��екомпактная кардиомиопатия. часть i: клинико-генетическая гетерогенность и предикторы неблагоприятного прогноза

Non-compaction cardiomyopathy (NCM) is a rare heart disease characterized by a two-layered ventricular wall, comprising a thinner compact epicardial layer and an inner non-compacted layer. However, only structural and morphological data without a thorough clinical assessment does not determine the NCM (regardless of the diagnostic criterion used). Aim . To study the NCM-related genes, phenotypic and genetic correlations, predictors of life-threatening ventricular tachyarrhythmias (VTA) and adverse clinical outcomes. Material and methods . Of 93 individuals with identified morphological criteria of NCM (median follow-up, 5 years), the study included 60 unrelated patients (38,5±13,8 years of age; men, 33 (55%); left ventricular ejection fraction (LVEF), 42,1±12,9%) with clinical verification of NCM (>1 obligate phenotypic trait). Adverse cardiovascular events were taken as the composite end point: life-threatening VTA, death, heart transplantation. Results . Pathogenic (or probably pathogenic) mutations were detected in 33 (55%) patients with NCM. The most common variants (57,9%) were identified in the sarcomere protein genes (TTN, MYBPC3, MYH7); digenic mutations were found in 21,6% of patients. Digenic mutations were associated with low LVEF and the highest risk of systolic dysfunction (OR, 38; 95% CI, 4,74-305; p=0,0001). Multivariate regression provided a predictive model (R=0,90; R2=0,81; F (5,41) =34,8; p<0,0001) and independent predictors of adverse clinical outcomes of NCM (genetic cause of the disease (pathogenic mutation), LV systolic dysfunction, myocardial fibrosis in 2 or more ventricular segments, and QRS prolongation. Regression and ROC-analysis identified electrical predictors of life-threatening VTA (fragmented QRS, QT prolongation, spatial QRS-T angle increase) and morphofunctional markers (myocardial fibrosis, systolic dysfunction). Conclusion . The study revealed a significant clinical and genetic heterogeneity of NCM with predominant mutations in the sarcomeric protein genes and determined the criteria for identification and prognosis of NCM.