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. 2023 Jun:69:101639.
doi: 10.1016/j.ppedcard.2023.101639. Epub 2023 Mar 15.

Major Adverse Dystrophinopathy Events (MADE) Score as Marker of Cumulative Morbidity and Risk for Mortality in Boys with Duchenne Muscular Dystrophy

Beth D Kaufman  1 , Ariadna Garcia  2 , Zihuai He  3 , Carolina Tesi-Rocha  3 , MyMy Buu  4 , David Rosenthal  1 , Heather Gordish-Dressman  5 , Christopher S Almond  1 , Tina Duong  3 ; CINRG DUCHENNE NATURAL HISTORY STUDY Investigators
Affiliations

Major Adverse Dystrophinopathy Events (MADE) Score as Marker of Cumulative Morbidity and Risk for Mortality in Boys with Duchenne Muscular Dystrophy

Beth D Kaufman et al. Prog Pediatr Cardiol. 2023 Jun.

Abstract

Background: Overlapping symptoms from cardiomyopathy, respiratory insufficiency, and skeletal myopathy confound assessment of heart failure in Duchenne Muscular Dystrophy. We developed an ordinal scale of multiorgan clinical variables that reflect cumulative disease burden-the Major Adverse Dystrophinopathy Event (MADE) Score. We hypothesized that a higher MADE score would be associated with increased mortality in boys with Duchenne Muscular Dystrophy. The Cooperative International Neuromuscular Research Group Duchenne Natural History Study dataset was utilized for validation.

Methods: Duchenne Natural History Study variables were selected based on clinical relevance to prespecified domains: Cardiac, Pulmonary, Myopathy, Nutrition. Severity points (0-4) were assigned and summed for study visits. MADE score for cohorts defined by age, ambulatory status, and survival were compared at enrollment and longitudinally.Associations between MADE score and mortality were examined.

Results: Duchenne Natural History Study enrolled 440 males, 12.6 ±6.1 years old, with 3,559 visits over 4.6 ±2.8 years, 45 deaths. MADE score increased with age and nonambulatory status. Mean MADE score per visit was 19 ±10 for those who died vs. 9.8 ±9.3 in survivors p=0.03. Baseline MADE score >12 predicted mortality independent of age (78% sensitivity, CPE.70). Rising MADE score trajectory was associated with mortality in models adjusted for enrollment age, follow-up time, and ambulatory status, all p<.001.

Conclusion: A multiorgan severity score, MADE, was developed to track cumulative morbidities that impact heart failure in Duchenne muscular dystrophy. MADE score predicted Duchenne Natural History Study mortality. MADE score can be used for serial heart failure assessment in males and may serve as an endpoint for Duchenne muscular dystrophy clinical research.

Keywords: Duchenne muscular dystrophy; dystrophinopathy; heart failure; mortality risk predictor.

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Figures

Figure 1.
Figure 1.
MADE score at enrollment by age group and ambulatory status
Figure 2.
Figure 2.
Kaplan-Meier curves corresponding to each of the Cox models for baseline MADE score risk category (high-risk = MADE>12) 1)Unadjusted 2) Adjusted by baseline age 3)Adjusted by age and ambulatory status at baseline 4)Adjusted by age, ambulatory status and steroid use, all at baseline
Figure 3.
Figure 3.
Longitudinal MADE Score trajectory adjusted for baseline age and ambulatory status
See this image and copyright information in PMC

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