93%] vs. 4/8 [50%] with PVC-phenotype, P=0.02) and had more often failed AADs (VT-phenotype: 12/14 (86%) vs. PVC-phenotype: 2/8 (25%), P=0.004). Patients age (VT-phenotype: 61 [IQR 49-67] vs. PVC-phenotype: 54 [IQR 44-64], P=0.3) and baseline LVEF (VT-phenotype: 40 [IQR 26-48] vs. PVC-phenotype: 47 [IQR 29-50], P=0.5) were similar between groups. All PVCs/NSVTs showed an inferior axis deviation and the majority had a left-bundle branch block morphology with an early transition (≤V2/V3) in 11/13 or positive concordant in 2/13 with a right-bundle branch block morphology and qR pattern in V1. Ventricular tachycardias and PVCs were predominantly attributed to intramural, basal anteroseptal substrates or LV summit/subaortic involvement in 20/22 patients (91%). PVC/NSVT sites of origin were located in the left ventricular outflow tract (11/13) or posterior RVOT/mid septal wall (2/13). Non-complete procedural success was 73% (16/22; VT-phenotype: 9 [64%] vs. PVC-phenotype: 7 [88%], P=0.5). Median follow-up was 31 (22-72) months (VT-phenotype: 25 [11-36] vs. PVC-phenotype: 82 [36-96], P=0.001). One patient was lost of follow-up and therefore excluded from outcome analysis. Eleven patients (55%) experienced SMVT during follow-up: 11/13 (85%) VT-phenotype vs. 0/8 (0%) PVC-phenotype, P<0.001. In addition, 5/13 patients with the VT-phenotype died (38%). Importantly, the type of arrhythmia at referral (SMVT vs. nsVT/PVC) was associated with a worse long-term VT-free survival, P<0.001.

Conclusion: Acute procedural success of CA for both VAs subtypes in TTN DCM is low, likely due to their predominant basal anteroseptal or LV summit origin. However, long-term survival free of life-threatening VAs was excellent in patients presenting with PVCs/nsVTs but poor in those with a VT phenotype, suggesting that MSVT but not PVCs/nsVT are an important prognostic marker.