Moderate vasomotor response to acetylcholine provocation test as an indicator of long-term prognosis

Abstract

The acetylcholine (ACh) provocation test (ACh-test) is used for the diagnosis of vasospastic angina (VSA). However, subjects often show a moderate spasm (MS) response for which diagnosis of VSA is not definitive, and the clinical significance of this response is unknown. We assessed moderate coronary vasomotor response to the ACh test as an indicator of long-term prognosis. A total of 298 consecutive patients who underwent the ACh test for suspected VSA were retrospectively investigated. Coronary spasm severity after intracoronary administration of isosorbide dinitrate was evaluated by measuring epicardial coronary artery diameter reduction after ACh injection. Patients were divided into three groups according to the diameter reduction during the ACh test: severe spasm (SS) showing ≥75 % diameter reduction, MS showing ≥50 % diameter reduction, and others (N). In Kaplan-Meier analysis, the major adverse cardiac event (MACE) rates with a median follow-up of 4.6 years were significantly worse in SS (11.1 %) and MS (8.5 %) than N (1.9 %), (SS vs N; P = 0.009, MS vs N; P = 0.029). Significant difference in MACE rates was not observed between SS and MS (P = 0.534). Cox regression analysis revealed that MS remained an independent predictor of MACE after adjustment for other confounders (HR: 7.18, 95 % CI 1.42-36.4, P = 0.017). Patients with MS by ACh test had a cardiac event rate comparable with that of patients with SS and significantly worse than that of patients with normal vasomotor responses.

Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis

“…One hundred fifty‐five articles received a complete review, and 56 studies met inclusion criteria and were included in the meta‐analysis (Figure 2 ). 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , …”

“…The prevalence of epicardial spasm was 0.40 (95% CI, 0.33–0.47; I 2 =96%), whereas the prevalence of microvascular spasm was 0.24 (95% CI, 0.21–0.28; I 2 =87%; Figure 7 , Figure S4 ). For most of the patients, acetylcholine was used for the provocation test (98%), 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 31 , 63 , 66 , 68 and 2 studies used ergonovine. 30 , 34 No significant difference was found considering the type of provocation test and prevalence of spasm 0.49 (95% CI, 0.38–0.55) for acetylcholine versus 0.48 (95% CI, 0.39–0.57) for ergonovine ( P =0.935).…”

Clinical Outcomes and Provoked Epicardial Spasm Phenotypes via Intracoronary Acetylcholine Testing in 680 Patients with Angina and Nonobstructive Coronary Arteries

“…In contrast, in our study, the prognosis in patients with an unclassified ACh test was similar to that in those with ES. Furthermore, according to previous reports, patients with moderate vasomotor response (50–75%) or inconclusive ACh test (vasoconstriction and/or electrocardiographic changes, but no chest pain) had MACEs similar to those with ES [ 28 , 29 ]. Treating patients with moderate vasoconstriction and inconclusive vasoreactivity testing with optimal medications is challenging.…”