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Updated: Mar 8, 2026
Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders
Published on: August 18, 2016
Indications, contraindications, and usefulness of acetylcholine testing
Fardeen Faiz1, Shivani Mehta1, Sierra Fleming1
1Georgia Heart Institute, Northeast Georgia Health System, Gainesville, GA, United States of America.
Insights
Acetylcholine (ACh) testing is a valuable tool for diagnosing coronary vasomotor dysfunction in angina with non-obstructive coronary arteries (ANOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA). This review highlights its updated protocols, safety, and role in precision medicine for these conditions.
Area of Science:
- Cardiology
- Clinical Pharmacology
- Diagnostic Testing
Background:
- Angina with non-obstructive coronary arteries (ANOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA) are linked to coronary vasomotor dysfunction.
- Intracoronary acetylcholine (ACh) testing is the standard for diagnosing coronary dysfunction but faces challenges in protocol standardization and safety.
- Existing protocols and safety data require contemporary updates to guide clinical practice.
Purpose of the Study:
- To review the indications, mechanisms, protocols, safety, and clinical utility of ACh provocation testing.
- To integrate recent multicenter registry data and mechanistic insights into ACh testing practices.
- To provide a practice-oriented guide for utilizing ACh testing in ANOCA and MINOCA.
Main Methods:
- Review of standardized ACh dosing strategies (bolus and infusion) and integration with hemodynamic assessment.
- Incorporation of data from the DISCOVER-INOCA registry and prospective multicenter endotype studies.
- Contemporary meta-analysis of ACh safety compared to ergonovine and updated contraindications based on 2024 ESC guidelines.
Main Results:
- ACh testing demonstrates high diagnostic yield and quantitative differentiation of various coronary vasomotor dysfunction endotypes.
- The incidence of major complications with ACh testing is very low (<1%).
- Emerging data support a shift towards mechanism-guided, endotype-specific therapy based on ACh testing results.
Conclusions:
- ACh testing, validated by North American registries and meta-analyses, enables quantitative endotype phenotyping.
- ACh testing serves as a diagnostic tool and a platform for precision medicine in ANOCA and MINOCA.
- Tailored therapy guided by ACh testing can improve patient-centered outcomes.
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.
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