Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy

Markman, Timothy M.; Ruble, Kathy; Loeb, David M.; Chen, Allen; Zhang, Yiyi; Beasley, Gary S.; Thompson, W. L.; Nazarian, Saman

doi:10.1002/pbc.26556

Cited by 31 publications

(21 citation statements)

References 32 publications

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“…Drug-induced QTc interval prolongation has been considered to be a critical risk factor for cardiac toxicity and probably leads to palpitations, syncope, and sudden cardiac death caused by severe ventricular arrhythmias [30; 33; 34]. With a follow-up study of cardiac function in 147 adult surviving patients who had previously suffered from childhood tumors and received anthracycline chemotherapy, Markman TM et al found that the prolonged QTc interval was related to the subsequent development of left ventricular dysfunction [14], suggesting that the QTc interval might be an earlier indicator for evaluating the impairment of cardiac function than LVEF. The normal range of the QTc interval is 350-450 ms in adult males and 360-460 ms in adult females [33].…”

Section: Discussionmentioning

confidence: 99%

Summed rest score in gated myocardial perfusion imaging is a good predicator for treatment-related cardiotoxicity after anthracycline chemotherapy in diffuse large B-cell lymphoma patients

Yang¹,

Wang²,

Xu³

et al. 2020

Preprint

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Background: Anthracycline chemotherapy is commonly used in the treatment of diffuse large B-cell lymphoma (DLBCL) patients. Treatment-related cardiotoxicity (TRC) may be observed during treatment and may induce severe cardiac failure or cardiac arrhythmia as the main cause of death, even several years after chemotherapy implementation. Herein, we performed a study to investigate the prognostic value of gated myocardial perfusion imaging (G-MPI) summed rest score (SRS) for the early detection of TRC caused by anthracycline chemotherapy in DLBCL patients.Methods: A total of 36 DLBCL patients were enrolled, and a series of parameters from the same individual patient were compared between baseline and after the end of the 6th R-CHOP chemotherapeutic regimen. According to whether TRC occurred during the observation period, the patients were divided into two groups, and parameters related to cardiac function were compared.Results: SRS in G-MPI and QTc interval in electrocardiogram were significantly different before and after chemotherapy (P = 0.012 and P = 0.015, respectively).By comparing parameters related to cardiac function between the TRC group (n = 22) and the no-TRC group (n = 14), only SRS was significantly different (P = 0.012). Multivariate logistic regression analysis showed that the SRS level was the only independent predicator for TRC (P = 0.018, HR = 6.053, 95% CI: 1.364-26.869). Receiver operating characteristic curve analysis identified an optimal SRS cutoff of >1for predicting TRC after anthracycline chemotherapy (P＜ 0.001).Conclusion: The G-MPI SRS level was an early indicator for TRC surveillance in DLBCL patients after anthracycline chemotherapy, thus contributing to early treatment and a subsequent decrease in mortality caused by such cardiovascular complications.

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Section: Discussionmentioning

confidence: 99%

Summed rest score in gated myocardial perfusion imaging is a good predicator for treatment-related cardiotoxicity after anthracycline chemotherapy in diffuse large B-cell lymphoma patients

Yang¹,

Wang²,

Xu³

et al. 2020

Preprint

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“…Two ECG endpoints were pre-specified: the sum of absolute QRS amplitudes in the 6 limb leads (ΣQRS(6 L)) and the corrected QT (QTc) interval. These endpoints were chosen based on preliminary data from previously published work [8,9,11]. Amplitudes were measured in millivolts (mV) from peak to trough of the QRS.…”

Section: Ecg Evaluationmentioning

confidence: 99%

“…Additionally, ECGs are inexpensive and technically straightforward to obtain. Preliminary studies have evaluated ECG changes after anthracycline exposure; however, these changes have not been extensively studied in larger or primarily pediatric cohorts [1,[8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure

et al. 2019

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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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“…In their current study, Markman et al . performed exploratory analyses to determine whether electrocardiographic abnormalities might help predict which anthracycline‐treated childhood cancer survivors will go on to develop left ventricular (LV) systolic dysfunction.…”

mentioning

confidence: 99%

“…In their current study, Markman et al 4 performed exploratory analyses to determine whether electrocardiographic abnormalities might help predict which anthracycline-treated childhood cancer survivors will go on to develop left ventricular (LV) systolic dysfunction. This is the first such study to attempt to explore this question using prospective analyses, that is, accounting for the temporality of events, albeit In their cohort study, the authors reviewed their institution's clinic records for adult survivors of childhood cancer who after finishing therapy that included anthracyclines had at least one electrocardiogram prior to having at least one echocardiogram.…”

mentioning

confidence: 99%

Electrocardiography's role in screening for cardiotoxicity in adult survivors of childhood cancer survivors treated with anthracyclines: Time for a true prospective study?

Adams

2017

Pediatric Blood & Cancer

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Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy

Abstract: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.

Cited by 31 publications

References 32 publications

Summed rest score in gated myocardial perfusion imaging is a good predicator for treatment-related cardiotoxicity after anthracycline chemotherapy in diffuse large B-cell lymphoma patients

Summed rest score in gated myocardial perfusion imaging is a good predicator for treatment-related cardiotoxicity after anthracycline chemotherapy in diffuse large B-cell lymphoma patients

Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure

Electrocardiography's role in screening for cardiotoxicity in adult survivors of childhood cancer survivors treated with anthracyclines: Time for a true prospective study?

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