Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine

There are no data concerning the incidence of provoked coronary arterial spasms via intracoronary administration of ergonovine (ER). This study sought to establish the incidence of spasms due to intracoronary injection of ER in Japanese patients who underwent coronary angiography. The subjects were 596 consecutive patients (369 men, mean age 64.2 +/- 10.3 years) who were studied with a selective ER test. ER was administered in total doses of 40 microg into the right coronary artery and 64 microg into the left coronary artery. A positive spasm was defined as a total or subtotal occlusion. Coronary vasospasms were determined in 173 patients (29.0%). Spasms occurred often in patients with ischemic heart disease (43.3%); during effort and rest in patients with angina (46.3%), exertional angina (27.7%), recent myocardial infarction (36.7%), healed myocardial infarction (34.1%), and especially in patients with rest angina (55.5%), but were relatively uncommon in patients with nonischemic heart disease (3.7%). The incidence of provoked coronary spasms in this study was 2.2-2.6 times higher than in previous reports with intravenous ER administration. More spasms were superimposed on significant atherosclerotic lesions than on nonfixed atherosclerotic lesions (42.8% vs 24.0%, p < 0.01). No serious or irreversible complications were observed in this study. In conclusion, intracoronary administration of ER was a safe and reliable test. Compared with Caucasian patients, in Japanese patients, coronary arterial spasms occurred 2-3 times more frequently with various cardiac disorders.     

Major complications during spasm provocation tests with an intracoronary injection of acetylcholine

This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.     

Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine

Multivessel coronary spasm has been described but its incidence in patients with variant angina still remains unclear. Thirty-three patients with variant angina were studied during coronary angiographic examination with selective intracoronary injection of acetylcholine (ACh). In all but three patients, the location of ischemia during attack was determined by the electrocardiographic findings, by exercise 201Tl myocardial scintigraphy, and by two-dimensional echocardiography during a hyperventilation test, and the coronary artery (or arteries) responsible for the attack was predicted before the study. ACh induced spasm of at least one coronary artery in all but one patient. ACh induced spasm of both the left and right coronary arteries (i.e., multivessel coronary spasm) in 24 patients: in two of the four patients who were predicted to have spasm of the left coronary artery, in six of the 11 predicted to have spasm of the right coronary artery, in 13 of the 15 predicted to have spasm of both the left and right coronary arteries, and in three of the three in whom coronary artery responsible for attack had not been predicted. This ACh-induced spasm of the left and right coronary arteries occurred separately and no patients showed hemodynamic instability during attack. In one patient in whom multivessel coronary spasm had been predicted and ACh failed to induice coronary spasm, ergonovine maleate (0.2 mg) induced spasm of both the left and right coronary arteries simultaneously, resulting in severe prolonged hypotension. Nineteen of the 25 patients in whom multivessel coronary spasm was documented showed angiographically normal or nearly normal coronary arteries after administration of nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Gender differences in sensitivity of acetylcholine and ergonovine to coronary spasm provocation test

We examined the sex difference concerning the coronary artery response between ACh and ER in this study. We already reported the difference of coronary response between acetylcholine (ACh) and ergonovine (ER). We performed both ACh and ER tests of 461 patients (male 294 patients, female 167 patients, mean age 64.4 ± 11.3 years) during 23 years. Positive coronary spasm was defined as >99 % transient luminal narrowing with usual chest pain and/or ischemic ECG changes. Firstly, ACh was administered in incremental doses of 20/50/(80) μg into the RCA and 20/50/100/(200) μg into the LCA over 20 s. Secondly, ER was administered in a total dose of 40 μg into the RCA and of 64 μg into the LCA over 2–4 min. Intracoronary injection of ACh and ER provoked spasm in 221 patients consisting of 160 male patients and 61 female patients. In female patients, the spasm provoked by ACh was almost perfect except in two patients (59 patients, 96.7 %), while ER provoked spasm in only 20 patients (32.8 %). In male patients, provoked spasm by ACh (129 patients, 80.6 %) was significantly higher than ER (97 patients, 60.6 %). As a spasm provocation test, ACh is more sensitive than ER in both sexes and especially in females. We may select two pharmacological agents by sex differences to provoke coronary artery spasm in the cardiac catheterization laboratory in the future.     

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)     

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.     

Comparative performance of intravenous and intracoronary ergonovine provocation in vasospastic angina

BackgroundVasospastic angina is an infrequent underlying cause of angina and is under-diagnosed. Ergonovine provocation tests can be performed via intravenous or intracoronary injections. Although the safety profile of intracoronary injection has been well documented, no study has yet compared the intracoronary and intravenous injections regarding the positivity rate of the test.AimsThis study sought to compare the positivity rate of intravenous versus intracoronary injection of ergonovine in the diagnosis of vasospastic angina.MethodsBetween January 2010 and February 2018, 427 patients with suspected vasospastic angina underwent an ergonovine provocation test in 2 tertiary hospitals in France and were retrospectively included in this study. Injection was performed via the intravenous or the intracoronary route. The primary endpoint was the positivity rate of the test. Propensity score matching was used to account for confounding factors.Results427 patients were included in the study. Mean age was 60.3 (+/- 12.4) years. There were 247 (58%) females and 97 (23%) smokers. The intracoronary route was used in 199 (47%) patients. The indication for the test was acute coronary syndrome for 121 (28%). No rhythmic complications or deaths were reported. After propensity-matching, the baseline characteristics of the 2 groups (148 patients in each) were comparable. The positivity rate was 24% in the intracoronary group and 9% in the intravenous group (OR [95%CI]: 3.2 [1.6, 6.4]).ConclusionsIntracoronary injection of ergonovine is safe and associated with a positivity rate of the test three times higher compared to intravenous injection.     

Variability of electrocardiographic responses to repeated ergonovine provocation in variant angina patients with coronary artery spasm

We reviewed our experience with serial ergonovine provocative tests for coronary artery spasm (CAS) in ten variant angina patients with angiographically proved CAS. Of the 26 ergonovine tests performed in the ten patients, only four patients exhibited reproducible ECG response to ergonovine. The remaining six patients had variable and unpredictable ECG responses to ergonovine. All patients were in an active phase of their disease. The variability of ST segment directional response to ergonovine is considered to be on the basis of disparate sensitivity of the coronary circulation to intravenous ergonovine. Because of this variable response, the ECG response alone should not be considered as the standard indicator for CAS presence but should be utilized with other hemodynamic and angiographic criteria.     

Oesophageal spasm and angina : diagnostic value of ergometrine (ergonovine) provocation

Oesophageal spasm can be difficult to distinguish from cardiacpain. Ergometrine (ergonovine) provocation with oesophagealmanomelry offers a useful diagnostic test.     

Induction of coronary artery spasm by two pharmacological agents: comparison between intracoronary injection of acetylcholine and ergonovine

BACKGROUND AND OBJECTIVES: There have been few studies comparing the clinical usefulness for the induction of coronary artery spasm (CAS) between acetylcholine (ACh) and ergonovine (ER). This study is designed: (1) to examine the duration of effect after intracoronary injection of ACh on the responsible vessels using a 0.014 inch, 15 MHz Doppler guide wire, and (2) to evaluate the efficacy of two pharmacological agents, ACh and ER, for the induction of CAS in patients with <50% stenosis in the cardiac laboratory. METHODS: Phasic coronary flow velocity patterns were recorded at rest and during ACh tests in 22 patients with normal or near-normal coronary arteries. The tip of the guide wire was placed on the proximal right coronary artery (RCA) and mid-left anterior descending artery. We measured the time required to baseline level of average peak velocity after intracoronary injection of ACh. We performed selective intracoronary administration of both ER and ACh in the same 171 patients (106 men, 65 women, mean age of 62+/-10 years) with <50% stenosis. Under no medication, ACh was injected first in incremental doses of 20, 50, and 80 microg into the RCA and of 20, 50, and 100 microg into the left coronary artery (LCA). Ten minutes later, ER was administered at 10 microg/min for four minutes for a maximal dose of 40 microg on the RCA and at 16 microg/min over four minutes for a total dose of 64 microg on the LCA. Positive spasm was defined as > or =99% luminal narrowing. RESULTS: The time-averaged peak velocity returned to baseline after intracoronary injection of ACh within 10 minutes in all 120 procedures, consisted of 19 with positive spasm (RCA (n=10): 245+/-33 s; LCA (n=9): 351+/-187 s) and 101 with negative spasm (RCA (n=48): 155+/-62 s, LCA (n=53): 248+/-106 s). In the overall results, there was no difference concerning the incidence of provoked spasm between the two pharmacological agents (ACh: 33% versus ER: 32%, NS). Coronary spasms were induced by either pharmacological agent in 134 vessels. Concordance in this study was 94% in all vessels, whereas the remaining 6% of vessels were different from each other. The non-concordance rate of the right coronary artery was significantly higher than that of the left coronary artery (10% versus 4%, p<0.01). However, ER provoked more focal spasms, whereas ACh provoked more diffuse and distal spasms, compared with each other. Seventy-four (55%) of the 134 vessels had coronary spasms in the same coronary arteries. Concordance of both provoked spasm sites and spasm configurations in the same coronary artery was observed in only 18 (13%) vessels. No serious or irreversible complications were observed during the two sequential tests. CONCLUSIONS: As a spasm provocation test, there were no differences between ACh and ER. We recommend the supplementary use of these two pharmacological agents for the induction of CAS in the cardiac laboratory, if available.     

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.     

Evaluation of adjunctive intracoronary administration of acetylcholine following intravenous infusion of ergonovine to provoke coronary artery spasm

A dilemma arises in patients with chest pain or other symptoms suggestive of coronary artery disease but without significant coronary artery stenosis or spasm even after the spasm provocation test by either ergonovine or acetylcholine. Incremental doses of intracoronary acetylcholine (up to 100 micrograms for left coronary artery and 50 micrograms for right coronary artery) were administered when intravenous infusion of ergonovine 0.4 mg showed negative results. A total of 39 patients were studied. Provocation test was performed because of chest pain suggestive of coronary artery disease (n = 19), atypical chest pain (n = 6), post balloon angioplasty status (n = 6), silent ischemia (n = 4), Adams-Stokes syndrome (n = 3), and dead-on-arrival (n = 1). Characteristics of chest pain indicated variant angina (n = 11), rest angina (n = 4), and effort angina (n = 4). No electrocardiographic evidence of ischemia was detected before this test in any patient. Spasm was induced in 23 patients (59.0%) with complete obstruction in 7 (30.4%), diffuse vasoconstriction (90-99%) in 14 (60.9%), and focal spasm in 2 (8.7%). The patients with chest pain showed the highest positive rate of 78.9%. Further, the patients with atypical chest pain and miscellaneous reasons also revealed positive rates of 33.3% and 42.9%, respectively. One ventricular tachycardia and 2 atrial fibrillations occurred but terminated spontaneously. This test is useful for detecting spasm in a variety of patients in whom intravenous ergonovine infusion fails to induce spasm.     

The sensitivity of intracoronary injection of acetylcholine in inducing coronary spasm differs in patients with stable and unstable angina.

In an attempt to clarify the role of coronary artery spasm in the pathogenesis of unstable angina, acetylcholine (20 and 50 micrograms) was injected directly into the coronary arteries of 19 patients with unstable effort angina (group 1), 30 patients with unstable spontaneous angina (group 2), and 15 patients with stable effort angina due to coronary artery organic stenosis (greater than or equal to 75%) (group 3). Coronary spasm was defined as severe vasoconstriction (greater than or equal to 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 19 patients (100%) of group 1 and 28 (93%) of group 2 but only 3 (20%) of group 3 (p less than 0.01). When acetylcholine was injected into the left and right coronary arteries separately, multivessel spasm (spasm of both coronary arteries) was induced in 5 of 12 (42%) patients of group 1 and in 9 of 23 (39%) patients of group 2. In contrast, intracoronary acetylcholine did not cause multivessel coronary spasm in any of 15 patients of group 3 (0%). These results suggest that coronary arteries in patients with unstable effort angina as well as spontaneous angina are susceptible to spasm and that coronary artery spasm may be responsible at least in part for the genesis of attacks in these patients.     

ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome

OBJECTIVES: The study examined whether patients with Brugada syndrome are sensitive to vagal stimulation or ischemia. BACKGROUND: Experimental studies have suggested that a prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of the action potential dome in the epicardium, but not in the endocardium, give rise to ST-segment elevation and subsequent ventricular fibrillation (VF). METHODS: We evaluated the frequency of coronary spasm, augmentation (> or =0.1 mV) of ST-segment elevation in leads V(1) to V(3), and induction of VF by intracoronary injection of acetylcholine (ACh) and/or ergonovine maleate (EM) in 27 symptomatic patients with Brugada syndrome and 30 control subjects. RESULTS: The coronary spasm was induced in 3 (11%) of the 27 patients with Brugada syndrome and in 13 (43%) of the 30 control subjects. ST-segment elevation was augmented by 11 (33%) of the 33 right coronary injections (ACh: 6/11 [55%]; EM: 5/22 [23%]), without coronary spasm, but not by any of the left coronary injections in patients with Brugada syndrome. Ventricular fibrillation was induced by 3 (9%) of the 33 right coronary injections (ACh: 2/11 [18%]; EM: 1/22 [5%]), but not by any of the left coronary injections. In contrast, neither ST-segment elevation nor VF was observed in any of the control subjects. CONCLUSIONS: Our results support the hypothesis that mild ischemia and vagal influences act additively or synergistically with the substrate responsible for the Brugada syndrome to elevate the ST-segment and precipitate VF. These observations suggest that Brugada patients may be at a higher risk for ischemia-related sudden death.     

Comparative sensitivity of intracoronary injection of acetylcholine for the induction of coronary spasm in patients with various types of angina pectoris

To elucidate the possible contribution of coronary artery spasm to the pathogenesis of angina pectoris, coronary arterial responses to intracoronary injection of acetylcholine were examined in patients with various types of angina pectoris. Coronary artery spasm with chest pain and/or electrocardiographic ischemic changes was angiographically demonstrated in 50 (85%) of 59 patients with angina pectoris. The sensitivity for coronary spasm was 92% (24 of 26) in patients with rest angina, 100% (16 of 16) in patients with both rest and effort angina, and 59% (10 of 17) in patients with effort angina, while it was only 6% (1 of 16) in patients without coronary artery disease. When patients with effort angina were subdivided according to the variability of anginal threshold for exertional angina, the sensitivity for coronary spasm was as high as 90% (9 out of 10) in patients with variable-threshold angina. In contrast, coronary spasm was less frequently (p less than 0.05) induced in patients with fixed-threshold angina (1 of 7, 14%). These results suggest that coronary arteries in patients with angina pectoris are quite susceptible to acetylcholine except in those patients with stable exercise tolerance or anginal threshold. Thus coronary artery spasm appears to play a significant role for the pathogenesis of angina pectoris in a large proportion of patients with effort angina as well as in patients with rest angina.     

Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations

BACKGROUND: There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. OBJECTIVES: We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. METHODS: We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh was injected in incremental doses of 20, 50 and 80 microg into the right coronary artery and 20, 50 and 100 microg into the left coronary artery. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. RESULTS: Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. CONCLUSION: Thus, both selective ACh and ER tests were useful as spasm provocation tests.