Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction.

Background: Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI.

Methods: The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation.

Results: Troponin ratio was lower in TTS patients 0.13 [0.10-0.20] vs. 0.62 [0.29-0.96], p<0.001). In the ROC curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients (AUC 0.869 [CI95% 0.789-0.948)] vs. 0.766 [CI95% 0.677-0.855], p=0.047). When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (CI 95% 0.465-0.732) and 0.816 (CI95% 0.712-0.921), p =0.003). At a cutoff point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients.

Conclusions: In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.