The identification of different phenotypic features of Hypertrophic Cardiomyopathy through Cardiovascular Magnetic Resonance imaging and evaluation of its relationship with genotype

OBJECTIVE: The aim of this study is to identify the phenotypic characteristics of hypertrophic cardiomyopathy (HCM) using cardiovascular magnetic resonance (CMR) and also determine the features contributing to the development of left ventricular outflow tract obstruction (LVOTO). The other purpose of this study is to determine the genetic distribution of HCM in the Turkish population, and evaluate the genotype-phenotype relationship. MATERIALS AND METHODS: Ninety-six patients diagnosed with HCM (mean age: 56.9±13.5, 32.3% female) were included in this cross-sectional study. LVOT gradient was assessed via echocardiography. Patients were divided into two groups; obstructive HCM (n:36) and non-obstructive HCM (n:60). All the patients underwent CMR (1.5 Tesla, Achieva, Philips Medical Systems, Best, Netherlands). 77 patients who had given formal approval before were utilized for genetic examination including 18 genes (using NGS method). Patients undergoing genetic testing were categorized into three groups; variant-negative group (n:48), variant of unknown significance (VUS) group (n:13), and likely pathogenic/pathogenic (LP/P) variant group (n:16). RESULTS: Interventricular septum (IVS) thickness, anterior and posterior mitral leaflet (AML and PML) lengths were higher in the obstructive HCM group, whereas LVOT diameter and ventricular arterial coupling (VAC) were lower in the obstructive HCM group. Mitral regurgitation (MR), residual leaflet, abnormal chordal attachment, and bifid papillary muscle (PM) were observed more in the obstructive HCM group. The anterolateral (AL) PM-septum distance measured at the end of diastole and systole was lower in the obstructive HCM group, while AL PM mobility calculated with these parameters was higher in the obstructive HCM group. In the multivariate logistic regression model; the ratio of AML length to LVOT diameter, the ratio of PML length to LVOT diameter, and AL PM mobility were associated with LVOTO independently of IVS thickness, abnormal chordal attachment, and bifid PM. The ratio of AML length to LVOT diameter of ≥2.30, the ratio of PML length to LVOT diameter of ≥1.83, and AL PM mobility of ≥57.7% were found as predictors of LVOTO with good sensitivity and specificity. In 29 (37.7%) patients out of 77, who underwent genetic testing, positive variants (VUS, LP, P) were found. In 16 (20.8%) patients out of 77, LP/P variant was detected which enable us to make sure the final molecular diagnosis. The most commonly identified genes were MYBPC3 and MYH7. When these three groups were compared, the significant differences were observed among them in terms of the posterior wall mid-segment thickness, LVOT diameter, AML length, the ratio of AML length to LVOT diameter, the ratio of PML length to LVOT diameter, and abnormal chordal attachment. CONCLUSION: The ratio of AML length to LVOT diameter, the ratio of PML length to LVOT diameter, and also AL PM mobility were associated with LVOTO independently of other phenotypic changes, especially IVS thickness. The rate of genetic diagnosis in HCM patients in the Turkish population was observed lower than the other populations, and our study was compatible with the other data from Turkish population. The result of genetic test may affect the phenotypic expression of HCM patients, however, in order to make an ultimate decision about this situation, we need further and comprehensive researches. KEYWORDS: abnormal chordal attachment, anterior mitral leaflet, bifid papillary muscle, papillary muscle mobility, posterior mitral leaflet