Diagnostic and prognostic role of nitroglycerin-induced dilation in patients with suspected vasospastic angina, combined with ergonovine provocation test.

The diagnostic and prognostic role of nitroglycerin-induced dilation (NID) combined with ergonovine provocation test in patients with suspected VSA patients is not clear. A total of 438 consecutive patients who underwent the ergonovine provocation test for the diagnosis of vasospastic angina (VSA) were enrolled. Patients with VSA (n = 52) had a significantly greater coronary response to ergonovine (- 84.3 ± 10.5% vs. - 38.4 ± 17.9%, p < 0.001) and NID (26.3 ± 31.0% vs. 12.5 ± 19.0%, p < 0.001) than non-VSA patients. However, positive NID (more than 13.8% dilation, n = 170) showed a poor accuracy (AUC 0.64 [95% CI: 0.56-0.73], p = 0.001, sensitivity 60.4%, specificity 61.3%) for the diagnosis of VSA by ergonovine provocation test. Major adverse cardiovascular events (MACE) occurred more frequently in the VSA group than in the non-VSA group (9.6% vs. 2.2%, p = 0.006). In addition, the positive NID group showed a lower rate of MACE than the negative NID group (1.2% vs. 4.3%, p = 0.021). Interestingly, the group of VSA with negative NID had poor prognosis than any other combinations (Log-rank, p < 0.0001). Although NID had a limited role in the detection of VSA defined by ergonovine provocation test, NID combined with the ergonovine provocation test has an additive prognostic role in the clinical outcomes in patients with suspected VSA.

Values of Radial Artery Provocation Tests at Different Doses of Ergonovine in the Diagnosis of Coronary Artery Spasm.

The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 µg and 100 µg of ergonovine than in 60 µg of ergonovine (all P < 0.001). The radial artery provocation test at 60 µg and 100 µg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 µg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 µg of ergonovine, 96.97% and 66.67% at 100 µg of ergonovine, and 90.91% and 95.83% at 160 µg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Rubidium-82 Positron Emission Tomography With Intravenous Ergonovine to Diagnose Vasospastic Angina.

The gold standard to diagnose vasospastic angina is intracoronary reactivity testing, which is performed selectively at dedicated centres. Noninvasive imaging with single-photon emission computerized tomography (SPECT) or echocardiography does not enable accurate localization of spasm or quantification of change in myocardial perfusion in response to an abnormal vasoreactivity. Rubidium-82 positron emission tomography myocardial perfusion imaging (82Rb PET-MPI) with intravenous ergonovine was used to diagnose refractory vasospastic angina in a patient with a complex ischemic syndrome, recent coronary stenting, and persistent atypical angina despite maximal tolerable doses of guideline-directed medical therapy.

Pharmacological spasm provocation testing in 2500 patients: provoked spasm incidence, complications and cardiac events.

Pharmacological spasm provocation tests such as acetylcholine (ACh) and ergonovine (ER) had been performed in the clinic. We retrospectively analyzed the incidence of provoked spasm, complications during testing and the cardiac events after these tests. From January 1991 and October 2018, we performed pharmacological spasm provocation tests in 2500 patients: 1810 ACh tests, 1232 ER tests, 542 both tests, and 310 ACh added after ER tests. ACh was injected in incremental doses of 20/50/100/200 µg into the LCA and 20/50/80 µg into the RCA. ER was administered as a total dose of 64 µg into the LCA and 40 µg into the RCA. When adding ACh after ER, the total dose was 50/80 µg into the RCA and 100/200 µg into the LCA. Positive spasm was defined as ≥ 90% stenosis and usual chest pain or ischemic ECG changes. Mean follow-up duration was 47.5 ± 29.9 months. Overall, provoked positive spasm was found in 1095 patients (43.8%). The incidence of positive provoked spasm during ACh testing was significantly higher than that during other tests (ACh: 48.7% vs. ER: 28.9%, Both: 24%, ACh added after ER: 33.5%, p < 0.001). Multiple spasms were remarkably more frequent during ACh testing compared with the other 3 types of testing (ACh: 28.2% vs. ER: 7.4%, Both: 4.1%, ACh added after ER: 13.2%, p < 0.001). No death or acute myocardial infarction was observed, while major complications during ACh testing were significantly more frequent than during ER testing. Readmission due to recurrent angina pectoris in spasm-positive patients was remarkably more frequent than in spasm-negative patients. The incidence of sudden cardiac death, ventricular fibrillation, and acute coronary syndrome were not different between the spasm-positive and spasm-negative groups during the follow-up periods. We could perform all spasm provocation tests without any irreversible complications. All sequential spasm provocation tests were useful for documenting coronary spasm.

Management of the third stage of labour: (for the Optimal Intrapartum Care series edited by Mercedes Bonet, Femi Oladapo and Metin Gülmezoglu).

The physiology of the third stage of labour is described. Active management reduces the risk of postpartum haemorrhage (PPH), due to the use of a uterotonic agent. Intramuscular Oxytocin 10 IU has the highest efficacy and lowest side effect profile, although ergometrine, carbetocin and misoprostol are also effective. The appropriate uterotonic in different settings such as home birth by unskilled attendants and at caesarean section is discussed. For the latter, there is less consensus on the optimal dose/route of oxytocin, this topic remaining on the research agenda. Delayed cord clamping enables transfusion of blood to the neonate and is recommended rather than early clamping. Controlled cord traction should only be performed by skilled birth attendants and confers minimal advantage in preventing retained placenta. The importance of early recognition of PPH, and preparedness, is emphasised. An approach to medical and surgical management of PPH is presented.

Clinical characteristics in patients with rest angina and hypoplastic right coronary artery.

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 < 0.001). Provoked spasm on both left anterior descending artery and LCX in patients with rest angina and H-RCA was also remarkably higher than in those without H-RCA (53.8% vs. 3.1%, p < 0,001). There were no clinical differences between patients with and without H-RCA rest angina. Two-vessel spasm (61.5% vs. 0%, p < 0.01) and LCX-provoked spasm (69.2% vs. o%, p < 0.01) were significantly higher in patients with H-RCA and rest angina than that in those with H-RCA and effort angina. In patients with rest angina and H-RCA, LCX-positive spasm was significantly higher and these patients may have a potential of high disease activity in the clinic as a coronary spastic angina.

Transitional changes of acetylcholine spasm provocation test procedures.

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.

Myocardial bridging is an independent predictor of positive spasm provocation testing by intracoronary ergonovine injections: a retrospective observational study.

The relationship between myocardial bridging (MB) and coronary spasms during spasm provocation testing (SPT) remains unclear. We aimed to investigate whether MB was correlated with the SPT by ergonovine (ER) injections in a retrospective observational study. Of the 3340 patients who underwent a first coronary angiography, 166 underwent SPT using ER injections and were divided into 2 groups: MB(+) (n = 23), and MB(-) (n = 143). MB was defined as an angiographic reduction in the diameter of the coronary artery during systole. The patients who had severe organic stenosis in the left anterior descending coronary artery were excluded. The MB(+) group more frequently had diabetes mellitus and chronic kidney disease, and a thicker interventricular septum thickness. The rate of SPT-positivity was higher in the MB(+) group than MB(-) group (56.5% vs. 22.4%, P = 0.001). A multivariate regression analysis showed that the presence of MB was independently associated with SPT-positivity (odds ratio 5.587, 95% confidence interval 2.061-15.149, P = 0.001). In conclusion, coronary spasms during provocation tests with ER independently correlated with the MB. MB may predict coronary spasms.

Intramuscular oxytocin versus oxytocin/ergometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: study protocol for a randomised controlled trial (the IMox study).

BACKGROUND: Postpartum haemorrhage remains a major cause of maternal mortality and morbidity worldwide. Active management of the third stage of labour reduces the risk of postpartum haemorrhage. Oxytocin and oxytocin/ergometrine are commonly used in the UK, with oxytocin/ergometrine being more effective at preventing moderate, but not severe, blood loss. Many guidelines specifically recommend using oxytocin for all vaginal births, as it is associated with fewer adverse events. However, a survey conducted by the Southmead Hospital Maternity Research Team revealed that 71.4% of UK obstetric units still routinely use oxytocin/ergometrine. Carbetocin is a newer medication that may be as effective but has fewer side effects. No studies have directly compared all three medications. METHODS: The IMox study aims to determine the most effective, acceptable and cost-effective drug for primary prevention of postpartum haemorrhage following vaginal birth. The IMox study is a prospective, multi-centre, double-blind, randomised trial directly comparing oxytocin, oxytocin/ergometrine and carbetocin given intramuscularly for the prevention of postpartum haemorrhage in the third stage of labour. The primary effectiveness outcome is the use of an additional uterotonic drug. Secondary effectiveness outcomes reflect maternal morbidity and mortality within the immediate postpartum period. Participant questionnaires and subjective reporting of side effects will be used to evaluate maternal acceptability. Maternal quality of life utilities will be collected antenatally, and on days 1 and 14 after birth to enable a cost-effectiveness assessment of each studied drug. Participants will be pregnant women planning a vaginal birth in six hospitals in England. Participants will be approached and invited to provide consent to participate from 20 weeks gestation until in established labour. A complete sample of 5712 participants (1904 per arm) providing data for the primary outcome will allow for a robust determination of efficacy between all three study drugs. Data will be collected until participants are discharged from the hospital and on postnatal days 1 and 14 regardless of location. All analyses will be on a modified intention-to-treat basis, and additionally repeated on a per protocol basis. Data collection commenced in Feburary 2015 and was completed in August 2018. DISCUSSION: This study is the first to directly compare oxytocin, oxytocin/ergometrine and carbetocin in the same population for the prevention of postpartum haemorrhage following vaginal birth. Furthermore, this study will be the first to directly compute health economic outcomes from such a three-way comparison. This study is limited to using short-term outcomes, and so will not provide evidence for important outcomes such as long-term maternal psychological well-being and time to next conception. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02216383 . Registered on 18 August 2014. EudraCT, 2014-001948-37. Registered on 23 September 2014. ISRCTN, ISRCTN10232550. Retrospectively registered on 6 March 2018).

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

BACKGROUND: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing. METHODS: A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion. RESULTS: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921). CONCLUSIONS: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.

Clinical efficacy of aspirin with identification of intimal morphology by optical coherence tomography in preventing event recurrence in patients with vasospasm-induced acute coronary syndrome.

Using optical coherence tomography (OCT), we found that there were morphological differences in the coronary intima between patients with vasospasm-induced acute coronary syndrome (VACS) and those with stable variant angina. We investigated whether aspirin use would protect against chest pain recurrence in patients with VACS. A retrospective cohort study was performed. Patients with ST-segment elevation who were confirmed to have VACS by a provocation test were included. OCT was performed at the index event and when chest pain recurred to assess intimal morphology. Chest pain recurrence was defined as the first revisit to the emergency room with angina. Propensity score matching was performed between the aspirin and non-aspirin groups. For 48 months, 154 patients were followed (77 patients in each group). The baseline characteristics and OCT findings were well balanced between the two groups after propensity score matching. Myocardial infarction (17 vs. 3%, p = 0.003) and chest pain recurrence (26 vs. 9%, p = 0.006) occurred more frequently in the non-aspirin group than in the aspirin group. Multiple Cox regression analysis showed that aspirin use was a significant predictor of lower risk of myocardial infarction [hazard ratio (HR) 0.13; 95% confidence interval (CI) 0.03-0.61] and chest pain recurrence (HR 0.33; 95% CI 0.12-0.71) during the follow-up period, after adjustments for relevant covariates including OCT findings. The use of aspirin may have a preventive effect on myocardial infarction and chest pain recurrence in patients with VACS. Randomized controlled trials are necessary to confirm the result.

Impact of pharmacological spasm provocation test in patients with a history of syncope.

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 (<1 year). Positive pharmacological response was observed in 48 patients, while the remaining 16 patients had negative tests. Positive spasm was defined as a transient ≥90% narrowing with ischemic electrocardiographic changes. Among the 64 patients, definite coronary spastic angina (CSA) was found in 35 patients (54.7%) and suspected CSA was found in 13 patients (20.3%). Among the 35 patients with definite CSA, 22 patients (62.9%) had chest symptoms before syncope, but 13 (37.1%) had no chest symptom before syncope. No difference in clinical characteristics was observed between the two groups. Focal spasm during pharmacological spasm provocation tests was significantly higher in patients with chest symptoms than in those without chest symptoms before syncope (54.3 vs. 12.0%, p < 0.002). CSA was observed in 75.0% of patients with a history of syncope (<1 year). Thirteen patients with definite CSA had neither chest pain nor chest pressure before syncope. We should therefore investigate coronary artery spasm as a potential etiology in patients with a history of syncope.

Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests.

Aims: Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded. Methods and results: We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients [mean age 63.0 ± 10.7 years, 40 (50%) male]. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0-60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause [12 (32.4%) vs. 2 (4.7%); P = 0.002], cardiac death [7 (18.9%) vs. 0 (0.0%); P = 0.005], and readmission for ACS [10 (27.0%) vs. 3 (7.0%); P = 0.015] as well as a worse angina status as assessed by SAQ [Seattle score: 88.0 (33.0-100.0) vs. 100.0 (44.0-100.0); P = 0.001] when compared with patients with a negative test. Conclusions: We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.

Relationships between more than 90% coronary luminal narrowing induced by ergonovine provocation test and ECG ischemic change as well as chest symptoms.

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.

Clinical outcome according to spasm type of single coronary artery provoked by intracoronary ergonovine tests in patients without significant organic stenosis.

BACKGROUND: This study aimed to evaluate clinical implications of single vessel coronary spasm provoked by intracoronary ergonovine provocation test in Korean population. METHOD: A total of 1248 patients who presented with single vessel coronary artery spasm induced by intracoronary ergonovine provocation test, excluding 1712 with negative spasms, multiple and mixed coronary artery spasms and missing data among 2960 patients in the VA-KOREA (Vasospastic Angina in Korea) registry, were classified into diffuse (n=705) and focal (n=543) groups. RESULTS: The 24-month incidences of a composite primary endpoints (cardiac death, new-onset arrhythmia, and acute coronary syndrome) were determined. Over a median follow-up of 30months, the composite primary end point occurred more frequently in the focal type patients than in the diffuse type patients (primary endpoint: adjusted hazard ratio [aHR], 1.658; 95% confidence interval [CI] 1.272 to 2.162, P<0.001). Especially, unstable angina in ACS components played a major role in this effect (hazard ratio [HR], 2.365; 95% confidence interval [CI] 1.100 to 5.087, P=0.028). CONCLUSION: Focal type of single vessel coronary artery spasm in vasospastic angina (VSA) patients is found to be associated with worse clinical outcomes. It is thought that the effect is stemmed from unstable angina among ACS rather than the other components of primary endpoint. Therefore, focal type of single vessel coronary artery spasm in patients with VSA should be more carefully assessed and managed with appropriate medication.

Gender differences in long-term clinical outcomes and prognostic factors in patients with vasospastic angina.

BACKGROUND: Men are more likely to suffer from vasospastic angina (VSA) than women; however, gender differences in the long-term prognosis of VSA patients have not been fully elucidated. We sought to investigate clinical outcomes and predictive factors of VSA patients according to gender. METHODS: A total of 986 patients (838 men and 148 women) with a positive result on intracoronary ergonovine provocation test between January 2003 and December 2014 were analyzed. The primary outcome was major adverse cardiac events (MACE), defined as a composite of cardiac death, acute myocardial infarction, revascularization, or rehospitalization due to recurrent angina. RESULTS: Women were younger and showed a lower prevalence of smoking or fixed coronary stenosis than men. The risk for MACE was similar between male and female patients (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65-1.39; p=0.79). In multivariable prediction models for MACE, high-sensitivity C-reactive protein (hs-CRP) level was a significant predictor of MACE in male patients (HR, 1.95; 95% CI, 1.25-3.06; p=0.003), but there was no significant predictor in female patients. There was a significant interaction between hs-CRP level and MACE rate across genders (interaction p=0.02). CONCLUSIONS: Long-term clinical outcome was not different between genders. Hs-CRP was an important predictor of long-term clinical outcomes in male patients with VSA, but not in female patients.

Safety of intracoronary provocative testing for the diagnosis of coronary artery spasm.

AIMS: Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary artery spasm. METHODS AND RESULTS: Review of all relevant publications using MEDLINE and EMBASE databases yielded 10 publications, totalling 9,444 patients. Prevalence of provoked spasm varied from 2.3% to 54.7% of patients tested in the selected studies. The wide variability in prevalence was due to heterogeneity of study populations and provocation protocols. No deaths were reported. Overall occurrence of major (0.8%) and minor (4.7%) complications for i.c. pharmacologic testing was low. Compared to ERGO, ACh showed significantly higher rate of major (1.09% vs 0.15%; p<0.001) and minor complications (5.87% vs 2.36%; p<0.001). CONCLUSION: Provocative testing with i.c. ACh or ERGO are safe and can facilitate the diagnosis of inducible coronary artery spasm during diagnostic coronary angiography. These tests should be part of the routine armamentarium of interventional cardiologists.

Differential Incidence and Morphology of Spasm According to Coronary Arterial Location by Intracoronary Ergonovine Spasm Provocation Testing.

BACKGROUND: We reported less provoked spasm in the left circumflex artery (LCX) by acetylcholine testing compared with the left anterior descending artery (LAD) and right coronary artery (RCA), so we investigated the clinical characteristics of provoked spasm in the LCX by ergonovine (ER) testing.Methods and Results:We retrospectively analyzed 1,185 consecutive cases of intracoronary ER testing during 25 years. Maximal ER dose was 64 µg into the left coronary artery (LCA) and 40 µg into the RCA. Positive spasm was defined as a transient ≥90% narrowing and usual chest symptoms or ischemic ECG changes. Positive provoked spasm was recognized in 347 patients (29.3%), including 207 RCA spasms, 166 LAD spasms, and 79 LCX spasms. Spasm was provoked in the LCX significantly less than in the other vessels (P<0.001). LCX-provoked spasm was obtained in 79 patients consisting of 16 patients (20.3%) with triple-vessel spasm, 38 patients (48.1%) with double-vessel spasm and 25 patients (31.6%) with single-vessel spasm. Less than 70% patients with LCX-provoked spasm had multiple spasms, whereas approximately 60% patients had single-vessel spasm in the RCA (64.3%) or LAD (59.6%). In 25 patients with LCX single-vessel spasm, 18 patients (72.0%) had a focal spasm. CONCLUSIONS: Under maximal ER dose of 64 µg into the LCA, LCX-provoked spasm occurred significantly less than spasm in the other vessels and less than 70% patients had multiple spasms.

Impact of epicardial adipose tissue volume quantified by non-contrast electrocardiogram-gated computed tomography on ergonovine-induced epicardial coronary artery spasm.

OBJECTIVE: Endothelial dysfunction of the coronary artery is thought to lead to the development of coronary spasms. Epicardial adipose tissue may be a marker of coronary atherosclerosis. This study investigated the diagnostic impact of epicardial fat volume (EFV), quantified with non-contrast electrocardiogram (ECG)-gated computed tomography (CT), on ergonovine-induced coronary spasms. METHODS: We included 97 patients with suspected coronary spastic angina who underwent ECG-gated CT and an ergonovine provocation test. The EFV was measured with CT data sets using dedicated software. Coronary spasm was defined as total or subtotal occlusion (compared with the relaxed state after nitroglycerin) that was associated with ischemic ECG changes and concurrent chest pain. RESULTS: Coronary spasms were observed in 27 patients (28%). The EFV was significantly higher in patients with spasms compared with those without spasms (175.0±57.8cm(3) vs. 129.7±57.8cm(3), p<0.01). Univariate logistic regression analyses indicated significant relationships between coronary spasms and EFV (per 10cm(3), odds ratio (OR): 1.13; p<0.01), male gender (OR: 3.34; p<0.01), and smoking (OR: 3.42; p<0.01). In the multivariate model, EFV (per 10cm(3), OR: 1.10; p=0.03) and male gender (OR: 5.94; p=0.02) remained significant predictors of coronary spasm. The optimal EFV threshold for predicting coronary spasm was 149.4cm(3), identified with a receiver operating characteristic curve. CONCLUSIONS: Increased EFV was associated with ergonovine-induced epicardial coronary artery spasms.

Overview of complications during pharmacological spasm provocation tests.

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.