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Novel Cardiac Imaging Risk Score for Mortality Prediction in Duchenne Muscular Dystrophy

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Abstract

Cardiovascular disease is the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD), but there is significant cardiomyopathy phenotypic variability. Some patients demonstrate rapidly progressive disease and die at a young age while others survive into the fourth decade. Criteria to identify DMD subjects at greatest risk for early mortality could allow for increased monitoring and more intensive therapy. A risk score was created describing the onset and progression of left ventricular dysfunction and late gadolinium enhancement in subjects with DMD. DMD subjects prospectively enrolled in ongoing observational studies (which included cardiac magnetic resonance [CMR]) were used to validate the risk score. A total of 69 subjects had calculable scores. During the study period, 12 (17%) died from complications of DMD. The median risk score was 3 (IQR [2,5]; range [0,9]). The overall risk score applied at the most recent imaging age was associated with mortality at a median age of 17 years (IQR [16,20]) (HR 2.028, p < 0.001). There were no deaths in subjects with a score of less than two. Scores were stable over time. An imaging-based risk score allows risk stratification of subjects with DMD. This can be quickly calculated during a clinic visit to identify subjects at greatest risk of early death.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Crisafulli S, Sultana J, Fontana A et al (2020) Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis 15:141. https://doi.org/10.1186/s13023-020-01430-8

    Article  PubMed  PubMed Central  Google Scholar 

  2. Eagle M, Baudouin SV, Chandler C et al (2002) Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 12:926–929. https://doi.org/10.1016/S0960-8966(02)00140-2

    Article  PubMed  Google Scholar 

  3. Bach JR, Martinez D (2011) Duchenne muscular dystrophy: continuous noninvasive ventilatory support prolongs survival. Respir Care 56:744–750. https://doi.org/10.4187/respcare.00831

    Article  PubMed  Google Scholar 

  4. Birnkrant DJ, Bushby K, Bann CM et al (2018) Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 17:347–361. https://doi.org/10.1016/S1474-4422(18)30025-5

    Article  PubMed  PubMed Central  Google Scholar 

  5. Silva MC, Meira ZMA, Gurgel Giannetti J et al (2007) Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol 49:1874–1879. https://doi.org/10.1016/j.jacc.2006.10.078

    Article  PubMed  Google Scholar 

  6. Hor KN, Taylor MD, Al-Khalidi HR et al (2013) Prevalence and distribution of late gadolinium enhancement in a large population of patients with Duchenne muscular dystrophy: effect of age and left ventricular systolic function. J Cardiovasc Magn Reson 15:107. https://doi.org/10.1186/1532-429X-15-107

    Article  PubMed  PubMed Central  Google Scholar 

  7. Menon SC, Etheridge SP, Liesemer KN et al (2014) Predictive value of myocardial delayed enhancement in Duchenne muscular dystrophy. Pediatr Cardiol 35:1279–1285. https://doi.org/10.1007/s00246-014-0929-z

    Article  PubMed  Google Scholar 

  8. Soslow JH, Hall M, Burnette WB et al (2019) Creation of a novel algorithm to identify patients with Becker and Duchenne muscular dystrophy within an administrative database and application of the algorithm to assess cardiovascular morbidity. Cardiol Young 29:290–296. https://doi.org/10.1017/S1047951118002226

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wittlieb-Weber CA, Knecht KR, Villa CR et al (2020) Risk factors for cardiac and non-cardiac causes of death in males with Duchenne muscular dystrophy. Pediatr Cardiol 41:764–771. https://doi.org/10.1007/s00246-020-02309-y

    Article  PubMed  Google Scholar 

  10. Florian A, Ludwig A, Engelen M et al (2014) Left ventricular systolic function and the pattern of late-gadolinium-enhancement independently and additively predict adverse cardiac events in muscular dystrophy patients. J Cardiovasc Magn Reson 16:81. https://doi.org/10.1186/s12968-014-0081-1

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wang M, Birnkrant DJ, Super DM et al (2018) Progressive left ventricular dysfunction and long-term outcomes in patients with Duchenne muscular dystrophy receiving cardiopulmonary therapies. Open Heart 5:e000783. https://doi.org/10.1136/openhrt-2018-000783

    Article  PubMed  PubMed Central  Google Scholar 

  12. Soslow JH, Xu M, Slaughter JC et al (2019) The role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in Duchenne muscular dystrophy cardiomyopathy. J Card Fail 25:259–267. https://doi.org/10.1016/j.cardfail.2019.02.006

    Article  PubMed  PubMed Central  Google Scholar 

  13. Raucci FJ, Xu M, George-Durrett K et al (2021) Non-contrast cardiovascular magnetic resonance detection of myocardial fibrosis in Duchenne muscular dystrophy. J Cardiovasc Magn Reson 23:48. https://doi.org/10.1186/s12968-021-00736-1

    Article  PubMed  PubMed Central  Google Scholar 

  14. James KA, Gralla J, Ridall LA et al (2020) Left ventricular dysfunction in Duchenne muscular dystrophy. Cardiol Young 30:171–176. https://doi.org/10.1017/S1047951119002610

    Article  PubMed  PubMed Central  Google Scholar 

  15. Soslow JH, Xu M, Slaughter JC et al (2016) Evaluation of echocardiographic measures of left ventricular function in patients with Duchenne muscular dystrophy: assessment of reproducibility and comparison to cardiac magnetic resonance imaging. J Am Soc Echocardiogr 29:983–991. https://doi.org/10.1016/j.echo.2016.07.001

    Article  PubMed  PubMed Central  Google Scholar 

  16. Harris PA, Taylor R, Thielke R et al (2009) Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42:377–381. https://doi.org/10.1016/j.jbi.2008.08.010

    Article  PubMed  Google Scholar 

  17. Harris PA, Taylor R, Minor BL et al (2019) The REDCap consortium: building an international community of software platform partners. J Biomed Inform 95:103208. https://doi.org/10.1016/j.jbi.2019.103208

    Article  PubMed  PubMed Central  Google Scholar 

  18. Corrado G, Lissoni A, Beretta S et al (2002) Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol 89:838–841. https://doi.org/10.1016/S0002-9149(02)02195-1

    Article  PubMed  Google Scholar 

  19. Schram G, Fournier A, Leduc H et al (2013) All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 61:948–954. https://doi.org/10.1016/j.jacc.2012.12.008

    Article  PubMed  Google Scholar 

  20. Brunklaus A, Parish E, Muntoni F et al (2015) The value of cardiac MRI versus echocardiography in the pre-operative assessment of patients with Duchenne muscular dystrophy. Eur J Paediatr Neurol 19:395–401. https://doi.org/10.1016/j.ejpn.2015.03.008

    Article  CAS  PubMed  Google Scholar 

  21. Jefferies JL, Eidem BW, Belmont JW et al (2005) Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 112:2799–2804. https://doi.org/10.1161/CIRCULATIONAHA.104.528281

    Article  PubMed  Google Scholar 

  22. Puchalski MD, Williams RV, Askovich B et al (2009) Late gadolinium enhancement: precursor to cardiomyopathy in Duchenne muscular dystrophy? Int J Cardiovasc Imaging 25:57–63. https://doi.org/10.1007/s10554-008-9352-y

    Article  PubMed  Google Scholar 

  23. Tandon A, Villa CR, Hor KN et al (2015) Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in Duchenne muscular dystrophy. J Am Heart Assoc. https://doi.org/10.1161/JAHA.114.001338

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bourke JP, Watson G, Spinty S et al (2021) Preventing cardiomyopathy in DMD: a randomized placebo-controlled drug trial. Neurol Clin Pract 11:e661–e668. https://doi.org/10.1212/CPJ.0000000000001023

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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Funding

Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL123938 and R56HL141248 (Bethesda, MD) (Soslow). The project was supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06 (Bethesda, MD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This project was supported by the Food and Drug Administration Orphan Products Grant R01FD006649 (Soslow). This project was supported by the Fighting Duchenne Foundation and the Fight DMD/Jonah & Emory Discovery Grant (Nashville, TN) (Soslow) and the Ackerman/Nicholoff Family (Indianapolis, IN) (Markham). The sponsors and funders had no role in the design and conduct of the study or in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. There are no relationships with industry or other entities to declare.

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Authors and Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, 2200 Children’s Way, Nashville, TN, 37212, USA

    Joseph R. Starnes, Kimberly Crum, Kristen George-Durrett, Justin Godown, David A. Parra & Jonathan H. Soslow

  2. Division of Cardiology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, 705 Riley Hospital Drive, Indianapolis, IN, 46202, USA

    Larry W. Markham

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  1. Joseph R. Starnes
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  2. Kimberly Crum
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  4. Justin Godown
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  7. Jonathan H. Soslow
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Contributions

JRS collected needed retrospective data, performed the data analysis, interpreted the data, and wrote the first draft of the manuscript. KC and KGD conducted primary data collection and provided substantial revisions of the manuscript. JG, DAP, LWM, and JHS conceived of the study, contributed to the design of the scoring system, and provided substantial revisions to the manuscript. All authors read and approved the final manuscript.

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Correspondence to Joseph R. Starnes.

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Competing interests

The authors have no competing interests to declare that are relevant to the content of this article.

Ethical Approval

This study was approved by the Institutional Review Board at Vanderbilt University Medical Center. This study was performed in line with the principles of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants or their legal guardians for all individuals included in the study.

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Starnes, J.R., Crum, K., George-Durrett, K. et al. Novel Cardiac Imaging Risk Score for Mortality Prediction in Duchenne Muscular Dystrophy. Pediatr Cardiol (2022). https://doi.org/10.1007/s00246-022-03040-6

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