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Giant coronary aneurysm is rare, but a life-threatening disease. We report a 67-year-old man with 39 mm coronary aneurysm. He was presented to our facility with acute coronary syndrome complicated by cardiogenic shock. Angiography demonstrated giant coronary aneurysm and occlusion of the right coronary artery. After cardiopulmonary resuscitation and cardiopulmonary support (PCPS), emergent excision of aneurysm and coronary artery bypass grafting was performed. The postoperative course was good without complications. Most giant coronary artery aneurysms are asymptomatic but some patients present with angina pectoris, sudden death, fistula formation, pericardial tamponade, compression of surrounding structures, or congestive heart failure. But once complications, such as thrombosis, distal embolization, fistula formation or rupture occurred, it is difficult to save life without aggressive surgery. At present, there are no specific guidelines for the treatment of giant coronary aneurysm. Surgical correction is a preferred approach for the treatment of giant coronary artery aneurysms.

Intracoronary acetylcholine (ACh) testing has become popular in the world as a spasm provocation test as well as an ergonovine test. Intracoronary ACh test based on the Japanese Circulation Society guidelines is necessary to insert a temporary pace maker (PM). We analyzed the ACh spasm provocation test procedures retrospectively. We performed 1829 ACh spasm provocation testing during 28 years. We investigated the procedural approach sites of artery and vein. Femoral artery and vein approach, brachial artery and femoral vein approach, brachial artery and vein approach, radial artery and brachial vein approach, radial artery and femoral vein approach were performed in 292 patients (16.0%), 498 patients (27.2%), 589 patients (32.2%), 252 patients (13.8%), and 175 patients (9.6%), respectively. We could perform the ACh testing by the femoral artery and brachial artery in all patients, while the success rate of radial artery approach was 97.1%. We could also insert the temporary PM by the brachial vein in 94.8% (841/887) of the study patients, whereas we could insert the temporary PM in all femoral vein approach [100% (965/965)]. We experienced the pulmonary embolism by the femoral artery and vein approach in two patients, while we also had the arterio-venous fistula necessary for surgical repair in two patients by the brachial artery and vein approach. Although there was no difference about the procedure-related major complications among the various procedures, we had no pulmonary embolism or arterio-venous fistula by the radial artery and brachial vein approach. Considering the disinfection with povidone iodine, procedural performance or procedure-related complications by the ACh testing, we recommend that radial artery and brachial vein approach is more comfortable method of the future ACh testing not only for patients but also for operators.

Objective Persistent renal damage (RD) three months after exposure to contrast media is associated with contrast-induced acute kidney injury (CI-AKI) and poor clinical outcomes. Little is known about the role of preprocedural hydration on persistent RD in patients with chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR)

Objectives The clinical characteristics in patients with catheter-induced spasm in the proximal right coronary artery (RCA) are controversial. We performed a clinical analysis of catheter-induced spasm in the RCA. Methods We retrospectively analyzed 5,296 consecutive patients who underwent diagnostic or follow-up angiography during a 26-year period. During this period, we found 40 patients with catheter-induced spasm in the RCA. We compared the clinical characteristics and procedures of cardiac catheterization in patients with catheter-induced spasm in the RCA with those in patients without such spasm. Results The frequency of catheter-induced spasm in the RCA was 0.75% (40/5,296). We performed pharmacological spasm provocation tests in 36 of 40 patients after spasm relief. Positive spasm was observed in 32 patients (88.9%), and 25 patients (78.1%) had multiple spasms. The catheter procedures, including the approach sites (radial/brachial/femoral), catheter size (4/5/6Fr) and catheter type (Judkins right/Sones/Shared/Judkins left 3.5/Amplatz) were not markedly different between the two groups. A multivariate analysis showed that positive spasm [odds ratio (OR): 7.030, 95% confidence interval (CI): 1.920-25.700], a younger age (OR: 0.937, 95% CI: 0.910-0.965) and diabetes mellitus (OR: 0.278, 95% CI: 0.083-0.928) were the determinant factors for the catheter-induced spasm. Conclusion Approximately 80% of patients with catheter-induced spasm in the proximal RCA had coronary spastic angina. Positive provoked spasm was the most powerful determinant factor for catheter-induced spasm.

When cardiologists diagnose patients with coronary spastic angina, Japanese Circulation Society (JCS) guidelines recommend the intracoronary injection of acetylcholine (ACh) and ergonovine (ER) as class I. However, the pharmacological difference between ACh and ER is controversial in the clinic. We performed both ACh and ER tests in the same 528 patients during 26 years. We investigated the provoked spasm configuration, spasm site, and clinical characteristics of provoked spasm between ACh and ER, retrospectively. We defined positive spasm as ≥90% luminal narrowing. Provoked positive spasm was observed in 161 right coronary arteries (RCA) including 83 ACh just positive, 35 ER just positive, and 43 both positive. In contrast, positive spasm was documented in 172 left coronary arteries (LCA) including 94 ACh just positive, 28 ER just positive, and 50 both positive. ACh provoked spasm more distally and diffusely, while ER induced spasm more proximally and totally or focally in the RCA. In the LCA, ACh provoked spasm more proximally, whereas ER induced spasm more distally. ER testing after the negative ACh tests of RCA and LCA documented new positive spasms in 10.3% (35/340) and 7.4% (28/376), respectively. Coronary artery trees may each have a sensitive receptor on each segment. We recommend the supplementary use of ACh and ER to document coronary artery spasm in the cardiac catheterization laboratory.

Objective Life-threatening ventricular arrhythmias are recognized in patients with coronary spastic angina. Implantable cardioverter-defibrillators (ICDs) are effective in patients with structural heart disease and ventricular fibrillation. However, the optimal medication for patients with aborted sudden cardiac death (SCD) due to coronary artery spasm after the implantation of ICD remains controversial. Methods We investigated the medications and the numbers of appropriate ICD shocks in 137 patients with a history of aborted SCD due to coronary spasm. Results Appropriate ICD shocks were observed in 24.1% (33/137) of patients with aborted SCD due to coronary spasm during 41 months of follow-up. Only 15 (15.6%) of the 96 patients with ICDs received aggressive medical therapy, including two or three calcium-channel antagonists. The rate of appropriate ICD shocks was significantly higher in Western countries than in Asian countries (42.9% vs. 19.3%, p

Coronary artery spasm is involved in the pathogenesis of various cardiac disorders. We investigated patients with a history of syncope who underwent elective coronary angiography. We retrospectively analyzed 5781 consecutive patients who had diagnostic or follow-up angiography during a 26-year period. During this period, we found 95 patients with a history of syncope before elective coronary angiography. Pharmacological spasm provocation testing was performed in 64 patients with a history of syncope (

In the clinic, patients with ≥90% luminal narrowing during ergonovine (ER) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90% luminal narrowing when performing ER tests, retrospectively. We performed 1210 ER tests over 26 years (1991-2016). We analyzed chest symptoms and positive ischemic ECG changes during ER tests. More than 90% luminal narrowing was found in 352 patients (29.1%) including 211 patients in the right coronary artery (RCA) and 217 patients in the left coronary artery (LCA). Chest symptom was observed in 290 patients (82.4%) including 162 patients in the RCA and 179 patients in the LCA. ST elevation was found in 154 patients including 98 in the RCA and 73 patients in the LCA, while ST depression was recognized in 81 patients including 38 patients in the RCA and 62 patients in the LCA. Two-third of patients with ≥90% luminal narrowing had significant ischemic ECG changes, whereas 60.5% of patients with ≥90% luminal narrowing complained usual chest pain accompanied with significant ischemic ECG changes. Unusual chest symptom was complained in 7.1% of patients with ≥90% luminal narrowing. Neither chest symptom nor ECG changes was found in 48 patients (13.6%) with ≥90% luminal narrowing. We should understand some limitation to diagnose positive coronary spasm during ER tests.

Acetylcholine (ACh) was administered for 3min in the ENCORE study, while the Japanese Circulation Society guidelines recommended the 20s ACh injection as an ACh test.We compared the ischemic findings between ACh administration for 3min and ACh injection for 20s in the same patients and in the same ACh doses without administration of nitrates in the left coronary artery.We investigated 30 patients with ischemic heart disease (25 men, 67±10 years, ACh 50μg: 3, ACh 100μg: 9, ACh 200μg: 18) by the above two ACh injection procedures. Temporary pacemaker was inserted and set at the rate of 40/min. Positive provoked spasm was defined as transient ≥90% narrowing and typical chest symptoms or ischemic electrocardiographic (ECG) changes.Provoked spasm was observed in 22 patients with ACh 20s injection, while 10 patients had provoked spasm by ACh 3min administration (73.3% vs. 33.3%, p0.05). Ischemic ECG changes (50.0% vs. 23.3%, p0.05) and chest symptoms (73.3% vs. 43.3%, p0.05) were significantly higher with ACh 20s injection than ACh 3min administration. Pacemaker rhythm was recognized in 19 patients with ACh 20s injection, whereas 7 patients with ACh 3min administration had a pacemaker rhythm (63.3% vs. 23.3%, p0.01). Maximal ST elevation by ACh 20s injection was significantly higher than that by ACh 3min administration (0.47±0.94 vs. 0.13±0.51, p0.05), while maximal ST depression was not different between the two procedures. Coronary artery diameter after ACh 20s injection was significantly lower than that after ACh 3min administration in the left anterior descending artery.ACh administration procedures (3min or 20s injection) may influence the ischemic findings in spasm provocation testing.

A 61-year-old man was admitted to our hospital due to chest pain on both rest and effort. After the computed tomography coronary angiography, coronary stenosis was recognized at segment 3. Because inferior ischemia on stress myocardial perfusion scintigraphy with 201 thallium chloride induced by adenosine was found, we planned to perform the coronary intervention. After control coronary angiography, no significant stenosis was found in the right coronary artery. Intracoronary acetylcholine testing disclosed diffuse spasm at segment 4, whereas intracoronary ergonovine administration documented the total spasm at segment 3. After the intracoronary administration of nitrate, we diagnosed him with coronary spastic angina without organic stenosis.

Hypoplastic coronary artery disease is a rare congenital abnormality reported to be associated with myocardial infarction and sudden cardiac death. Provoked positive spasm in the left circumflex coronary artery (LCX) with pharmacological spasm provocation tests was remarkably lower than other coronary arteries. We sometimes encountered patients with rest angina and hypoplastic right coronary artery (H-RCA). Among 5953 patients with diagnostic and follow-up coronary arteriography, we found 93 patients (1.6%) with H-RCA. During the same period, we could perform spasm provocation tests in 564 patients with rest angina including 13 patients with H-RCA and 249 patients with effort angina including 10 patients with H-RCA. Pharmacological spasm provocation tests were performed in 51 of 93 patients including 34 patients with ischemic heart disease (IHD) and 17 patients with non-IHD. Provoked spasm incidence in patients with IHD was higher than in those with non-IHD but not significant (52.9% vs. 29.4%, p = 0.1114). Provoked positive spasm in the LCX in patients with rest angina and H-RCA was significantly higher than that in those without H-RCA (69.2% vs. 23.4%, p

BACKGROUND Temporary pace maker is necessary because of transient block or bradycardia during the intracoronary acetylcholine spasm provocation tests based on the Japanese Circulation Society guidelines. OBJECTIVES We examined the feasibility and safety of the acetylcholine spasm provocation test via the radial artery and brachial vein approach. METHODS We tried to perform the acetylcholine spasm provocation tests in 252 patients via the radial artery and brachial vein approach procedures during 5 years. Acetylcholine was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and 20/50/100/200 μg into the left coronary artery (LCA). Back-up pacing rate was set at 40 beats/min. Positive spasm was defined as transient ≥90% luminal narrowing and ischemic electrocardiographic change or usual chest pain. RESULTS The procedure success of radial artery and brachial vein access was 94.4% (238/252) and 93.3% (235/252), respectively. We performed 221 patients (87.7%) with acetylcholine tests by radial artery and brachial vein approach. We changed to the brachial approach due to the failures of radial artery access in 14 patients. We also changed to the femoral vein in 11 patients and internal jugular vein in two patients. Back-up pace maker rhythm was observed in 92.1% (232/252) of all study patients, while it was significantly higher in the RCA testing than that in the LCA tests (84.9% (191/225) vs. 52.2% (131/251), P < 0.001). No irreversible complication was found. CONCLUSIONS We recommend the radial artery and brachial vein approach for safety and convenience when performing the acetylcholine spasm provocation tests.

We examined the clinical usefulness of treadmill exercise tests (TETs) in diagnosing coronary spastic angina (CSA).We performed the TETs and 24-h Holter monitoring in 300 CSA patients consisting of 152 patients with rest angina, 77 patients with effort angina, and 71 patients with rest and effort angina. Organic stenosis (75%) was observed in 44 patients. Multiple spasms were recognized in 204 patients (68%).Positive TETs were recognized in 113 patients (38%) and borderline was observed in 30 patients (10%). Positive response was significantly higher in patients with organic stenosis than those without fixed stenosis (63.6% vs. 33.2%, p0.001). Moreover, ST elevation was more frequent in patients with organic stenosis than those without fixed stenosis (27.3% vs. 1.2%, p0.001). Positive response in patients with effort angina (46.8%) was higher than those in patients with rest angina (33.6%) and rest and effort angina (36.6%), but not significant. Positive response was not different between single spasm and multiple spasms. In all 300 patients, ST segment elevation was observed in only four patients (1.3%) on the 24-h Holter monitoring.TET was useful in documenting ischemia in patients with CSA. More than a third of patients with CSA had positive TETs. Moreover, we obtained the pathologic TET response in approximately half of patients with CSA.

Arterial sheath insertion (cannulation) is the first procedure of cardiovascular catheterization, and sometimes performed by residents. But there is little data regarding bleeding complications after resident’s cannulation compared with senior cardiologist’s cannulation. Consecutive 334

A 75-year-old man was admitted to our hospital for follow-up coronary angiography. Just after starting coronary angiography, his electrocardiogram showed ST-segment elevation in the V1-6, I, II, and aVF leads, and he fell into catastrophic cardiogenic shock. His left coronary arteriogram showed proximal total obstruction in the left anterior descending artery and proximal subtotal occlusion in the left circumflex artery. Because pulseless electrical activity arrest was recognized, cardiopulmonary support was started. After more than 15 minutes' cardiac massage, his blood pressure gradually returned to baseline. During the cardiogenic shock due to pulseless electrical activity arrest, neither ventricular fibrillation nor ventricular tachycardia was recognized.

Positive provoked spasm in the left circumflex artery (LCX) is lower than that in the left anterior descending artery and right coronary artery (RCA).We examined the provoked positive spasm in the LCX between the maximal acetylcholine (ACh) 100 μg period (January 1991 to July 2012, 1474 patients: the former period) and the maximal ACh 200 μg period (August 2012 to August 2018, 336 patients: the latter period). ACh was injected in incremental dose of 20/50/100/200 μg into the left coronary artery and of 20/50/80 μg into the RCA. Positive spasm was defined as at least 90% stenosis and usual chest symptoms or ischemic ECG changes.Provoked positive spasm in the latter period was significantly higher than that in the former period (65.5 vs. 39.1%, P0.001). The positive spasm increase of RCA and left anterior descending artery was 143 and 159%, whereas the increase of LCX was 204%. Multiple-vessel spasm was also increased in the latter period.Maximal ACh dose into the left coronary artery may affect the positive spasm in the LCX and multiplevessel spasm.

We examined the clinical usefulness of sequential spasm provocation tests as follows: first, acetylcholine (ACh) test, second, ergonovine (ER) test, and finally, the ACh test following the ER test.We performed the ACh and ER tests in 461 patients (294 men, 64.4±11.3 years of age) during a 23-year period. In addition, we administered an intracoronary injection of ACh after the ER tests in 240 patients. First, ACh [right coronary artery (RCA): 20/50/(80) μg, left coronary artery (LCA): 20/50/100/(200) μg] was administered incrementally over 20 s. Second, ER (RCA: 40 μg, LCA: 64 μg) was administered over 2-4 min. If a provoked spasm did not occur, we administered an intracoronary injection of ACh (50/80 μg into the RCA and 100/200 μg into the LCA) just after the ER tests. A positive spasm was defined as more than 99% transient luminal narrowing.A positive spasm was observed in 221 (47.9%) patients including 181 ACh-positive (39.3%) and 119 ER-positive (25.8%) patients by the ACh or ER tests. In the 240 patients with a negative spasm in the ACh and ER tests, 48 (10.4%) patients developed provoked spasms on adding ACh after the ER test. The distributions of various cardiac disorders and provoked spasm vessels were similar among the three positive groups. Focal spasm was frequently observed in the ER-positive group, whereas diffuse spasm was frequently obtained in the ACh-positive group and by adding ACh after ER in the positive group. No major complications were recognized during the sequential spasm provocation tests.Sequential spasm provocation tests might overcome a limitation of standard spasm provocation tests.

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 today's 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.

OBJECTIVE The majority of cardiologists do not perform spasm provocation tests in patients with non-ischemic heart disease (non-IHD) or non-obstructive coronary artery disease (non-ob-CAD). We herein examined the frequency of provoked spasms in non-IHD and non-ob-CAD patients, including those with atypical chest pain (Aty), valvular heart disease (Val), hypertrophic cardiomyopathy (HCM), congestive heart failure (CHF), and others (Oth). METHODS & RESULTS We performed acetylcholine (ACh) spasm provocation tests over a period of 22 years (1991-2012) among 1,440 patients, including 981 IHD and 459 non-IHD subjects. A total of 43 patients with significant organic stenosis were excluded, and the remaining 416 patients with non-IHD or non-ob-CAD disease were assessed. ACh was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and 20/50/100/(200) μg into the left coronary artery (LCA). Positive coronary spasms were defined as transient luminal narrowing of >99%. Positive coronary spasms were noted in 17.3% of the non-IHDs patients (72/416), compared to 11.4% (15/132), 19% (8/42), 16.7% (5/30), 23.9% (16/67), and 19.3% (28/145), in the patients in the Aty, Val, HCM, CHF, and Oth groups, respectively. The rate of positive provoked spasms was higher in men than women, although not significantly [20.6% (46/223) vs. 13.4% (26/193), ns], and significantly higher in the late period (2001-2012) than in the early period (1991-2000) (36.8% vs. 7.0%, p

Background: Japanese Circulation Society guidelines for coronary spastic angina recommended the step-by-step bolus administration of acetylcholine (ACh) dose on both coronary arteries (left coronary artery (LCA): 20/50/100 µg, right coronary artery (RCA): 20/50 µg). Our routine practice employed the maximal 80 µg ACh into the RCA and 200 µg ACh into the LCA not to misdiagnose the patients with coronary spasm. At least from five to seven times procedures are necessary during ACh spasm provocation tests. Radiation exposure and the adverse effect of contrast medium is one of the problems. Objectives: We investigated the procedures of the ACh administration on both coronary arteries in the real clinical practice retrospectively. Methods: We analyzed the consecutive 150 patients who had maximal ACh dose of 200 µg into the LCA. We compared clinical issues with and without saving ACh dose. Positive spasm was defined as a transient >90% narrowing and usual chest symptom or ischemic ECG changes. Results: Among 150 patients, 63 patients (42.0%) had positive provoked spasm. Patients with step-by-step ACh dose into the LCA were significantly higher than those with step-by-step ACh dose into the RCA. Saving of ACh 20 µg, 50 µg, and 100 µg into the LCA was observed in 59 patients, 18 patients, and one patient, respectively. Saving of 20 µg ACh and 50 µg ACh into the RCA was found in 98 patients and 60 patients, respectively. Positive spasm frequency was not different between the patients with and without saving ACh procedures. Radiation exposure time/dose and total used amount of contrast medium in saving ACh tests were significantly lower than those in step-by-step ACh tests. No serious irreversible complications were found. Conclusions: We should reconsider the saving ACh spasm provocation tests in the real clinical practice.

Exercise test, hyperventilation test or cold pressor test was employed to reproduce ST elevation in patients with variant angina. However, cardiologists could not get the high positive frequency from these tests in patients without high disease activity. Now a days, cardiologists can easily perform coronary angiography or coronary computed tomography. Cardiologists skipped the non-invasive spasm provocation tests such as hyperventilation test or cold pressor test to diagnose patients with coronary artery spasm. Approximately a half patient with coronary spasm had pathologic responses of exercise tests. More than a third patient with coronary spasm and without fixed stenosis had ischemic findings on exercise tests, whereas more than two-third patients with coronary spasm and with organic stenosis had pathologic responses on exercise testing. We should reconsider the usefulness of exercise tests to obtain the ischemic findings due to coronary artery spasm in the clinic before performing the cardiac catheterization.

We examined the safety of acetylcholine (ACh) and ergonovine (ER) tests retrospectively and investigated the optimal protocol of provocation test for diagnosis of multivessel coronary spasm. We performed 1546 ACh tests and 1114 ER tests during 23 years. ACh was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and of 20/50/100/200 μg into the left coronary artery (LCA) over 20 s. ER was administered in total doses of 40 μg into the RCA and of 64 μg into the LCA over 2–4 min. When a coronary spasm was induced and did not resolve spontaneously within 3 min after the completion of ACh/ER injection, or when hemodynamic instability due to coronary spasms occurred, 2.5–5.0 mg of nitrate was administered into the responsible vessel. To relive provoked spasm, it is necessary to administer nitrate in 31 cases by ACh and in 76 cases by ER (2.0 vs. 6.8 %, p

As a spasm provocation test of acetylcholine (ACH), incremental dose up (20/50/100 μg) into the left coronary artery (LCA) is recommended in the guidelines established by Japanese Circulation Society. Recently, Ong et al. reported the ACOVA study which maximal ACH dose was 200 μg in the LCA. We compared the angiographic findings between ACH 100 μg and ACH 200 μg in the LCA and also examined the usefulness and safety of ACH 200 μg in Japanese patients without variant angina. As a spasm provocation test, we performed intracoronary injection of ACH 200 μg after ACH 100 μg in 88 patients (55 males, 68.4 ± 11.7 years old) including 59 ischemic heart disease (IHD) patients and 29 non-IHD patients. Positive spasm was defined as >99 % transient stenosis (focal spasm) or 90 % severe diffuse vasoconstriction (diffuse spasm). Positive spasm by ACH 200 μg was significantly higher than that by ACH 100 μg (36 pts: 40.9 % vs. 17 pts: 19.3 %, p < 0.01). Diffuse distal spasm on the left anterior descending artery was more recognized in ACH 200 μg than in ACH 100 μg (30.7 vs. 13.6 %, p < 0.01). In 29 rest angina patients, positive spasm by ACH 200 μg (19 pts) was significantly higher than that by ACH 100 μg (7 pts) (65.5 vs. 24.1 %, p < 0.01). No serious irreversible complications were found during ACH 200 μg. Administration of ACH 200 μg into the LCA was safe and useful. We may reexamine the maximal ACH dose into the LCA.

Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6-month follow-up. The blood pressure from baseline to 6 months had significantly decreased (24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m(2) to 111.3 ± 23.9 g/m(2), P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system.

70-year-old man admitted to our hospital because of chest discomfort on effort. Because we inserted the 6 Fr sheath into the wrong radial vein, we replaced the 5 Fr sheath into the radial vein. We inserted the 6 Fr sheath into the radial artery. We performed the acetylcholine and ergonovine spasm provocation tests under the temporary pace maker insertion. After the procedures, we compressed the radial artery and vein with radial band simultaneously. No bleeding or hematoma was found after the removal of radial band. We could perform the acetylcholine test via the radial artery and vein without any complications.

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in developed countries, although percutaneous coronary intervention and coronary artery bypass grafting have developed recently. Appropriate diagnosis will improve the prevention, treatment, and care of all patients. We could diagnose only calcification in the coronary arteries with the past computed tomography. Recently, multislice computed tomography has been already accepted as an efficient non-invasive tool for the detection of coronary artery stenosis. We get to estimate the coronary artery stenosis with cardiac computed tomography. We discuss the usefulness of cardiac computed tomography for the risk stratification of coronary artery atherosclerosis.

The spasm provocation tests of ergonovine and acetylcholine have been employed in the cardiac catheterization laboratory. Ergonovine acts through the serotogenic receptors, while acetylcholine acts through the muscarinic cholinergic receptors. Different mediators may have the potential to cause different coronary responses. However, there are few reports concerning the coronary response between ergonovine and acetylcholine in the same patients. Acetylcholine is supersensitive for females; spasm provoked by ergonovine is focal and proximal, whereas provoked spasm by acetylcholine is diffuse and distal. We should use both tests as supplementary in the clinic because ergonovine and acetylcholine have self-limitations to induce coronary spasms during daily life. The maximal pharmacological doses, administration methods, and the angiographical positive definition are remarkably different for each institution in the world. We recommend the pharmacological spasm provocation tests as Class I in the guidelines in patients with vasospastic angina throughout the world.

We investigated the clinical situations and the present knowledge of Japanese cardiologists about coronary artery spasm before and after the establishment of guidelines for this condition in the real world. A questionnaire was developed regarding the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests before (2008) and after (2014) the establishment of the Japanese Circulation Society (JCS) guidelines for coronary artery spasm and the status of spasm provocation tests. The questionnaire was sent to members of the Japanese Cine-angio Association in 81 cardiology hospitals in Japan. The completed surveys were returned from 20 hospitals, giving a response rate of 24.7%. Pharmacological spasm provocation tests increased in 2014 and vasospastic angina and variant angina also increased in 2014 compared with 2008, but the increase was not significant. Non-invasive spasm provocation tests such as hyperventilation tests and cold stress tests decreased remarkably in 2014. Spasm provocation tests were initially performed in the left coronary artery was employed in just 30% of the hospitals. The majority of institutions did not perform the spasm provocation testing in patients with unknown causes of heart failure or in survivors of ventricular fibrillation. Although 40% of the hospitals were not satisfied with standard spasm provocation tests, the majority of the hospitals agreed that spasm provocation tests will be necessary in the future. In general, the JCS guidelines contributed to the widespread use of provocative testing for coronary artery spasm in the real world. However, some issues about spasm still remained in the clinic.

BACKGROUND We encounter a less provoked spasm in the left circumflex artery (LCX) by acetylcholine (ACh) testing compared with left anterior descending artery and right coronary artery (RCA) in the real world. OBJECTIVES We investigated the clinical characteristics of provoked spasm in the LCX by ACh testing. METHODS We retrospectively analyzed consecutive 1392 ACh testing over 20 years (1991-2011). The maximal ACh dose was 100 μg into the left coronary artery and 80 μg into the RCA. Positive spasm was defined as transient of more than or equal to 90% narrowing and usual chest symptoms or ischemic ECG changes. RESULTS Positive provoked spasm was recognized in 622 patients (44.7%) including 456 RCA spasms, 448 left anterior descending artery spasms, and 176 LCX spasms. LCX-provoked spasm was significantly lower than other vessels (P

Pharmacological spasm provocation tests are invasive methods and we always have the potential to encounter complications when performing these tests. In 1980, Buxton et al. reported three deaths when they performed intravenous ergonovine testing. However, we now employ the intracoronary ergonovine test instead of the intravenous injection of ergonovine from a safety procedure point of view. Past serious major complications of intravenous ergonovine tests, intracoronary ergonovine tests, and intracoronary acetylcholine tests were 0.31% (26/8419), 0.51% (11/2173), and 0.95% (148/15,527), respectively. Selective intracoronary testing had the serious major complications in 0.89% of patients including just one death (0.006%) and two acute myocardial infarctions (0.01%). Selective spasm provocation tests had no additional risks compared with performing diagnostic coronary angiography alone. In the Western countries, the pharmacological spasm provocation tests are not familiar in the clinic except for some specialized institutions. We need international clinical studies using the same protocol of spasm provocation tests to compare the frequency, clinical features, and prognosis of acetylcholine- or ergonovine-provoked coronary spasm between Western and Asian countries. And we hope that Western guidelines give spasm provocation testing a class I indication similar to Japanese Circulation Society guidelines because coronary artery spasm may have fewer racial differences and borders.

Objectives To develop a clinically significant and practical enzyme-linked immunosorbent assay (ELISA) for the detection of MxA protein in human whole blood, a biological marker of viral infection. Design and Methods A sandwich ELISA suitable for the measurement of human MxA protein in whole blood was developed using mouse monoclonal antibodies (mAbs) raised against the GTP-binding domain of human MxA protein. Prior to the assay, the whole blood sample was treated with special buffer to extract the MxA protein, improve its stability, and avoid interference from hemoglobin. Results This ELISA meets all the requirements for use in routine clinical assays, especially in terms of sensitivity (detection limit: 1.3 ng/ml whole blood), accuracy (recovery: 93.0–100.0%), and rapidity (

SummaryBackgroundAbnormal coronary response on acetylcholine test is observed in patients with early coronary atherosclerosis.ObjectivesWe analyzed retrospectively the abnormal response rate during 17 years of spasm provocation tests in 2093 consecutive patients.MethodsWe 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.ResultsThe 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

Summary Background There have been no reports concerning the correlation between heart failure and coronary artery spasm. Methods and results From January 2000 to December 2007, 201 patients with heart failure were hospitalized at our institution. We could perform coronary arteriography and spasm provocation tests in 37 (22 men, 67 ± 11 years) out of 201 patients with heart failure before discharge. Atrial fibrillation was observed in 13 patients (35%). After controlling heart failure and 24 h cessation of vasoactive drugs, pharmacological spasm provocation tests were performed. Positive spasm was defined as >90%. Coronary spasm was observed in 12 patients (32%) and multiple spasm was recognized in 10 (83%) out of 12 patients. Though ejection fraction on admission was not different between the two groups (42 ± 18% vs. 43 ± 11%, ns), left ventricular end-diastolic and end-systolic dimension after medical therapy over 1 year was significantly smaller in patients with positive spasm than that in patients with negative spasm. There was no difference concerning medications except the administration of nitrate and nicorandil between two groups. Conclusions Coronary artery spasm, especially multiple spasm, may cause transient heart failure in a small part of unknown origin heart failure in Japan.

A 58-year-old male with dyslipidemia and coronary spastic angina suddenly experienced pain in the right limb while walking on November 1, 2008. Right-ankle brachial pressure index (ABI) was decreased (0.80) and left-ABI was normal (1.24). Bilateral ABI was normal during January 2008. Ultrasonography in the right-lower limb artery revealed severe stenosis in the right-popliteal artery with extended and large echolucent plaques containing an isoechoic area. We carried out lower limb angiography: subtotal occlusion of the popliteal artery was found. By intravascular ultrasound (IVUS), right-popliteal artery plaques were echolucent and eccentric; ulceration with a thin fibrous cap was noted. Percutaneous transluminal angioplasty was done and popliteal artery blood flow was improved. Right-ABI improved to 1.13 after 4 days. To prevent the progression and rupture of the plaques, lipid-lowering therapy and antiplatelet therapy were started. Plaque rupture of the popliteal artery was diagnosed by these characteristics on IVUS. Patients with peripheral artery disease may have plaque rupture similar to those with acute coronary syndromes who have identical unstable plaques and unstable atheromas. In addition to appropriate local revascularization, systemic therapy to stabilize the unstable plaque is indicated because failure to do so may cause recurrent events. © 2009 Wiley-Liss, Inc.

Summary Objetives We examined some recommendations for performing acetylcholine (ACh) tests safely. Methods and results We performed 1000 ACh tests from 1991 to December 2004. ACh was injected in incremental doses of 20/50/80 μg into the RCA and of 20/50/100 μg into the LCA. During these periods, we encountered various major/minor complications; 12 ventricular tachycardia (1.2%) necessary one dc, one ventricular fibrillation (0.1%) necessary dc, 3 shock like the left main stem spasm (0.3%), one cardiac tamponade necessary surgical drainage (0.1%), and 164 Paf (164/959:17.1%) necessary administration of antiarrhythmic agents to sinus rhythm in about one third patients (31.7%). We did not experience irreversible severe complications, such as acute myocardial infarction or death. Recommendations (1) Stand by direct current with pasting, (2) Thump version when ventricular tachycardia or fibrillation occurred, (3) Over infusion to avoid hypovolemia, (4) Perform angiography before complete spasm provocation if a severe spasm, (5) Drainage if cardiac tamponade occurred, (6) Cibenzoline or disopyramid administration when ACh induced paroxysmal atrial fibrillation, (7) Incremental ACh dose up should be performed, (8) Administer small amount of noradrenaline if shock observed and (9) Test shot should be performed before 1-min angiography. Conclusions We recommend STOP DCIAT for performing ACh tests safely.

A 54-year-old man was admitted to our hospital due to abnormal electrocardiogram (ECG) changes. He had experienced no chest pain or chest discomfort during daily life until then. Ischemic ECG change was obtained by the treadmill exercise test but he complained of no chest pain or chest oppression. We performed coronary angiography and found near normal coronary artery with hypoplasty of right coronary artery. He complained of no chest symptoms irrespective of ischemic ECG change [ST depression in V3-6 leads (2.0–3.0mm)], when intracoronary injection of 50μg acetylcholine provoked subtotal spasm at mid left anterior descending artery and focal spasm at proximal left circumflex artery. After the administration of calcium-channel antagonist for four months, ischemic ECG changes were improved by the treadmill exercise test. He had experienced some slight fatigue during daily life and cold sweating during sleep three or four times a month before the medication. However, he had experienced less slight fatigue and no cold sweating during sleep after taking the calcium-channel antagonist. He experienced silent coronary spastic angina.

Background: We investigated the complications of spasm provocation tests, including acetylcholine (ACh) tests, ergonovine (ER) tests and adding ACh after ER tests, retrospectively. Methods: We performed 1546 ACh tests and 1114 ER tests during 23 years, including 240 adding ACh after ER tests. ACh (RCA: 20/50/(80) g, LCA: 20/50/100/(200) g) was injected incrementally over 20 seconds, whereas ER (RCA: 40 g, LCA: 64 g) was administered over 2-4 minutes. In addition, we administered adding intracoronary injection of ACh (RCA: 50/80 g, LCA: 100/200 g) after ER tests. Serious major complications were defined as ventricular fibrillation, sustained ventricular tachycardia, shock, severe hypotension (< 60 mmHg), cardiac arrest and cardiac tamponade. Results: Serious major and major complications were higher in ACh tests than ER tests (1.8% vs. 0.4%, p

Pistipino et al. reported that provoked spasm by acetylcholine testing in patients with acute myocardial infarction was three times higher in Japanese patients than Italian Caucasian patients in a small series in 2000. Provoked spasm was investigated between Caucasian and Japanese patients who had undergone spasm provocation testing in the past consecutive series. The incidence of provoked spasm was not different between French Caucasian and Japanese patients with the intravenous injection of ergonovine (12.3% vs. 12.8%, ns). And intracoronary administration of acetylcholine had the same positive provoked spasm between German Caucasian and Japanese populations (33.4% vs. 32.3%, ns). Although the racial difference about coronary spasm was evolved in the past, we may have less racial difference concerning the provoked spasm between Caucasian and Japanese patients, when we performed the spasm provocation testing routinely in the cardiac catheterization laboratory.

In an effort to assess the cardiovascular benefits of combined angiotensin receptor blockage and calcium channel antagonism, we assessed the chronic effects of the angiotensin type 1 receptor blocker candesartan, the calcium channel blocker benidipine, and the use of a combination therapy in Dahl salt-sensitive (DS) rats. DS rats receiving a high salt diet were treated with either benidipine (4 mg/kg), candesartan (1 mg/kg) or both. Rat blood pressure was measured using a tail-cuff method. Following 12 weeks, the effect on heart weight, plasma-oxidized low-density lipoprotein (ox-LDL) level, endothelium-dependent vasorelaxation, and histology of the heart and aorta was assessed. Blood pressure, heart weight and plasma ox-LDL levels increased, while endothelium-dependent vasorelaxation decreased in the DS rats. Candesartan and benidipine inhibited the increase in blood pressure and heart weight, and the decrease in endothelium-dependent vasorelaxation. The use of benidipine alone or a combination significantly inhibited the increase in ox-LDL levels, whereas candesartan alone had no significant effect on ox-LDL levels. The present findings indicate that, if the monotherapy using ARB could not achieve adequate control of blood pressure, the combination therapy with ARB and benidipine provides the additional reductions in hypertension and cardiac hypertrophy. Moreover, the combination therapy inhibits cardiovascular dysfunction and ox-LDL levels more effectively than use of ARB alone. These results contribute to the possibility of lowering ox-LDL levels as a means of enhancing cardiovascular protection.

BACKGROUND Because there are no guidelines concerning coronary spasm in Japan, the present study examined the current status of the spasm provocation test. METHODS AND RESULTS Questionnaires concerning the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests over 3 years (2001-2003) and the status of spasm provocation tests were sent to members of the Japanese Circulation Society in 120 cardiology hospitals in the Chugoku and Shikoku areas. Completed surveys were returned from 45 hospitals, giving a collection rate of 38%. As a spasm provocation agent, acetylcholine tests were performed in 29 hospitals, and ergonovine tests in 18 hospitals. Non-invasive spasm provocation tests were performed in only 9 hospitals (20%). In total, 5,267 patients underwent acetylcholine spasm provocation test (2,387 patients) or ergonovine spasm provocation test (2,880 patients) and vasospastic angina was diagnosed in 1,663 (2.4%) patients. Invasive spasm provocation tests were performed in 7.8% of patients with diagnostic catheterization and the spasm-positive rate was 31.6%. The difference among hospitals concerning the number of invasive spasm provocation tests was remarkable, and the angiographic spasm-positive standard and acetylcholine/ergonovine dose varied among the hospitals. CONCLUSIONS Guidelines on coronary spasm in Japan are essential to overcome the current differences between institutions.

There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests.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.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 transient99% luminal narrowing.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%, P0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P0.01). 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%, P0.01). 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.Thus, both selective ACh and ER tests were useful as spasm provocation tests.

Background Various skin lesions occur in association with rheumatoid arthritis (RA). Observation We report a distinctive skin lesion observed in 4 patients with RA. All patients had RA for many years and developed asymptomatic, irregularly shaped erythema over the swollen elbow joints and the nearby part of the forearm. Histopathologically, all cases showed massive aggregates mainly composed of histiocytes in markedly dilated vessels in the dermis, accompanied by a dermal infiltrate of lymphocytes, plasma cells, neutrophils, or a combination of these. A total of 9 cases, including ours, showing similar histopathologic findings have been reported in the literature, of which 7 were associated with RA and presented relatively common clinical appearance. Conclusion In spite of some disagreement as to whether the dilated vessels are blood vessels or lymphatics, it is most likely that these 7 cases belong to the same clinical entity closely associated with RA.

We have developed and tested an enzyme-linked immunosorbent assay system for individual measurement of deoxynivalenol, nivalenol, and T-2 + HT-2 toxin using monoclonal antibodies for 3,4,15-triacetyl-nivalenol, for both 3,4,15-triacetyl-nivalenol and 3,15-diacetyl-deoxynivalenol, and for acetyl-T-2 toxin. The assay system comprised three kits (desinated the DON + NIV kit, the NIV kit, and the T-2 + HT-2 kit). The practical performance of the enzyme-linked immunosorbent assay system was assessed by assaying trichothecene mycotoxins in wheat kernels. The enzyme-linked immunosorbent assay system meets all the requirements for use in a routine assay in terms of sensitivity (detection limit: deoxynivalenol 80 ng/g, nivalenol 80 ng/g, T-2 toxin 30 ng/g), reproducibility (total coefficient of variation: 1.9-6.2%), accuracy (recovery: 93.8-112.0%), simplicity and rapidity (time required:2 h), mass handling (42 samples/assay), and a good correlation with gas chromatography-mass spectrometry (r=0.9146-0.9991). Components derived from the wheat extract did not interfere with the assay kits. The enzyme-linked immunosorbent assay system is a useful alternative method to gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, or liquid chromatography-ultraviolet absorption for screening cereals and foods for trichothecene mycotoxin contamination.