Diagnostic Criteria for Acetylcholine-Provoked Coronary Spasm ― Do We Need Both Symptoms and Ischemic Electrocardiogram Change? ―
Article ID: CJ-25-0371
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Article ID: CJ-25-0371
The guidelines for vasospastic angina/coronary spastic angina (VSA/CSA) have been published multiple times, with concurrent revisions of the positive diagnostic criteria for coronary spasm during pharmacological provocation testing.1–3 The central concept of these positive diagnostic criteria has been the establishment of universally applicable, standardized angiographic findings (i.e., transient, total or subtotal focal occlusion with >90% vasoconstriction) to ensure consistent diagnosis of coronary spasm across institutions. Recently, diagnostic criteria for diffuse coronary spasm have been added, based on findings from several clinical studies.4–8 Among those studies, Sato et al. demonstrated that diffuse coronary spasm in response to acetylcholine (ACh) occurs frequently and is associated with a higher incidence of positive lactate production compared with focal spasm, suggesting that diffuse spasm might be a type that induces myocardial ischemia following ACh administration. Given the etymology of “angina”, chest pain is the primary clinical suspicion, and ischemic changes on electrocardiogram (ECG) are essential confirmatory evidence in the majority of angina cases. Therefore, guideline authors have historically recognized both chest pain and ischemic ECG changes as critical diagnostic criteria during pharmacological coronary spasm provocation testing. This requirement is consistent in both Japanese and international guidelines, in which chest pain and ischemic ECG changes are mandatory for the diagnosis of coronary spasm induced by pharmacological agents, and reports from Europe have also used these guidelines for diagnosis.9,10
Article doi:10.1253/circj.CJ-25-0172
In this issue of the Journal, Ohnaga et al.11 evaluate the necessity of these 2 elements (the presence of chest pain and ischemic ECG changes during ACh provocation testing) by categorizing patients into 3 groups: the narrow definition group (patients presenting ACh-provoked epicardial spasm with both chest pain and ischemic ECG changes), the broad definition group (patients with ACh-provoked epicardial spasm and either chest pain or ischemic ECG changes), and a negative group (including patients with ACh-provoked epicardial spasm but without both chest pain and ischemic ECG changes) (Figure). Of them, 53.6% met the positive criteria; notably, approximately one-third would not have been diagnosed as VSA/CSA using the narrow definition. Although there were significant differences in baseline characteristics between the ACh-positive and -negative groups, no differences were identified between the narrow and broad definition groups. Furthermore, adverse events during provocation tests and long-term clinical outcomes were comparable between the 2 positive groups.
Chest pain and ECG changes in the definitions of acetylcholine-positive criteria. According to current guidelines,1–3 the positive criteria for coronary spasm require both usual chest pain and ischemic ECG changes as essential components (narrow definition). In the broad definition, one-third of the positive criteria in this study were met.
Based on these findings, the authors conclude that the simultaneous presence of chest pain and ischemic ECG changes may not be essential for diagnosing VSA/CSA during pharmacological provocation testing. However, the interpretation of these results is challenging due to the retrospective and observational nature of the study, along with potential paradoxical findings influenced by chance. For example, medications presented in the baseline characteristics did not account for adjustments made after ACh provocation tests, obscuring the effect of subsequent medical interventions on patient prognosis. Moreover, the absence of multivariable analysis adjusted for confounding factors limits the reliability of conclusions drawn from univariable analyses alone.
Nonetheless, the present study suggests that angiographic vasoconstrictive responses alone as the primary criteria for a positive coronary spasm provocation test might be clinically acceptable, especially for patients with clinically suspected VSA/CSA. The positivity rate using the narrow definition in this study was 36.6%, which was lower than results of other previous studies using the current guideline definition (including diffuse spasm and both chest pain and ischemic ECG changes as diagnostic criteria), where positivity rates exceed 50%.6,8 However, using the broad definition, the positivity rate in this study increased to 53.6%, and furthermore, the positivity rate increased to 60.4% when including patients with ACh-provoked epicardial spasm alone as the positive criterion. It is possible that differences in timing or positivity criteria for assessing symptoms and ischemic ECG changes during ACh provocation testing may affect the positivity rates across studies using the narrow definition.
Additionally, some patients with epicardial coronary spasm but without both chest pain and ECG changes are currently categorized as negative and managed without optical medical therapy; however, the need for pharmacological intervention in this subgroup requires further investigation. Future guideline revisions should critically reassess the diagnostic criteria to ensure diagnostic accuracy, appropriate pharmacological therapy, and optimal patient prognosis. Crucially, patients who genuinely require treatment must not be overlooked due to overly stringent diagnostic criteria, potentially depriving them of necessary pharmacological management.
We used ChatGPT-4o to assist with English language editing of this manuscript and to create a figure illustrating chest pain symptoms.
Name of the ethics committee: N/A. Reference number: N/A.
K.K. is a member of Circulation Journal’s Editorial Team. M.I. reports no conflicts.
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