Takotsubo syndrome is a sudden heart condition that most commonly affects postmenopausal women and can be triggered by severe emotional or physical stress. It represents about 2 percent of patients initially thought to be having a heart attack (and up to one in ten women with acute coronary syndrome), but it can be extremely difficult to differentiate from a heart attack during the early stages of evaluation.
People with Takotsubo syndrome may suddenly experience chest pain, abnormal electrocardiogram results, and elevated levels of cardiac enzymes, all signs that can closely resemble a heart attack. The key difference is that Takotsubo syndrome does not involve blocked coronary arteries. Because the two conditions can appear almost identical at first, many patients undergo invasive cardiac catheterization before doctors can determine what is causing their symptoms.
A new way to identify Takotsubo syndrome
An international team of researchers, in close collaboration with scientists from the universities of Zurich and Greifswald, has developed and validated a diagnostic scoring system designed to identify Takotsubo syndrome before performing cardiac catheterization.
The new tool, known as the BioTAK score, combines biological sex with several blood biomarkers linked to different processes in the cardiovascular system. The researchers used artificial intelligence to determine which combination of biomarkers provided the most useful diagnostic information and then incorporated those markers into a clinical decision tool.
In an independent validation group of nearly 1,800 additional patients, the BioTAK score identified Takotsubo syndrome with high accuracy. Using predefined thresholds, the system correctly classified nearly 90 percent of participants before undergoing 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,” says Florian A. Wenzl, co-first author of the study at the Center for Molecular Cardiology at the University of Zurich and the Radcliffe Department of Medicine at the University of Oxford. “At the same time, biomarkers provide information about the biological processes that distinguish Takotsubo syndrome from a classic heart attack,” adds co-author Victor Schweiger from University Hospital Zurich.
Clues to the brain-heart connection
Beyond its potential diagnostic value, the BioTAK score also offers new information about the biology of Takotsubo syndrome. Two newly identified biomarkers included in the score point to an important role for the so-called brain-heart axis and suggest that the condition develops through mechanisms independent of atherosclerosis.
One of the proteins helps activate a variety of neuropeptides involved in responses to stress, anxiety, vascular tone, and autonomic nervous system activity. The other protein is associated with the stability of atherosclerotic plaques. Together, the two markers reveal a biological pattern that is fundamentally different from that typically seen in 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 final co-author Thomas Lüscher from the National Heart and Lung Institute at Imperial College London.
Potential use in emergency care
The researchers say the BioTAK score could become a useful addition to the early emergency evaluation of patients with suspected acute coronary syndrome.
“The BioTAK score is not a substitute for cardiac catheterization when medically necessary. However, it could help guide diagnostic procedures more effectively and avoid unnecessary invasive testing in selected patients,” says final co-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 gaining a better understanding of the underlying mechanisms of the disease.”
Additional research will examine whether adding the BioTAK score to routine clinical care can improve how Takotsubo syndrome is diagnosed and treated.
Data from the main international registries
The research was based on potential patient groups from Switzerland, the SPUM-ACS Registry and the International Takotsubo Registry (InterTAK), with cohorts that overlapped in both time and location.
Established in 2010, the InterTAK Registry is one of the world’s largest international research infrastructures focused on Takotsubo syndrome. For the study, published in the European Heart MagazineThe researchers analyzed data from more than 3,600 patients with acute coronary syndrome, or Takotsubo syndrome.