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Updated: Jun 2, 2025
Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders
Published on: August 18, 2016
Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic
C Crooijmans1, Tijn P J Jansen1, Joan G Meeder2
1Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands.
Insights
Lower acetylcholine doses during coronary function tests correlate with more frequent angina in patients with epicardial spasm. This finding suggests acetylcholine provocation dose may aid in risk stratification for coronary vasomotor dysfunction.
Area of Science:
- Cardiology
- Diagnostic Testing
- Pharmacology
Background:
- Coronary function tests (CFT) diagnose coronary vasomotor dysfunction in angina patients with nonobstructive coronary arteries (ANOCA).
- Acetylcholine is a standard agent for spasm provocation during CFT.
- Understanding the relationship between acetylcholine dose and symptom severity is crucial for ANOCA management.
Purpose of the Study:
- To investigate the association between the severity of anginal symptoms and the provocative dose of acetylcholine used in CFT.
- To explore the potential of acetylcholine provocation dose as a risk stratification factor.
Main Methods:
- Retrospective analysis of ANOCA patients undergoing CFT from the NL-CFT registry.
- Patients with epicardial spasm were categorized by acetylcholine dose (low, middle, high).
- Comparison of angina frequency and symptom change between groups and with controls.
Main Results:
- An inverse relationship was observed between acetylcholine provocation dose and baseline angina frequency in epicardial spasm (P=0.003).
- Lower doses were associated with more frequent angina.
- A trend suggested improvement with higher doses and deterioration with lower doses.
Conclusions:
- A significant dose-dependent relationship exists between acetylcholine-induced spasm provocation and anginal complaints.
- Acetylcholine provocation dose may serve as a valuable factor for risk stratification and as a surrogate outcome in clinical trials for ANOCA.
Background:
A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose.
Methods And Results:
We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL-CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2-20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow-up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm 61±21, controls 64±21, overall P=0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group.
Conclusions:
A significant dose-dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT06083155.
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