A Blood Test for a “Broken Heart”? New BioTAK Score Could Spot Takotsubo Syndrome Before Angiography

Imagine walking into an emergency room with crushing chest pain, an abnormal ECG, and blood tests showing your heart is under stress, the classic signature of a heart attack. But for a small percentage of patients, especially older women, the real culprit isn’t a blocked artery at all. It’s takotsubo syndrome (TTS), sometimes called “broken heart syndrome,” a condition where the heart’s main pumping chamber balloons and weakens, often triggered by intense emotional or physical stress, without any coronary blockage in sight.

The problem is that takotsubo mimics acute coronary syndrome (ACS) so closely that doctors currently can’t tell them apart without sending patients for invasive coronary angiography, threading a catheter into the heart to look for blocked arteries directly. A new international study, just published in the European Heart Journal, proposes a much simpler alternative: a blood-based diagnostic score called BioTAK.

Why the confusion happens

TTS accounts for roughly 1–4% of patients who show up with suspected ACS. Existing tools to flag it early, like the InterTAK diagnostic score, lean heavily on psychiatric and neurological history and on identifying an emotional or physical “trigger” information that’s subjective, slow to gather, and not always available in the middle of an emergency. Established blood biomarkers, meanwhile, have only shown modest value on their own.

Building BioTAK

Researchers from the University of Zurich and collaborators across Europe and China pooled data from two large, overlapping patient registries, SPUM-ACS and InterTAK, covering more than 3,600 patients treated between 2011 and 2023. Using machine-learning-guided feature selection, they narrowed dozens of candidate biomarkers down to five factors measurable from a single blood draw taken before angiography:

·         NT-proBNP – a marker of myocardial (heart muscle) stress

·         PAM (peptidylglycine α-amidating monooxygenase) – linked to vasoconstriction and anxiety regulation

·         sLOX-1 – a marker of unstable atherosclerotic plaque

·         LDL cholesterol

·         Sex

Together, these formed a simple 0–60 point score.

How well does it work?

The score was developed in a cohort of 1,823 patients and then tested on an entirely separate group of 1,792 patients it had never seen. In the development group, BioTAK distinguished TTS from ACS with near-perfect accuracy (AUC 0.97). On the independent validation cohort, it still performed strongly (AUC 0.93), and crucially, it wasn’t just accurate on average, it was well-calibrated, meaning its predicted probabilities matched real-world outcomes.

Using pre-set thresholds, BioTAK was able to confidently sort almost 90% of patients into a “likely” or “unlikely” TTS category before anyone picked up a catheter. At the high end of the score, it correctly ruled in TTS with 99% specificity; at the low end, it ruled TTS out with over 99% negative predictive value. Notably, the researchers found BioTAK performed just as well as the older InterTAK score, despite not requiring any psychiatric or neurological history-taking at all.

Why it matters

If validated further and adopted clinically, a tool like BioTAK could let doctors flag likely takotsubo patients using objective lab values alone, potentially sparing some patients an invasive procedure they don’t need, while still directing genuinely ambiguous or ACS-like cases to angiography. That’s a meaningful shift toward faster, less invasive, and less subjective diagnosis for a condition that, despite its poetic name, can be every bit as dangerous as a heart attack.

Original paper: Wenzl FA, Schweiger V, Smolle MA, et al. “Takotsubo syndrome diagnosis: the biomarker-based BioTAK score.” European Heart Journal, 2026. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag597/8768556 

Source: A Blood Test for a “Broken Heart”? New BioTAK Score Could Spot Takotsubo Syndrome Before Angiography