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

Summary

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.

Abstract

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.

Introduction

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 interventions^1,2,3,4,5,6. 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....

Protocol

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 article¹⁵.

2. Preparation of adenosine solution for intracoronary injection

1. Take....

Results

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).

Spasm of the co.......

Discussion

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.......

Materials

List of materials used in this article

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