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Updated: Sep 9, 2025

Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders
Published on: August 18, 2016
Clinical Characteristics and Outcomes of Patients with a Positive Finding for the Coronary Spasm Provocation Test at
Hiroki Kuji1,2, Yuichi Saito1, Shota Kuranaga3
1Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Japan.
Insights
The intracoronary acetylcholine (ACh) provocation test diagnoses coronary spastic angina (CSA). A low-dose positive response may indicate distinct mechanisms and outcomes compared to high-dose responses in CSA patients.
Area of Science:
- Cardiology
- Diagnostic Testing
- Vascular Medicine
Background:
- The intracoronary acetylcholine (ACh) provocation test is the standard invasive method for diagnosing coronary spastic angina (CSA).
- Current guidelines recommend incremental ACh doses, but the clinical significance of positive responses at lower doses remains unclear.
Purpose of the Study:
- To investigate the clinical relevance and outcomes of low-dose versus high-dose positive results in the intracoronary ACh provocation test for diagnosing CSA.
- To compare intraprocedural adverse events and long-term clinical outcomes between patients with low-dose and high-dose positive ACh test results.
Main Methods:
- A retrospective analysis of 636 patients with suspected CSA undergoing intracoronary ACh provocation testing.
- Patients with positive ACh tests were categorized into 'low-dose positive' (positive at initial dose) and 'high-dose positive' (requiring higher doses).
- Comparison of baseline characteristics, procedural events, and long-term outcomes between the two positive groups.
Main Results:
- Out of 636 patients, 4.1% were low-dose positive and 47.8% were high-dose positive for CSA.
- The low-dose positive group showed a higher incidence of ST-segment elevation during testing and unstable angina during follow-up compared to the high-dose positive group.
- Despite differing event frequencies, overall long-term clinical outcomes were similar between the low-dose and high-dose positive groups.
Conclusions:
- Approximately 10% of CSA diagnoses via ACh testing occur at low doses, suggesting a potential subgroup with unique characteristics.
- The dose-dependent response in ACh testing may reflect distinct underlying pathophysiological mechanisms in CSA.
- Further research is warranted to elucidate the specific mechanisms and refine management strategies for low-dose positive CSA patients.
Abstract:
Objective The intracoronary acetylcholine (ACh) provocation test is an invasive standard for diagnosing coronary spastic angina (CSA)/vasospastic angina. Although the guidelines recommend incremental doses of ACh, the clinical relevance of the significant response to lower ACh doses is unclear. Methods From April 2012 to June 2024, 636 patients with no significant epicardial coronary disease undergoing intracoronary ACh provocation testing for the diagnosis of CSA were included. Patients with positive ACh test results were divided into two groups: the low-dose positive group, defined as those who tested positive at the initial dose of ACh in the left and/or right coronary arteries without further dose escalation, and the high-dose positive group, including those who required higher doses for a positive result. The occurrence of intraprocedural adverse events and long-term outcomes was also evaluated. Results Of the 636 patients, 306 (48.1%) were classified as negative, 304 (47.8%) as high-dose positive, and 26 (4.1%) as low-dose positive based on the ACh provocation tests. The baseline characteristics did not differ significantly between the high- and low-dose positive groups. ST-segment elevation on electrocardiography during ACh tests and unstable angina during the follow-up period were more frequent in the low-dose positive group than in the high-dose positive group, while the overall clinical outcomes were similar among the groups. Conclusion Among patients with CSA diagnosed using ACh provocation testing, nearly 10% had a positive diagnosis at a low dose. There may be distinct underlying mechanisms and clinical outcomes depending on the ACh dose required for a positive test result.
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