Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure
Lajja Desai1,2, Lauren Balmert2, Jennifer Reichek2,3
11Division of Cardiology, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 East Chicago Avenue, Box 21, Chicago, IL 60611 USA.
Insights
Electrocardiogram (ECG) changes, specifically decreased QRS amplitude and prolonged QT interval (QTc), can predict anthracycline-induced cardiomyopathy in children. These ECG findings may serve as early, non-invasive risk stratification tools for this serious condition.
Area of Science:
- Pediatric Oncology
- Cardiology
- Pharmacology
Background:
- Anthracycline chemotherapy is crucial for treating childhood cancers but can induce cardiomyopathy, a significant cause of morbidity and mortality.
- Early detection of anthracycline-induced cardiomyopathy is vital for improving patient outcomes, yet effective risk stratification tools are lacking.
- This study investigates whether specific electrocardiogram (ECG) changes can precede echocardiographic evidence of cardiomyopathy in pediatric patients.
Purpose of the Study:
- To evaluate the predictive value of ECG parameters, including the sum of absolute QRS amplitudes in 6 limb leads (ΣQRS(6 L)) and corrected QT interval (QTc), for anthracycline-induced cardiomyopathy in children.
- To determine if ECG abnormalities can serve as an early, non-invasive risk stratification tool for identifying children at high risk of developing cardiomyopathy.
- To assess the association between ECG changes, cardiomyopathy development, and overall mortality in pediatric cancer patients treated with anthracyclines.
Main Methods:
- A retrospective analysis was conducted on 589 pediatric cancer patients who received anthracyclines.
- ECG parameters, ΣQRS(6 L) and QTc, were measured and analyzed.
- Cardiomyopathy was diagnosed using echocardiographic criteria (ejection fraction <50%, shortening fraction <26%, or LV end-diastolic diameter z-score >2.5).
Main Results:
- 19.5% of patients developed cardiomyopathy.
- A decrease in ΣQRS(6 L) and an increase in QTc were significantly associated with an increased risk of developing cardiomyopathy.
- Higher anthracycline doses independently predicted decreases in ΣQRS(6 L) and increases in QTc, irrespective of cardiomyopathy status; cardiomyopathy was linked to increased mortality.
Conclusions:
- Decreased ΣQRS(6 L) and prolonged QTc are associated with an elevated risk of anthracycline-induced cardiomyopathy in pediatric patients.
- ECG monitoring shows promise as a non-invasive tool for early risk stratification of anthracycline-induced cardiomyopathy.
- Prospective validation is needed to confirm the utility of ECG parameters in clinical practice for predicting and managing cardiotoxicity.
Background:
Early 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.
Methods:
We 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.
Results:
Median 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).
Conclusion:
In 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.
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