Survival implications: Hypertrophic cardiomyopathy in noonan syndrome

Objectives. To understand relationships and survival implications between structural heart disease and hypertrophic cardiomyopathy in Noonan syndrome (Noonan syndrome-HCM), we reviewed the clinical course of 138 children with Noonan syndrome diagnosed with cardiovascular abnormalities and compared survival with the 30 children with Noonan syndrome-HCM with 120 contemporaneous children with nonsyndromic HCM. Methods. Study cohorts represent consecutive cases diagnosed at our institution 1966 through 2006. Outcomes were modeled using multiphase parametric techniques followed by multivariable regression with bagging. Results. Cardiac abnormalities in Noonan syndrome: Cardiac abnormalities in the 138 Noonan syndrome children included pulmonary valve dysplasia (52%), hypertrophic cardiomyopathy (22%), atrial septal defect (20%), ventricular septal defect (10%), mitral valve dysplasia (6%), coarctation (3%), and Fallot's tetralogy (2%). Need for surgery was high but not different from children with structural defects coexisting with HCM. Overall, late survival in children with Noonan syndrome and cardiac defects was good (91 ± 3% at 15 years), although significantly worse for those with Noonan syndrome-HCM (P < .01). Noonan syndrome-HCM vs. nonsyndromic HCM: In the 30 children with Noonan syndrome-HCM, structural cardiac malformations coexisted in 18 (57%). The incidence of structural cardiac malformations in nonsyndromic HCM was instead 3/120 (2.5%, P < .001). Risk-adjusted late survival was significantly worse for Noonan syndrome-HCM than for nonsyndromic HCM (P= .02). Conclusions. Noonan syndrome-HCM frequently coexists with structural cardiac malformations, whereas nonsyndromic HCM does not; their natural histories may therefore be different. Late survival is significantly worse for Noonan syndrome-HCM than nonsyndromic HCM.