title: Impact of systolic dysfunction in genotyped hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere, and approximately 5% of cases of HCM show systolic dysfunction with poor prognosis. Few data exist regarding the systolic dysfunction in a large population of genotyped HCM subjects.
  
  
  OBJECTIVE
  The aim of this study was to assess the systolic dysfunction and prognosis in sarcomere gene mutation carriers.
  
  
  METHODS
  The study included 157 sarcomere gene mutation carriers from 69 unrelated HCM families (87 males; mean age, 46.5 ± 20.5 years). After exclusions for systolic dysfunction at baseline, 107 subjects underwent serial echocardiograms.
  
  
  RESULTS
  At a mean follow-up of 7.0 years, 12 subjects experienced systolic dysfunction. In multivariate Cox analysis, systolic dysfunction was related to age and ejection fraction at initial evaluation (P < 0.001 and P = 0.020, respectively), and was associated with the absence of mutations in the cardiac myosin-binding protein C gene (MYBPC3) (P = 0.042). When the subjects were divided into MYBPC3 and non-MYBPC3 mutation carriers, and time from birth to development of systolic dysfunction was compared, the rate of systolic dysfunction was higher in the non-MYBPC3 group than in MYBPC3 group (Kaplan-Meier, log-rank test, P = 0.010). After the onset of systolic dysfunction, 11 of 12 subjects died during a mean follow-up of 8.3 years.
  
  
  CONCLUSIONS
  Non-MYBPC3 mutation carriers developed left ventricular systolic dysfunction more frequently than MYBPC3 mutation carriers, and the majority of sarcomere gene mutation carriers with systolic dysfunction had fatal outcomes during follow-up. This suggests that subjects with mutations in sarcomeric genes require careful management for systolic dysfunction.
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa-City, Japan. nfujino@mhs.mp.kanazawa-u.ac.jp
authors.forename: Noboru
authors.initials: N
authors.lastname: Fujino
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Konno
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hodatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Toyonobu
authors.initials: T
authors.lastname: Tsuda
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagata
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Kawashiri
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ino
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000235:genetics; D013599:Systole / Q000235:genetics; D013997:Time Factors; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000235:genetics*; D017725:Ventricular Pressure / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C