New blood-based score distinguishes broken-heart syndrome from a real heart attack before catheterization

An international team of cardiologists has developed a blood-based scoring system that can distinguish Takotsubo syndrome, commonly known as broken-heart syndrome, from a genuine heart attack before a patient ever reaches the catheterization lab. The tool, called the BioTAK score, combines a patient's biological sex with five blood biomarkers and was described in a study published August 31 in the European Heart Journal.

Takotsubo syndrome causes sudden, severe weakening of the heart muscle, often triggered by intense emotional or physical stress, and it produces chest pain, shortness of breath and electrocardiogram changes that are nearly indistinguishable from an acute coronary syndrome at first presentation. The only reliable way to tell the two apart has generally been coronary angiography, an invasive procedure that threads a catheter through the blood vessels to the heart. The new score is designed to flag likely Takotsubo cases earlier, using a blood draw instead.

The numbers

The researchers built the score using a development cohort of 1,823 patients with suspected acute coronary syndrome, of whom 1,754 turned out to have true coronary events and 69 had Takotsubo syndrome, drawn from the Swiss SPUM-ACS registry. They then tested it in an independent validation cohort of 1,792 patients, including 1,715 with acute coronary syndrome and 77 with Takotsubo syndrome, sourced from the International Takotsubo Registry, a multinational research infrastructure that has enrolled patients since 2010. In total, the analysis drew on data from more than 3,600 patients.

The score achieved an area under the curve of 0.97 in the development cohort and 0.93 in external validation, a measure of how well the tool discriminates between the two conditions on a scale where 1.0 is perfect and 0.5 is no better than chance. Using predefined thresholds, BioTAK correctly classified close to 90 percent of patients in the validation group before they underwent catheterization, according to the University of Zurich announcement accompanying the paper.

How researchers got here

Takotsubo syndrome takes its name from a Japanese octopus trap, a round pot with a narrow neck, because the stunned heart's left ventricle can balloon into a similar shape on imaging. It accounts for roughly 2 percent of patients initially suspected of having a heart attack, but that share rises to about one in ten when only women are considered, and studies of the International Takotsubo Registry have found close to 90 percent of cases occur in postmenopausal women, often following an acute emotional or physical stressor. Researchers have proposed that falling estrogen levels after menopause may contribute to the blood-vessel dysfunction seen in the condition, though the underlying biology remains only partly understood.

To build BioTAK, the team used machine-learning-guided feature selection to sift through a wide panel of circulating biomarkers and identify which combination best separated Takotsubo patients from those with true coronary events. The final score settled on five elements: a marker of cardiac strain called NT-proBNP, along with biomarkers tied to vasoconstriction and anxiety regulation, atherosclerotic plaque instability, and lipid metabolism, combined with the patient's biological sex. That mix reflects a working theory of Takotsubo syndrome as a whole-body stress response rather than a purely mechanical blockage of a coronary artery, with the nervous system, hormones and blood vessels all playing a part in how the heart muscle temporarily stuns itself.

"A simple combination of blood biomarkers and biological sex can identify these patients with remarkable accuracy even before cardiac catheterization," said Florian A. Wenzl, co-first author of the study and a researcher at the University of Zurich's Center for Molecular Cardiology and the University of Oxford's Radcliffe Department of Medicine, in the university's announcement.

Who stands to benefit

The intended beneficiaries are patients who arrive at an emergency department with chest pain and ECG findings that look like a heart attack but who are actually experiencing Takotsubo syndrome, along with the clinicians trying to sort the two apart quickly. Because coronary angiography carries its own risks and resource costs, a blood test that can rule Takotsubo in or out before the procedure could reduce unnecessary invasive testing in some patients, according to the study team, whose members are based at the University of Zurich, University Hospital Zurich, the University of Greifswald, the University of Oxford and Imperial College London's National Heart and Lung Institute.

The researchers are careful to frame BioTAK as an adjunct rather than a substitute for catheterization when it remains medically necessary, since roughly one in ten cases in the validation cohort was still misclassified. Elderly patients, postmenopausal women, and those with a history of stress-triggered symptoms are the groups in whom the score is likely to matter most in practice, given how disproportionately Takotsubo syndrome affects that population. Emergency physicians and cardiologists working in busy chest-pain units are the other group with a direct stake in the tool, since a faster and less invasive way to triage suspected heart attacks could ease pressure on catheterization labs that are often in high demand.

"Our goal is to identify patients with Takotsubo syndrome earlier and more reliably in the future," said Christian Templin, co-senior author of the study, director of the Department of Internal Medicine B at University Medical Center Greifswald and founder of the International Takotsubo Registry.

Reaction and next steps

Coverage of the findings, including a summary carried by ScienceDaily and an independent writeup on News-Medical, has focused on the score's potential to streamline emergency diagnostic pathways rather than replace them outright. Co-senior author Thomas F. Lüscher, a cardiologist involved in the work, described BioTAK as a way of turning complex disease mechanisms into a tool that can be used at the bedside, according to the University of Zurich release.

The authors say the next step is prospective testing of the score in real-world emergency settings, where it would need to perform reliably across different hospitals, patient populations and laboratory platforms before it could be adopted into routine clinical guidelines. Regulatory approval and incorporation into cardiology society recommendations, if the score continues to perform well, would likely take additional years of validation, and the authors note that the biomarker assays used in the study would need to be readily available in routine hospital laboratories before the score could be deployed at scale. For now, the paper stands as an initial, peer-reviewed demonstration that a blood draw, rather than a catheter, might one day be the first step in telling a broken heart from a damaged one.