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Spotlight on sudden arrhythmic death syndrome

: Sudden cardiac death (SCD) is de ﬁ ned as death from a cardiac cause within 1 hr of symptom onset or, if unwitnessed, in a person last seen well within 24 hrs. Sudden arrhythmic death syndrome (SADS) describes cases of SCD with no abnormalities found on expert autopsy attributable as the cause of death. The epidemiology of these conditions has been challenging to study as de ﬁ nitions have changed over time; however, it is apparent that the incidence of SCD increases with age whilst SADS decreases as coronary artery disease becomes more prevalent. Accurate reporting of truly negative autopsies of SCDs has been assisted by guidelines from governing bodies such as The Association for European Cardiovascular Pathology, allowing identi ﬁ cation of SADS cases. Primary arrhythmic cardiac conditions like ong QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are the predominant etiologies of SADS. When the decedent did not have a known phenotype for these conditions, clinical evaluation using screening tests like echocardiogram, resting and stress electrocardiograms and holter mon-itoring, followed by specialized testing when appropriate such as cardiac magnetic resonance and pharmacological provocation testing of surviving family members becomes crucial in potentially identifying the cause and guide targeted genetic testing. Although advancement in gene analysis such as next-generation sequencing has also allowed the application of “ molecular autopsy ” to identify pathogenic variants to establish the cause of death and enable cascade testing and risk strati ﬁ cation of family members, many of the genetic variants identi ﬁ ed through this method have been classi ﬁ ed as non-pathogenic since the establishment of standards and guidelines by the American College of Medical Genetics. Whilst majority of cases of SADS are still unexplained, there is increasing awareness and understanding of this syndrome allowing appropriate identi ﬁ cation of surviving family members at risk and implementation of measures to prevent further premature death.