Background: Clinical differentiation between takotsubo syndrome (TTS) and acute myocardial infarction prior to coronary angiography is extremely challenging as there are no biomarkers to distinguish between both entities. Small scale studies have suggested that specific biomarker indices can distinguish TTS from AMI with high accuracy. The aim of the present study was to validate previously proposed biomarker indices in a large cohort of TTS and acute coronary syndrome (ACS) patients.

Methods: In the present study, a total of 1,007 TTS patients and 1,658 ACS patients were included. Proposed admission and peak ratios of BNP/Tn, BNP/CK, Tn/CK and a diagnostic score* were compared between TTS and ACS patients. For standardization among all participating sites, biomarker levels were expressed as the upper limit of their normal range. For each comparison, patients were matched equally as reported in the respective study. The matching baseline characteristics of these subgroups were mostly age and female sex with the study population of both Pirlet et al. and Budnik et al. being 100% female. The ACS patient population of Doyen et al. exclusively had anterior ACS. All biomarker ratios with an AUC above 0.8 were tested for their accuracy.

Results: The biomarker ratio and AUC values from the previous publications and the corresponding values from the InterTAK registry are displayed in Table 1 in addition to the number of TTS patients in the publication cohort (N TTS) and in the InterTAK cohort (TTS N INTERTAK).

Table 1. Biomarker ratios and diagnostic score reported in previous publication in comparison to ratios found in the InterTAK cohort. N: Number of patients, AUC: area under the curve, TTS: Takotsubo, STEMI: ST-elevation myocardial infarction, NSTEMI: non-ST-elevation myocardial infarction, BNP: Brain Natriuretic Peptide, Tn: Troponin, CK: Creatine Kinase.                   
*Exp(-0.031+0.013xage+0.0003x(BNP/Tn)-0.077xLVEF+2.71+1(gender=1)-2.77x1(psy+=1))           1+exp(-0.031+0.013xage+0.0003(BNP/Tn)-0.077xLVEF+2.71x1(gender=1)-2.77x1(psy+=1) 

Conclusion: In conclusion, previously proposed biomarker ratios for the differentiation of TTS from ACS performed only moderate in a larger study cohort, further emphasizing the importance of identifying new diagnostic biomarkers. Though, peak values differentiated better, their clinical usability is heavily diminished, as stemi-ACS necessitates early coronary angiography, but the peak of most biomarkers is reached only hours after admission.