P341Life-threatening events in patients with non-compaction cardiomyopathy and mutations in ion channel genes

Abstract

Abstract Purpose to analyze life-threatening events during follow-up in patients with non-compaction cardiomyopathy (NCCM) who have mutations in the genes responsible for the functioning of ion channels. Methods the study included 64 unrelated pts (aged 38.63 ± 14.72 years, 34/53.12% male, LVEF 43.02 ± 8.65%) with criteria of NCCM confirmed by imaging techniques (echocardiography (Jenni) and cardiovascular magnetic resonance (Petersen). Mutation search was carried out by the next generation sequencing (NGS). Pathogenic mutations or rare substitutions with possible clinical significance were found in 12 unrelated pts in the ion channel genes: KCNH2, KCNJ2, CACNA1C, RYR2, HCN4, TRPM4, PKP2, TRPM4. Mutations in other genes (PLN, DSP, NOTCH1, RBM20) were detected in 4 pts (1 pathogenic and 3 VUS). Results mutations in genes associated with long QT syndrome (LQTS) were found in 5 pts with NCCM: c.3107G > A (p.Gly1036Asp), с.2653С>T (p.Arg885Cys) in KCNH2 gene (16.7%); c.T28076 (p.F936C) in CaCNA1C gene (8.3%); c.1165G > C (p.Asp389Asn) in KCNJ2 gene (8.3%). There was no prolongation of the QTc interval > 480 msec on ECG; frequent episodes of nonsustained ventricular tachycardia (VT) were recorded on 24-hour ECG-monitoring. During the follow-up period (median follow-up of 2.4 years), two pts with mutations in KCNH2 genes with suddenly developed sustained VT were implanted with ICD. A 32-year-old patient with a mutation in CACNA1C gene and ST-elevation myocardial infarction of thromboembolic genesis underwent PCI. 58-year-old patient with widening of QRS > 130 msec and frequent paroxysms of nonsustained VT was implanted with CRT-D. An ICD was implanted in a 60-year-old patient with a mutation c.12665_12667del(p.4223del) in the RYR2 gene and suddenly developed a sustained VT. In the remaining two pts with RYR2 gene mutations c.12272C > T (p.Ala4091Val), c.12944G > A(p.Gly4315Glu), frequent episodes of nonsustained VT were recorded, which were corrected medically. Orthotopic heart transplantation and Accucinch transcatheter direct mitral valve annuloplasty system implantation were performed in two pts with ventricular tachyarrhythmias and severe systolic and diastolic dysfunction of the left ventricle with mutations c.3224T > C (p.Leu1075Pro), c.1459_1494del36 (p.Lys487_Leu498del) in the TRPM4 gene. In other pts with mutations in HCN4 (8.3%), DPP6 (8.3%), PKP2 (8.3%) genes ventricular tachyarrhythmias were treated with antiarrhythmic drugs. Conclusion the presence of mutations in the genes controlling the functioning of ion channels is an additional risk factor for adverse events in patients with NCCM.