Sudden Death Risk in Patients With RASopathy Hypertrophic Cardiomyopathy

Quick Takes

  • Compared with primary hypertrophic cardiomyopathy (P-HCM), patients with RAS-HCM had similar risk for sudden cardiac death (SCD), transplant, and all-cause death, but a higher risk for nonarrhythmic death.
  • Death during infancy in RAS-HCM was related to nonarrhythmic (heart failure) death and during adolescence was related to SCD.
  • Despite similar risk for SCD compared with P-HCM patients, RAS-HCM patients were 5 times less likely to receive an ICD.

Study Questions:

What is the incidence of sudden cardiac death (SCD), nonarrhythmic death, transplant, and implantable cardioverter-defibrillator (ICD) use in RAS-hypertrophic cardiomyopathy (HCM) compared with nonsyndromic, primary HCM (P-HCM)?


This was a multicenter, retrospective cohort study of pediatric patients with RAS-HCM and P-HCM across 21 sites. It included all phenotype-positive probands under 18 years of age with septal or posterior wall thickness >2 standard deviations above mean for body surface area on echocardiography. RAS-HCM was diagnosed clinically or based on genetic testing.


The cohort included 188 phenotype-positive patients with RAS-HCM and 567 patients with P-HCM. RAS-HCM was diagnosed at a younger age, included more females, and predominantly included patients with Noonan syndrome (81%). There was no difference in incidence of myectomy at 10 years between the two groups, but RAS-HCM patients were younger at myectomy (median age, 6.2 vs. 11.4 years). The 10-year incidence of all-cause death or transplant was not statistically significant but numerically higher in the RAS-HCM group (15.7% vs. 9.6%). In the RAS-HCM group, risk for all-cause death or transplant was higher in the first year of life and a second risk period between 11-16 years of life. The 10-year risk for SCD was not different in the two cohorts but the 10-year incidence of nonarrhythmic death or transplant was higher in the RAS-HCM group (11% vs. 5.4%). Death during infancy in RAS-HCM patients was related to nonarrhythmic deaths and adolescent deaths were related to SCD. RAS-HCM patients were less likely to receive an ICD (6.9% vs. 36.6%).


In a large multicenter cohort of RAS-HCM patients, compared with P-HCM patients, death in infancy was most likely due to heart failure and adolescent deaths were due to SCD. Despite similar burden of SCD in RAS-HCM patients, these patients were much less likely to receive ICDs compared with P-HCM patients.


RASopathies are a common cause for HCM in the pediatric population, accounting for 33% of infantile HCM and 12.5% of pediatric HCM. This study presents data from one of the largest cohorts of RAS-HCM patients and presents clinical trajectory for this cohort. RAS-HCM patients were younger at presentation and at myectomy. The 10-year incidence of all-cause death or transplant or SCD did not differ between the two cohorts, but incidences of nonarrhythmic death or transplant were higher in the RAS-HCM group. Most importantly, despite a similar risk for SCD compared with the P-HCM group, patients with RAS-HCM were over 5 times less likely to receive an ICD. Accordingly, better risk stratification systems are needed to inform timing for an ICD for primary prevention in RAS-HCM patients.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Heart Transplant, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound

Keywords: Adolescent, Arrhythmias, Cardiac, Cardiomyopathy, Hypertrophic, Death, Sudden, Death, Sudden, Cardiac, Defibrillators, Implantable, Echocardiography, Genetic Testing, Heart Failure, Heart Transplantation, Noonan Syndrome, Pediatrics, Phenotype, Primary Prevention, Risk Assessment

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