Multiple ANOCA Endotypes Commonly Coexist and Are Linked to Worse Angina Symptoms: JAMA
An recent observational cross-sectional study published in the Journal of the American Medical Association found that multiple endotypes frequently coexist in patients with ANOCA (angina with nonobstructive coronary arteries). A higher number of endotypes identified on coronary function testing (CFT) was associated with more severe angina symptoms. Although individual endotypes appeared to produce a similar angina burden, the coexistence of multiple mechanisms was linked to worse overall symptom severity.
ANOCA is increasingly recognized as a complex condition in which patients experience angina-like chest pain despite the absence of significant coronary artery blockages. Potential causes include abnormalities in blood vessel function, microvascular dysfunction, coronary vasospasm, and myocardial bridging, a condition in which a coronary artery is compressed by heart muscle during contraction.
This research analyzed data from 485 patients who underwent extensive coronary function testing between August 2007 and February 2025. The study determined whether the presence of multiple ANOCA endotypes was associated with more severe angina symptoms.
The study population had a mean age of 52 years, and nearly three-quarters of participants were women. Using acetylcholine provocation testing, adenosine-mediated physiology testing, and intravascular ultrasound with hemodynamic assessment, investigators evaluated both endothelium-dependent and endothelium-independent abnormalities, as well as functionally significant myocardial bridging.
The results showed that overlapping endotypes were common. Only 7% of patients had normal test findings, while 31% had one abnormality, 44% had two endotypes, and 17% had three distinct abnormalities identified through testing.
Using the Seattle Angina Questionnaire (SAQ), this study measured the angina burden and quality of life. While average SAQ scores were similar among patients with individual endotypes, symptom burden worsened significantly as the number of abnormalities increased.
The patients with normal coronary function testing had the highest average SAQ score of 55.9, which indicated a lower angina burden. Scores progressively declined among those with one endotype (53.8), two endotypes (51.2), and three endotypes (45.7).
After adjusting for other factors, each additional ANOCA endotype identified was associated with a statistically significant reduction in SAQ scores.
The researchers concluded that multiple coronary dysfunction mechanisms frequently coexist in ANOCA patients and that a greater number of endotypes is linked to more severe angina. Overall, the findings illuminate the importance of comprehensive coronary function testing, which may help clinicians better understand symptom drivers and tailor treatment strategies to individual patients.
Source:
Wong, C. C. Y., Pargaonkar, V. S., Dawson, L. P., Penumaka, R. R., Rehan, R., Yong, A. S. C., Ng, M. K. C., Honda, Y., Fearon, W. F., Schnittger, I., & Tremmel, J. A. (2026). Multiple endotypes and angina burden in patients with nonobstructive coronary arteries. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2026.1234
