A 10-year follow-up study on diagnostic yield in families of sudden cardiac death patients

Sudden cardiac death (SCD) accounts for 10-20% of all deaths in Western countries, and inherited cardiac diseases account for a significant proportion of SCD. Despite being a major public health issue with a profound impact on affected families, efficient strategies for risk stratification and prevention are lacking, as half of SCDs occur in individuals with no prior medical history.

The aim of this study was to assess the 10-year diagnostic yield of inherited cardiac diseases in a large cohort of families with a proband fulfilling criteria for SCD.

In this retrospective, observational, single-center study, we collected data from SCD patients aged >1 year and their relatives, referred to the Unit for Inherited Heart Diseases between 1 January 2005 and 1 October 2018. The cause of death in SCD probands was assessed through autopsy reports, genetic test results, and premortem medical records. Upon referral, first-degree relatives were screened in accordance with current guidelines, and diagnostic yield was assessed after five and ten years of follow-up.

A total of 304 SCD probands (75% males, median age of 41 years at death) and their 686 relatives (47% males, median age of 35 years at baseline) were included. Relatives were followed for a median period of 10.9 years, during which 3% were lost to follow-up. A diagnosis of an inherited cardiac disease was established in 116 probands (38.2%), and a total of 79 relatives (11.5%) had been diagnosed at the end of follow-up. The most common diagnosis among both probands and relatives was arrhythmogenic right ventricular cardiomyopathy, as shown in Table 1. Among the diagnosed relatives, 54% came from families with a diagnosed proband (n=43; 24 families), while the remaining 46% came from families with an undiagnosed proband (n=36; 29 families). When combining findings from both probands and relatives, an inherited cardiac disease was identified in 143 SCD families (47%) after five years of follow-up and in 145 families (48%) after ten years of follow-up (see Figure 1).

An inherited cardiac disease was diagnosed in nearly half of the SCD families, when combining pre- and postmortem findings in SCD probands with clinical evaluation of their relatives over ten years. Arrhythmogenic right ventricular cardiomyopathy was the most common diagnosis across families, and more than one in ten relatives received a diagnosis over the follow-up period. The diagnostic yield increased by only 1% between five- and ten-years of follow-up in the SCD families, which suggests a stable long-term prognosis in SCD relatives.Table 1  Figure 1