Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration

Summary

This protocol presents the acetylcholine rechallenge after nitroglycerine as an add-on procedure to spasm provocation testing. The purpose of this technique is to unmask co-existing microvascular spasm in patients with epicardial spasm and to assess the protective efficacy of nitroglycerine on a per-patient level to guide medical therapy.

Abstract

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) using acetylcholine (ACh) spasm provocation testing. CAS can further be divided into different subtypes (e.g., focal, diffuse epicardial, or microvascular spasm), each with different pathophysiological mechanisms that may require tailored drug treatment. The evidence behind the role of nitrates in the setting of each CAS subtype is lacking, and the effectivity can vary on a per-patient basis. In order to assess on a per-patient level whether nitroglycerine (NTG) can prevent inducible spasm, the vasospastic ACh dose can be readministered after NTG administration as part of the spasm provocation test. The preventive effect of NTG is assessed by evaluating improvements in the severity of induced symptoms, ischemic ECG changes, and by reassessing the site and mode of spasm on angiography. This technique can therefore be used to assess the nitrate responsiveness on a per-patient level and unmask co-existing microvascular spasm in patients with epicardial spasm that is prevented with NTG. The NTG rechallenge, therefore, allows to further guide targeted therapy for CAS and provide new insights into the pathophysiological mechanism behind vasospastic disorders.

Introduction

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina and non-obstructive coronary artery disease (ANOCA) by means of spasm provocation testing with acetylcholine(ACh)^1,2,3,4.The recent CorMicA trial demonstrated that identification and concurrent tailored treatment of CAS persistently improve the patient's quality of life and reduce the burden of angina⁵. Usually, once CAS is diagnosed, it is regarded as one distinct disease and treated with anti-vasospastic medicati....

Protocol

Intracoronary ACh testing has been approved by the local ethics committee of the Academic Medical Centre, and the protocol follows the guidelines of Amsterdam UMC for human research.

1. Preparation of the ACh stock solution

1. Mix the 20 mg of ACh with the 2 mL of solvent provided with the package (Table of Materials).
2. Add 1 mL of the ACh solution to 499 mL of 0.9% NaCl to create the stock solution, corresponding to a 20 µg/mL dose.
3. Fill a sterile dish with 50 mL of the stock solution, which will be used to prepare the syringes under sterile conditions.

Results

Interpretation of the ACh-test and rechallenge are based on criteria defined by the COVADIS study group⁴. A positive diagnosis for CAS is defined as (i) reproduction of the previously reported symptoms such as chest pain, shortness of breath, or other symptoms and (ii) the induction of ischemic ECG changes (ST-segment elevation or depression, or U-waves) in reaction to ACh. (Figure 2). It is therefore important to register a 12-lead-ECG continuously throughout the tes.......

Discussion

The usefulness of the ACh after NTG rechallenge has shown to be two-fold: (1) to unmask the co-existence of microvascular spasm in patients with epicardial spasm and (2) to assess the preventive efficacy of NTG on a per-patient level in order to guide medical therapy¹². Regardless of the result of the spasm provocation test, intracoronary NTG is always routinely administered into the target vessel after the test or when severe symptoms, ischemic ECG changes, or epicardial spasm occur. Adding .......

Materials

Name	Company	Catalog Number	Comments
Cannula (various manufacturers)	BBraun	4206096
ComboMap system	Volcano-Philips	Model No. 6800 (Powers Up)
ComboWire XT Guide Wire	Volcano-Philips	9515	Doppler guidewire
Diagnostic catheter	Boston scientific	34356-661	H749343566610/ MODEL-6F MACH 1 JL3.5
Diagnostic catheter	Boston scientific	34356-686	H749343566860/MODEL - 6F MACH 1 JR4
FINECROSS MG Coronary Micro-Guide Catheter	Terumo	NC-F863A
Intracoronary NTG	hameln pharma gmbh	RVG 119982
Lidocaine HCL	Fresenius Kabi	RVG 51673
Miochol-E Acetylcholine chloride	Bausch & Lomb	NDC 240208-539-20
Sheath Radialis	Teleflex	AA15611S
Syringe- 10 mL	BBraun	4606108V
Visipaque	GE Healthcare	RVG 17665	Iodixanol injectable contrast medium