Young at Heart: Examining the Incidence and Etiology of Sudden Cardiac Death in the Young

Sudden cardiac death (SCD) in children and young adults is an unpredictable event with poor outcomes that are devastating to families and society. SCD in the young is frequently attributed to structural heart disease and electrophysiologic abnormalities with a genetic predilection.¹ However, for those younger than 31, unexplained etiologies account for 40% of SCD, while coronary artery disease is the most common etiology in those between 31 and 35 years of age.¹ The current literature exploring the incidence of SCD has varied widely, given the differences in the ages of those dying in study cohorts as well as the methodology deployed to identify young victims of sudden cardiac death.² Therefore, interpreting trends in incidence and improvements over time have been challenging.

In this issue of Circulation: Cardiovascular Quality and Outcomes, Ha et al. completed a retrospective study of patients between the ages of 1 and 35 who suffered SCD in Australia over a 17-year time interval in their manuscript entitled “Sudden Cardiac Death in the Young: Incidence, Trends and Risk Factors in a Nationwide Study”.³ The authors aimed to determine the incidence and trends of SCD in the young as well as potential modifiable risk factors for SCD. The authors found that the incidence of SCD in this cohort was declining and that this reduction was driven by the 31 to 35 year-old cohort with coronary artery disease as their etiology of arrest. Interestingly, the authors also report that individuals in non-metropolitan areas had an increased risk of SCD in comparison to those living in metropolitan areas, supporting their hypothesis that geographical remoteness is associated with SCD in the young. SCD in the young was also associated with obesity, as those with higher BMI had an increased risk of SCD in comparison to individuals of normal weight. The National Coronial Information System registry (NCIS) is a prospectively maintained government registry that includes data for death cases referred to the coroner and provided a wealth of detailed information not often seen in other studies of this kind. Unique to this study is the high rate of autopsy in this cohort, where 95% of subjects (1898/2006) underwent autopsy allowing a more detailed assessment of causes of SCD. The study clearly identifies the methodology for case selection and excluded those less than one year of age, or who had non-cardiac causes of death (ex. toxicologic etiology or cerebrovascular events). Overall, the strength to this study results from the large dataset, with high completion rate of autopsy, that encompasses all of Australia allowing for a comprehensive analysis exploring the incidence of SCD. There are several important issues that deserve further discussion.

SCD secondary to CAD is the most common cause in the “older” young and is decreasing

Ha et al. identified a reduction in incidence of SCD in young persons during the study period ranging from 0.91-1.48 per 100,000 age-specific person-years., when compared to previous literature that reported ranges between 1.3 to 2.9 per 100,000 person years depending on age and case definition.³ While this decline is notable, the authors identify that this decline in incidence over time is secondary to the decline in CAD-related SCD. Of note, the incidence of CAD in this cohort was significantly higher at 40% of the total cohort in comparison to different study from Denmark where ischemic heart disease only affected 29.4% of the total cohort.⁴ Given that overall trends in the incidence of coronary heart disease have been declining⁵ and improvements in basic life support and increased access to public access automated external defibrillators,⁶ the observation that SCD due to CAD is declining is anticipated. The authors discuss the incidence of obesity in their cohort as a notable predictor, however, this is challenging to interpret as a large proportion of their cohort is missing measures of BMI (43%), despite having access to autopsy data.

Non-CAD related SCD in the “young” young is not declining and is challenging to identify prior to an SCD event

While a positive outcome, this reduction in SCD due to CAD does not touch upon the concerning side of SCD in the young (<31 years of age) who succumb to SCD secondary to undiagnosed structural or arrhythmogenic disease.³ Notably in this national study of SCD in the “young”, the cohort of individuals who are less than 31 years of age, specifically those who do not frequently suffer SCD due to ischemic heart disease, do not experience similar trends in reduced incidence of death.³ Overall, sudden arrhythmic death syndrome (SADS) accounts for 14% (the second highest) of causes of SCD in the young, and it accounts for 53% of SCD in patients who are 6-25 years in age.³ Ha et al. state that this incidence did not change over the course of the 17 years of the study, and that SAD accounted for a higher proportion of overall SCD over time. This data indicates that while advances have been made in reducing the incidence of SCD in young patients with CAD, similar trends have not been made in SADS patients who ultimately have less comorbidity, are younger, and represent a cohort of young patients for which their initial episode or event may result in their untimely and devastating death. While the authors are able to describe a global decline in SCD in the young, those with structural or arrhythmogenic etiologies to their arrest have not declined over time.

Preventing SCD by early detection is challenging to health systems and the current study shows value in determining risk factors for these events

Identifying risk factors for SCD in order to adequately identify individuals at high risk for SCD is desirable, however, this has proven to be incredibly challenging. Different from the diagnosis of CAD, the diagnosis of a structural or arrhythmogenic event is frequently identified when SCD occurs tragically.² Identifying genetic risk factors or tools for appropriate diagnostic screening to detect those at risk of a potential structural or arrhythmogenic event have made scientific progress, however, the practice of screening populations to identify disease in the young have been challenging to implement. Preventing the SCD event primarily is the best way to reduce the morbidity and mortality of SCD in the young, however, the tools to do this are still under development, implementing these screens will be challenging to do effectively, and risk factors for SCD in the young that is not secondary to CAD have not been identified.

So what lessons can we derive from this study? Although a decline in the incidence of SCD in the young attributed to a reduction in the incidence of CAD is promising, individuals who suffer SCD earlier due to the devastating effects of frequently heritable conditions such as arrhythmogenic death or structural disease persists. Preventing SCD in this latter cohort should be prioritized in future investigation. Pathologic investigation and molecular autopsy may be useful to counsel first degree relatives of those who have succumbed to SCD. As advances in genetic testing occur, the role of broader screening and surveillance of young people may be valuable to prevent SCD but these will need to be balanced against the risks of treatments such as implantable defibrillators and drugs. For the young at heart who may be at risk for such a devastating event, much work remains to done.