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Cardiac Function in Children and Young Adults Treated with MEK Inhibitors: A Retrospective Cohort Study

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Abstract

MEK inhibitors (MEKi) have shown efficacy in pediatric low-grade glioma as well as plexiform neurofibroma. MEKi have been associated with acute cardiac dysfunction in adults. Cardiac consequences in children are unknown. We performed a single center retrospective cohort study evaluating cardiac function by echocardiography (echo) in children and young adults < 21 years receiving MEKi between October 2013 and May 2018. Blinded assessment of left ventricular function by fractional shortening (FS) and ejection fraction (EF) was performed on all available echocardiograms performed before, during, and following therapy, as well as after re-initiation of therapy. Twenty-six patients underwent MEKi therapy with echo follow-up during the study period. Twenty-four of these had complete echo data. Median follow-up was 12 months. Borderline EF (EF 53–57.9%) occurred in 12 (50%) patients; and 3 (12.5%) progressed to abnormal EF (EF < 53%). Cardiac dysfunction, when it occurred, was mild (lowest documented EF was 45%, and lowest FS was 24.4%). EF abnormalities typically fluctuated during therapy, resolved off therapy, and recurred with MEKi re-initiation. No clinical or demographic differences were detected between those who maintained normal cardiac function and those who developed borderline or overt cardiac dysfunction. Symptomatic heart failure did not occur. In this cohort of children and young adults, MEKi use was associated with a high (50%) incidence of borderline or mildly decreased left ventricular function. There was no evidence of permanent cardiac dysfunction. Further evaluation in larger prospective trials is needed.

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Data Availability

Raw data supporting the findings of this study are available from the corresponding authors upon request.

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Acknowledgements

The authors would like to thank Ashley S. Margol, Tom Belle Davidson, Anat Erdreich-Epstein, Kasey Rangan, Kaaren Waters, and Kimberly Bira for their intellectual contributions and assistance with data collection. The authors would also like to thank Cecilia Patino-Sutton, Todd Alonzo, and Yueh-Yun Chi for their editorial review of the manuscript drafts. MJF was a participant in the University of Southern California/CHLA Summer Oncology Research Fellowship (SORF) Program.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Children’s Hospital Los Angeles, 4650 W. Sunset Blvd, MS#54, Los Angeles, CA, 90027, USA

    Nathan J. Robison & Jemily Malvar

  2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Nathan J. Robison, Jennifer A. Su & Jondavid Menteer

  3. Division of Cardiology, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Jennifer A. Su & Jondavid Menteer

  4. Chicago Medical School at Rosalind Franklin University, North Chicago, IL, USA

    Melody J. Fang

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  1. Nathan J. Robison
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Contributions

Study conception: All authors. Data collection: MJF, NJR. Echocardiogram central review: JAS, JDM. Data analysis and interpretation: All authors. Initial manuscript draft: MJF, NJR, JAS. Revised and approved final manuscript: All authors.

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Correspondence to Nathan J. Robison.

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Conflict of Interest

The authors declare that they have no financial or non-financial conflict of interest.

Ethical Approval

The study was approved by the Children’s Hospital Los Angeles Institutional Review Board (IRB), with waiver of consent.

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Preliminary data were presented under the title “Cardiac Effects of MEK Inhibitors in Children” at the American Heart Association Scientific Sessions, Nov 2019, Philadelphia; meeting abstract published in Circulation. 2019;140:A12608.

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Robison, N.J., Su, J.A., Fang, M.J. et al. Cardiac Function in Children and Young Adults Treated with MEK Inhibitors: A Retrospective Cohort Study. Pediatr Cardiol 43, 1223–1228 (2022). https://doi.org/10.1007/s00246-022-02842-y

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  • DOI: https://doi.org/10.1007/s00246-022-02842-y

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