Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy

Timothy M. Markman, Kathy Ruble, David Loeb, Allen R Chen, Yiyi Zhang, Gary S. Beasley, Reid Thompson, Saman Nazarian

Research output: Contribution to journalArticle

Abstract

Background: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction. Methods: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed. The association between dysfunction and baseline characteristics, treatment history, and electrocardigraphic parameters were analyzed using multivariable logistic regression. Additionally, a longitudinal generalized estimating equation (GEE) model was used to examine the temporal association between repeated measure corrected QT (QTc) intervals and subsequent LV function. Results: In our population, 24% of patients had LV dysfunction. The initial posttreatment QTc interval was longer in patients with LV dysfunction (438 ± 35 vs. 420 ± 20 msec, P = 0.002). In logistic regression analysis, QTc interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the QTc was longer than on ECGs preceding a normal echocardiogram (451 ± 32 msec vs. 423 ± 25 msec, P < 0.001). Mean time from QTc ≥ 450 msec to evidence of LV dysfunction was 1.8 ± 2.9 years. In the longitudinal GEE model, QTc prolongation was associated with subsequent decreased fractional shortening. Conclusions: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.

Original languageEnglish (US)
JournalPediatric Blood and Cancer
DOIs
StateAccepted/In press - 2017

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Anthracyclines
Left Ventricular Dysfunction
Survivors
Pediatrics
Neoplasms
Electrocardiography
Logistic Models
Left Ventricular Function
Cardiac Arrhythmias
History
Regression Analysis
Radiation
Population

Keywords

  • Anthracycline
  • Arrhythmia
  • Cardiotoxicity after chemotherapy
  • QTc interval

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy. / Markman, Timothy M.; Ruble, Kathy; Loeb, David; Chen, Allen R; Zhang, Yiyi; Beasley, Gary S.; Thompson, Reid; Nazarian, Saman.

In: Pediatric Blood and Cancer, 2017.

Research output: Contribution to journalArticle

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AU - Markman, Timothy M.

AU - Ruble, Kathy

AU - Loeb, David

AU - Chen, Allen R

AU - Zhang, Yiyi

AU - Beasley, Gary S.

AU - Thompson, Reid

AU - Nazarian, Saman

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N2 - Background: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction. Methods: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed. The association between dysfunction and baseline characteristics, treatment history, and electrocardigraphic parameters were analyzed using multivariable logistic regression. Additionally, a longitudinal generalized estimating equation (GEE) model was used to examine the temporal association between repeated measure corrected QT (QTc) intervals and subsequent LV function. Results: In our population, 24% of patients had LV dysfunction. The initial posttreatment QTc interval was longer in patients with LV dysfunction (438 ± 35 vs. 420 ± 20 msec, P = 0.002). In logistic regression analysis, QTc interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the QTc was longer than on ECGs preceding a normal echocardiogram (451 ± 32 msec vs. 423 ± 25 msec, P < 0.001). Mean time from QTc ≥ 450 msec to evidence of LV dysfunction was 1.8 ± 2.9 years. In the longitudinal GEE model, QTc prolongation was associated with subsequent decreased fractional shortening. Conclusions: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.

AB - Background: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction. Methods: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed. The association between dysfunction and baseline characteristics, treatment history, and electrocardigraphic parameters were analyzed using multivariable logistic regression. Additionally, a longitudinal generalized estimating equation (GEE) model was used to examine the temporal association between repeated measure corrected QT (QTc) intervals and subsequent LV function. Results: In our population, 24% of patients had LV dysfunction. The initial posttreatment QTc interval was longer in patients with LV dysfunction (438 ± 35 vs. 420 ± 20 msec, P = 0.002). In logistic regression analysis, QTc interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the QTc was longer than on ECGs preceding a normal echocardiogram (451 ± 32 msec vs. 423 ± 25 msec, P < 0.001). Mean time from QTc ≥ 450 msec to evidence of LV dysfunction was 1.8 ± 2.9 years. In the longitudinal GEE model, QTc prolongation was associated with subsequent decreased fractional shortening. Conclusions: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.

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