Acetylcholine spasm provocation test by trans-radial artery and brachial vein approach.

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.

Differential incidence and morphology of provoked spasm between intracoronary acetylcholine and ergonovine testing: recommendation of supplementary use.

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.

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.

Safety and optimal protocol of provocation test for diagnosis of multivessel coronary spasm.

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 < 0.01) before another vessel attempts. Multivessel spasms were often observed in LCA testing than in RCA testing on both agents [ACh: 78.6 % (11/14) vs. 11.8 % (2/17), p < 0.001, ER: 37.8 % (14/37) vs. 20.5 % (8/39), ns]. Even after the administration of nitrates, positive coronary spasm was obtained in 21.1 % by ACh and 52.9 % by ER tests on another coronary artery. No irreversible complications were recognized on both tests. We should firstly perform spasm provocation tests in the LCA and we may be able to diagnose another vessel spasm by performing the complete spasm provocation tests after the administration of nitrates to relieve provoked spasm in the first attempt.

Complete definite positive spasm on acetylcholine spasm provocation tests: comparison of clinical positive spasm.

In the clinical grounds, patients with ≥90 % luminal narrowing during acetylcholine (ACh) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90 % luminal narrowing when performing ACh tests, retrospectively. We performed 763 ACh tests over 13 years (2001-2013). We analyzed chest symptoms and positive ischemic ECG changes during ACh tests. More than 90 % luminal narrowing was found in 441 patients (57.8 %) including 355 patients in the right coronary artery (RCA) and 363 patients in the left coronary artery (LCA). Chest symptom was observed in 386 patients (87.5 %) including 293 patients in the RCA and 304 patients in the LCA. ST elevation was found in 161 patients including 110 in the RCA and 85 patients in the LCA, while ST depression was recognized in 146 patients including 119 patients in the RCA and 117 patients in the LCA. Three quarter of patients with ≥90 % luminal narrowing had significant ischemic ECG changes, whereas two-third of patients with ≥90 % luminal narrowing complained usual chest pain accompanied with significant ischemic ECG changes. Unusual chest symptom was complained in 7.3 % patients with ≥90 % luminal narrowing. Neither chest symptom nor ECG changes were found in 30 patients (6.8 %) with ≥90 % luminal narrowing. A third of these patients had ischemic findings on non-invasive tests before catheterization and six patients had subtotal or total occlusion. We should realize some limitation to define positive coronary spasm based on the ischemic ECG change and chest symptom during ACh tests.

Maximal acetylcholine dose of 200 µg into the left coronary artery as a spasm provocation test: comparison with 100 µg of acetylcholine.

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.

Catheter-induced Spasm in the Proximal Right Coronary Artery.

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.

Cardiogenic Shock due to Pulseless Electrical Activity Arrest Associated with Severe Coronary Artery Spasm.

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.

Approximately half of patients with coronary spastic angina had pathologic exercise tests.

OBJECTIVES: We examined the clinical usefulness of treadmill exercise tests (TETs) in diagnosing coronary spastic angina (CSA). METHODS: 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%). RESULTS: 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%, p<0.001). Moreover, ST elevation was more frequent in patients with organic stenosis than those without fixed stenosis (27.3% vs. 1.2%, p<0.001). 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. CONCLUSIONS: 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.

Silent coronary spastic angina: A report of a case.

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 (2.0-3.0 mm)], when intracoronary injection of 50 µg 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. .

Sequential spasm provocation tests might overcome a limitation of the standard spasm provocation tests.

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: Sequential spasm provocation tests might overcome a limitation of standard spasm provocation tests.

One of six patients with non-ischemic heart disease exhibit provoked coronary spasms: non-ischemic heart disease associated with ischemia?

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<0.001). CONCLUSION: Physicians should perform spasm provocation tests in patients with IHD as well as non-IHD with non-ob-CAD, as one of six non-IHD patients in this study exhibited provoked coronary spasms.

Spasm provocation tests performed under medical therapy: a new approach for treating patients with refractory coronary spastic angina on emergency admission.

Objective There are no objective methods for evaluating the severity of vasospasms in patients with refractory coronary spastic angina (R-CSA) under adequate medical therapy. We examined whether spasm provocation tests performed under adequate medication are useful for evaluating the severity of disease in R-CSA patients on emergency admission. Methods and Results We performed spasm provocation tests before and after the administration of medical therapy in eight R-CSA patients, including one ventricular fibrillation survivor (VF-S) and seven patients with unstable angina (UAP) on emergency readmission. We also performed these tests only after medical therapy on urgent admission in four R-CSA patients, including two patients with UAP, one patient with VF-S and one patient with acute coronary syndrome. All 12 R-CSA patients had been medicated with ≥ 2 vasodilator drugs. Positive coronary spasms were defined as >99% transient narrowing. The coronary artery spasms disappeared in three patients under medication, and mitigation of vasospasticity was observed in three patients. In these six cases we continued the same medications. Meanwhile in two patients, we recommended a consultation for psychosomatic medicine. In contrast, the remaining six R-CSA patients exhibited higher levels of vasospasticity, irrespective of the administration of aggressive medical therapy, in which the doses of vasoactive drugs were increased in order to suppress coronary artery spasms. Conclusion In some R-CSA patients on emergency admission, performing spasm provocation tests under medical therapy is useful for determining the subsequent treatment strategy. Therefore, this test may become a new tool in the treatment of R-CSA.