Tadao Uraoka

Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine

This study examines the incidence of spasm by intracoronary injection of acetylcholine in Japanese patients who underwent coronary angiography. The subjects were 685 consecutive patients (477 men, mean age 63.2 +/- 7.5 years) who were studied with an acetylcholine test. Acetylcholine 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. Spasm was defined as total or subtotal occlusion. Coronary vasospasm was determined in 221 patients (32.3%). Spasm occurred often during effort and rest in patients with angina (25 of 51, 49.0%), exertional angina (25 of 74, 33.8%), recent myocardial infarction (30 of 80, 37.5%), healed myocardial infarction (14 of 37, 37.8%), and especially in patients with rest angina (83 of 124, 66.9%), whereas spasm was relatively uncommon in patients with nonischemic heart disease (23 of 252, 9.1%). Spasm was superimposed on significant atherosclerotic lesions in 35.9% of patients as well as on nonfixed atherosclerotic lesions in 30.8% of patients. We conclude that >9% of Japanese patients may have coronary vasospasm with intracoronary injection of acetylcholine and recommend the provocation test for evaluating coronary vasospasm if coronary angiography is undertaken.

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.

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 µg into the right coronary artery and 64 µg 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.

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

BackgroundThere are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. ObjectivesWe 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. MethodsWe 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 μg into the right coronary artery and 20, 50 and 100 μg into the left coronary artery. ER was administered as 10 μg/min over 4 min for a maximal dose of 40 μg in the right coronary artery and as 16 μg/min over 4 min for a total dose of 64 μg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. ResultsIntracoronary 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. ConclusionThus, both selective ACh and ER tests were useful as spasm provocation tests.

Clinical and angiographical characteristics of acetylcholine- induced spasm: relationship to dose of intracoronary injection of acetylcholine.

ObjectivesThe purpose of this study was to clarify clinical and angiographical characteristics of acetylcholine (ACh)-induced spasm in the right and left coronary artery. Methods and resultsWe performed 557 consecutive procedures of spasm provocation tests of ACh from January 1991 to December 2000 in patients without significant stenosis. ACh was injected in incremental doses of 20, 50 and 80 μg into the right coronary artery and in incremental doses of 20, 50 and 100 μg into the left coronary artery if spasm had not been provoked. Coronary spasm was defined as positive with more than 99% transient luminal narrowing. Proximal spasm was defined as that of segments 1, 2, 5, 6, 7 and 11 and distal spasm as that of segments 3, 4, 8, 9, 12, 13 and 14. Low-ACh-dose-induced spasms showed the clinical findings and angiographical characteristics of higher incidence of variant angina, proximal spasms, focal spasms, more ST elevation and ischemic heart disease. In contrast, angiographical characteristics of high-Ach-dose-induced spasms were distal spasms and diffuse spasms and there was less variant angina and less ST elevation. ConclusionsLower ACh doses induced spasms more proximally and focally in the coronary artery, while higher doses of ACh provoked spasms more distally and diffusely.

Clinical Characteristics of Female Patients With Coronary Spastic Angina

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Coronary abnormal response has increased in Japanese patients: Analysis of 17 years’ spasm provocation tests in 2093 cases

BACKGROUND Abnormal coronary response on acetylcholine test is observed in patients with early coronary atherosclerosis. OBJECTIVES We analyzed retrospectively the abnormal response rate during 17 years of spasm provocation tests in 2093 consecutive patients. METHODS We performed 2093 spasm provocation tests, consisting of 1198 acetylcholine tests and 895 ergonovine tests, between January 1991 and December 2007. Spasm provocation test was mainly performed in patients with ischemic heart disease. Abnormal response was defined as transient >90% luminal narrowing during spasm provocation tests. We classified these 17 years into two periods: former period from January 1991 to December 2000, and the latter period from January 2001 to December 2007. In the former period, 1300 spasm provocation tests were performed and 793 spasm provocation tests were done in the latter period. RESULTS The incidences of hypertension, dyslipidemia, and diabetes mellitus were significantly increased in the latter period. The values of total cholesterol, triglycerides, and fasting blood sugar were also significantly increased in the latter period. The frequency of abnormal response in the latter period was significantly higher than that in the former period (46.0% vs. 33.2%, p<0.05). The frequency of abnormal coronary response to acetylcholine in the latter period was significantly higher than that in the former period (60.0% vs. 34.0%, p<0.01), whereas there was no difference concerning abnormal response of ergonovine between the two periods (31.9% vs. 30.7%, ns). CONCLUSIONS In Japanese patients, abnormal coronary response to acetylcholine has increased and coronary endothelial dysfunction is suggested to have progressed.

Overview of the Acetylcholine Spasm Provocation Test

The acetylcholine (ACh) spasm provocation test proposed by Yasue, Okumura et al more than a quarter‐century ago has become a popular method for induction of coronary spasm. This test is safe and has a low rate of complications. However, it may be limited in its ability to document attacks in daily life because previously it was the gold‐standard method for diagnosing active variant angina. There may be some clinical issues to modify for the next generation of cardiologists. A maximal ACh dose of 50/100 µg in the right coronary artery/left coronary artery is recommended in the Japanese Circulation Society guidelines. We often experienced the usefulness of a maximal ACh dose of 80/200 µg for the induction of coronary spasm in some cases with low or moderate disease activity. It may be necessary to reconsider the maximal ACh dose as a modified method for todays real‐world clinical practice. In young patients with rest angina, intracoronary injection of ACh is less sensitive for diagnosis; in these cases, we recommend performing sequential spasm provocation tests. Especially in female patients, to document coronary artery spasm we recommend performing ACh tests first, instead of ergonovine tests, due to the supersensitivity of ACh. We also recommend supplementary use of ACh and ergonovine. This review summarizes our experiences with the ACh spasm provocation test over a period of 24 years. We have found it to be a reliable and useful method for contributing a variety of clinical information and recommend it to the next generation of cardiologists.

New non-invasive protocol for detection of coronary spastic angina with significant organic stenosis.

ObjectivesThis study sought to determine whether a newly‐combined test, accelerated exercise following mild hyperventilation (HV) is more beneficial to detect ischaemic evidence in patients with pharmacology‐induced coronary artery spasm (CAS) and luminal narrowing of > 75% than classic methods. Methods and ResultsForty consecutive patients who all had luminal narrowing of > 75% but < 90% and pharmacology‐induced coronary vasospasms of fixed lesions were involved in this study. In these patients, initial HV test, followed by treadmill (TM) exercise test and lastly the newly combined test were performed on three consecutive days. Of the 40 patients, firstly six, secondarily 16 and lastly 32 had positive responses to the HV test, TM exercise test, and newly combined test, respectively. The remaining six patients (15%) had negative results, although the triple sequential tests were performed. Thus, sensitivity of the HV test, the TM exercise test, and the newly combined test was 15% (6/40), 40% (16/40), and 84% (32/38), respectively. Specificity of the three tests were all 100% (46/46). Non‐sustained ventricular tachycardia and hypotension were observed in two (5%) patients. However, no serious or irreversible complications were encountered in this study. ConclusionsWe recommend the newly combined protocol rather than the classic tests for the detection of ischaemic evidence in patients with coronary spastic angina and fixed stenosis.

Membranous Glomerulonephritis Associated with Enterococcal Endocarditis

An autopsy case of membranous glomerulonephritis associated with enterococcal endocarditis was reported. Although enterococcal antigen was not identified in glomerular deposits, the eluate from the patient’s renal tissue was shown to specifically recombine with cells of the enterococcus isolated from his own ante mortem blood. Hypocomplementemia, circulating immune complexes and antienterococcal antibodies were also observed. These findings suggest that enterococcus-related immune complexes played a role in the pathogenesis of glomerulonephritis associated with enterococcal endocarditis in this patient.