2 Insights into the aetiology and temporal trends in cardiac mortality in the young: a 21-year review of national and registry data in england and wales

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Background An accurate representation of the incidence and aetiology of cardiac and sudden cardiac death (SCD) is vital for healthcare policymakers to effectively allocate resources for preventative strategies. Aim We aimed to report on the incidence and causes of cardiac and SCD among individuals under the age of 35 years in England and Wales over a 21-year period (2001 to 2021), with a focus on identifying any temporal trends in mortality. Methods Annual mortality data from the Office for National Statistics (ONS) pertaining to cardiovascular (CV) and possible CV deaths in individuals under the age of 35 years were analyzed using International Classification of Diseases-10 (ICD-10) codes. Deaths were categorized into four classes: A1- definitive cardiac deaths without identifiable structural heart disease (consistent with sudden arrhythmic death syndrome, SADS); A2- definitive cardiac deaths with identified structural heart disease; A3- definitive cardiac deaths with an indeterminate cause; and B- potential cardiac deaths. Incidence rates were computed based on ONS census data of the annual resident population. Additionally, insights were gleaned from the Cardiac Risk in the Young Centre for Cardiac Pathology (CRYCCP) nationwide registry, where each case underwent evaluation by an expert cardiac pathologist. Results The mean annual number of definitive cardiac deaths (classes A1+A2+A3) was 414 (SD 27.4), resulting in an incidence of young cardiac and SCD of 1.68/100,000 individuals/year. Ischaemic heart disease (28.4%), cardiomyopathies (25.9%), and SADS (21.8%) were the most prevalent cardiac conditions (figure 1). Cardiomyopathies and SADS related mortality peaked in the 10-to-19 age group, while ischaemic heart disease peaked in the 30-to-35 age group. A mean of 573 (SD 76.6) possible cardiac deaths (class B) occurred, these primarily included ill-defined/unspecified causes (33.5%), epilepsy (32.4%), sudden infant death syndrome (24.2%), and drowning (7%). Both definitive and possible cardiac deaths showed a male preponderance (male to female ratios of 2.3:1 and 1.6:1, respectively). A declining trend in cardiac mortality was observed with a 1.3% (95% CI: 1.0%-1.7%) incidence rate reduction per year over the 21-year time period (p<0.001) (figure 2). This was associated with a 2.5% annual incidence rate reduction for deaths attributed to structural heart disease (p<0.001), but an 8.5% annual incidence rate increase for deaths attributed to SADS (p<0.001). The shift in the cause of mortality correlated with increasing numbers of deaths referred to the CRYCCP where an expert cardiac pathologist diagnosed SADS in over 52% of cases. Conclusions Over 21 years in England and Wales, national datasets suggest the incidence of young cardiac and SCD is 1.68/100,000/year, with a small but appreciable declining mortality trend. The rise in SADS rates and contemporaneous decline in deaths attributed to structural heart disease may signify increased awareness and accessibility to expert cardiac pathologists. Furthermore, ensuring accurate mortality coding is crucial for thoroughly assessing first-degree family members in cases of suspected inherited cardiac conditions. Conflict of Interest None

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