A blood-based score may help clinicians distinguish takotsubo syndrome from acute coronary syndrome earlier in the diagnostic pathway, according to a study published in the European Heart Journal.
Takotsubo syndrome, commonly referred to as broken heart syndrome, causes temporary dysfunction of the left ventricle. Patients often present with chest pain, electrocardiographic changes, and elevated cardiac biomarkers, closely resembling acute coronary syndrome. Diagnosis usually requires cardiac imaging and invasive coronary angiography to exclude an obstructed coronary artery.
Florian Wenzl at the Center for Molecular Cardiology at the University of Zurich, and colleagues developed the BioTAK score using data from 3,615 patients enrolled in two prospective registries.
The development cohort included 1,823 patients treated at University Hospital Zurich, of whom 69 had takotsubo syndrome and 1,754 had acute coronary syndrome. The score was validated in a separate cohort of 1,792 patients, including 77 with takotsubo syndrome and 1,715 with acute coronary syndrome.
Blood samples were collected when patients presented and before coronary angiography. The researchers measured established and emerging cardiovascular biomarkers, then used machine learning and logistic regression to identify the most informative combination.
The resulting score uses four biomarkers and patient sex. The biomarkers are:
N-terminal pro-B-type natriuretic peptide, or NT-proBNP, which reflects ventricular wall stress
Low-density lipoprotein (LDL) cholesterol
Soluble lectin-like oxidized LDL receptor-1, or sLOX-1, which is associated with endothelial activation and plaque disruption
Peptidylglycine alpha-amidating monooxygenase, or PAM, which is involved in sympathetic activity and anxiety regulation
Patients with takotsubo syndrome had higher NT-proBNP and PAM levels. Patients with acute coronary syndrome had higher sLOX-1 and LDL cholesterol levels, consistent with the role of atherosclerotic plaque disruption in many acute coronary events.
BioTAK achieved an area under the receiver operating characteristic curve of 0.97 in the development cohort and 0.93 in the validation cohort. An area under the curve of 1.0 indicates perfect discrimination, while 0.5 represents performance no better than chance.
Using predefined thresholds, the score placed 89.2 percent of patients in either a low- or high-probability group. A score below 27 had 95.7 percent sensitivity and a negative predictive value of 99.8 percent, suggesting that the tool may be particularly useful for identifying patients unlikely to have takotsubo syndrome.
A score of 33 or higher had 99 percent specificity, but its positive predictive value was 59.1 percent. This means that a high score alone would not be sufficient to confirm the diagnosis. The score performed similarly in patients with and without ST-segment elevation and across several clinical subgroups.
BioTAK was also noninferior to existing diagnostic scores that require psychiatric or neurological history, identification of a trigger, or cardiac imaging. Because it uses objective laboratory and demographic data, it could support assessment when reliable history-taking is difficult.
However, the score is not intended to replace urgent coronary angiography in patients with ST-segment elevation, hemodynamic instability, or other high-risk features. Its most likely role may be in stable patients without ST-segment elevation, but this has not yet been tested in clinical implementation studies.
Laboratory availability is another barrier. Routine assays for sLOX-1 and PAM are not currently available, and the methods used in the study require approximately three to five hours. Further assay development and transfer to automated platforms would be necessary for routine use.
Both cohorts came from closely related registry systems, and relatively few participants had takotsubo syndrome. Independent validation is therefore needed. The study also did not determine whether using BioTAK reduces angiography, shortens time to diagnosis, or improves patient outcomes.
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