title: Manifest disease, risk factors for sudden cardiac death, and cardiac events in a large nationwide cohort of predictively tested hypertrophic cardiomyopathy mutation carriers: determining the best cardiological screening strategy.
abstract: OBJECTIVE
  We investigated the presence of a clinical diagnosis of hypertrophic cardiomyopathy (HCM), risk factors for sudden cardiac death (SCD), and cardiac events during follow-up in predictively tested-not known to have a clinical diagnosis of HCM before the DNA test-carriers of a sarcomeric gene mutation and associations with age and gender to determine the best cardiological screening strategy.
  
  
  RESULTS
  One hundred and thirty-six (30%) of 446 mutation carriers were diagnosed with HCM at one or more cardiological evaluation(s). Male gender and higher age were associated with manifest disease. Incidence of newly diagnosed manifest HCM was <10% per person-year under the age of 40 years and >10% in older carriers, although numbers were small in carriers <15 years. Twenty-three percent of carriers, with and without manifest disease, had established risk factor(s) for SCD (no significant difference). During an average follow-up of 3.5 ± 1.7 years two carriers, both with manifest disease, died suddenly (0.13% per person-year). A high-risk status for SCD (≥2 risk factors and manifest HCM) was present in 17 carriers during follow-up (2.4% per person-year). Age but not gender was associated with a high-risk status for SCD.
  
  
  CONCLUSIONS
  Thirty percent of carriers had or developed manifest HCM after predictive DNA testing and risk factors for SCD were frequently present. Our data suggest that the SCD risk is low and risk stratification for SCD can be omitted in carriers without manifest disease and that frequency of cardiological evaluations can possibly be decreased in carriers between 15 and 40 years as long as hypertrophy is absent.
authors: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, the Netherlands.
authors: Imke
authors: I
authors: Christiaans
authors: Erwin
authors: E
authors: Birnie
authors: Gouke J
authors: GJ
authors: Bonsel
authors: Marcel M A M
authors: MM
authors: Mannens
authors: Michelle
authors: M
authors: Michels
authors: Daniëlle
authors: D
authors: Majoor-Krakauer
authors: Dennis
authors: D
authors: Dooijes
authors: J Peter
authors: JP
authors: van Tintelen
authors: Maarten P
authors: MP
authors: van den Berg
authors: Paul G A
authors: PG
authors: Volders
authors: Yvonne H
authors: YH
authors: Arens
authors: Arthur
authors: A
authors: van den Wijngaard
authors: Douwe E
authors: DE
authors: Atsma
authors: Apollonia T J M
authors: AT
authors: Helderman-van den Enden
authors: Arjan C
authors: AC
authors: Houweling
authors: Karin
authors: K
authors: de Boer
authors: Jasper J
authors: JJ
authors: van der Smagt
authors: Richard N W
authors: RN
authors: Hauer
authors: Carlo L M
authors: CL
authors: Marcelis
authors: Janneke
authors: J
authors: Timmermans
authors: Irene M
authors: IM
authors: van Langen
authors: Arthur A M
authors: AA
authors: Wilde
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology; D042241:Early Diagnosis; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D012307:Risk Factors; D012737:Sex Factors