Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)-Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy

Background-The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (beta-myosin heavy chain) and MYBPC3 (beta-myosin-binding protein C). Phenotypic differences between patients with mutations in these 2 genes have been inconsistent. Scarce data exist on the genotype-phenotype association as assessed by tomographic imaging using cardiac magnetic resonance imaging. Methods and Results-Cardiac magnetic resonance imaging was performed on 358 consecutive genotyped hypertrophic cardiomyopathy probands at 5 tertiary hypertrophic cardiomyopathy centers. Genetic testing revealed a pathogenic mutation in 159 patients (44.4%). The most common genes identified were MYH7 (n=53) and MYBPC3 (n=75); 33.1% and 47% of genopositive patients, respectively. Phenotypic characteristics by cardiac magnetic resonance imaging of these 2 groups were similar, including left ventricular volumes, mass, maximal wall thickness, morphology, left atrial volume, and mitral valve leaflet lengths (all P=non-significant). The presence of late gadolinium enhancement (65% versus 64%; P=0.99) and the proportion of total left ventricular mass (% late gadolinium enhancement; 10.4 +/- 13.2% versus 8.5 +/- 8.5%; P=0.44) were also similar. Conclusions-This multicenter multinational study shows lack of phenotypic differences between MYH7-and MYBPC3-associated hypertrophic cardiomyopathy when assessed by cardiac magnetic resonance imaging. Postmutational mechanisms appear more relevant to thick-filament disease expression and outcome than the disease-causing variant per se.