What about the heart - pediatric ALL survivors show cardiopulmonary limitations in the MinimALL Study

Childhood survivors of acute lymphoblastic leukemia (ALL) and Hodgkin disease (HD) are at risk of long-term cardiopulmonary impairments due to cardiotoxic chemotherapy and inactivity. This study aims to assess the cardiopulmonary fitness and cardiac function of pediatric cancer survivors (PCS) using cardiopulmonary exercise testing (CPET) and echocardiography, including strain imaging, to determine the extent of functional limitations and their underlying causes. This prospective, single-center study included 27 PCS (21 with ALL, 6 with HD) and 27 age-matched healthy controls. Participants underwent echocardiography with strain analysis and CPET on a treadmill to evaluate cardiac function and exercise capacity. Key parameters such as ejection fraction (EF), global longitudinal strain (GLS), E/E' ratio, peak oxygen uptake ( $\dot{V}{O}_{2}peak$ ), and breathing efficiency were analyzed. PCS exhibited significantly lower $\dot{V}{O}_{2}peak$ compared to controls (38.3 ± 7.7 ml/kg/min vs. 46.4 ± 5.4 ml/kg/min, p = 0.001), along with a reduced peak heart rate (p = 0.001). Echocardiographic analysis showed that while EF and GLS remained within normal ranges, E/E' septal was significantly elevated (p = 0.001). Pulmonary parameters did not indicate significant ventilatory limitations.

Our study underscores the importance of diastolic assessments and advanced echocardiographic techniques in monitoring PCS, with E/E' septal emerging as a key marker. CPET provides valuable insights into the functional impact of early cardiac changes. Despite signs of diastolic dysfunction at rest, stroke volume and pulmonary function were preserved during exercise, suggesting that detraining may partly contribute to reduced $\dot{V}{O}_{2}peak$ .

NCT06093334.

• Childhood survivors of ALL and HD are at risk of long-term cardiopulmonary impairments due to chemotherapy-related cardiotoxicity and reduced physical activity. • CPET and echocardiography, including strain imaging, are valuable tools for assessing cardiac function and exercise capacity in this population.

• Early diastolic dysfunction detected: despite normal EF and GLS, PCS exhibit an elevated E/E' septal ratio, reinforcing its role as a key marker for early cardiac changes.• Reduced exercise capacity linked to detraining: PCS show significantly lower $\dot{V}{O}_{2}peak$ and peak heart rate, while stroke volume and pulmonary function remain preserved, suggesting detraining as a contributing factor.