Ventricular Arrhythmia Ablation in Inherited Cardiomyopathy: Phenotype Variability and Outcomes Based on Functional Genotypes.

BACKGROUND

Inherited cardiomyopathies cause ventricular tachycardia (VT) and heart failure, yet genotype-based substrate characterization is limited.

METHODS

Patients with inherited cardiomyopathy undergoing VT (n=80) or premature ventricular complex (n=25) ablation between 2010 and 2024 were evaluated for arrhythmia substrate, ablation, and heart failure outcomes.

RESULTS

Among 105 patients, the median age was 51 years, 72% were men, and the cohort comprised desmosomal (desmoplakin [DSP], 11%; non-DSP, 24%), titin (22%), lamin A/C (LMNA; 20%), sarcomeric (14%), ion-channel (5%), and cytoskeletal/Z-disk (4%) genotype groups. In the VT cohort, low-voltage substrate was predominantly septal in the LMNA (55%), titin (67%), and sarcomeric (75%) groups; both septal (75%) and lateral left ventricle (75%) in the cytoskeletal/Z-disk group; perimitral (71%) and lateral left ventricle (57%) in the DSP desmosomal group; and right ventricular free wall (91%) in the non-DSP desmosomal group. Ablation eliminated clinical VT in 90%, with noninducibility of any VT in 52 of 80 (65%) cases. VT-free survival was 51% during 3 years (1.8-6.3 years). Among recurrences, 11 of 39 (28%) patients had a single VT episode. VT-free survival was highest in the non-DSP desmosomal group and lowest in the LMNA group (66% versus 20%, P=0.03). Residual VT inducibility (hazard ratio [HR], 2 [95% CI, 1.05-3.77]) and LMNA variant (HR, 2.25 [95% CI, 1.1-4.57]) predicted recurrence. In the premature ventricular complex cohort, the burden decreased from 12% (interquartile range [IQR]=Q3-Q1, 21-8) to 3.75% (IQR 3-1, 6-1), and 17 of 25 (68%) had ≤5% burden. End-stage heart failure outcome (left ventricular assist device, transplant, or death) occurred in 29% overall and 52% in the LMNA group.

CONCLUSIONS

Genotype correlates with VT substrate. Ablation successfully reduced VT and premature ventricular complex burden; however, long-term VT recurrence was common except in non-DSP desmosomal variants. LMNA variants portend worse outcomes.