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Risk Factors for Cardiac and Non-cardiac Causes of Death in Males with Duchenne Muscular Dystrophy

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Abstract

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9–24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0–19.1) years] than those dying of cardiac [18 (IQR 15.5–24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5–23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

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Funding

Database creation and management was funded by the Division of Pediatric Cardiology at Golisano Children’s Hospital, University of Rochester Medical Center, Rochester, New York. David R. Weber received salary support from NIH Grant K23DK114477.

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Author notes

  1. Carol A. Wittlieb-Weber

    Present address: Division of Cardiology, The Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Golisano Children’s Hospital, University of Rochester Medical Center, Rochester, NY, USA

    Carol A. Wittlieb-Weber & David R. Weber

  2. Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Kenneth R. Knecht

  3. The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Chet R. Villa

  4. Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada

    Chentel Cunningham & Jennifer Conway

  5. Loma Linda University Children’s Hospital, Loma Linda, CA, USA

    Matthew J. Bock

  6. Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Katheryn E. Gambetta

  7. Primary Children’s Hospital, University of Utah, Salt Lake City, UT, USA

    Ashwin K. Lal

  8. C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, USA

    Kurt R. Schumacher

  9. Morgan Stanley Children’s Hospital of New York Presbyterian, New York, NY, USA

    Sabrina P. Law & Irene D. Lytrivi

  10. Children’s National, Washington, D.C., USA

    Shriprasad R. Deshpande

  11. Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA

    Shawn C. West

  12. Seattle Children’s Hospital, Seattle, WA, USA

    Joshua M. Friedland-Little

  13. University of Virginia Children’s Hospital, Charlottesville, VA, USA

    Michael A. McCulloch

  14. Children’s Medical Center of Dallas, UT Southwestern Medical Center, Dallas, TX, USA

    Ryan J. Butts

  15. Mayo Clinic Children’s Center, Rochester, MN, USA

    Jonathan N. Johnson

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  1. Carol A. Wittlieb-Weber
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  2. Kenneth R. Knecht
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  3. Chet R. Villa
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  4. Chentel Cunningham
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  5. Jennifer Conway
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  12. Shawn C. West
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  15. Michael A. McCulloch
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  16. Ryan J. Butts
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  17. David R. Weber
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Corresponding author

Correspondence to Carol A. Wittlieb-Weber.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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A waiver of informed consent was obtained for this study given the retrospective nature.

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Wittlieb-Weber, C.A., Knecht, K.R., Villa, C.R. et al. Risk Factors for Cardiac and Non-cardiac Causes of Death in Males with Duchenne Muscular Dystrophy. Pediatr Cardiol 41, 764–771 (2020). https://doi.org/10.1007/s00246-020-02309-y

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  • DOI: https://doi.org/10.1007/s00246-020-02309-y

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