Abstract
BACKGROUND: Noonan syndrome-associated hypertrophic cardiomyopathy (NS-HCM) is often lethal when presenting severely in infancy, especially when associated with structural heart disease. Trametinib, an MEK inhibitor that attenuates abnormal signaling in the RAS/MAPK pathway, has been shown to improve NS-HCM outcomes. Surgery for associated heart defects in hypertrophic cardiomyopathy remains worrisome for increased risk of complications. FIRST-IN-HUMAN/EARLY REPORTS SUMMARY: An infant presented with a large secundum atrial septal defect complicating NS-HCM. The patient was treated with trametinib to improve cardiac hypertrophy and then underwent successful surgical closure of the atrial septal defect. DISCUSSION: This serial strategy allowed for rescue from severe heart failure presentation to eventual discharge home without cardiac symptoms. NOVELTY: This is, to our knowledge, the first patient with NS-HCM to undergo medical treatment with trametinib and then cardiac surgery for a structural heart defect. TAKE-HOME MESSAGES: Infants with severe presentations of NS-HCM and congenital heart defects can be medically stabilized with trametinib and then undergo successful structural heart surgery.