Key result
Female sex is linked to ~3-fold higher odds of microvascular spasm preceding epicardial spasm in ANOCA.
Why the study?
Intracoronary provocative testing in ANOCA patients may reveal microvascular and/or epicardial spasm, but the relationship between these two spasm types had not been systematically investigated.
Observational (n=142)
In ANOCA patients with confirmed epicardial spasm, 35% also demonstrate preceding microvascular spasm at lower acetylcholine doses, a phenomenon occurring three times more frequently in women than men.
Attention to lower acetylcholine doses may be warranted in women during ANOCA testing; extends spasm phenotyping but leaves open protocol changes.
Background Patients with Angina and unobstructed coronary arteries (ANOCA) frequently suffer from coronary spasm. Intracoronary provocative testing to diagnose coronary spasm is recommended by current guidelines. This approach may reveal microvascular and/or epicardial spasm. However, the relationship of these two spasm types has not been investigated systematically. The aim of the present study was to assess the frequency and clinical characteristics of patients showing microvascular spasm at lower acetylcholine doses and proof of epicardial spasm at higher doses. Methods From our ACOVA registry study we enrolled 142 ANOCA patients (mean age 63 years, 44% female) between 2008 and 2025. All patients underwent invasive angiography and acetylcholine testing with confirmation of epicardial spasm at the highest acetylcholine dose (200µg) in the left coronary artery according to the COVADIS criteria. In all patients, demographic data, cardiovascular risk factors and procedural data were recorded. The latter included any symptoms and/or ischemic ECG shifts during lower acetylcholine doses (i.e. 2µg, 20µg, 100µg). This enabled diagnosis of microvascular spasm before documentation of epicardial spasm. Results Overall, 49 out of 142 patients (35%) fulfilled the criteria of microvascular spasm before documentation of epicardial spasm (Figure 1). Statistical analysis revealed no significant differences between patients with and without microvascular spasm regarding cardiovascular risk factors (hypertension, diabetes, smoking, hypercholesterolemia, positive family history). However, patients with microvascular spasm were significantly more often female (55% vs. 29%, p=0.037). Multivariable analysis revealed female sex as significant predictor for the occurrence of microvascular spasm (OR 3.0 CI 1.15-7.8, p=0.021). Conclusion In ANOCA patients with confirmed epicardial spasm microvascular spasm at lower acetylcholine doses can be diagnosed in 35%. Independent of cardiovascular risk factors women are affected by this scenario three times more often than men. Our results underline the importance of the coronary microcirculation and sex-specific differences in the pathophysiology of coronary spasm.
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Fischer et al. (2026) conducted an observational in Angina and unobstructed coronary arteries (ANOCA) with confirmed epicardial spasm (n=142). Intracoronary acetylcholine testing / Female sex vs. Patients without preceding microvascular spasm / Male sex was evaluated on Occurrence of microvascular spasm at lower acetylcholine doses (2µg, 20µg, 100µg) before documentation of epicardial spasm at 200µg (OR 3.0, 95% CI 1.15-7.8, p=0.021). Intracoronary acetylcholine testing identified microvascular spasm preceding epicardial spasm in 35% of ANOCA patients, with female sex independently predicting its occurrence (OR 3.0, 95% CI 1.15-7.8, p=0.021).
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