Endotyping of patients with INOCA: a single Ukrainian center experience

Background

Ischemia with Non-Obstructive Coronary Arteries (INOCA) is associated with a more than three-fold increase in the risk of major adverse cardiovascular events, including myocardial infarction and heart failure, compared to the healthy population. Despite current guidelines recommending invasive functional testing, its implementation remains limited in routine clinical practice. We present our experience in implementing a standardized acetylcholine (Ach) provocation protocol for precise endotyping of INOCA patients.

Purpose

To improve the diagnostic efficiency and personalized treatment of patients with INOCA by differentiating clinical endotypes and optimizing the diagnostic algorithm.

Methods

The study enrolled 68 patients with symptoms of coronary artery disease who presented to our center between February 2025 and January 2026. All patients underwent a clinical evaluation, including echocardiography and a graded exercise stress test. Subsequently, all patients underwent coronary angiography, supplemented by an acetylcholine provocation test. In patients with evidence of coronary atherosclerosis, fractional flow reserve (FFR) was measured to exclude the hemodynamic significance of stenoses

Results

The mean age of the patients was 57.7 ± 10.5 years. Women accounted for 42.6%. Among the risk factors, hypertension (91.2%), dyslipidemia (50.0%), smoking (23.5%), and diabetes mellitus (13.2%) prevailed. Following the acetylcholine provocation test, the following conditions were verified: endothelial dysfunction – 26.5%, vasospastic angina – 44.1%, microvascular spasm – 11.8%, and symptomatic myocardial bridges – 17.6%. Overall, 54.4% of bridges were detected, but they were not associated with spasm in all patients.

The procedure was safe; transient complications, including AV blocks (13.2%) and supraventricular arrhythmias (4.4%), were self-limiting and successfully managed in the catheterization laboratory.

Conclusion

Invasive endotyping via acetylcholine provocation is safe and provides essential diagnostic clarity in patients with INOCA. Our findings highlight the significant role of symptomatic myocardial bridges in triggering vasospasm, a mechanism often overlooked during routine angiography. Implementing this standardized protocol—the first of its kind in Ukraine—facilitates a paradigm shift from empirical management to personalized, endotype-specific therapy, which is crucial for improving clinical outcomes in this underserved patient population.