IQVIA, Pyramidvägen 7, 169 56, Solna, Stockholm, Sweden.
Division of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Research Institute, University of Ottawa, Ottawa, ON, Canada.
Orphanet J Rare Dis. 2024 Sep 28;19(1):359. doi: 10.1186/s13023-024-03372-x.
Duchenne muscular dystrophy (DMD) is a rare disease that causes progressive muscle degeneration resulting in life-threatening cardiac complications. The objective of this systematic literature review was to describe and grade the published evidence of predictors of cardiac disease in DMD.
The review encompassed searches of Embase, MEDLINE ALL, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of cardiac disease in DMD. The certainty of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
We included 33 publications encompassing 9,232 patients with DMD. We found moderate- to high-quality evidence that cardiac medication (i.e., ACE inhibitors [enalapril and perindopril], β-blockers [carvedilol], and mineralocorticoid receptor antagonists [eplerenone]) are significantly associated with preserved left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular circumferential strain (LVCS). DMD mutations in exons 51 and 52 were found to be significantly associated with lower risk of cardiomyopathy; deletions treatable by exon 53 skipping and mutations in the Dp116 coding region with improved LVEF and prolonged cardiac dysfunction-free survival; and exons 45-50 and 52 with early left ventricular systolic dysfunction (low/very low-quality evidence). We found high-quality evidence that glucocorticoids (deflazacort) are significantly associated with preserved LVEF and improved fractional shortening (FS), and low-quality evidence that glucocorticoids (deflazacort, prednisone, and/or prednisolone) are associated with improved ejection fraction (EF) and lower risk of cardiomyopathy, ventricular dysfunction, and heart failure-related mortality. Full-time mechanical ventilation was found to be significantly correlated with LVEF (low-quality evidence), muscle strength with FS (low-quality evidence), and genetic modifiers (i.e., LTBP4 rs10880 and ACTN3) with LVEF, lower risk of cardiomyopathy and left ventricular dilation (low-quality evidence).
Several sources of cardiac disease heterogeneity are well-studied in patients with DMD. Yet, the certainty of evidence is generally low, and little is known of the contribution of non-pharmacological interventions, as well as the impact of different criteria for initiation of specific treatments. Our findings help raise awareness of prevailing unmet needs, shape expectations of treatment outcomes, and inform the design of future research.
杜氏肌营养不良症（DMD）是一种罕见疾病，可导致肌肉进行性退化，从而引发危及生命的心脏并发症。本系统文献综述的目的是描述和评估 DMD 中心脏疾病预测因子的已发表证据，并对其进行分级。
本综述纳入了 2000 年 1 月 1 日至 2022 年 12 月 31 日期间，Embase、MEDLINE ALL 和 Cochrane 系统评价数据库中关于 DMD 中心脏疾病预测因子的检索。使用推荐评估、制定与评价分级（GRADE）框架评估证据的确定性（即极低到高）。
我们纳入了 33 篇文献，共纳入了 9232 名 DMD 患者。我们发现了高质量到极高质量的证据表明，心脏药物（即血管紧张素转换酶抑制剂[依那普利和培哚普利]、β受体阻滞剂[卡维地洛]和盐皮质激素受体拮抗剂[依普利酮]）与左心室射血分数（LVEF）、左心室收缩末期容积（LVESV）和左心室圆周应变（LVCS）的保留显著相关。我们发现，外显子 51 和 52 的 DMD 突变与发生心肌病的风险降低显著相关；外显子 53 跳跃可治疗的缺失和 Dp116 编码区的突变与 LVEF 改善和心脏功能障碍无生存时间延长相关；外显子 45-50 和 52 与早期左心室收缩功能障碍（低/极低质量证据）相关。我们发现了高质量的证据表明，糖皮质激素（地夫可特）与 LVEF 的保留和 FS 的改善显著相关，而低质量的证据表明，糖皮质激素（地夫可特、泼尼松和/或泼尼松龙）与 EF 的改善和发生心肌病、心室功能障碍和心力衰竭相关死亡率降低相关。我们发现，全职机械通气与 LVEF 显著相关（低质量证据），肌肉力量与 FS 显著相关（低质量证据），遗传修饰因子（即 LTBP4 rs10880 和 ACTN3）与 LVEF、发生心肌病和左心室扩张的风险降低显著相关（低质量证据）。
在 DMD 患者中，多种心脏疾病异质性的来源得到了很好的研究。然而，证据的确定性通常较低，对于非药物干预的作用以及不同启动特定治疗的标准的影响知之甚少。我们的研究结果有助于提高对当前未满足需求的认识，影响对治疗结果的预期，并为未来的研究提供信息。
