Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T.
Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T.
复制标题
DOI：
10.1161/circulationaha.121.058489
复制
发表时间：
2022-06-14
期刊：
影响因子：
37.8
通讯作者：
Mueller, Christian
中科院分区：
文献类型：
--
作者：
du Fay de Lavallaz, Jeanne;Prepoudis, Alexandra;Wendebourg, Maria Janina;Kesenheimer, Eva;Kyburz, Diego;Daikeler, Thomas;Haaf, Philip;Wanschitz, Julia;Loescher, Wolfgang N.;Schreiner, Bettina;Katan, Mira;Jung, Hans H.;Maurer, Britta;Hammerer-Lercher, Angelika;Mayr, Agnes;Gualandro, Danielle M.;Acket, Annemarie;Puelacher, Christian;Boeddinghaus, Jasper;Nestelberger, Thomas;Lopez-Ayala, Pedro;Glarner, Noemi;Shrestha, Samyut;Manka, Robert;Gawinecka, Joanna;Piscuoglio, Salvatore;Gallon, John;Wiedemann, Sophia;Sinnreich, Michael;Mueller, Christian
心肌肌钙蛋白（cTnT）和cTnI被认为是心脏特异性的，在急性心肌梗死的诊断中是等效的。以往的研究表明，罕见的骨骼肌病变作为cTnT的非心脏来源。我们旨在确认cTnT在各种骨骼肌疾病（SMD）患者中的可靠性/心脏特异性。我们在2个国家的4家医院前瞻性招募了出现肌肉不适（≥2周）的患者进行择期评价。心脏检查后，将患者判定为3种预定义的心脏疾病类别。使用高灵敏度（hs-）cTnT（hs-cTnT-Elecsys）和3种hs-cTnI检测试剂盒（hs-cTnI-Architect、hs-cTnI-Access、hs-cTnI-Vista）评估cTnT/I浓度和导致的cTnT/I错配，并与急诊科判定为非心源性胸痛的无SMD对照受试者（n=3508;平均年龄55岁; 37%为女性）进行比较。在有骨骼肌活检的患者中，将TNNT/I1-3 mRNA差异基因表达与无SMD的对照受试者的活检进行比较。在211例患者（平均年龄57岁; 42%为女性）中，108例（51%）被判定为无心脏病，44例（21%）被判定为轻度心脏病，59例（28%）被判定为重度心脏病。所有检测结果显示，从无心脏病患者到轻度和重度心脏病患者，hs-cTnT/I浓度均显著升高（均P<0.001）。SMD患者的hs-cTnT-Elecsys浓度显著高于对照受试者（中位数，16纳克/升[四分位距（IQR），7-32.5纳克/升]对比5纳克/升[IQR，3-9纳克/升]; P<0.001），而hs-cTnI浓度基本相似（hs-cTnI-Architect，2.5 ng/L [IQR，1.2-6.2 ng/L] vs 2.9 ng/L [IQR，1.8-5.0 ng/L]; hs-cTnI-Access，3.3 ng/L [IQR，2.4-6.1 ng/L] vs 2.7 ng/L [IQR，1.6-5.0 ng/L];和hs-cTnI-Vista，7.4 ng/L [IQR，5.2-13.4 ng/L]对比7.5 ng/L [IQR，6-10 ng/L]）。55%的SMD患者hs-cTnT-Elecsys浓度高于正常上限，而对照组仅13%（P<0.01）。对骨骼肌活检组织（n=33）（主要来自非炎性肌病和肌炎个体（n=24））的mRNA分析显示，编码cTnT的TNNT 2上调8倍（但编码cTnI的TNNI 3无）与对照受试者（n=16，PWald<0.001）;表达与病理疾病活动相关（R=0.59，Pt-统计<0.001）和循环hs-cTnT浓度（R=0.26，Pt-统计=0.031）。在活动性慢性SMD患者中，cTnT浓度升高很常见，大多数不归因于心脏疾病。cTnI未观察到这一点，可能部分原因是骨骼肌中cTnT的再表达。URL：https://www.clinicaltrials.gov;唯一标识符：NCT 03660969。
Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs). We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT–Elecsys) and 3 hs-cTnI assays (hs-cTnI–Architect, hs-cTnI–Access, hs-cTnI–Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P<0.001). hs-cTnT–Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7–32.5 ng/L] versus 5 ng/L [IQR, 3–9 ng/L]; P<0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI–Architect, 2.5 ng/L [IQR, 1.2–6.2 ng/L] versus 2.9 ng/L [IQR, 1.8–5.0 ng/L]; hs-cTnI–Access, 3.3 ng/L [IQR, 2.4–6.1 ng/L] versus 2.7 ng/L [IQR, 1.6–5.0 ng/L]; and hs-cTnI–Vista, 7.4 ng/L [IQR, 5.2–13.4 ng/L] versus 7.5 ng/L [IQR, 6–10 ng/L]). hs-cTnT–Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (P<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI) versus control subjects (n=16, PWald<0.001); the expression correlated with pathological disease activity (R=0.59, Pt-statistic<0.001) and circulating hs-cTnT concentrations (R=0.26, Pt-statistic=0.031). In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03660969.