Importance of provoked spasms at the sites of nonobstructive stenosis as well as at the sites of obstructive stenosis in patients with obstructive coronary arteries and coronary spasm.

OBJECTIVES: There are few reports regarding the prognosis in patients with obstructive coronary artery disease (OCAD) and vasospastic angina (VSA). This study investigated the clinical characteristics and clinical outcomes in patients with VSA and OCAD, especially regarding provoked spasm phenotypes and sites. METHODS: This was a retrospective, observational, single-center study of 403 patients with typical or atypical angina-like chest pain undergoing acetylcholine (ACH) spasm provocation testing and OCAD. An obstructed coronary artery was defined as ≥50% luminal narrowing. We defined positive epicardial spasm as ≥90% transient stenosis and usual chest symptoms or ischemic ECG changes. RESULTS: Among these 403 patients with OCAD, positive spasm by intracoronary ACH testing was observed in 196 patients (49%), whereas negative spasm was found in the remaining 207 patients (51%). The clinical outcomes in the patients with OCAD and provoked spasm were not different according to the provoked-spasm phenotypes. Furthermore, the clinical outcomes were unsatisfactory in the patients with spasm at the site of nonobstructive lesion alone compared with those with spasm at the site of obstructive and nonobstructive lesions. CONCLUSION: We should precisely diagnose patients with OCAD who have provoked spasm by using intracoronary ACH testing and medicate the nonobstructive vessels in patients with OCAD and VSA under optimal coronary vasodilators.

Clinical Limitations of Vasoreactivity Testing as a Diagnostic Tool in Patients with Vasospastic Angina.

The Japanese Circulation Society guidelines recommend a class I vasoreactivity test to diagnose patients with vasospastic angina (VSA). However, the acetylcholine or ergonovine test has been established as the gold standard for variant angina (VA). The sensitivity and specificity of intracoronary vasoreactivity testing in patients with VA were acceptable. Cardiologists have employed these vasoreactivity tests to conveniently diagnose the presence of coronary spasms in patients with all VSA. The majority of VSAs may have lower disease activity than VA cases. We have summarized the usefulness of spasm provocation tests in patients with VA and VSA. A positive-provoked spasm diagnosed by standard vasoreactivity testing may indicate a disease state similar to that of VA, whereas a negative-provoked spasm after standard vasoreactivity testing may indicate a lower disease state than that of VA. Cardiologists should reconsider the limited usefulness of vasoreactivity testing when diagnosing the presence of coronary spasms in all VSAs, but not VA.

What is the meaning of provoked spasm phenotypes by vasoreactivity testing?

Coronary artery epicardial spasm is involved in the pathogenesis of many cardiac disorders. Vasoreactivity testing, such as intracoronary injection of acetylcholine (ACH) or ergonovine (ER), is the gold standard method for the diagnosis of vasospastic angina. Provoked epicardial spasm phenotypes are classified as focal spasm and diffuse spasm. Multiple factors, including sex, ethnicity, and use of coronary vasoactive stimulators, are related to the provoked phenotypes of epicardial spasm. Diffuse-provoked spasm is often observed in females, where focal-provoked spasm is markedly more common in males. ACH provokes more diffuse and distal spasms, whereas ER induces more focal and proximal spasms. Yellow plaque and coronary thrombi are often observed in lesions with focal spasms, and intimal thickness with a sonolucent zone is significantly more common in lesions with focal spasm. Furthermore, clinical outcomes in patients with focal spasm are unsatisfactory compared with those in patients with diffuse spasm. However, the reproducibility and eternality of provoked spasm phenotypes by vasoreactivity testing is uncertain. Coronary atherosclerosis or endothelial damage may affect coronary vasomotor tone. Although coronary artery spasm may persist in the same coronary artery, provoked coronary spasm phenotypes may exhibit a momentary coronary reaction by intracoronary ACH or ER testing.

Sex-related differences in coronary vasomotor disorders: Comparisons between Western and Japanese populations.

Sex-related differences in the prevalence of cardiac disorders have been elucidated beyond races. Angina/ischemia with nonobstructive coronary artery disease (AINOCA) is often observed in females. Coronary microvascular dysfunction (CMD) and coronary epicardial spasm (CES) are the principal cause of AINOCA. The clinical outcomes of Western patients with CMD were less satisfactory than expected, while the prognosis of Japanese patients with CES treated with medications including calcium channel blockers was favorable. However, the incidence and clinical features of coronary spasm endotypes were different between Western and Japanese populations. Furthermore, sex-related differences in the clinical manifestations and outcomes of patients with different spasm endotypes remain uncertain beyond race. In this article, we will review the sex differences in Japanese AINOCA patients with coronary vasomotor disorders, including CMD and CES, and compare them with those of Western patients.

Clinical Outcomes and Provoked Epicardial Spasm Phenotypes via Intracoronary Acetylcholine Testing in 680 Patients with Angina and Nonobstructive Coronary Arteries.

Background: Epicardial spasm (ES) phenotypes may be related to the prognosis in patients with coronary spastic angina. Objectives: The purpose of this study was to elucidate the relationship between angiographic coronary vasomotor responses to intracoronary acetylcholine (ACh) injection and prognosis in patients with angina and nonobstructive coronary artery disease (ANOCAD). Methods: This was a retrospective, observational, single-center study of 680 patients with ANOCAD. ACh spasm provocation tests on both coronary arteries were performed without administering nitroglycerine to relieve provoked spasm in a first-attempt artery. ACh was injected in incremental doses of 20/50/100/200 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Positive ES was defined as ≥90% stenosis and usual chest pain and ischemic ECG changes. Results: Provoked positive ES was observed in 310 patients (46%), including 85 patients (13%) with focal spasm, 150 patients (22%) with diffuse spasm, and 75 patients (11%) with combined spasm (diffuse spasm and focal spasm), whereas the remaining 370 patients (54%) had no provoked spasm. An unclassified ACh test was observed in 186 patients (27%), while 184 patients (27%) had a complete negative ACh test. The clinical outcomes in patients with complete negative ES were satisfactory compared with those with positive ES and unclassified ACh test results. The prognosis in patients with an unclassified ACh test was not different from those with a positive ES. Furthermore, prognosis in patients with ES phenotypes was not different among the three groups. Conclusions: There was no correlation between provoked ES phenotypes via intracoronary ACh testing and prognosis in patients with ANOCAD; however, clinical outcomes in patients with positive ES and unclassified ACh tests were worse compared to those with complete negative ACh tests. We should focus on the treatments in patients with unclassified ACh tests as well as those with ESs.

Intracoronary acetylcholine testing among 746 consecutive Japanese patients with angina-like chest pain and unobstructed coronary artery disease.

Aims : Intracoronary acetylcholine (ACh) testing is useful for the detection of epicardial spasm (ES) and coronary microvascular spasm (CMS). We retrospectively analysed the incidence of ES and CMS in consecutive Japanese patients with unobstructed coronary artery disease. Methods and results: From January 1991 to February 2019, we performed intracoronary ACh testing of 1864 patients. Among these patients, a total of 746 consecutive patients (254 women, mean age 64 ± 11 years) who underwent first diagnostic angiography for suspected myocardial ischaemia and had unobstructed coronary arteries (<50%) were enrolled. Epicardial spasm was defined as ≥90% stenosis and usual chest symptoms and ischaemic ECG changes, while CMS was defined as <75% stenosis and usual chest symptoms and ischaemic ECG changes. We performed intracoronary ACh testing on both coronary arteries in 96% (716/746) of all subjects. Overall, ES was found in 329 patients (44%), whereas CMS was revealed in 40 patients (5%) including 4 patients with coexisting ES. In patients with ES, women made up 22%, and approximately three-quarters of the patients had resting chest pain. In contrast, women composed 65% (26/40) of those with CMS, and 15 patients with CMS had another chest symptom. Coronary microvascular spasm was frequently observed in the left coronary artery (LCA) but not the right coronary artery. Electrical cardioversion was necessary for two patients. Conclusions : Coronary microvascular spasm was recognized in only 5% of consecutive Japanese patients with unobstructed coronary artery disease, whereas ES was revealed in 44% of those patients. Coronary microvascular spasm was often observed in women and in the LCA.

Impact of statins in patients with vasospastic angina: A multicenter registry study of the Japanese Coronary Spasm Association.

BACKGROUND: Statins are generally used for patients with coronary artery disease. However, the impact of statins in patients with vasospastic angina (VSA) is not fully understood. METHODS: In a multicenter registry study of the Japanese Coronary Spasm Association (n = 1429), patients with or without statins were compared. The primary endpoint was major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, unstable angina, heart failure, and appropriate implantable cardioverter defibrillator shock. Propensity score matching and a multivariable Cox proportional hazard model were used to adjust for selection bias in treatment and potential confounding factors. RESULTS: In the whole population, 469 patients received statins, while 960 patients did not receive statins. Patients with statins had a greater prevalence of comorbidities, including hypertension, diabetes, dyslipidemia, and smoking, in comparison to those without statins. The prevalence rates of previous myocardial infarction, significant organic stenosis, and medication use (including calcium channel blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, and beta blockers) were greater in patients with statins than in those without statins. After propensity matching (n = 211 for both groups), a Kaplan-Meier curve analysis revealed that the incidence of MACE was comparable between patients with and without statins (p = 0.686). MACEs occurred in 6.0% of patients with statins and in 5.9% of those without statins (p = 0.98). CONCLUSION: In this multicenter registry study, statin therapy did not reduce clinical events in VSA patients.

Intracoronary ergonovine testing among 505 consecutive Japanese patients with angina-like chest pain and unobstructed coronary artery disease.

Intracoronary ergonovine (ER) testing is useful for the detection of epicardial spasm (ES) and coronary microvascular spasm (CMS). We retrospectively analyzed the incidence of ES and CMS in consecutive Japanese patients with unobstructed coronary artery disease. From January 1991 to February 2019, we performed intracoronary ER testing of 1196 patients. Among these patients, a total of 505 consecutive patients (207 women, mean age 64 ± 11 years) who underwent first diagnostic angiography for suspected myocardial ischemia and had unobstructed coronary arteries (< 50%) were enrolled. Resting chest pain was reported by 229 patients, exertional chest pain was reported by 62 patients, exertional and resting chest pain was reported by 61 patients, and another chest symptom (not typical chest pain but suspected to be myocardial ischemia) was reported by 153 patients. ES was defined as ≥ 90% stenosis and usual chest symptoms and ischemic ECG changes, while CMS was defined as < 75% stenosis (no epicardial spasm) and usual chest symptoms and ischemic ECG changes. We performed intracoronary ER testing on both coronary arteries in 86% (432/505) of all subjects. Overall, ES was found in 82 patients (16%), whereas CMS was revealed in 12 patients (2%). In patients with ES, women made up 9%, and 70% of the patients had resting chest pain. In contrast, women composed 67% (8/12) of those with CMS, and 5 patients with CMS had another chest symptom. Ventricular fibrillation was observed in two patients who had sinus rhythm after thump version or cardiac resuscitation. However, we observed no irreversible complications during ER testing. CMS was recognized in only 2% of consecutive Japanese patients with unobstructed coronary artery disease by intracoronary ER testing, whereas ES was revealed in 16% of those patients. CMS was often observed in women.

A case report: intracoronary acetylcholine testing without a pacemaker may be one option in the left coronary artery.

BACKGROUND: The intracoronary acetylcholine (ACh) and ergonovine (ER) test is employed as a pharmacological spasm provocation test. ACh causes vasoconstriction in patients with coronary endothelial dysfunction such as coronary atherosclerosis, while ER induces coronary vasoconstriction through the activation of coronary smooth muscle. CASE SUMMARY: An 84-year-old Japanese man was admitted to our hospital due to resting angina and syncope. Computed tomography coronary angiography (CTCAG) revealed severe proximal left anterior descending (LAD) coronary artery stenosis, but hybrid images of CTCAG and thallium-adenosine myocardial scintigraphy revealed no ischaemia. During syncope, inverted T waves on V5, V6 leads were recognized. After coronary arteriography, mild atherosclerotic stenosis (50%) was found at the proximal LAD artery, and we administered intracoronary ER 104 µg and 80 µg into the left and right coronary arteries because of suspected coronary spasm. However, no provoked spasm was obtained in either vessel. We administered 20, 50, and 100 µg intracoronary ACh into the left coronary artery (LCA) for 30 s without a pacemaker, because neither bradycardia nor cardiac arrest has occurred. Diffuse distal spasm was provoked after the administration of 100 µg ACh and the patient complained of typical chest pain and prodrome before syncope. The patient was diagnosed with coronary spastic angina by the ACh test but not the ER test. DISCUSSION: Different coronary responses between ACh and ER were observed in this case. Intracoronary ACh testing without a pacemaker may be one option in the LCA if no bradycardia or arrest occurs.

Coronary artery spasm-induced acute myocardial infarction in patients with myocardial infarction with non-obstructive coronary arteries.

Coronary artery spasm-induced acute myocardial infarction (CASIAMI) is one of the etiologies of myocardial infarction with non-obstructive coronary arteries (MINOCA). We retrospectively analyzed the incidence and clinical characteristics of Japanese patients with CASIAMI and non-obstructive coronary arteries. We experienced 62 patients with MINOCA (10 thrombosis, 7 unknown causes, and 45 CASIAMI) among 991 patients with suspected AMI. Pharmacological spasm provocation testing was performed in 37 patients. CASIAMI without obstructive coronary arteries was found in 4.5% of patients with suspected AMI and was observed in 73% of patients with MINOCA. Patients with CASIAMI were frequently males and had relatively small AMIs. Spontaneous spasm was recognized in 8 patients. We could reproduce provoked spasm in 37 patients with MINOCA, including 23 patients with multiple spasm. No patients died during the follow-up period. The clinical outcomes in patients with CASIAMI under optimal coronary vasodilators were satisfactory.

Sex-related Differences in Patients with Positive Coronary Spasm as Identified by Acetylcholine Testing.

Objective A pathological acetylcholine (ACh) test was observed at lower ACh doses in females compared with males in European populations. We retrospectively analyzed the sex-related differences in Japanese patients with provoked positive spasm by ACh spasm provocation testing. Methods We performed the ACh spasm provocation tests in 1,854 patients from Jan 1991 until Mar 2019. ACh was injected in incremental doses of 20/50/100/200 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Positive spasm was defined as >90% stenosis and usual chest pain or ischemic ECG changes. We compared the clinical characteristics, angiographical findings during ACh testing, and clinical outcomes between female and male patients with and without provoked positive spasm. Results Positive provoked spasm was diagnosed in 917 patients including 737 (80.4%) males and 180 (19.6%) females. The incidence of provoked positive spasm in females was significantly lower than that in males (33.5% vs. 56.0%, p<0.001). Female patients with provoked positive spasm tended to be older, have less history of smoking, less provoked spasm in the left circumflex artery, or less focal type spasm than male patients with provoked positive spasm. The incidence of ST elevation during ACh testing in male patients was significantly higher than that in female patients, whereas the frequency of ST depression in females was remarkably higher than that in males. The mean maximum used ACh dose for provoked positive spasm on both coronary arteries in female patients was significantly higher than that in male patients. The observed major complications during ACh testing did not differ substantially between the sexes. In addition, the prognosis in females with provoked positive spasm was not different from males. Conclusion Provoked positive spasm by ACh test was obtained at lower mean maximum ACh doses in males compared with females in Japanese patients.

Coincidence between spontaneous and inducible coronary spasm: acetylcholine test is clinically valued for diagnosing coronary spasm.

There is no report regarding the correlation between spontaneous documented coronary spasm and acetylcholine (ACh)-inducible spasm. We retrospectively analyzed the coincidence between angiographical spontaneous coronary spasm and ACh-inducible spasm in the same patients. We recruited 28 patients with 30 angiographical spontaneous coronary spasm in 6009 patients with diagnostic and follow-up coronary arteriography from Jan 1991 and Mar 2019 in the cardiac catheterization laboratory. We could perform intracoronary ACh testing in 19 patients with 20 vessels. ACh was injected in incremental dose of 20/50/100 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Positive spasm was defined as > 90% stenosis and ischemic ECG changes. Angiographical documented spontaneous coronary spasm was observed in 0.47% (28/6009) of patients with diagnostic and follow-up coronary angiography. Intracoronary administration of ACh reproduced 15 spontaneous coronary spasm and no provoked spasm was observed in the remaining 5 vessels due to the administration of nitroglycerine or under medications. Spasm-provoked sites by ACh tests and ACh-inducible spasm configurations were almost similar to spontaneous spasm. Coincidence of provoked spasm site (93.3% vs. 6.7%, p < 0.001) and spasm configuration (93.3% vs. 6.7%, p < 0.001) was markedly higher than discordance. Intracoronary ACh testing can reproduce spontaneous coronary artery spasm in 75% of vessels with almost similar sites and same morphological characteristics irrespective of the administration of nitroglycerine or vasodilators. ACh test is a reliable method to document coronary artery spasm in the clinic.

Bronchial Asthma and Rest Angina: Is It Safe to Perform Acetylcholine Spasm Provocation Tests in These Patients?

Objective Acetylcholine (ACh) use in patients with bronchial asthma (BA) is contraindicated. We examined the clinical usefulness and safety of ACh spasm provocation tests in rest angina patients with BA. Patients The study subjects were 495 rest angina patients (mean age: 64.4±10.9 years old, male: 81.0%). Organic stenosis was found in 69 patients (13.9%). Methods We investigated 495 rest angina patients who underwent ACh spasm provocation tests. ACh was injected in incremental doses of 20/50/100/200 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Provoked positive spasm was defined as transient ≥90% luminal narrowing and usual chest pain or ischemic electrocardiogram changes. Results Among 495 rest angina patients, 13 (2.6%) were complicated with BA. Eleven patients with BA were controlled under medications, and two patients had a history of medication for BA. The clinical characteristics were not markedly different between rest angina patients with and without BA. The rate of multi-vessel spasm was markedly higher in patients with BA than that in those without BA. No complications during ACh spasm provocation tests were recognized in rest angina patients with BA, whereas major complications in those without BA were observed in eight patients including two ventricular fibrillations, three non-sustained ventricular tachycardias, and three shocks. We were able to perform all 495 ACh spasm provocation tests without any irreversible complications, while electrical defibrillation was necessary for 2 patients without BA. Conclusion We were able to perform ACh spasm provocation tests in rest angina patients with BA irrespective of the off-label use of ACh.

The impact of antiplatelet therapy on patients with vasospastic angina: A multicenter registry study of the Japanese Coronary Spasm Association.

BACKGROUND: Antiplatelet therapy (APT) is generally used in patients with coronary artery disease. However, for patients with vasospastic angina (VSA), the impact of APT is not fully understood. METHODS: In a multicenter registry study of the Japanese Coronary Spasm Association (n = 1429), patients with or without APT were compared. The primary endpoint was major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, unstable angina, heart failure and appropriate ICD (Implantable cardioverter defibrillator) shock. Propensity score matching and a multivariable cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. RESULTS: In the whole population, 669 patients received APT, while 760 patients did not receive APT. Patients with APT had a greater prevalence of comorbidities, such as hypertension, diabetes, dyslipidemia and smoking, than those without APT. The prevalences of previous myocardial infarction, spontaneous ST changes, significant organic stenosis and medications including calcium channel blocker, nitrate, statin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were greater in patients with APT than those without APT. After propensity matching (n = 335 for both groups), during the median follow-up period of 32 months, the incidence rate of MACE was comparable between the patients with and without APT (P = 0.24). MACEs occurred in 5.7% of patients with APT and in 3.6% of those without APT (P = 0.20). All-cause death occurred in 0.6% of patients with APT and 1.8% of those without APT (p = 0.16). CONCLUSION: In this multicenter registry study, anti-platelet therapy exerted no beneficial effects for VSA patients.

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

Pharmacological spasm provocation testing in 2500 patients: provoked spasm incidence, complications and cardiac events.

Pharmacological spasm provocation tests such as acetylcholine (ACh) and ergonovine (ER) had been performed in the clinic. We retrospectively analyzed the incidence of provoked spasm, complications during testing and the cardiac events after these tests. From January 1991 and October 2018, we performed pharmacological spasm provocation tests in 2500 patients: 1810 ACh tests, 1232 ER tests, 542 both tests, and 310 ACh added after ER tests. ACh was injected in incremental doses of 20/50/100/200 µg into the LCA and 20/50/80 µg into the RCA. ER was administered as a total dose of 64 µg into the LCA and 40 µg into the RCA. When adding ACh after ER, the total dose was 50/80 µg into the RCA and 100/200 µg into the LCA. Positive spasm was defined as ≥ 90% stenosis and usual chest pain or ischemic ECG changes. Mean follow-up duration was 47.5 ± 29.9 months. Overall, provoked positive spasm was found in 1095 patients (43.8%). The incidence of positive provoked spasm during ACh testing was significantly higher than that during other tests (ACh: 48.7% vs. ER: 28.9%, Both: 24%, ACh added after ER: 33.5%, p < 0.001). Multiple spasms were remarkably more frequent during ACh testing compared with the other 3 types of testing (ACh: 28.2% vs. ER: 7.4%, Both: 4.1%, ACh added after ER: 13.2%, p < 0.001). No death or acute myocardial infarction was observed, while major complications during ACh testing were significantly more frequent than during ER testing. Readmission due to recurrent angina pectoris in spasm-positive patients was remarkably more frequent than in spasm-negative patients. The incidence of sudden cardiac death, ventricular fibrillation, and acute coronary syndrome were not different between the spasm-positive and spasm-negative groups during the follow-up periods. We could perform all spasm provocation tests without any irreversible complications. All sequential spasm provocation tests were useful for documenting coronary spasm.

Spasm Provocation Tests under Medication May Help Decide on Medical or Mechanical Therapy in Patients with Aborted Sudden Cardiac Death due to Coronary Spasm.

Objective The decision to perform medical or mechanical therapy in patients with aborted sudden cardiac death (ASCD) due to coronary spasm is controversial. The Japanese Circulation Society guidelines for the diagnosis and treatment of patients with coronary spastic angina mentioned that implantable cardioverter-defibrillator (ICD) is one option in patients with ASCD due to coronary spasm. We investigated the usefulness of spasm provocation tests under medications in five patients with ASCD due to coronary spasm. Methods We performed the spasm provocation tests under medications in five ASCD patients due to coronary spasm. Pharmacological spasm provocation tests, including five acetylcholine (ACh) tests, two ergonovine (ER) tests, and two ACh added after ER tests, were performed to estimate the effect of medications to suppressing the next fatal spasms. Results ACh tests under medications did not provoke spasm in one patient but did provoke in two patients. In the remaining two patients, neither the ACh test nor the ER test provoked spasm, but the ACh added after ER test induced a focal spasm in one coronary artery. We increased the medication dosage in four patients. An ICD was implanted in two patients, including one with refractory spasm and one with left main trunk spasm. One patient died due to pulseless electrical activity without ventricular fibrillation, while the remaining four patients survived. Conclusion Spasm provocation tests under medication in patients with ASCD due to coronary spasm may be an option when deciding on medical or mechanical therapy.