Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging

Abstract

HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing. Methods Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death. Results We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020).

Genotype-Related Clinical Characteristics and Myocardial Fibrosis and Their Association with Prognosis in Hypertrophic Cardiomyopathy

“…These findings may partially explain the higher event rate in the detected group. As reports on the genotypic-phenotypic relationship in HCM based on CMR are scarce at this time but will likely be pursued more aggressively in the future [43,44], we predict that findings similar to ours will be found in larger studies in the near future.…”

Radiomic Analysis of Native T1 Mapping Images Discriminates Between MYH7 and MYBPC3‐Related Hypertrophic Cardiomyopathy

“…2 In addition, according to Miller et al, there was no significant difference in LGE burden in patients with MYH7 compared to MYBPC3 variants. 35 Our global and slice models further confirmed, via native T 1 assessment, that there are no significant differences in fibrosis between patients carrying these variants. Previous studies reported that increased LGE burden was associated with an increase in sustained ventricular tachycardia or cardioverter-defibrillator shock.…”

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

“…The symptoms and clinical severity are dominantly determined by the combination of diastolic dysfunction, mitral apparatus abnormalities, and LV outflow tract obstruction [35,36]. A recent study by Miller et al [37] established that patients with pathogenic, likely pathogenic or rare MYH7 variants had higher LV ejection fraction than those with MYBPC3 variants (68.8 vs. 59.1, p < 0.001) and higher right ventricle ejection fraction (67.3 vs. 60.8, p = 0.018). Additionally, patients with MYBPC3 variants were more likely to have LV ejection fraction < 55% (29.7% vs. 4.9%, p = 0.005).…”