New BioTAK score accurately identifies Takotsubo syndrome before catheterization

Takotsubo syndrome is an acute heart condition that primarily affects postmenopausal women and is often triggered by severe emotional or physical stress. Although it affects about 2 percent of all patients with suspected heart attacks – and as many as one in ten women with acute coronary syndrome – the condition remains difficult to distinguish from a heart attack.

Affected individuals suddenly develop chest pain, changes in the electrocardiogram and elevated cardiac enzymes – symptoms that are nearly identical to those of a heart attack. Unlike a heart attack, however, Takotsubo syndrome does not involve blocked coronary arteries. Since the two conditions are virtually indistinguishable during the initial evaluation, most patients must first undergo invasive cardiac catheterization to determine the cause.

An international research team, working in close collaboration with researchers from the universities of Zurich and Greifswald, has now developed and validated a simple diagnostic score that can identify Takotsubo syndrome even before cardiac catheterization.

High accuracy

In addition to biological sex, the new BioTAK score incorporates several blood biomarkers that reflect various processes in the cardiovascular system. Using artificial intelligence, the researchers identified the most informative combination of these markers and used it to develop a diagnostic decision-making tool. In an independent validation study involving nearly 1,800 additional patients, BioTAK identified Takotsubo syndrome with a high degree of accuracy. Predefined thresholds enabled the correct classification of nearly 90 percent of study participants even before cardiac catheterization.

Our study shows that a simple combination of blood biomarkers and biological sex can identify these patients with remarkable accuracy even before cardiac catheterization."

Florian A. Wenzl, co-first author of the study, Center for Molecular Cardiology, University of Zurich and the Radcliffe Department of Medicine, University of Oxford

"At the same time, the biomarkers provide insights into the biological processes that distinguish Takotsubo syndrome from a classic heart attack," adds co-first author Victor Schweiger of University Hospital Zurich.

New insights into disease mechanisms

The study also provides new insights into the pathophysiology of Takotsubo syndrome. The BioTAK score includes two novel biomarkers that point to the central role of the so-called brain-heart axis and to a disease mechanism that is independent of atherosclerosis. One protein is involved in activating numerous neuropeptides that regulate stress responses, anxiety, vascular tone and the activity of the autonomic nervous system, while the other is associated with the stability of atherosclerotic plaques. Together, these markers reveal a biological pattern that differs fundamentally from that of a classic heart attack. "By capturing signaling pathways related to stress responses, cardiac dysfunction and plaque stability, the BioTAK score translates complex disease mechanisms into a practical diagnostic tool," explains co-last author Thomas Lüscher of the National Heart and Lung Institute at Imperial College London.

Potential for clinical practice

The researchers view the BioTAK score as a valuable addition to the initial emergency evaluation of patients with suspected acute coronary syndrome. "The BioTAK score is not a substitute for cardiac catheterization when it is medically necessary. However, it could help guide diagnostic procedures more effectively and avoid unnecessary invasive tests in selected patients," says co-last author Christian Templin, director of the Department of Internal Medicine B at the University Medical Center Greifswald and founder of the InterTAK Registry. "Our goal is to identify patients with Takotsubo syndrome earlier and more reliably in the future, while also gaining a better understanding of the underlying disease mechanisms."

Future studies will aim to determine whether incorporating the BioTAK score into routine clinical practice can further improve the diagnosis and treatment of patients.