title: Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy.
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.
  
  
  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 (allP=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.
authors.affiliation: 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.).
authors.forename: Adaya
authors.initials: A
authors.lastname: Weissler-Snir
authors.affiliation: 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.).
authors.forename: Waseem
authors.initials: W
authors.lastname: Hindieh
authors.affiliation: 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.).
authors.forename: Christiane
authors.initials: C
authors.lastname: Gruner
authors.affiliation: 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.).
authors.forename: Dana
authors.initials: D
authors.lastname: Fourey
authors.affiliation: 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.).
authors.forename: Evan
authors.initials: E
authors.lastname: Appelbaum
authors.affiliation: 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.).
authors.forename: Ethan
authors.initials: E
authors.lastname: Rowin
authors.affiliation: 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.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Care
authors.affiliation: 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.).
authors.forename: John R
authors.initials: JR
authors.lastname: Lesser
authors.affiliation: 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.).
authors.forename: Tammy S
authors.initials: TS
authors.lastname: Haas
authors.affiliation: 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.).
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.affiliation: 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.).
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Manning
authors.affiliation: 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.).
authors.forename: Iacopo
authors.initials: I
authors.lastname: Olivotto
authors.affiliation: 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.).
authors.forename: Benedetta
authors.initials: B
authors.lastname: Tomberli
authors.affiliation: 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.).
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Maron
authors.affiliation: 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.).
authors.forename: Martin S
authors.initials: MS
authors.lastname: Maron
authors.affiliation: 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.).
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Crean
authors.affiliation: 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.).
authors.forename: Harry
authors.initials: H
authors.lastname: Rakowski
authors.affiliation: 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.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Chan
mesh_terms: D000328:Adult; D002170:Canada; D024722:Cardiac Myosins / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D003287:Contrast Media / Q000008:administration & dosage; D005060:Europe; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D012042:Registries; D012307:Risk Factors; D013318:Stroke Volume; D062606:Tertiary Care Centers; D014481:United States; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D003287:Contrast Media; D019786:Gadolinium DTPA; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human
keywords: cardiomyopathy, hypertrophic; genotype; magnetic resonance imaging; myosin heavy chain; myosin-binding protein C; phenotype