Background

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have used troponin I (cTnI) as a biomarker of toxicity, but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP) in a DMD cohort.

Methods

DMD patients were prospectively enrolled and followed for 3 years. Serum was drawn at the time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers.

Results

All subjects were asymptomatic at the time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy.

Conclusions

CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials.

Impact

• Asymptomatic patients with Duchenne muscular dystrophy (DMD) exhibit transient troponin I leak.

• NT-proBNP correlated with indexed left ventricular end diastolic volume and indexed maximum left atrial volume.

• Other cardiac biomarkers did not correlate with cardiac magnetic resonance (CMR) markers of cardiomyopathy.

中文翻译：

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Duchenne 肌营养不良症患者：无症状肌钙蛋白渗漏及其对药物毒性研究的影响

背景

心肌病是杜兴氏肌营养不良症 (DMD) 的主要死因，但研究表明心力衰竭生物标志物与心肌病的严重程度相关性较差。DMD 临床试验使用肌钙蛋白 I (cTnI) 作为毒性生物标志物，但尚不清楚无症状 DMD 患者是否具有升高的 cTnI。我们纵向评估了 DMD 队列中的 cTnI、脑利钠肽 (BNP) 和 N 末端 pro-BNP (NT-proBNP)。

方法

前瞻性招募 DMD 患者并随访 3 年。在心脏磁共振 (CMR) 时抽取血清。正常生物标志物值来自健康受试者。生物标志物与 CMR 标志物相关。

结果

所有受试者在入组时均无症状。一些 DMD 受试者的 cTnI 短暂升高。那些 cTnI 升高的人更有可能在基线 CMR 上有晚期钆增强。NT-proBNP 与指数左心室舒张末期和最大左心房容积相关。否则，标准心脏生物标志物与心肌病的 CMR 标志物不相关。

结论

CTnI、BNP 和 NT-proBNP 与心肌病进展的 CMR 评估无关。一部分 DMD 患者具有临床意义不确定的无症状 cTnI 渗漏，但如果在未来的药物试验中使用 cTnI 评估心脏毒性，则这一点至关重要。

影响

• 杜兴氏肌营养不良症 (DMD) 的无症状患者表现出短暂的肌钙蛋白 I 渗漏。

• NT-proBNP 与指数左心室舒张末期容积和指数最大左心房容积相关。

• 其他心脏生物标志物与心肌病的心脏磁共振 (CMR) 标志物无关。