Focus issue: Sudden cardiac arrestClinicalDiagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: The experience of a tertiary referral center in The Netherlands
Introduction
When autopsy is performed after the sudden death of an individual aged 1–50 years, structural cardiac disease is diagnosed in ∼69%,1 termed sudden cardiac death (SCD). Most causes of SCD are (potentially) inherited. The cause of the fatal event remains unexplained after autopsy in ∼18% (range 6%–35%) of patients.1, 2, 3, 4, 5, 6, 7 In these cases of sudden unexplained death (SUD), molecular autopsy of the deceased and cardiologic and genetic examination of relatives may unmask the cause of death in a significant proportion.8, 9, 10, 11 Identification of inherited cardiac diseases provides the opportunity to identify surviving relatives at risk for SCD and to take preventive measures.
The causes of aborted cardiac arrest (ACA) in victims aged 1–50 years likely are similar to those in SCD, and the eventual outcome of cardiac arrest (death in SCD and alive in ACA) is mostly determined by circumstances at the time of cardiac arrest.12, 13 Thus, identification of the underlying cause of ACA in the young has comparable significance for relatives as SCD/SUD in the young. However, no studies on the causes of ACA in the young have been published, apart from 10 pediatric ACA victims from our center.10 ACA at any age is estimated to be idiopathic in only ∼5%.14
In this study, we sought to determine and compare the yield of comprehensive cardiologic and genetic examination in surviving relatives of SUD victims aged 1–50 years and in victims of ACA of the same age to gain insight into the state of the art of the current diagnostic strategies used in both populations in our dedicated tertiary referral center.
Section snippets
Sudden unexplained death
SUD was defined as out-of-hospital natural death in a previously healthy individual whose family had no known inherited cardiac disease in whom death occurred within 1 hour after the start of complaints or within 24 hours of the victim being seen alive and well, and in whom autopsy was not performed or initially did not explain the death.
Aborted cardiac arrest
ACA was defined as an out-of-hospital unexpected, abrupt loss of consciousness with loss of vital signs (pulse, blood pressure, respiration) within 1 hour of
SUD families
The study included the surviving relatives of 140 SUD victims aged 1–50 years (Table 1). Ninety-nine (71%) were male, and 21 (15%) experienced at least one previous unexplained syncope. Two (1%) had a previous unexplained ACA in the 1980s and did not receive an implantable cardioverter-defibrillator. Autopsy was performed in 64 (46%) cases.
In six families, only one second-degree relative of the SUD victim presented to the cardiogenetics department. In the remaining 134 families, 340 (53%) of
Main findings
In this series of cardiologic and genetic assessment of both surviving relatives of SUD victims and victims of ACA aged 1–50 years, a diagnosis was made in 33% and 61%, respectively. Inherited cardiac diseases accounted for 96% of the diagnoses in the SUD families and 74% of the diagnoses in the ACA victims.
Comparison of yield in SUD families and ACA victims
The diagnostic yield within the two populations described in the present study cannot be well compared because the SUD victims formed a selected population (noncardiac and structural cardiac
Conclusion
Comprehensive cardiologic and genetic examination of relatives of young SUD victims results in a certain or probable diagnosis in one third of cases. In young ACA victims, the yield of the current diagnostic workup is 61%. In both groups, the majority of detected diagnoses is inherited.
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Drs. van der Werf, van Langen, and Wilde were supported by a grant from ZorgOnderzoek Nederland Medische Wetenschappen (ZonMW, Grant 120610013). Dr. Wilde was supported by a grant from Fondation Leducq Trans-Atlantic Network of Excellence, Preventing Sudden Death (Grant 05-CVD-01). Dr. Tan was supported by the Netherlands Organization for Scientific Research (NWO, Grant ZonMW-VICI 918.86.616).