Background: Anthracyclines (ANT) are a common class of chemotherapeutic agents among pediatric oncologic diseases and can cause dilated or restrictive cardiomyopathy. However, overt ventricular dysfunction often does not develop until adulthood. Therefore, screening cardiac function by echocardiogram (echo) may not be sufficiently sensitive to detect early stages of ANT toxicity in children. Exercise capacity is known to be reduced among adult recipients of ANT and may be related to subclinical cardiomyopathy. Our study sought to examine whether echo findings correlate with the extent of cardiorespiratory fitness in pediatric cancer patients treated with ANT. 

Methods: Retrospective cohort analysis including 35 patients who underwent echo and cardiopulmonary exercise testing (CPET) from our chemotherapy cardiac surveillance clinic was completed. Cardiac MRI was performed in 21 of these patients. Pearson’s or Spearman’s correlations were used to identify the relationship between echo parameters and CPET variables. Univariate and multivariate logistic regression analyses were performed to investigate various effects on peak VO2% including echo findings and oncologic data.

Results: Mean age was 17 years (10-23y). Mean time from ANT exposure was 8 years (1.8 -16.2y) and the mean doxorubicin dose was 327 mg/m^2. The most common oncologic diagnoses were lymphocytic leukemia and Hodgkin’s lymphoma. The mean peak VO2 was 27±7.2 mL/kg/min, mean peak VO2% was 62% ±2.7, and 88% of participants had a peak VO2 below 80% predicted. There was no significant correlation between peak VO2% and left ventricular (LV) systolic function. However, there was a positive correlation between LV chamber size (LV internal dimension in diastole; LVIDd) and peak VO2% (R2 0.57, p=0.006), which was also true in multivariate analysis (estimate 6.3, p<0.001). LV volume by MRI (LVEDV Z-score) also correlated with peak VO2% (R2 0.46, p =0.0012).

Conclusion: Most of our patients who received ANT had reduced exercise capacity, despite having normal cardiac function. However, LV size correlated closely with exercise capacity. CPET is a valuable adjunct to echo for detecting subclinical cardiomyopathy. Future studies should explore the utility of echo as a screening tool for ANT-induced cardiomyopathy.