Genetic variants, clinical characteristics and outcomes of non-compact cardiomyopathy

Aim: evaluate clinical and structural-functional characteristics, including adverse events and outcomes, in patients with noncompact cardiomyopathy (NCM) with various genetic variants.Material and Methods. 51 unrelated patients with NCM were examined (mean age 37 [28; 47]; men (54.9%), women (45.1%)), observed for 7 to 211 months (in average 38 months). Clinical and instrumental examination included checkup, collection of individual and family history, ECG-12 registration, 24-hour Holter ECG monitoring, echocardiography, magnetic resonance imaging (MRI) of the heart with late contrast enhancement. The search for mutations in the coding sequences of 174 genes associated with cardiovascular pathology was carried out by high-throughput sequencing (NGS).Results and discussion. In 24 of 51 (47.1%) patients, 27 mutations of pathogenicity classes IV and V were detected, while in 21 (41.2%) patients, mutations were in the genes of sarcomeric proteins, of which 37.5% were in the MYBPC3 gene, 25.0% in the MYH7 gene, and in the TTN gene, leading to a shortened protein (TTNtv) - 33.3%, there is a mutation in the ACTC1 - 1 gene (4.2%). In 5.9% of patients, mutations were detected in genes encoding structural proteins and ion channel subunits. Two or more genetic variants were found in 10 out of 24 (41.7%) patients. No significant genetic variants were identified in 14 (27.4%) patients. Patients with mutations in the TTNtv gene were associated with severe systolic dysfunction, dilation of the left ventricle. Carriers of mutations in the MYBPC3 gene and several genetic variants were more likely to have adverse events and outcomes: progression of chronic heart failure (CHF), ventricular tachyarrhythmias, sudden cardiac death (SCD) with successful resuscitation, mortality. Patients with mutations in the MYH7 gene had no adverse outcomes.Conclusion. Comparative analysis showed that patients with NCM had the most severe form of the disease with significant clinical manifestations, episodes of clinical death with subsequent resuscitation and cardioverter defibrillator implantation in probands with mutations in TTNtv gene, mutations in the MYBPC3 gene or multiple genetic variants.