Kaufman Beth D, Garcia Ariadna, He Zihuai, Tesi-Rocha Carolina, Buu MyMy, Rosenthal David, Gordish-Dressman Heather, Almond Christopher S, Duong Tina
Department of Pediatrics (Cardiology), Stanford University School of Medicine, Palo Alto, CA.
Quantitative Sciences Unit, Stanford University, Palo Alto, CA.
Prog Pediatr Cardiol. 2023 Jun;69. doi: 10.1016/j.ppedcard.2023.101639. Epub 2023 Mar 15.
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 ajor dverse ystrophinopathy vent ) 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.
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.
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.
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.
杜氏肌营养不良症中心肌病、呼吸功能不全和骨骼肌病的重叠症状使心力衰竭的评估变得复杂。我们制定了一个反映累积疾病负担的多器官临床变量序贯量表——主要不良肌营养不良蛋白病事件（MADE）评分。我们假设较高的MADE评分与杜氏肌营养不良症男孩的死亡率增加有关。利用国际神经肌肉合作研究组杜氏自然病史研究数据集进行验证。
根据与预先指定领域的临床相关性选择杜氏自然病史研究变量：心脏、肺、肌病、营养。为研究访视分配严重程度评分（0-4）并求和。比较入组时和纵向队列中按年龄、行走状态和生存情况定义的MADE评分。检查MADE评分与死亡率之间的关联。
杜氏自然病史研究纳入了440名男性，年龄为12.6±6.1岁，在4.6±2.8年期间进行了3559次访视，45人死亡。MADE评分随年龄和非行走状态增加。死亡者每次访视的平均MADE评分为19±10，而幸存者为9.8±9.3（p=0.03）。基线MADE评分>12可独立于年龄预测死亡率（敏感性78%，CPE.70）。在根据入组年龄、随访时间和行走状态调整的模型中，MADE评分上升轨迹与死亡率相关，所有p<0.001。
开发了一种多器官严重程度评分MADE，以跟踪影响杜氏肌营养不良症心力衰竭的累积发病率。MADE评分可预测杜氏自然病史研究的死亡率。MADE评分可用于男性心力衰竭的系列评估，并可作为杜氏肌营养不良症临床研究的终点。
