Indications, contraindications, and usefulness of acetylcholine testing.

BACKGROUND

Angina with non-obstructive coronary arteries (ANOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA) are increasingly recognized as manifestations of coronary vasomotor dysfunction. Intracoronary acetylcholine (ACh) testing remains the gold standard for diagnosing endothelial-dependent coronary dysfunction, epicardial spasm, and microvascular spasm; however, variability in protocols and safety concerns has limited broader adoption.

OBJECTIVES

To provide a contemporary, practice-oriented review of the indications, mechanisms, protocols, safety profile, and clinical utility of ACh provocation testing, integrating emerging multicenter registry data and recent mechanistic insights.

METHODS AND

RESULTS

We review standardized ACh dosing strategies (bolus and continuous infusion), diagnostic endotypes, and integration with wire-based hemodynamic assessment. Building upon prior state-of-the-art reviews, this article incorporates new data from abstracts presented in 2025 from the DISCOVER-INOCA registry and recent prospective multicenter endotype studies demonstrating (1) high diagnostic yield, (2) quantitative differentiation of epicardial spasm, microvascular spasm, isolated endothelial dysfunction, and enhanced nociception, and (3) a very low incidence of major complications (<1%). Contemporary meta-analysis further clarifies the safety profile of ACh relative to ergonovine. We also provide updated contraindications aligned with 2024 ESC chronic coronary syndrome guidance and MINOCA recommendations. Importantly, emerging data support a shift from purely qualitative spasm provocation toward mechanism-guided, endotype-specific therapy.

CONCLUSIONS

This review advances the field by integrating prospective North American registry validation, contemporary safety meta-analyses, and quantitative endotype phenotyping frameworks. ACh testing is repositioned not only as a diagnostic tool but as a platform for precision medicine in ANOCA and MINOCA, enabling tailored therapy and improved patient-centered outcomes.