Are individuals within families with premature truly sudden unexplained death at risk during long-term follow-up?

Christian Van Der Werf, Lotte Stiekema, Nynke Hofman, Marielle Alders, Allard C. Van Der Wal, Hanno L. Tan, Irene M. Van Langen, Arthur A. Wilde

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Introduction: After young sudden unexplained death (SUD), comprehensive cardiologic and genetic examination in surviving first-degree relatives unmasks inherited cardiac disease in ∼40% of families, enabling timely prophylactic treatment. It is unknown, however, whether individuals from diagnosis-negative families (in which such investigations revealed no inherited cardiac disease) are at risk of developing manifest disease or cardiac events during follow-up. Methods: We obtained vital status of surviving first-degree relatives from all 86 families who presented to our cardiogenetics department in 1996-2009 because of SUD of >1 relative aged 1-50 years, in whom no diagnosis was made. Moreover, we contacted relatives who previously attended our center for detailed information on themselves and their relatives. Results: We obtained detailed follow-up (median duration of 5.6 years [range: 1.8-11.5]) in 492 first-degree relatives from 75 diagnosis-negative families (87.2%). Vital status, checked in all relatives, showed that 6 (1.2%) died during follow-up. One relative committed suicide, while in 3 relatives over the age of 50 years information on the cause of death was unavailable. One young woman died from a one-sided car accident without clear cause. None of these relatives had been evaluated in our center. One 10year-old girl died suddenlywhile watching television. She belonged to a family with multiple previous cases of (aborted) SUD, in which 2 other children were successfully resuscitated during follow-up. Inherited cardiac disease was diagnosed in 2 families (2.3%): Brugada syndrome in a man who underwent his first cardiologic examination during follow-up, and familial thoracic aortic aneurysms/dissections due to a TGFBR1 mutation in a man who had a slightly dilated aorta during initial cardiologic examination. Conclusions: In first-degree relatives of young SUD victims with no manifest abnormalities during initial cardiologic examination, the risk of developing manifest inherited cardiac disease or cardiac events during follow-up is low. This does not applyto families with a clear idiopathic inherited arrhythmia syndrome.
Original languageEnglish
Pages (from-to)S420-S438
Number of pages19
JournalHeart Rhythm
Issue number5
Publication statusPublished - May-2012


  • heart rhythm
  • follow up
  • risk
  • society
  • death
  • human
  • heart disease
  • examination
  • diagnosis
  • male
  • female
  • mutation
  • Brugada syndrome
  • cause of death
  • child
  • suicide
  • television
  • girl
  • heart arrhythmia
  • victim
  • aorta
  • traffic accident

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