Acetylcholine Rechallenge: A First Step Toward Tailored Treatment in Patients With Coronary Artery Spasm

Andreas Seitz*, Rutger Feenstra, Regina E. Konst, Valeria Martínez Pereyra, Sascha Beck, Marcel Beijk, Tim van de Hoef, Niels van Royen, Raffi Bekeredjian, Udo Sechtem, Peter Damman, Jan J. Piek, Peter Ong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objectives: The present study aimed to assess the feasibility and clinical value of acetylcholine (ACh) rechallenge for the detection of coexisting epicardial and microvascular spasm and to determine the efficacy of nitroglycerin in these spasm endotypes. Background: The coexistence of epicardial and microvascular spasm is difficult to identify; thus, its frequency is unknown. Nitroglycerin treatment is equally recommended for both epicardial and microvascular coronary spasm despite contradictory data. Methods: In this multicenter study, 95 patients with coronary spasm were included to undergo ACh rechallenge, which consisted of repeated ACh provocation 3 minutes after intracoronary nitroglycerin administration using the same dose that previously induced spasm. Results: In total, 95 patients (age 61 ± 12 years, 69% female) were included. Fifty-five patients (58%) had microvascular spasm, and 40 patients (42%) had epicardial spasm during initial ACh provocation. In 48% of patients with epicardial spasm, ACh rechallenge revealed coexisting nitroglycerin-persistent microvascular spasm. Nitroglycerin administration before ACh rechallenge prevented reinducibility of epicardial spasm in all patients with focal spasm and in 80% of patients with diffuse spasm. Microvascular spasm was prevented in only 20% by prior nitroglycerin administration but was attenuated in another 49% of patients. Conclusions: This study demonstrates a high frequency of epicardial spasm with coexisting nitroglycerin-persistent microvascular spasm. Intracoronary nitroglycerin was very effective in preventing reinducibility of epicardial spasm, whereas it prevented microvascular spasm in only 20% of patients. ACh rechallenge is a novel method that facilitates the detection of coexisting spasm endotypes and may pave the way towards tailored treatment of vasospastic angina.
Original languageEnglish
Pages (from-to)65-75
Number of pages11
JournalJACC: Cardiovascular Interventions
Issue number1
Publication statusPublished - 10 Jan 2022
Externally publishedYes

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