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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.
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.
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 medication, such as calcium antagonists and nitrates1. Although, CAS can be divided into different subtypes with different pathophysiological mechanisms that may require tailored drug treatment6. CAS can occur on an epicardial level, either focally or diffusely, throughout the epicardial coronary arteries or on a microvascular level. The former is defined as vasospastic angina (VSA) and the latter as microvascular angina (MVA) due to microvascular spasm according to the COronary VAsomotor DISorders study group (COVADIS)3,4. Moreover, combinations of endotypes of CAS may co-exist that can further complicate tailored treatment. This is especially important as the occurrence of microvascular spasm may be masked during spasm provocation when a simultaneous epicardial spasm occurs.
As a consequence, treatment of these patients in clinical practice can be cumbersome and initiates a period of trial and error based treatment with various anti-vasospastic or anti-anginal medications. Nitrates, in particular, are often initiated as first-line treatment in short-acting form as rescue medication for acute anginal attacks or in the long-acting form as maintenance therapy. 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. Especially in the case of microvascular or diffuse distal epicardial spasm, the effect of NTG is controversial7,8. Furthermore, the therapeutic efficacy of chronic NTG treatment has to be weighed against potential side effects, such as severe headaches and a worsened exercise capacity9,10,11.
Recently Seitz et al. demonstrated the clinical usefulness of the ACh rechallenge technique after NTG administration as an add-on procedure to the spasm provocation test12. This is performed after a positive spasm provocation test by readministering the vasospastic dose of ACh in a similar fashion as the vasospastic dose itself 3 min after NTG administration. To this end, the COVADIS criteria are revisited in order to evaluate the preventive effect of NTG, e.g., improvement in symptoms, ischemic ECG changes, and reassessment of the site and mode of spasm by angiography3,4. Moreover, prevention of epicardial spasm during rechallenge can unmask the co-existence of microvascular spasm.
The purpose of the rechallenge after NTG, therefore, is two-fold: (1) to assess the preventive effect of NTG on the re-occurrence of spasm on a per patients level in order to improve clinical outcomes and tailor treatment immediately after diagnosis that is made during spasm provocation and (2) to assess the co-existence of microvascular spasm in patients with epicardial coronary artery spasm10,13.
A previous publication by Ong et al. extensively covered the spasm provocation test14. In our institute, we use a variation of this protocol where the ACh dosages are administered in 60 s instead of 20 s. The purpose of this paper is to describe the NTG rechallenge as an add-on procedure to the ACh spasm provocation test. This technique can be performed with each type of protocol, as demonstrated by Seitz et al. since the results of the NTG rechallenge did not differ among the participating centers that used different protocols.
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
2. Preparation of the syringes containing ACh for intracoronary injection
3. Diagnostic coronary angiography
4. Preparations for Doppler flow assessment
NOTE: Here, ComboWire was used as the Doppler guidewire with the ComboMap system (Table of Materials)
5. Intracoronary administration of ACh
6. Rechallenge
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...
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 ...
The authors have nothing to disclose.
None
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 |
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