Diagnostic Validity of Acetylcholine Provocation Protocols in the Evaluation of Coronary Artery Spasm in Patients With ANOCA

BACKGROUND: Coronary artery spasm (CAS) is a common cause of angina with nonobstructive coronary arteries (ANOCA). While acetylcholine provocation testing is the diagnostic gold standard, protocol variations have led to discrepancies in diagnostic accuracy. This study aimed to compare the diagnostic validity of conventional versus high-dose acetylcholine regimens in patients with ANOCA. METHODS: Multivessel acetylcholine provocation testing was systematically performed in patients with ANOCA and a control cohort undergoing invasive coronary angiography for noncoronary indications. Incremental acetylcholine doses in the left (20–200 μg) and right (20–80 μg) coronary arteries were manually injected over 20 seconds to induce CAS. RESULTS: The study included 62 patients with ANOCA with typical CAS symptoms and 20 controls. Conventional-dose acetylcholine testing identified CAS in 67.1% (55/82) of patients, while high-dose testing detected CAS in 79.3% (65/82). Among patients with inducible spasm, 93.4% (61/65) had typical angina consistent with CAS. High-dose acetylcholine demonstrated significantly higher sensitivity (98% versus 87%, P =0.008), but a nonsignificant trend toward lower specificity (80% versus 95%, P =0.08). The high-dose regimen also showed a higher negative predictive value (94% versus 70%, P =0.01), while positive predictive values were comparable (93% versus 98%, P =0.12). CONCLUSIONS: High-dose acetylcholine provocation improves the detection of CAS in patients with ANOCA but may increase the risk of overdiagnosis. This approach should be reserved for patients with a high clinical suspicion of CAS, with the results interpreted within the broader clinical context.