Sudden cardiac death in the young : incidence and consequences

Sudden cardiac death (SCD) and sudden unexplained death (SUD) in the young (1-44 years) is rare and is often caused by inherited cardiac diseases. Relatives of young SCD and SUD victims have an increased risk of carrying the inherited predisposition to develop cardiac disease. Early detection of inherited cardiac diseases in families offers opportunities to prevent SCD through treatment. Although the yield of screening, in terms of the detection of inherited diseases, has been investigated for relatives of SUD victims, studies on the cost-effectiveness of screening of relatives with the aim to prevent SCD are scarce. The purpose of this thesis was to provide information on the incidence and causes of SCD and SUD in the young (1-44 years) in the Netherlands and to estimate the proportion of inherited cardiac diseases. Furthermore, we studied the yield of cardiogenetic screening of first-degree relatives in the usual care to identify inherited cardiac diseases. Also, we simulated the cost-effectiveness of genetic cascade screening of relatives of patients with hypertrophic cardiomyopathy (HCM). During one year, we collected all victims aged 1-44 years of SUD and SCD in four study regions in the Netherlands. In total 175 sudden death cases were registered. The incidence of sudden death was 6.8 (95% CI; 5.8-7.8) per 100.000 person-years and the incidence of SCD was 5.5 (95% CI; 4.6-6.4) per 100,000 person-years. In the Netherlands, SUD and SCD account for approximately 500 deaths each year in persons aged 1-44 years. Of all victims, an inherited cardiac disease was suspected, or could not be excluded, in 79% of the cases. A clinical autopsy was performed in a minority (35%) of young sudden death victims and often the cause of death remained unclear. To improve the detection of inherited cardiac diseases, elaborate postmortem investigation is required. We expect that the autopsy rate will increase by creating awareness among physicians, coroners and the lay public, and by improving the logistics and removing of currently existing financial barriers. Furthermore, we studied the yield of cardiogenetic screening of relatives of unselected victims of SCD and SUD aged 1-40 years in a regional hospital. The total yield of screening of these surviving first-degree relatives was 14% (95% CI; 3%-25%), which is substantial but lower than expected based on previous studies performed in tertiary referral hospitals. A less structured and extensive screening approach, as performed in the usual care, might explain this lower detection rate of inherited cardiac diseases among relatives. A centralized, expert setting for cardiogenetic screening of relatives of SCD and SUD victims is likely to lead to higher detection rates of inherited cardiac diseases. Also, we developped a decision analytical model to assess the cost-effectiveness of cardiogenetic screening of relatives of patients with HCM. In 20-year-old relatives, screening prevented almost half of the SCD events (6% vs.12%), increased life expectancy (44.0 vs. 42.7 years), increased quality-adjusted life-years (QALY) (30.2 vs. 29.9 QALYs) but also increased costs (€13,218 vs. €580 per patient). Screening of first-degree relatives of SCD victims in whom HCM was diagnosed strongly improved cost-effectiveness. These results are relevant for the development of future guidelines concerning the genetic cascade screening for HCM