Many people come to hospital because of recurring chest pain. Often, a circulatory disorder of the heart is suspected. However, if no narrowing of the coronary arteries is found, the findings are usually considered normal. This is difficult for those affected to understand, as the symptoms persist. This condition is called ANOCA (angina with non-obstructive coronary arteries). This refers to symptoms similar to angina pectoris, i.e. chest tightness or a feeling of pressure, which typically occur when there is reduced blood flow to the heart. ANOCA affects more than a third of people with angina pectoris and is particularly common in women.
The prospective multicentre study was conducted under the scientific direction of Prof. Tommaso Gori (Mainz University Medical Centre, DZHK German Centre for Cardiovascular Research, Rhine-Main site). A total of nine centres participated. The results show that the underlying mechanisms can be clearly distinguished and have been published in the European Heart Journal. First author Dr Ornela Velollari (also University Medical Centre Mainz and DZHK) was awarded the Young Investigator Award 2025 by the European Society of Cardiology for her work.
Why angina without vasoconstriction often goes undetected
In standard diagnostics, coronary angiography is used to examine the large coronary arteries in order to identify narrowings. However, in many patients with ANOCA, the causes lie in the small vessels, in the vascular response or in pain processing. These changes remain invisible in routine diagnostics. The study shows how often this is the case: 77 per cent of the people examined were found to have functional disorders that explain their symptoms and point to different treatment options.
A closer look at coronary physiology
The researchers used an invasive method to measure blood flow and vascular responses in real time. The team tested 1,001 patients to see how their coronary arteries reacted to the active substances adenosine and acetylcholine. While adenosine provides information about how well the vessels can dilate and increase blood flow, acetylcholine reveals whether there are spasms or abnormal reactions in the vessel walls. On this basis, the researchers described eight different mechanisms, known as endotypes. Each of these is based on a specific disorder in the vascular system. These endotypes include various forms of circulatory disorders and vascular reactions, including spasms, changes in circulatory reserve, disorders of the vascular wall and increased sensitivity to pain. Each of these endotypes is associated with its own clinical patterns.
‘We see many people with clear chest pain but no visible narrowing of the coronary arteries. The study helps us to better understand the underlying mechanisms and treat them in a more targeted manner,’ says Prof. Tommaso Gori from Mainz University Medical Centre, whose research group is supported by the DZHK.
New approaches to tailored treatment
Based on the data, an international panel of experts developed recommendations for endotype-specific therapy. This makes it possible to treat patients more individually and close the gap between diagnosis and therapy. Planned follow-up studies will investigate whether these approaches lead to a lasting improvement in symptoms and quality of life.
This scientific publication was selected as Paper of the Month December 2025 by the DZHK Board of Directors.
Original publication:
Miner S, Mejia-Renteria H, Leone AM, et al. Endotypes of angina with non-obstructive coronary arteries: a prospective multicentre study. Eur Heart J. Published online November 11, 2025. doi:10.1093/eurheartj/ehaf839
