title: Genotype-positive status in patients with hypertrophic cardiomyopathy is associated with higher rates of heart failure events.
abstract: BACKGROUND
  The aim of the study was to clarify the relationship between genotype status and major cardiovascular outcomes in a large cohort of patients with hypertrophic cardiomyopathy.
  
  
  RESULTS
  Genetic testing was performed in 558 consecutive proband patients with hypertrophic cardiomyopathy. Baseline and follow-up (mean follow-up 6.3 years) clinical and echocardiographic data were obtained. Pathogenic mutations were identified in 198 (35.4%) patients. Genotype-positive patients were more likely to be women (44% versus 30%; P=0.001), younger (39 versus 48 years; P<0.001), and have a family history of hypertrophic cardiomyopathy (53% versus 20%; P<0.001), as well as family history of sudden cardiac death (17% versus 7%; P=0.002). There were no significant differences in the rates of atrial fibrillation, stroke, or septal reduction procedures. Multivariable analysis demonstrated that genotype-positive status was an independent risk factor for the development of combined heart failure end points (decline in left ventricular ejection fraction to <50%, New York Heart Association III or IV in the absence of obstruction, heart failure-related hospital admission, transplantation, and heart failure-related death; hazards ratio, 4.51; confidence interval, 2.09-9.31; P<0.001). No difference was seen in heart failure events between the myosin heavy chain and myosin-binding protein C genotype-positive patients.
  
  
  CONCLUSIONS
  The presence of a pathogenic sarcomere mutation in patients with hypertrophic cardiomyopathy was associated with an increase in heart failure events, with no differences in event rates seen between myosin heavy chain and myosin-binding protein C genotype-positive patients. The presence of a disease-causing mutation seems more clinically relevant than the specific mutation itself.
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.). qin.li@mail.utoronto.ca.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Christiane
authors.initials: C
authors.lastname: Gruner
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Chan
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Care
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Katherine
authors.initials: K
authors.lastname: Siminovitch
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Lynne
authors.initials: L
authors.lastname: Williams
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Anna
authors.initials: A
authors.lastname: Woo
authors.affiliation: From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
authors.forename: Harry
authors.initials: H
authors.lastname: Rakowski
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005838:Genotype; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018995:Myosin Heavy Chains / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C
keywords: cardiomyopathy, hypertrophic; heart failure