Wildi Karin, Gimenez Maria Rubini, Boeddinghaus Jasper, Nestelberger Thomas, Lopez-Ayala Pedro, Koechlin Luca, Gerstenberger Mareike, Carter Naomi, Bima Paolo, Glaeser Jonas, Spagnuolo Carlos, Miró Oscar, Martín-Sánchez F Javier, Christ Michael, Keller Dagmar I, Gualandro Danielle M, Kawecki Damian, Rentsch Katharina, Mahfoud Felix, Mueller Christian
Department of Cardiology, University Heart Center Basel, and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel University of Basel Switzerland.
GREAT Network.
J Am Heart Assoc. 2025 May 20;14(10):e040468. doi: 10.1161/JAHA.124.040468. Epub 2025 May 13.
Possible misdiagnosis of acute myocardial infarction (AMI) may occur due to inappropriate upper limit of normal (ULN) for cardiac troponin and has the potential to harm patients. In this observational international multicenter study, we aimed to assess to what extent the novel hs-cTn-assays are affected.
A total of 6646 patients presenting with suspected AMI to the emergency department were enrolled. All level pairs (n=18 732) of 4 widely used high-sensitivity cardiac troponin T/I (hs-cTnT/I) assays using (1) the regulatory-approved uniform and sex-specific clinical ULN and (2) mathematically derived close-to-bioequivalent ULNs were assessed. The primary outcome was the quantification of the incidence of inconsistencies in the diagnosis of AMI. Inconsistency was defined as hs-cTnT/I concentration above the recommended ULN in one but not the other assay: for example, hs-cTnT-Elecsys+/hs-cTnI-Architect- or hs-cTnT-Elecsys-/hs-cTnI-Architect+.
AMI was the adjudicated diagnosis in 1422 patients (21.4%). When the regulatory-approved uniform ULN was used, the rate of inconsistent AMI diagnoses was 17.6% (Elecsys/Architect), 18.8% (Elecsys/Centaur), 14.2% (Elecsys/Access), 4.9% (Architect/Centaur), 8.3% (Architect/Access), and 7.4% (Access/Centaur), respectively. Overall, diagnostic mismatches were not decreased, but in fact increased using regulatory-approved sex-specific ULNs. In women as compared with men, they were 23.8% versus 17.6% (Elecsys/Architect), 30.1% versus 19.1% (Elecsys/Centaur), 23.2% versus 15% (Elecsys/Access), 7.2% versus 4.5% (Architect/Centaur), 8.3% versus 8.7% (Architect/Access) and 7.8% versus 8.2% (Access/Centaur), respectively. Using close-to-bioequivalent ULNs reduced inconsistencies by 15% to 20% (<0.001). Findings were confirmed in a sensitivity analysis among all level pairs with final diagnosis of AMI (mismatches in 7.3%-20.5%).
Current regulatory-approved uniform and sex-specific ULNs for hs-cTnT/I result in discordances in binary assay results, possibly impacting the diagnosis of AMI. A regulatory process that defines bioequivalent ULNs could reduce inconsistencies significantly.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.
由于心肌肌钙蛋白正常上限（ULN）设定不当，可能会出现急性心肌梗死（AMI）的误诊情况，这有可能对患者造成伤害。在这项观察性国际多中心研究中，我们旨在评估新型高敏肌钙蛋白检测方法受影响的程度。
共纳入6646例因疑似AMI到急诊科就诊的患者。对4种广泛使用的高敏心肌肌钙蛋白T/I（hs-cTnT/I）检测方法的所有水平对（n = 18732）进行评估，使用（1）监管部门批准的统一且针对性别的临床ULN，以及（2）数学推导得出的接近生物等效的ULN。主要结局是对AMI诊断不一致发生率的量化。不一致定义为一种检测方法中hs-cTnT/I浓度高于推荐的ULN，而另一种检测方法中则未高于：例如，hs-cTnT-Elecsys+/hs-cTnI-Architect- 或hs-cTnT-Elecsys-/hs-cTnI-Architect+。
1422例患者（21.4%）的最终诊断为AMI。当使用监管部门批准的统一ULN时，AMI诊断不一致率分别为17.6%（Elecsys/Architect）、18.8%（Elecsys/Centaur）、14.2%（Elecsys/Access）、4.9%（Architect/Centaur）、8.3%（Architect/Access）和7.4%（Access/Centaur）。总体而言，使用监管部门批准的针对性别ULN时，诊断不匹配情况并未减少，实际上反而增加了。与男性相比，女性的诊断不匹配率分别为23.8%对17.6%（Elecsys/Architect）、30.1%对19.1%（Elecsys/Centaur）、23.2%对15%（Elecsys/Access）、7.2%对4.5%（Architect/Centaur）、8.3%对8.7%（Architect/Access）以及7.8%对8.2%（Access/Centaur）。使用接近生物等效的ULN可使不一致情况减少15%至20%（<0.001）。在所有最终诊断为AMI的水平对的敏感性分析中（不匹配率为[7.3%-20.5%]），这一结果得到了证实。
目前监管部门批准的hs-cTnT/I统一及针对性别的ULN会导致二元检测结果出现不一致，可能影响AMI的诊断。定义生物等效ULN的监管流程可显著减少不一致情况。
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