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Updated: Feb 13, 2026

Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders
Published on: February 3, 2021
Non-invasive Coronary Functional Tests in Patients with Angina and Non-obstructive Coronary Artery Disease
Nello Cambise1,2, Angelo Giuseppe Marino1, Fabio De Benedetto1
1Università Cattolica del Sacro Cuore Rome, Italy.
Background:
Invasive coronary functional tests (I-CFTs) can identify the mechanism(s) of angina in patients with non-obstructed coronary arteries (ANOCA). In this study, we assessed whether non-invasive coronary functional tests (NI-CFTs) can also produce reliable results when assessing these mechanisms.
Methods:
We performed NI-CFTs by recording coronary blood flow velocity (CBFV) in the left anterior descending coronary artery by transthoracic Doppler echocardiography in 18 patients with ANOCA who had undergone I-CFTs (an acetylcholine provocation test and an adenosine stress test) and 13 healthy controls. The NI-CFTs included hyperventilation, a dipyridamole stress test and a cold pressor test.
Results:
Acetylcholine induced epicardial or coronary microvascular spasm in 11 patients (61.1%), whereas adenosine coronary flow reserve (CFR) was reduced (<2.5) in seven (39%). Hyperventilation-induced coronary vasoconstriction produced a reduction in CBFV >10% compared to baseline in eight patients (44.4%) and none in the control group (p=0.005). Dipyridamole-CFR was lower in the patient group than in the control group (2.25 ± 0.49 versus 2.76±0.49; p=0.01) and correlated with adenosine-CFR (r=0.75; p<0.001). Full agreement in coronary abnormalities detected during I-CFTs and NI-CFTs (hyperventilation/dipyridamole stress test) was found in 14 patients (77.8%). Furthermore, cold pressor test-CFR was lower in patients than in the control group (1.33 ± 0.18 versus 1.52 ± 0.22; p=0.019); cold pressor test-CFR <1.35 identified three patients who showed both normal I-CFTs and a normal response to hyperventilation and dipyridamole at NI-CFTs.
Conclusion:
In ANOCA patients, the results of NI-CFTs performed with transthoracic Doppler echocardiography of the left anterior descending coronary artery showed a high correlation with coronary function abnormalities detected using I-CFTs. Our data suggest that NI-CFTs deserve investigation in larger multicentre studies to assess their usefulness in guiding clinical management of ANOCA patients.
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