Stress-Induced Ventricular Tachicardia as a Manifestation of Arithmogenic Right Ventricular Cardiomyopathy

Background: arrhythmogenic right ventricular cardiomyopathy (ARVC) is a clinically and genetically heterogeneous myocardial disorder. About 60% of the ARVC cases are caused by mutations in the genes encoding desmosomal proteins. Mutations in the non-desmosomal genes can be found in less than 10% of all cases. Gene TMEM43 encodes transmembrane protein 43 (TMEM43) which function is to be elucidated. The role of mutations in this gene in the ARVC pathogenesis was shown recently and still matter of discussion.

The aim: to describe rare genetic ARVC variant in a 48-year-old woman presenting with unstable stress-induced ventricular tachycardia (VT).

Material and methods: physical examination, medical history, ECG specific protocols to identify ARVC, veloergometry (VE), 24-hours Holter monitoring (HM), EchoCG, cardiac MRI, myocardial biopsy. Mutation testing was performed by semiconductor sequencing on the IonTorrent platform for the PKP2, DSG2, DSP, DSC2, JUP, LMNA, DES, TMEM43, TGFB3, PLN, and SCN5A genes. All findings were confirmed by capillary Sanger resequencing. Prognostic value of the revealed genetic variants was estimated based on ACHG Consensus Recommendation.

Results: Female patient, 47 y.o., had arrhythmic manifestation with ventricular parasystole (VP): single and pair at the peak of the physical activity in VE. During HM the heart rate was 110 bpm, episodes of unsustainable VT, and more than 5000 PVC were recorded, syncope (-). Radiofrequency catheter VT ablation was completed successfully. Severe fibrosis and lipomatosis of the RV and interventricular septum were found by biopsy. Diagnosis ARVC was definite according to the Marcus criteria (2010).

Heterorozygous pathogenic mutation p.R312W was detected in the TMEM43 gene.

Conclusion: We have identified a TMEM43-related variant of the ARVC in patient with definite diagnosis of ARVC. This genetic variant is exclusively rare in Russian population. Despite the low detection rate of the mutations in non-desmosomal genes in Russia, the large-scale panel genetic testing is reasonable for ARVC patients.