Abstract
BackgroundEarly recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking. This study evaluates whether electrocardiogram (ECG) changes precede echocardiographic abnormalities in children with anthracycline-induced cardiomyopathy.MethodsWe performed a retrospective analysis of 589 pediatric cancer patients who received anthracyclines at a tertiary referral center. ECG endpoints were sum of absolute QRS amplitudes in the 6 limb leads (ΣQRS(6 L)) and corrected QT interval (QTc). Cardiomyopathy was defined by echocardiogram as ejection fraction < 50%, shortening fraction < 26%, or left ventricular end-diastolic diameter z-score > 2.5.ResultsMedian age at start of therapy was 7.8 years (IQR 3.7–13.6); median follow-up time was 3.6 years (IQR 1.1–5.8). 19.5% of patients met criteria for cardiomyopathy. Male sex, race, older age at first dose, and larger body surface area were associated with development of cardiomyopathy. A 0.6 mV decrease in ΣQRS(6 L) and 10 ms increase in QTc were associated with an increased risk of developing cardiomyopathy with hazard ratios of 1.174 (95% CI = 1.057–1.304, p = 0.003) and 1.098 (95%CI = 1.027–1.173, p = 0.006) respectively. Kaplan-Meier estimates showed a lower chance of cardiomyopathy-free survival for QTc ≥ 440 ms and ΣQRS(6 L) ≤ 3.2 mV over time. After controlling for confounders, total anthracycline dose predicted a decrease in ΣQRS(6 L) and an increase in QTc independent of cardiomyopathy status (p = 0.01 and p < 0.001 respectively). Cardiotoxic radiation did not predict changes in ECG parameters. Cardiomyopathy was associated with increased mortality (34% versus 12%, p < 0.001).ConclusionIn children receiving anthracyclines, decrease in ΣQRS(6 L) and QTc prolongation are associated with increased risk of developing cardiomyopathy. ECG is a potential non-invasive risk stratification tool for prediction of anthracycline-induced cardiomyopathy and requires prospective validation.
Highlights
Recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking
Race, older age at first dose, larger body surface area (BSA) and total anthracycline dose were associated with development of cardiomyopathy (Table 1)
Our study demonstrates that clinically measurable ECG changes, a decrease in ΣQRS(6 L) and prolongation of the corrected QTc interval (QTc) interval, are associated with an increased risk of developing anthracycline-induced cardiomyopathy
Summary
Recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking. This study evaluates whether electrocardiogram (ECG) changes precede echocardiographic abnormalities in children with anthracycline-induced cardiomyopathy. Prevention or early recognition of anthracyclineinduced cardiomyopathy is important in children to reduce long-term morbidity and mortality. Anthracyclineinduced cardiomyopathy can develop acutely (within the there are long-term cardiotoxicity screening guidelines for survivors of childhood, adolescent and (2019) 5:10 young adult cancers developed by The Children’s Oncology Group (COG), there continues to be debate on the diagnostic modalities to use and frequency of monitoring. There are no current guidelines on the timing or type of cardiac testing outside of echocardiograms that should be done for children during anthracycline treatment and in the acute and early exposure period [1,2,3, 7]. Preliminary studies have evaluated ECG changes after anthracycline exposure; these changes have not been extensively studied in larger or primarily pediatric cohorts [1, 8,9,10,11]
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