Sudden Cardiac Death and ICD Use in Rasopathy-Associated Hypertrophic Cardiomyopathy

Abstract

<h3>Purpose</h3> The incidence and risk factors for sudden cardiac death in Rasopathy patients with hypertrophic cardiomyopathy (Ras-HCM) are not well understood. We compared the cumulative incidence of sudden death and ICD therapy in Ras-HCM compared to primary HCM. <h3>Methods</h3> Phenotype-positive pediatric patients with Ras-HCM (n=157) and primary HCM (n=720) were included in this 22-center retrospective cohort study. The primary outcome was 5-year freedom from sudden death events, defined as a composite of sudden death, resuscitated sudden cardiac arrest, and aborted events i.e. appropriate shock from a primary prevention ICD, estimated using the Kaplan Meier method. <h3>Results</h3> There were 17 deaths in Ras-HCM patients - 8 sudden death, 9 from noncardiac causes. The 5-year freedom from sudden death events was higher in Ras-HCM than in primary HCM (97.2% vs 93.8% respectively, p=0.039) (Figure 1A). The median age at diagnosis was lower in Ras-HCM (1.1 yr) versus primary HCM (10 yrs) (p<0.001) as was the median age at the first SCD event (0.6 yrs vs 14.4 yrs, respectively) (p=0.013). 7/157 (4.4%) Ras-HCM patients received a primary prevention ICD with no appropriate shocks during follow-up; no Ras-HCM patient received a secondary prevention ICD including the 3(2%) patients who experienced a resuscitated sudden cardiac arrest. The freedom from ICD insertion was higher at 94.6% in Ras-HCM versus 79.1% in primary HCM (p<0.001) (Figure 1B). The median age at ICD insertion was not different between the two groups - 15.2 yrs for Ras-HCM and 14.8 yrs for primary HCM. <h3>Conclusion</h3> The incidence of sudden cardiac death is lower in pediatric Rasopathy patients with HCM compared to primary HCM with most events occurring in infancy. It is less likely for Rasopathy patients to receive an ICD than a primary HCM patient even for secondary prevention, possibly due to younger patient age at the time of the event. Further research on risk factors for and mechanisms of sudden death in Ras-HCM is warranted.