Mutation in a non-desmosomal gene is associated with poor outcome of endo-epicardial ventricular tachycardia ablation in patients with nonischaemic cardiomyopathy

Abstract

Abstract Background Nonischaemic cardiomyopathy (NICM) represents a heterogenic disorder with a variable arrhythmogenic substrate. Its location is often epicardial and catheter ablation in this location proved to be an effective therapeutic modality in NICM patients with recurrent ventricular tachycardias (VTs). Purpose To determine the impact of the type of genetic mutation on the long-term outcome of endo-epicardial ablation in patients with NICM. Methods We investigated 82 patients (age 47±15 years, 10 women) with NICM who underwent endo-epicardial ablation for frequent VTs. Of them, 59% had a history of failed endocardial ablation. Patients had a left ventricular ejection fraction of 44±14% and all were implanted with cardioverter-defibrillator. One hundred candidate genes were examined using the new generation sequencing technique. Results Mutation in genes coding desmosomal complex (genes: PKP2, DSC, DSP, and DSG) was found in 30% of patients (“desmosomal” group). In 23% of patients, other gene mutations (genes: LMNA/C, MYH7, DES, TTN, RYR2, TPM1, MYPN, FLNC, and SCN5A) were detected (“non-desmosomal” group). In 46% of subjects no pathogenic mutation could be identified (“none” group). During a mean follow up of 34±33 months, patients in the “non-desmosomal” group were at significantly higher risk of VT recurrence and death/heart transplant compared to patients in the “desmosomal” group (Figure 1). Conclusion Potentially pathogenic mutation can be detected in about half of patients with NICM undergoing endo-epicardial VT ablation. Most commonly, mutations can be found in genes coding desmosomal complex and the endo-epicardial ablation is then associated with a satisfactory low VT recurrence rate and excellent survival in the long-term. On the other hand, patients with a mutation in non-desmosomal genes have poor outcomes despite endo-epicardial ablation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237 Figure 1