Impact of low-dose aspirin on coronary artery spasm as assessed by intracoronary acetylcholine provocation test in Korean patients

High-dose aspirin has been reported to aggravate coronary artery spasm (CAS). However, it is unknown whether low-dose aspirin (LDA; 100mg) has deleterious impact on CAS. We assessed the impact of LDA on CAS induced by intracoronary acetylcholine (ACh) provocation test. A total of 2789 consecutive patients without significant coronary artery disease who underwent ACh test between November 2004 and March 2010 were enrolled. The patients were divided into two groups: the aspirin group taking LDA before ACh test (n=221) and the no aspirin group not taking aspirin (n=2568). At baseline, the prevalence of old age, diabetes mellitus, hypertension, and hyperlipidemia were higher in the aspirin group. During the ACh test, the incidence of significant CAS, ischemic chest pain, as well as severe and multivessel spasm was higher in the aspirin group. The response rate to lower ACh dose was higher in the aspirin group. Multivariate analysis showed that the previous use of LDA was an independent predictor of CAS (adjusted odds ratio, 1.6, 95% confidence interval, 1.0-2.3; p=0.031). However, it is likely that the association of LDA and CAS that we have observed is not causal but may be hypothesis generating due to significant baseline differences. Further, male gender, old age, lipid-lowering drugs, baseline spasm, and myocardial bridge were independent predictors of CAS. LDA was more frequently associated with CAS and ischemic symptoms, as well as severe and multivessel spasm, suggesting the patients who have received LDA would require more intensive medical therapies and close follow up.     

Provocation of coronary spasm by dopamine in patients with active variant angina pectoris

The effects of dopamine on arteries are different depending on the dose, route of administration, and receptor population. Its administration can cause vasodilation by stimulation of dopaminergic receptors, vasoconstriction by stimulation of alpha-adrenergic and serotonergic receptors, and even spasm of cerebral arteries when given intracisternally in dogs. The ability of dopamine to provoke coronary spasm was assessed in 18 patients with active vasospastic angina in whom this amine was infused at rates of 5, 10, and 15 micrograms/kg/min for periods of 5 min each. The 12-lead electrocardiogram and blood pressure (cuff) were monitored throughout the whole test. In nine patients dopamine caused angina and ischemic electrocardiographic changes suggestive of coronary spasm: ST segment elevation in six patients and ST segment depression in the absence of important coronary stenoses in the remaining three. Infusion of dopamine was repeated during coronary angiography in three patients with positive test results: this provoked occlusive coronary spasm with ST segment elevation in two patients and nonocclusive spasm with ST segment depression in the remainder. In conclusion, infusion of dopamine provokes coronary spasm in a sizeable proportion of patients with active vasospastic angina. Its administration may be detrimental in patients susceptible to coronary spasm, such as those with acute myocardial infarction.     

Provocation of coronary spasm by dobutamine stress echocardiography in a patient with angiographically minimal coronary artery disease

Dobutamine stress echocardiography (DSE) has been widely used for the noninvasive diagnosis of obstructive coronary artery disease. The ST-segment elevation during DSE has been reported as an infrequent event, caused by old myocardial infarction and/or critical coronary narrowings. The patient presented here was a 35-year-old man with a recent history of nonexertional chest pain. He had hyperc-holesterolemia and a history of heavy smoking as risk factors. The patient developed ST-segment elevation with chest pain during 40 mcg/min dobutamine infusion for the stress echocardiographic examination. Subsequent coronary angiograms revealed only mild coronary atherosclerosis. It is speculated that coronary spasm occurred in this patient as a paradoxical response to increased coronary blood flow with dobutamine administration.     

Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 micrograms ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of the 25 of the 27 patients. The injection of 20 to 100 micrograms ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection of ACh is a useful test for provocation of coronary spasm.     

Severe coronary artery spasm with anaphylactoid shock caused by contrast medium--case reports

This study reports 2 cases of severe coronary artery spasm with anaphylactoid shock caused by contrast medium. The first patient had anaphylactoid shock in response to contrast medium and severe coronary spasms of both the left anterior descending coronary artery and the left circumflex coronary artery. The patient developed ventricular arrhythmia and complete atrioventricular block following the severe coronary spasm. The second patient had a totally occluded right coronary artery, owing to a spasm after anaphylactoid shock. Anaphylactoid shock should always be considered when persistent shock is noted after the coronary artery spasm has been relieved.     

乙酰胆碱诱发冠状动脉痉挛时的心电图改变及其与血管内皮功能关系

目的探讨血管内皮细胞功能紊乱与乙酰胆碱试验诱发冠状动脉痉挛时心电图ST段变化与缓慢型心律失常的关系。方法选择以静息性胸痛为主要临床表现、接受乙酰胆碱激发试验的患者为研究对象,根据是否发生冠状动脉痉挛分为阳性组和阴性组,冠状动脉痉挛发作时心电图变化分为ST段抬高和非ST段抬高组以及缓慢型心律失常和无缓慢型心律失常组,测定其血浆一氧化氮和内皮素1浓度,比较各组一氧化氮和内皮素1水平以及痉挛血管的分布。结果ST段抬高组一氧化氮水平显著低于阴性组,而内皮素1显著高于阴性组(P<0.01),非ST段抬高组一氧化氮水平亦显著低于阴性组,但高于ST段抬高组(P<0.05),而内皮素1显著高于阴性组但低于ST段抬高组(P<0.05);缓慢型心律失常组和无缓慢型心律失常组的血浆一氧化氮和内皮素1水平以及痉挛血管的分布差异无统计学意义(P>0.05)。结论乙酰胆碱试验诱发的冠状动脉痉挛以及ST段变化与血管内皮细胞功能紊乱有关,乙酰胆碱试验中的缓慢型心律失常与血管内皮细胞功能或痉挛血管的分布无关。     

Shock during spasm provocation tests with acetylcholine: four case reports

Four patients suffered shock during the spasm provocation test with acetylcholine. An 84-year-old man with acute coronary syndrome was treated with stent implantation in the mid left anterior descending artery. Before discharge, acetylcholine test demonstrated coronary spasm in both the proximal left anterior descending artery and proximal left circumflex artery. A 61-year-old woman was admitted to the hospital because of recurrent rest and effort chest pain. Coronary arteriography showed no significant stenosis but shock was observed by intracoronary injection of acetylcholine due to diffuse severe coronary vasospasm in the proximal left anterior descending artery and left circumflex artery. Shock occurred in 4 of 1110 (0.36%) consecutive acetylcholine tests. Coronary spasm was gradually relieved and recovered from shock by the intraarterial administration of small amounts of norepinephrine and isosorbide dinitrate. Although the acetylcholine spasm provocation test is safe and reliable, care is required even during a selective procedure.     

Induction of coronary artery spasm by intracoronary acetylcholine: comparison with intracoronary ergonovine.

To investigate the mechanism of coronary spasm, we compared the action of acetylcholine with that of ergonovine in 11 patients with vasospastic angina (group 1) and in 15 patients with chest pain (group 2). Coronary arteriography was performed immediately after the patients received intracoronary injections of titrated increments of each agent. In the patients in group 1 occlusive or near-occlusive (99% luminal narrowing) coronary spasm associated with angina and ischemic electrocardiographic ST changes was noted in nine of 11 patients receiving acetylcholine and in all 11 patients receiving ergonovine. The region and the degree of the most severe coronary spasm on coronary arteriograms evoked by the two agents were the same in nine of the 11 patients in group 1. In the other two patients in group 1, spontaneous focal coronary spastic stenosis in the baseline coronary arteriogram was relieved by the intracoronary injection of acetylcholine, and a focal coronary occlusive spasm in the same region was induced repeatedly by the subsequent intracoronary injection of ergonovine (paradoxic phenomenon). In contrast, occlusive or near-occlusive coronary spasm was not induced by either agent in any patient in group 2. These results suggest that the two provocative tests for coronary spasm that involve acetylcholine and ergonovine are clinically useful in the diagnosis of vasospastic angina, but testing with intracoronary ergonovine is needed when a spontaneous focal coronary spasm is relieved by the intracoronary injection of acetylcholine. The results also indicate that in many patients with vasospastic angina, nonspecific hypersensitivity to acetylcholine or ergonovine in a definite region of the coronary arteries generally plays an important role in the induction of coronary spasm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial infarction in patients with coronary artery spasm demonstrated by angiography

Twelve cases of myocardial infarction (MI) were documented in 11 of 39 patients who had coronary artery spasm (CAS) that was observed by angiography either before MI (3 patients), after MI (5 patients), or both before and after MI (3 patients). MI corresponded in location to sites of ECG changes of myocardial ischemia during spontaneous angina pectoris in 7 of 7 patients and to the region of myocardium supplied by the vessel in which CAS was observed by angiography in each patient. MI occurred in the distribution of the right coronary artery in 8 patients and of the left coronary artery in 4 patients. Of 12 vessels that supplled infarcted regions of myocardium, 7 vessels had ≥50% diameter fixed coronary artery narrowing (CAN), but the remaining 5 vessels had minimal (10%) or no fixed CAN. In those patients who were studied after MI, coronary angiography demonstrated that only 3 of 9 vessels in the distribution of infarcted regions of myocardium were completely occluded. Clinical follow-up for an average of 1.3 years after MI showed that 7 patients continued to have chest pain, 2 patients were asymptomatic, and 2 patients died suddenly 9 weeks and 1 year, respectively, after MI. Therefore, among our patients with CAS demonstrated by angiography, Mis (1) were frequent (28%), (2) occurred in the distribution of observed coronary spasm, (3) were frequently (5 of 12 arteries) in the distribution of vessels having minimal or no fixed narrowing, and (4) were often (6 of 9 arteries) in the distribution of vessels that were demonstrated to be patent after MI.     

冠状动脉痉挛致一过性室壁瘤l例

1临床资料患者,女,42岁,因反复剑突下隐痛1月,复发加重20min,于2005年1月31日入院。入院前1月,患者反复出现剑突下隐痛,无放射,约1~2d发作一次,持续数分钟至2h可自行缓解,多在活动时出现,伴心悸,无反酸、嗳气,无恶心、呕吐,一直按胃炎"治疗。入院前20min,解大便后出现剑突下剧烈疼痛,伴双肩及双上肢放射痛,急诊入院。入院时检查:T:36.7℃,P:90次/min,R:21次/min,BP:130/60mmHg,双肺未闻及干湿性音,心率90次/min,律齐,未闻及病理性杂音,剑下轻压痛,无反跳痛。化验检查:血磷酸肌酸激酶(CK):398U/L,磷酸肌酸激酶同工酶(CK-MB)52U/L,肌钙…     

Provocative testing with prolonged hyperventilation and ergometrine in patients suspected of coronary artery spasm: a comparative study

We induced coronary vasoconstriction by hyperventilation for 6 minutes (arterial pH = 7.6 +/- 0.06) and ergometrine (0.4 mg) in 24 patients suspected of coronary vasospasm. ST deviation greater than or equal to 1 mm was induced in 12 patients by hyperventilation and in 10 by ergometrine. Using spontaneous ST deviation as the independent reference the sensitivity of hyperventilation was 86% and the sensitivity of ergometrine 77%. Ergometrine caused sinus bradycardia and hypotension in 3 patients; hyperventilation caused no untoward reactions. In 12 of the patients coronary angiogram and wedge pressure were obtained during provocative testing. A computer-assisted analysis of coronary diameters in 43 arterial segments (3-4 per patient) showed a 16 +/- 12.6% and 14 +/- 16.7% reduction after hyperventilation and ergometrine, respectively. The maximal coronary diameter reduction induced by hyperventilation and ergometrine was 26 +/- 13.9% and 28 +/- 15.0%, respectively, and showed a significant correlation between the two tests (r = 0.77, N = 12, P less than 0.01). The wedge pressure increase induced by hyperventilation correlated to the maximal coronary diameter reduction (r = 0.63, N = 12, P less than 0.05), while no such correlation was found by ergometrine testing. We conclude that hyperventilation leading to arterial pH about 7.6 has essentially the same potency as 0.4 mg ergometrine, but the hyperventilation test appears to be safer.     

非典型性冠状动脉痉挛患者的临床特点及近期预后

目的总结非典型性冠状动脉痉挛患者的临床特点。方法选择临床具有静息性胸痛或胸闷,且冠状动脉造影无显著狭窄的64例患者进行乙酰胆碱冠状动脉痉挛激发试验,将乙酰胆碱试验阳性即冠状动脉痉挛患者根据胸痛或胸闷发作时心电图上是否有ST段抬高分为典型变异型心绞痛组（典型组）和非典型变异型心绞痛性冠状动脉痉挛组（非典型组）,比较两组的临床症状特点（危险因素、心电图和核素心肌灌注显像负荷试验结果以及冠状动脉造影和乙酰胆碱试验的影像学）。结果共有46例（72％,46／64）患者诱发冠状动脉痉挛,其中典型组和非典型组分别为12及34例。典型组的平均年龄偏低（P〈0．05）,血脂代谢紊乱在非典型组更常见,运动心电图试验两组多为阴性,核素灌注心肌显像负荷试验两组均表现有反向再分布,冠状动脉造影典型组多为轻度局限性狭窄或节段性内膜不光滑,肌桥发生率更高,乙酰胆碱试验多诱发节段性痉挛。而非典型组为弥漫性血管细小、内膜不光滑、僵硬,血管迂曲伴远端血流缓慢,乙酰胆碱试验多诱发弥漫性血管痉挛,并可见多支血管同时痉挛。结论非典型性冠状动脉痉挛较典型变异型心绞痛更常见,且具有一定的特征性,应引起临床医生高度重视。     

Induction of coronary arterial spasm by intracoronary administration of acetylcholine in patients with vasospastic angina

To examine whether intracoronary injections of acetylcholine induce coronary artery spasm in patients with vasospastic angina, incremental doses (20, 30 and 50 micrograms) were injected directly into the coronary arteries in 12 patients with variant angina (Group A: rest angina with electrocardiographic ST-segment elevation during attacks), 19 with vasospastic angina (Group B: rest angina and/or effort angina with variable threshold in the treadmill exercise stress test), 11 with organic coronary artery stenosis but without angina (Group C), and 14 without coronary artery disease (Group D). A temporary cardiac pacemaker was positioned in the right ventricle. Coronary artery spasm was defined as severe vasoconstriction (greater than or equal to 90% of reduction in the luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in all 12 patients (100%) of Group A, in 18 (95%) of Group B, in two (18%) of Group C, and in two (14%) of Group D. Thus, the sensitivity of this method for inducing coronary spasm was 100% in group A, 95% in Group B, and 97% in Group A plus Group B. The specificity for inducing spasm was 86% in Group D, and 84% in Group C and Group D. When acetylcholine was injected separately into the left and right coronary arteries, spasm of both the coronary arteries was observed in two (40%) of Group A, in five (33%) of Group B, and none (0%) of Group C and Group D. Acetylcholine (20 micrograms) induced coronary spasm in 10 (83%) of Group A and only in nine (47%) of Group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cimetidine induces coronary artery spasm in patients with vasospastic angina

We have previously reported that cimetidine, a histamine H2-receptor blocker, augments the histamine-induced coronary vasoconstriction at the site of spastic segments in the atherosclerotic coronary arteries of swine. To elucidate whether cimetidine has a coronary vasoconstrictive effect in humans, 14 patients with vasospastic angina (group 1) and 14 controls with atypical chest pain (group 2) were examined angiographically. Nitroglycerin-effective spontaneous angina with electrocardiographic ST-T changes and ergonovine-induced coronary artery spasm were confirmed in group 1, but not in group 2. Cimetidine was administered intravenously in a dose of 200 mg. Cimetidine induced coronary artery spasm in 4 patients in group 1 but none in group 2(29% vs. 0%, p less than 0.01). The extent of coronary vasoconstriction induced by cimetidine was greater at the site of spastic coronary segments than that at the site of non-spastic segments in group 1 or all segments in group 2 [14% vs. 4%, (p less than 0.01) or 14% vs. 2%, (p less than 0.01)] as well as the extent of ergonovine-induced coronary vasoconstriction [46% vs. 14%, (p less than 0.01) or 46% vs. 14%, (p less than 0.01)] and nitroglycerin-induced coronary vasodilatation [58% vs. 25%, (p less than 0.01) or 58% vs. 17%, (p less than 0.01)]. As it was suggested that cimetidine has potential vasoconstrictive effects in patients with coronary artery spasm, it should be administered with caution in patients with the vasospastic angina pectoris.     

Acute coronary syndrome in adult patients with coronary artery lesions caused by Kawasaki disease: review of case reports

Information about acute coronary syndrome caused by Kawasaki disease-related coronary artery lesions in adults is sketchy. We reviewed the clinical features of 50 adult patients who had an acute coronary syndrome caused by coronary artery lesions due to Kawasaki disease or probable Kawasaki disease from 1980 to 2008. Of the 50 patients, 43 (90%) were male and seven were female (10%). Their ages at the onset of acute coronary syndrome ranged from 18 to 69 years, with a median of 28 years. The culprit lesion in 43 patients was thrombotic occlusion of an aneurysm, and 40 patients had giant aneurysms. In the three patients in whom no aneurysms were seen in coronary angiograms performed at the time of acute myocardial infarction, either giant aneurysms or aneurysms had been visualised in childhood. The initial treatment of acute coronary syndrome was as follows: intracoronary thrombolysis, 11; primary percutaneous coronary intervention, 9; emergency coronary artery bypass grafting, 3; and medication, 26. Elective coronary artery bypass grafting was performed in 15 patients. Three patients (6%) died. Of the 27 patients with additional coronary risk factors, 20 were smokers. Giant aneurysms due to Kawasaki disease continued to cause acute coronary syndrome in adult life with onset at a younger age than typifies that due to atherosclerosis in the general population, especially in male population rather than female population. Even when giant aneurysms regressed after the acute phase, a few patients still developed acute coronary syndrome in adult life. Smoking appears to be the most prominent additional risk factor.     

冠状动脉痉挛致一过性室壁瘤1例

1临床资料 患者，女，42岁，因反复剑突下隐痛1月，复发加重20min．于2005年1月31日入院。入院前1月，患者反复出现剑突下隐痛，无放射，约1～2d发作一次，持续数分钟至2h可自行缓解，多在活动时出现，伴心悸，无反酸、嗳气，无恶心、呕吐，一直按“胃炎”治疗。入院前20min，解大便后出现剑突下剧烈疼痛，伴双肩及双上肢放射痛，急诊入院。     

Usefulness of intracoronary injection of acetylcholine as a provocative test for coronary artery spasm in patients with vasospastic angina

Summary In order to examine both the sensitivity and specificity of coronary artery spasm induced by intracoronary injection of acetylcholine in patients with vasospastic angina, incremental doses of acetylcholine (20, 30, and 50 µg) were injected directly into each coronary artery in 21 patients with variant angina (group A), in 28 patients with other types of vasospastic angina (group B), and in 20 patients without any significant coronary artery disease (group C). Coronary artery spasm was defined as severe vasoconstriction (90% of reduction in luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 20 patients (95%) of group A, in 27 patients (96%) of group B, and in only 2 patients (10%) of group C. The low dose of acetylcholine (20 µg) induced coronary spasm more frequently in group A patients (81%) than in group B patients (43%) (P<0.05). ST-segment elevation associated with anginal attacks was significantly (P<0.05) more frequent in group A (71%) than in group B (39%). When acetylcholine was injected separately into the left and right coronary arteries, spasm of both coronary arteries was observed in 7 out of 14 of group A (50%), in 8 out of 22 of group B (36%), and in none of the 20 of group C. We concluded that intracoronary injection of acetylcholine is a sensitive and reliable method for the induction of coronary spasm in patients with vasospastic angina as well as in those with variant angina.