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Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders

Published: February 3rd, 2021



1Department of Cardiology and Angiology, Robert Bosch Hospital

Coronary vasomotion disorders represent frequent functional causes of angina in patients with unobstructed coronaries. The underlying mechanism of angina (endotype) in these patients can be determined by a comprehensive invasive diagnostic procedure based on acetylcholine provocation testing followed by Doppler-derived assessment of the coronary flow reserve and microvascular resistance.

More than 50% of patients with signs and symptoms of myocardial ischemia undergoing coronary angiography have unobstructed coronary arteries. Coronary vasomotor disorders (impaired vasodilatation and/or enhanced vasoconstriction/spasm) represent important functional causes for such a clinical presentation. Although impaired vasodilatation may be assessed with non-invasive techniques such as positron emission tomography or cardiac magnetic resonance imaging, there is currently no reliable non-invasive technique for the diagnosis of coronary spasm available. Thus, invasive diagnostic procedures (IDP) have been developed for the diagnosis of coronary vasomotor disorders including spasm testing as well as assessment of coronary vasodilatation. The identification of the underlying type of disorder (so called endotype) allows the initiation of targeted pharmacological treatments. Despite the fact that such an approach is recommended by the current European Society of Cardiology guidelines for the management of chronic coronary syndromes based on the CorMicA study, comparability of results as well as multicenter trials are currently hampered by major differences in institutional protocols for coronary functional testing. This article describes a comprehensive IDP protocol including intracoronary acetylcholine provocation testing for diagnosis of epicardial/microvascular spasm, followed by Doppler wire-based assessment of coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) in search of coronary vasodilatory impairment.

In recent years interventional cardiology has made substantial progress in various areas. This not only comprises interventional treatment of the heart valves using transcatheter aortic valve replacement and edge-to-edge repair of the mitral and tricuspid valve, but also coronary interventions1,2,3,4,5,6. Among the latter are advances in techniques for treatment of chronic total occlusions as well as calcified lesions using rotablation and shock wave therapy. In addition t....

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Intracoronary ACh testing has been approved by the local ethics committee and the protocol follows the guidelines of our institution for human research. A previous JoVE article covered a protocol showing preparation of the ACh solutions as well as preparation of the syringes for intracoronary injection of ACh15.

1. Preparation of the ACh solutions and preparation of the syringes for intracoronary injection of ACh

  1. Please refer to a previously published JoVE a.......

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According to the diagnostic criteria suggested by COVADIS9, vasospastic angina can be diagnosed if the following criteria apply during ACh provocation testing: transient ECG changes indicating ischemia, reproduction of the patient´s usual anginal symptoms and > 90% vasoconstriction of an epicardial vessel as confirmed during coronary angiography (Figure 2).


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Management of patients with angina and unobstructed coronary arteries is often demanding and sometimes frustrating. An important step during the work-up of these patients is that the underlying pathophysiological mechanism(s) for the patient's symptoms are adequately investigated. This is challenging as often not only one mechanism is responsible and various aetiologies including cardiac and non-cardiac as well as coronary and non-coronary need to be taken into account.

Frequently patients.......

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This project was supported by the Berthold-Leibinger-Foundation, Ditzingen, Germany.


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Name Company Catalog Number Comments
Cannula 0,95 x 50 mm (arterial punction) BBraun 4206096
Cannula 23 G 0,6 x 25 mm (local anesthesia) BBraun 4670025S-01
Coronary angiography suite (AXIOM Artis MP eco) Siemens n/a
Contrast agent Imeron 350 with a 10 mL syringe for contrast injection Bracco Imaging 30699.04.00
Diagnostic catheter (various manufacturers) e.g. Medtronic DXT5JR40
Glidesheath Slender 6 Fr Terumo RM*RS6J10PQ
Heparin 5,000 IU (25,000 IU / 5 mL) BBraun 1708.00.00
Mepivacaine 10 mg/mL PUREN Pharma 11356266
Sodium chloride solution 0.9 % (1 x 100 mL) BBraun 32000950
Syringe 2 mL (1x) (local anesthesia) BBraun 4606027V
Syringe 10 mL (1x) (Heparin) BBraun 4606108V
Acetylcholine chloride (vial of 20 mg acetylcholine chloride powder and 1 ampoule of 2 mL diluent) Bausch & Lomb NDC 240208-539-20
Cannula 20 G 70 mm (2x) BBraun 4665791
Glyceryle Trinitrate 1 mg/mL (5 mL) Pohl-Boskamp 07242798
Sodium chloride solution 0.9 % (3 x 100 mL) BBraun 32000950
Syringe 2 mL (1x) BBraun 4606027V
Syringe 5 mL (5x) BBraun 4606051V
Syringe 10 mL (1x) BBraun 4606108V
Syringe 50 mL (3x) BBraun 4187903
Adenosine 6 mg/2 mL Sanofi-Aventis 30124.00.00
ComboMap Pressure/Flow System Volcano Model No. 6800 (Powers Up)
Pressure/Flow Guide Wire Volcano 9515
Sodium chloride solution 0.9 % (1 x 100 mL) BBraun 32000950
Syringe 10 mL (3x) BBraun 4606108V

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