Diagnostic yield in families to sudden cardiac death victims: a 10-year follow-up study

Abstract

Aims: Up to 70% of sudden cardiac death (SCD) cases in younger individuals are potentially caused by an inherited heart disease. However, long-term diagnostic yield and risk of cardiac events in SCD relatives remain unclear. This study aimed to determine the 10-year diagnostic yield of inherited heart diseases and frequency of cardiac events in SCD relatives.

Methods and results: This retrospective study included SCD probands and their relatives referred to the Unit for Inherited Heart Diseases at Rigshospitalet, Denmark, from 2005 to 2018. Relatives underwent guideline-recommended screening and follow-up. Diagnoses and cardiac events, such as new-onset reduced left ventricular ejection fraction ≤45%, sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, cardiac death, and (aborted) SCD, were registered. A total of 686 relatives (47% males, median baseline age 35 years) to 299 probands (75% males, median death age 41 years) were followed for a median of 10.6 years. At 10-year follow-up, 12% of relatives (n = 82) were diagnosed with an inherited heart disease, with 93% (n = 76) diagnosed within 5 years. Cardiac events occurred in 18 (3%) and 24 (4%) relatives after 5- and 10-year follow-up, respectively. Five (0.7%) relatives of probands with no established diagnosis, who had no diagnosis nor cardiac event within 5 years of follow-up, were diagnosed between >5 and 10 years of follow-up.

Conclusion: Long-term follow-up identified an inherited heart disease in 12% of SCD relatives, primarily diagnosed within 5 years. Cardiac events were rare (4%). These findings suggest that follow-up may be considered limited to 5 years for specific adult SCD relatives.

Keywords: Autopsy; Family screening; Genetic testing; Inherited heart disease; Prevention; Sudden cardiac death.

Graphical Abstract

Figure 1

Kaplan-Meier illustrating the probability of being diagnosed with an inherited heart disease in relatives to SCD victims, stratified by the proband’s diagnostic status. Time from baseline to diagnosis of an inherited heart disease, censoring (due to death or emigration), or study termination is shown on the x-axis (in years), and the probability of diagnosis is shown on the y-axis. A risk table shows the number at risk at year 0–10. Diagnoses given before or at baseline are included at time = 0. The P-value reflects the difference between the two groups over 10 years of follow-up.

Figure 2

The figure illustrates the number of relatives to SCD victims diagnosed with an inherited heart disease or experiencing a cardiac event over 10 years of follow-up, stratified by the proband’s diagnostic status. Cardiac events are defined as new-onset reduced LVEF ≤45%, sustained VT, appropriate implantable cardioverter-defibrillator therapy, cardiac death, and (aborted) SCD.