The Prevalence and Association of Exercise Test Abnormalities with Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients.In an international cohort study with 20 centers, phenotype-positive children with primary HCM <18 years at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response, and new or worsened ST-T wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of an abnormal exercise test with transplant and SCD event-free survival.Of 724 eligible patients, 630 underwent at least one exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8yrs (IQR 4.7yrs); 78% were male, 39% were receiving beta-blockers. 175 (28%) had an abnormal test. Patients with an abnormal test had more severe septal hypertrophy, higher left atrial diameter z-scores, higher resting LV outflow tract gradient, and higher frequency of myectomy compared to those with a normal test (p<0.05). Compared to those with a normal test, an abnormal test was independently associated with a lower 5-year transplant-free survival (97% vs. 88% respectively, p=0.005). Those with exercise-induced ischemia were most likely to experience all-cause death or transplant [Hazard ratio (HR) 4.86, CI 1.69-13.99], followed by those with an abnormal blood pressure response (HR 3.19, CI 1.32-7.71). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (HR 3.32, CI 1.27-8.70). Exercise-induced ectopy was not associated with survival.Exercise abnormalities are common in childhood HCM. An abnormal exercise test was independently associated with lower transplant-free survival especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.