Adaya Weissler-Snir1, Waseem Hindieh1, Christiane Gruner1, Dana Fourey1, Evan Appelbaum1, Ethan Rowin1, Melanie Care1, John R Lesser1, Tammy S Haas1, James E Udelson1, Warren J Manning1, Iacopo Olivotto1, Benedetta Tomberli1, Barry J Maron1, Martin S Maron1, Andrew M Crean1, Harry Rakowski1, Raymond H Chan2. 1. From the Division of Cardiology (A.W.-S., W.H., C.G., D.F., M.C., A.M.C., H.R., R.H.C.) and Joint Department of Medical Imaging (A.M.C.), University Health Network, Toronto, Ontario, Canada; Division of Cardiology, Cardiovascular Center, University Hospital Zurich, Switzerland (C.G.); Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (E.A., W.J.M., R.H.C.); Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, MA (E.R., J.E.U., B.J.M., M.S.M.); The Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, MN (J.R.L., T.S.H.); and Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O., B.T.). 2. From the Division of Cardiology (A.W.-S., W.H., C.G., D.F., M.C., A.M.C., H.R., R.H.C.) and Joint Department of Medical Imaging (A.M.C.), University Health Network, Toronto, Ontario, Canada; Division of Cardiology, Cardiovascular Center, University Hospital Zurich, Switzerland (C.G.); Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (E.A., W.J.M., R.H.C.); Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, MA (E.R., J.E.U., B.J.M., M.S.M.); The Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, MN (J.R.L., T.S.H.); and Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy (I.O., B.T.). raymond.chan@utoronto.ca.
Abstract
BACKGROUND: The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (β-myosin heavy chain) and MYBPC3 (β-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.
BACKGROUND: The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (β-myosin heavy chain) and MYBPC3 (β-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.
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