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    • br Difference between ACh and

    2023-01-30


    Difference between ACh and ER tests There are few reports concerning the provoked spasm between ER and ACh in the same patients [51], [52], [53]. Different mediators may have the potential of different coronary responses. In our experience, spasm provoked by intracoronary injection of ER is focal and proximal, while intracoronary administration of ACh provoked spasm distally and diffusely. Moreover, concordance of both provoked spasm sites and spasm configurations in the same coronary artery was just 13% of vessels [53]. In our 461 patients in whom we performed both ER and ACh tests, the provoked spasm frequency by ACh test was significantly higher than that oxytocin antagonist by ER tests [ACh: 39.3% (181/461) vs. ER: 25.8% (119/461), p<0.001]. In particular, ACh is supersensitive in female patients (ACh: 96.7% vs. ER: 32.8%, p<0.001) [54]. We should recognize that ER is remarkably different from ACh as a spasm provocation agent. In contrast, as shown in Table 5, Suzuki et al. reported that the positive spasm by ACh testing was 82%, while the positive provoked spasm by ER test was 100% [51]. According to the report by Kanazawa et al., the intracoronary injection of ACh provoked positive spasm in 80%, whereas the intracoronary administration of ER induced positive spasm in 65% [52]. However, there were no differences concerning the provoked spasm between ACh and ER tests in the small studies including our initial report. However, we should investigate the coronary response between the ER test and the ACh test in worldwide future studies.
    Investigation of microvascular dysfunction in patients with VSA For the evaluation of coronary microvascular function in patients with VSA after the diagnosis by the administration of intracoronary ACh/ER and intravenous ER, a Doppler flow guidewire was employed [55], [56], [57]. Akasaka et al. employed the Doppler guidewire for the evaluation of microvascular function after the intravenous administration of ER [55], while Teragawa investigated the microvascular function by using a 0.0014 Doppler flow guidewire after the intracoronary ACh and ER [56]. However, the conflicting results regarding the microvascular dysfunction in patients with VSA have been reported. Recently, Yamanaga et al. reported the impaired endothelial-independent microvascular relaxant function in patients with VSA by using a Combowire (Volcano Corp., Rancho Coldova, CA, USA) equipped with a Doppler velocity probe and a pressure sensor after the diagnosis with the intracoronary administration of Ach [57]. Although a Combowire is superior to a Doppler flow guidewire, it is controversial which pharmacological agent is the best selection in patients with VSA for the evaluation of mlicrovascular function. Further study is necessary for the investigation/evaluation of microvascular dysfunction in patients with VSA.
    Comparison with international group [Coronary Vasomotion Disorders International Study Group (COVADIS)] Table 6 shows the comparisons of indications for spasm provocation testing between the JCS guidelines and the COVADIS group [13], [58], [59]. The indications for provocative spasm testing of the COVADIS group are similar to those of the JCS guidelines. Pharmacological spasm provocation tests are defined as Class I in the COVADIS recommendation, whereas ESC and ACC/AHA gave spasm provocation testing as Class oxytocin antagonist IIa or Class IIb, respectively. The COVADIS group recommended that the provocative spasm testing should be performed in patients with unexplained syncope with antecedent chest pain and unexplained resuscitated cardiac arrest as Class I. According to the report of COVADIS group, the gold standard method for provocative spasm testing involves the administration of a provocative stimulus (typically intracoronary ACh but alternatively intracoronary or intravenous ER) during invasive coronary angiography with the monitoring of patient symptoms, ECG, and angiographic documentation of coronary spasm. However, in these reports [58], [59], we could find neither the dose of ACh/ER nor detailed procedures. The JCS guidelines do not recommend the intravenous ER tests due to unselective method, whereas the COVADIS group is allowed to employ the intravenous ER method as well as the intracoronary ER testing. The COVADIS group summarized the international standardization of diagnostic criteria for VSA. However, this statement has no detailed procedures of invasive pharmacological spasm provocation tests.