An international research team working closely with scientists at the universities of Zurich and Greifswald has developed and validated a scoring system that distinguishes broken heart syndrome from a genuine heart attack using blood biomarkers and biological sex, correctly classifying nearly 90 percent of patients before they reached the catheterization lab. The work was published in the European Heart Journal.
The condition it targets, Takotsubo syndrome, is a sudden weakening of the heart muscle usually triggered by intense emotional or physical stress. It most often strikes postmenopausal women, and it accounts for roughly 2 percent of patients who initially appear to be having a heart attack, rising to as many as one in ten women presenting with acute coronary syndrome.
The clinical problem is that it looks almost identical to a heart attack in the emergency department. Chest pain, abnormal electrocardiogram readings, and elevated cardiac enzymes all show up in both. The one reliable difference, that Takotsubo does not involve blocked coronary arteries, is currently confirmed by threading a catheter into the heart. That means a substantial number of patients undergo an invasive procedure to rule out something they do not have.
Cardiac catheterization is generally safe but not trivial. It requires arterial access, contrast dye that stresses the kidneys, radiation exposure, and a recovery period. Avoiding it in patients who do not need it is the practical case for a blood-based tool, and it fits a broader push toward less invasive cardiac assessment, including the recently cleared test that estimates a heart pressure normally measured with a catheter.
Building the Score From Registries of 3,600 Patients
The team drew on prospective patient cohorts from Switzerland, the SPUM-ACS Registry and the International Takotsubo Registry, known as InterTAK, analyzing data from more than 3,600 patients with either acute coronary syndrome or Takotsubo syndrome. InterTAK was launched in 2010 and is among the largest research infrastructures devoted to the condition.
Researchers used artificial intelligence to identify which combination of blood biomarkers carried the most diagnostic information, then folded those markers together with biological sex into a clinical decision tool. In an independent validation group of nearly 1,800 additional patients, the score correctly classified close to 90 percent using predefined thresholds.
Florian A. Wenzl, co-first author, of the Center for Molecular Cardiology at the University of Zurich and the Radcliffe Department of Medicine at the University of Oxford, said in the University of Zurich announcement that "a simple combination of blood biomarkers and biological sex can identify these patients" with remarkable accuracy even before catheterization.
Two Markers Pointing Toward the Brain Heart Connection
Beyond its diagnostic function, the score offers a window into what actually happens in Takotsubo syndrome, which has never been fully explained.
Two newly identified biomarkers in the score point toward the so-called brain-heart axis. One protein helps activate neuropeptides that regulate stress responses, anxiety, vascular tone and autonomic nervous system activity. The other is associated with the stability of atherosclerotic plaque. Together they describe a biological pattern that differs fundamentally from a classic heart attack, and one that appears to operate through mechanisms independent of atherosclerosis.
That finding gives weight to something patients with the condition have long described and clinicians have struggled to quantify. Severe emotional stress does something measurable to heart muscle, and it leaves a chemical trace in the blood that differs from the trace left by a clogged artery.
Co-last author Thomas Lüscher of the National Heart and Lung Institute at Imperial College London said the score "translates complex disease mechanisms into a practical diagnostic tool."
A Tool Meant to Guide Testing, Not Replace It
The researchers were direct about the limits of what they built, and that boundary deserves emphasis because it is the part most likely to get lost.
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, said the score is "not a substitute for cardiac catheterization when it is medically necessary." He added that it could help guide diagnostic procedures more effectively and avoid unnecessary invasive tests in selected patients.
The score is not currently available in American emergency departments. It has been validated against registry data but has not been tested to see whether adding it to routine care actually improves how patients are diagnosed and treated. That study is the next step the team describes, and it is the one that would determine whether the tool reaches clinical practice.
Diagnostic scores also carry a specific risk. A tool that is right nine times out of ten is wrong once, and in a condition where the alternative diagnosis is a blocked artery, a misclassification has serious consequences. That is precisely why the researchers frame it as guidance for sequencing tests rather than a replacement for them.
Chest Pain Guidance Has Not Changed
Nothing about this research alters what anyone should do when symptoms appear.
Chest pain, pressure or tightness, shortness of breath, pain spreading to the arm, jaw, neck or back, sudden sweating, nausea or lightheadedness all warrant calling 911 immediately. Broken heart syndrome can itself cause serious complications including heart failure and dangerous rhythm disturbances. It is not a benign condition that can be waited out at home, and no one can distinguish it from a heart attack without testing.
Women, and particularly postmenopausal women, remain the group most affected. Anyone who has previously been diagnosed with Takotsubo syndrome should discuss their individual risk of recurrence with a cardiologist, since recovery of heart function does not eliminate the possibility of another episode.
The broader direction of cardiology is toward earlier and less invasive characterization of heart disease, a theme running through the rewritten European heart failure guidelines released this year and through new advice on kidney testing for heart patients. Whether this particular score joins that shift depends on trials that have not yet been run.
Key Questions Answered
What is broken heart syndrome? Takotsubo syndrome is a sudden weakening of the heart muscle usually triggered by intense emotional or physical stress. Unlike a heart attack, it does not involve blocked coronary arteries.
How common is it? It accounts for roughly 2 percent of patients initially thought to be having a heart attack, and up to one in ten women presenting with acute coronary syndrome. Postmenopausal women are most affected.
Is the BioTAK score available to patients now? No. It has been validated using registry data but is not in clinical use. Researchers still need to test whether adding it to routine care improves diagnosis and treatment.
Would this replace cardiac catheterization? No. The researchers state explicitly that it is not a substitute when catheterization is medically necessary. It is intended to help sequence testing and avoid unnecessary invasive procedures in selected patients.
How accurate was the score? In an independent validation group of nearly 1,800 patients, it correctly classified close to 90 percent using predefined thresholds. That also means roughly one in ten was misclassified.
Does this change what to do during chest pain? No. Chest pain, shortness of breath, pain spreading to the arm or jaw, sweating or nausea warrant calling 911. Broken heart syndrome can cause heart failure and dangerous rhythm problems.
What did researchers learn about the cause? Two biomarkers in the score point toward the brain-heart axis, involving stress response signaling and autonomic nervous system activity, and suggest mechanisms independent of atherosclerosis.
