Ventricular Arrhythmia Ablation in Inherited Cardiomyopathy: Phenotype Variability and Outcomes Based on Functional
Arian Afzalian1, Alireza Oraii1, Timothy M Markman1
1Section of Cardiac Electrophysiology, Cardiovascular Division, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA.
Journal of the American Heart Association
|July 17, 2026
Summary
Genetics influence ventricular tachycardia (VT) substrate in inherited cardiomyopathies. Ablation reduces VT burden, but recurrence is common, especially in LMNA variants, while non-DSP desmosomal variants show better outcomes.
Area of Science:
- Cardiology
- Genetics
- Electrophysiology
Background:
- Inherited cardiomyopathies are a significant cause of ventricular tachycardia (VT) and heart failure.
- Current understanding of VT substrate based on genetic diagnosis is limited.
Purpose of the Study:
- To characterize VT substrate in inherited cardiomyopathies based on genotype.
- To evaluate the efficacy of ablation for VT and premature ventricular complexes (PVCs) in these patients.
- To assess long-term outcomes including VT recurrence and heart failure progression.
Main Methods:
- Retrospective analysis of 105 patients with inherited cardiomyopathy undergoing VT (n=80) or PVC (n=25) ablation.
- Evaluation of arrhythmia substrate, ablation success, VT recurrence, and heart failure outcomes.
- Genotyping included desmosomal (DSP, non-DSP), titin, lamin A/C (LMNA), sarcomeric, ion-channel, and cytoskeletal/Z-disk variants.
Main Results:
- VT substrate location varied by genotype, with LMNA, titin, and sarcomeric groups showing predominantly septal substrate, cytoskeletal/Z-disk involving septal and lateral LV, DSP involving perimitral and lateral LV, and non-DSP desmosomal involving the RV free wall.
- Ablation eliminated clinical VT in 90% of cases, with 65% achieving noninducibility.
- Three-year VT-free survival was 51%, with highest survival in non-DSP desmosomal and lowest in LMNA groups (66% vs. 20%, P=0.03).
- LMNA variants and residual VT inducibility predicted recurrence.
- PVC burden decreased significantly post-ablation.
- End-stage heart failure occurred in 29% overall, and 52% in the LMNA group.
Conclusions:
- Genotype is a significant determinant of VT substrate location in inherited cardiomyopathies.
- Ablation effectively reduces VT and PVC burden, but long-term VT recurrence remains a concern, particularly for LMNA variants.
- Non-DSP desmosomal variants demonstrate superior long-term VT-free survival compared to other genotypes.
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