Abstract 11055: Outcomes and Progression of Rasopathy-Associated Hypertrophic Cardiomyopathy

Abstract

Background: RASopathy associated hypertrophic cardiomyopathy (HCM) is a frequent cause of pediatric onset HCM. RAS pathway inhibitors are a precision therapeutic option for RASopathy associated HCM. However, limited understanding of HCM progression and correlation with clinical outcomes currently restrict use to a compassionate basis, primarily in infancy. We hypothesize review of RASopathy associated HCM progression and outcomes will demonstrate burden of disease throughout childhood with the goal to identify high risk populations who may benefit from targeted therapies. Methods: A single-center retrospective review identified 59 patients with a diagnosis of HCM and a RASopathy. Echocardiographic, clinical, and molecular data were collected through chart review with echocardiographic measurements at set time points from neonate to young adult. Results: There was high overall mortality in our cohort (20.3%, n = 12). Cardiac arrest, transplant, or death was significantly higher in patients with heart failure in infancy (defined by need for diuretic use) (p<0.001) (Fig 1A). There were no differences by syndrome or genotype. Pulmonary valve (PV) intervention was 16.9% (n = 10) and largely limited to infancy with median age 0.79 years (IQR 0.34-1.63) at first intervention. Incidence of atrial arrhythmias was 13.6% (n = 8) with median age of onset 0.44 years (IQR 0.35-0.88). Rates of septal myectomy were high (23.7%, n = 14). Myectomies, however, were not limited to infancy with median age at first myectomy 3.10 years (IQR 1.09-10.49) (Fig 1B). 21.4% (n = 3) required repeat myectomy. Conclusions: In contrast to previous research, our data suggest there is significant continued HCM growth outside of infancy as evidenced by high incidence of myectomy throughout childhood and young adulthood with frequent need for repeat myectomy. These suggest potential use of targeted therapies outside of infancy with further study needed to identify high-risk populations.