60 Chapter 4 INTRODUCTION Coronary artery spasm (CAS), encompassing epicardial and microvascular spasm, is increasingly recognized as the substrate for both chronic and acute coronary syndromes especially in patients with angina and no obstructive coronary artery disease (ANOCA). Importantly CAS is associated with repeat hospitalizations, impaired quality of life and higher incidence of adverse cardiac events.1 To date, the established method for the diagnosis of CAS is invasive spasm provocation testing using intracoronary administration of acetylcholine (Ach) or ergonovine (Ergo)2 and has recently been endorsed in the European guidelines for evaluation of chronic coronary syndromes in the absence of obstructive coronary artery disease.3 However, a consistent spasm provocation testing protocol for detecting epicardial and microvascular spasm is still lacking, leading to various protocols used across continents, and even between expert centers. This involves differences in both the applied doses, administration protocols, including the diagnostic agent used.4 Moreover, diagnostic criteria to define a pathological response to spasm provocation testing have long remained ambiguous. Taken together, different testing protocols and diagnostic criteria hamper comparison of study results, including assessment of ethnic and sex differences in CAS. To unify the diagnosis of CAS, the Coronary Vasomotion Disorders International Study Group (COVADIS) proposed diagnostic criteria in 2015, which since, unfortunately, have not been widely implemented in both clinical practice and research initiatives.5, 6 As a result, extrapolation of study results remains cumbersome. Considering the variety of data available in contemporary literature, we want to provide clinicians with a state-of-the art overview of the data currently available. Therefore, the aim of the present report is to provide a structured overview of the available evidence regarding the prevalence, clinical characteristics, and prognosis of CAS in men and women with ANOCA across different continents. METHODS Protocol and registration This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.7 The study protocol was prospectively developed and registered at The International Prospective Register of Systematic Reviews (PROSPERO, crd.york.ac.uk/PROSPERO), registration number CRD42021272100). Search strategy Search strategies were developed in consultancy with a medical librarian and PubMed, Embase.com and Web of Science were searched. Thesaurus terms and free-text words, including synonyms and closely related words, were used for the following concepts: “coronary vasospasm”, “ANOCA” and “INOCA”. In Supplementary Appendix 1. of the
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