Pulmonary Hypertension in Pediatric Patients with Noonan Syndrome Undergoing Cardiac Catheterization

Noonan syndrome (NS) is an autosomal dominant genetic disorder associated with a high incidence of cardiovascular disease. We investigated pulmonary hypertension (PH) in patients with NS, characterizing the prevalence, genetic, and clinical features including hemodynamics, cardiovascular interventions, and transplant-free survival. A retrospective, descriptive cohort study was conducted among pediatric patients with NS who underwent cardiac catheterization. Patient demographic, clinical, and hemodynamic data were collected for cohorts of patients with and without PH. We identified 87 patients with NS who had undergone cardiac catheterization including hemodynamics at Boston Children's Hospital between 2000 and 2020. Of them, 59 (68%) had a NS-associated genetic mutation in the RAS-MAPK signaling pathway, while 28 (32%) had a clinical diagnosis of NS. In the cohort, 11/87 (13%) had PH. There were significant differences in NS-associated genetic mutations; variants in RAF1 (p = 0.013) and KRAS (p = 0.015) were more common among PH patients. Hypertrophic cardiomyopathy (p = 0.009) was more common in PH patients, while valvar, subvalvar, or supravalvar PS (p = 0.011) was less common. PH patients had more aortic-valve interventions (p = 0.025) and fewer valvar right-sided heart interventions (p = 0.037). Transplant-free survival was lower in the PH group than the non-PH group (p = 0.004). There are novel features to cardiovascular outcomes for genetically defined subsets of patients with NS, including significant differences in the NS-associated causative genes, associated hypertrophic cardiomyopathy, structural heart disease, interventions, and transplant-free survival.