Ergonovine testing in a coronary care unit

This study describes the results of ergonovine testing in 100 consecutive patients who underwent this procedure in a coronary care unit. All patients had recently undergone coronary arteriography. A bolus injection of ergonovine was administered at 5 minute intervals in the following doses (mg): 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4. The criterion for a positive test was the appearance of S-T elevation greater than 1 mm. The test was positive in all 17 patients known to have variant angina and in 18 (40 percent) of 45 patients who had a history of chest pain judged strongly suggestive of variant angina but who had no electrocardiogram recorded during pain. Of 38 patients with a history of chest pain classified as not entirely typical of variant angina, only 1 (2.6 percent) had a positive test.Of the 64 patients with a negative ergonovine test, 47 had chest pain and 25 had nausea but none had more serious complications. Ventricular arrhythmia accompanied S-T elevation in 18 of the 36 patients with a positive test but occurred in only 4 of the 64 with a negative test (p < 0.0005). No patient needed treatment with antiarrhythmic drugs. Four of the 36 patients with a positive test had serious complications: severe translent hypotension (2 patients), recurrent episodes of angina with S-T elevation (1 patient) and a subendocardial infarction (1 patient). Thus, ergonovine testing is useful in patients with a typical clinical history of variant angina but without an electrocardiogram recorded during pain. in this study, a small but definite incidence of serious complications occurred during a positive test.     

Ergonovine maleate provocative test for coronary arterial spasm

Ergonovine maleate was evaluated as a provocative agent for inducing coronary spasm during coronary arteriography. The study group consisted of 98 patients with either mild fixed obstructions of coronary luminal diameter (less than 50 percent) or normal coronary arteriograms. The test was considered positive if the drug precipitated severe coronary spasm. A positive ergonovine test occurred in 10 of 11 patients with Prinzmetal's variant angina (P < 0.02). Two of these patients had a transmural myocardial infarction in the distribution of the spastic artery. Ergonovine tests were negative in (1) the 15 control patients with no clinically suspected coronary artery disease (P < 0.001), (2) 63 of 66 patients with angina-like chest pain (P < 0.001), and (3) all 6 patients with myocardial infarction and no history of Prinzmetal's variant angina (P < 0.05). No major complications occurred as a result of this test.Thus, ergonovine maleate test is a safe, sensitive and specific method for reproducing coronary spasm in patients with Prinzmetal's variant angina and no major coronary obstructions. The results suggest that coronary spasm can be implicated as a cause of myocardial infarction in patients with normal coronary arteriograms who also have Prinzmetal's variant angina. Coronary spasm was not demonstrated in patients who had normal coronary arteriograms and a history of myocardial infarction as an isolated clinical event. Also, coronary spasm could not be demonstrated in the majority of patients who had angina-like chest pain and no major coronary obstruction.     

Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris

Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (< 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H₁ receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS). Histamine, at intravenous dose of 0.5 to 1.0 μg/kg/min, provoked CAS in four patients. In six patients neither histamine nor ergonovine provoked spasm, and these patients were considered by chronic follow-up evaluation to have noncardiac etiology for their chest pain syndrome. In one patient CAS was provoked with ergonovine but not by histamine, and one ergonovine-positive patient had an equivocally positive histamine result. Pretreatment with cimetidine (H₂ receptor antagonism) was necessary to avoid unpleasant side effects of histamine. Thus these observations indicate that histamine should be included among the specific agents capable of inducing CAS and provide new insight concerning the mechanism(s) causing variant angina pectoris.     

Limitations of ergonovine testing in patients with variant angina

Fourteen patients with variant angina underwent ergonovine testing during diagnostic coronary angiography. The clinical electrocardiographic or angiographic manifestations of coronary artery spasm could not be reproduced in six of these patients. Five patients had chest pain and transient ST-segment elevation within 4 days of the ergonovine study, including three who developed coronary spasm in the catheterization laboratory. It appears that the sensitivity of ergonovine testing in the diagnosis of coronary spasm is lower than previously emphasized.     

Ergonovine Testing in Patients with Exertional Angina

ABSTRACT. Nordlander R, Orinius E (Division of Cardiology, Department of Internal Medicine, Thoracic Clinics, Karolinska Hospital, Stockholm, Sweden). Ergonovine testing in patients with exertional angina. Acta Med Scand 1987; 221:47–52. Injection of ergonovine has been suggested as a diagnostic test in patients with suspicion of a vasospastic component in the pathophysiology of angina pectoris. However, a thorough case history has been considered by others to give the same information regarding the anginal mechanism. Therefore a bedside ergonovine test (0.075–0.675 mg i.v.) was performed in 21 consecutive patients with effort angina in order to study the relation between the outcome of the test and the case history concerning angina at rest. A coronary angiography was performed in all cases and showed significant stenoses in 17 patients and normal coronary arteries in 4. Eight patients had angina only during effort, 11 had angina both during effort and at rest and 2 patients had atypical chest pain. Ten of the 11 patients with concomitant rest angina developed chest pain at the ergonovine test and 9 coexisting ECG changes. However, these effects were about as common among the 8 patients without angina at rest: 7 developed chest pain and 4 also ECG changes. The two patients with atypical chest pain had normal coronary angiograms and in these patients ergonovine provoked the same atypical chest pain but no ECG changes. Thus, a concomitant angina at rest is a common finding among patients with severe effort angina. However, the response to ergonovine was as common in the group with only effort angina as in the group with concomitant rest angina, indicating the limited value of this test in patients with severe angina.     

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

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

Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.     

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

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

Provocative ergonovine testing in patients without obstructive coronary disease

Ergonovine administration during coronary angiography is frequently used to rule out coronary spasm as a cause of chest pain. We performed this study to determine which electrocardiographic variables (other than ST segment elevation with pain) and which chest pain characteristics might be predictive of ergonovine test outcome in patients without obstructive coronary disease. Thirty-one patients had an electrocardiogram recorded during chest pain. Three of four patients (75%) who had an ischemic electrocardiogram with pain had a positive ergonovine test while only 1 of 27 (4%) patients who had a nonischemic electrocardiogram during chest pain had a positive ergonovine test (p less than 0.001) Pain that occurred predominantly at rest was present in five of five patients with positive ergonovine tests but pain occurring predominantly at rest was also present in 76% of patients with negative ergonovine tests (85%). Prompt relief of pain with nitroglycerine was also present in all patients with a positive ergonovine test but was also seen in 58% of patients with a negative test (NS). Association of chest pain with nausea, vomiting, diaphoresis, or radiation to left arm, jaw or neck were similarly poor predictors of ergonovine test outcome. We conclude that ergonovine testing in patients without obstructive coronary disease is of low yield if an electrocardiogram recorded during pain does not show evidence of ischemia. Historical features of the chest pain are not good predictors of test outcome.     

Coronary artery spasm as a cause of chest pain in a patient with anomalous origin of the right coronary artery from the left sinus of valsalva

The cause of chest pain in patients with anomalous origin of the right coronary artery from the left sinus of Valsalva has not yet been elucidated. In the following case, this anomaly was demonstrated, upon angiography, in a patient with recurrent chest pain and a negative stress test; in addition, spasm of the left anterior descending coronary artery was documented during ergonovine provocation. To our knowledge, this is the first time coronary artery spasm has been documented in a patient with this anomaly. On the basis of this case, we recommend ergonovine testing for all angina patients with aberrant coronary arteries in whom no other cause of chest pain is found at cardiac catheterization.     

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Two patients complained of chest pain while at rest and during physical activities. However there seemed to be no direct relation between exertional angina and an increasing level of work performed, indicating that these patients had a variable threshold of angina during exercise. In one patient spontaneous chest pain was associated with transient S-T segment changes in precordial leads, and during coronary arteriography the administration of ergonovine induced spasm of the left anterior descending coronary artery. The other patient showed S-T segment elevation in inferior leads during an ergonovine-induced anginal attack and coronary arteriography revealed a spontaneous spasm of the right coronary artery. In both patients repeated exercise tests yielded different results, because the chest pain and S-T segment depression occurred at different work loads with large differences in heart rate-systolic blood pressure product.It is concluded that a variable threshold of angina during exercise is a clinical manifestation in some patients with vasospastic angina and is probably due to the difference in coronary arterial tone at the onset of exercise.     

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 ± 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patiénts, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 ± 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient.We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.     

Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant.

Coronary artery spasm plays an important role in acute ischemic events, and it has a close relationship with coronary atherosclerosis. Thus we attempted to determine the most significant risk factor for coronary artery spasm. Among 3000 consecutive patients who underwent coronary cineangiography with ergonovine maleate testing, 330 with typical angina pectoris (group 1) and 294 with old myocardial infarction (group 2) were studied. We divided each group into three or four subgroups according to the presence of fixed organic stenosis (FOS+) or a positive reaction to ergonovine maleate (coronary artery spasm [CAS]+). We examined the relationship between coronary artery spasm and eight coronary risk factors: age, sex, hypertension, diabetes mellitus, smoking, and serum cholesterol, uric acid, and high-density lipoprotein cholesterol levels. The proportion of smokers in the subgroups with CAS(+) was significantly higher than in the subgroups with CAS(-)(p less than 0.01). There was no correlation between smoking and fixed organic stenosis. According to the results of multiple regression analysis, there was a positive correlation between smoking and CAS(+) and between serum high-density lipoprotein cholesterol levels and CAS(+)(p less than 0.01). Thus we concluded that smoking is the most significant risk factor in discriminating between patients with and without coronary artery spasm.     

Myocardial ischemia due to coronary artery spasm during dobutamine stress echocardiography

Dobutamine stress echocardiography (DSE) is a useful and safe provocation test for myocardial ischemia. Until now, the test has been focused only on the organic lesion in the coronary artery, and positive DSE has indicated the presence of significant fixed coronary artery stenosis. The aim of the present study is to examine whether myocardial ischemia due to coronary spasm is induced by dobutamine. We performed DSE on 51 patients with coronary spastic angina but without significant fixed coronary artery stenosis. All patients had anginal attacks at rest with ST elevation on the electrocardiogram (variant angina). Coronary spasm was induced by intracoronary injection of acetylcholine, and no fixed coronary artery stenosis was documented on angiograms in all patients. DSE was performed with intravenous dobutamine infusion with an incremental doses of 5, 10, 20, 30, and 40 microg/kg/min every 5 minutes. Of the 51 patients, 7 patients showed asynergy with ST elevation. All 7 patients (13.7%) had chest pain during asynergy, and both chest pain and electrocardiographic changes were preceded by asynergy. These findings indicate that dobutamine can provoke coronary spasm in some patients with coronary spastic angina. When DSE is performed to evaluate coronary artery disease, not only fixed coronary stenosis, but also coronary spasm should be considered as a genesis of asynergy.     

Diagnosis of important fixed coronary stenosis in patients with variant angina by exercise tests after treatment with calcium antagonists.

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.     

Diagnosis of important fixed coronary stenosis in patients with variant angina by exercise tests after treatment with calcium antagonists

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.     

Safety of ergot stress echocardiography for non-invasive detection of coronary vasospasm.

BACKGROUND: The safety of ergonovine/ergometrine stress testing for coronary vasospasm when performed outside the cardiac catheterization laboratory (cath lab) has been questioned vigorously. AIM: To assess the tolerability and safety of ergonovine/ergometrine stress testing performed in the echocardiographic laboratory (echo lab). METHODS: We retrospectively reviewed the data prospectively collected in the echo lab of the Institute of Clinical Physiology from 1 January 1985 to 1 June 2000, from 587 tests performed on 573 patients (either ergonovine or ergometrine stress echocardiography testing). By selection, all patients had a history of chest pain, consistent with vasospastic angina, negative exercise stress testing or stress echocardiography (with dipyridamole, dobutamine or exercise), and normal or near normal resting left ventricular function. Ergonovine or ergometrine maleate was injected up to a total cumulative dosage of 0.35 mg, under continuous 12-lead electrocardiographic and two-dimensional echocardiographic monitoring. RESULTS: There were no deaths, myocardial infarctions, ventricular fibrillations or third degree AV blocks. One patient had non-sustained ventricular tachycardia associated with transient ST segment elevation 30 min after the test. Three patients had second degree AV block associated with a positive echocardiography test that was promptly reversed by nitrates administration. Transient regional myocardial dysfunction occurred in 79 patients (13%). Limiting ischaemia-independent side effects were present in 17 patients (3%): hypotension in one, arterial hypertension in five, non-sustained ventricular tachycardia in two and nausea or vomiting in ten. The test was well tolerated and echocardiograms were interpretable in 97% of the tests performed. CONCLUSION: Pharmacological stress echocardiography with either ergonovine or ergometrine is well tolerated and can be performed with relatively low risk in the echo lab in properly selected patients in whom coronary vasospasm is suspected.     

Coronary arterial spasm as a cause of exercise-induced ST-segment elevation in patients with variant angina.

Four patients with variant angina pectoris exhibited reproducible exercise-induced chest pain and ST-segment elevation. Coronary arterial spasm was documented with arteriography during exercise-induced ST-segment elevation (three patients) or after intravenous administration of ergonovine maleate (one patient). Our observations show that in patients with variant angina exercise can trigger coronary arterial spasm, thus inducing anginal pain and ST-segment elevation.     

Spectrum of exercise thallium-201 myocardial perfusion imaging in patients with chest pain and normal coronary angiograms.

Twenty-seven consecutive patients with chest pain and no significant obstructive coronary lesions on arteriography were studied with thallium-201 myocardial imaging during exercise and at rest. Fifteen of the patients had typical and 12 atypical angina pectoris. All underwent treadmill exercise electrocardiographic testing; the results were abnormal in 10 patients (37 percent), normal in 14 (52 percent) and uninterpretable in 3 (11 percent). The exercise and resting thallium-201 myocardial images were normal in 23 patients (85 percent); the results of exercise testing were normal in 12 of these patients, abnormal in 8 and uninterpretable in 3. Four patients had a perfusion defect on exercise thallium-201 myocardial imaging; the defect filled in by 4 hours in two patients but persisted in the other two. In contrast, when thallium-201 myocardial imaging was performed in 28 consecutive patients with angiographic coronary artery disease, only 5 patients (16 percent) had normal exercise and resting thallium-201 myocardial images. Therefore, thallium-201 myocardial imaging offers a more effective means of identifying patients with chest pain and no obstructive coronary artery disease than the clinical history or the exercise electrocardiographic test, or both. However, 15 percent of these patients will have abnormal exercise thallium-201 myocardial images because of factors that have not yet been identified.     

The use of ergonovine in the hemodynamics laboratory]

In our department we have reviewed the use of ergonovine maleate as a provocative agent for inducing coronary spasm during coronary arteriography. From January 1978 to December 1991 the test has been performed in 116 patients. According to their symptoms, the patients were divided into 4 groups: (A) patients with exertional angina: 16 patients (13.8%), (B) patients with angina at rest: 64 patients (55.2%), (C) patients with atypical chest pain: 29 patients (25%), and (D) patients with previous myocardial infarct: 7 patients (6%). We have subdivided the patients with angina at rest, according to the electrocardiogram recorded during pain, into: (1) 16 patients with ST-segment elevation; (2) 14 patients with ST-segment depression or T wave inversion; (3) 5 patients with electrocardiogram unchanged during angina; (4) 29 patients with no electrocardiogram recorded during angina. In 67 patients (57.7%) the coronaries were normal, 17 patients (14.6%) had mild irregularities, 26 patients (22.4%) had non critical fixed obstructions (< or = 70%), and in 6 patients (3.5%) there were fixed coronary narrowings > or = 70%. The left ventricle was normal in 85 subjects (73.2%), hypo or akinetic in 31 (26.8%). After routine coronary angiography and ventriculography, ergonovine maleate, 0.05 up to 0.4 mg, was given intravenously. The ergonovine test was considered positive when a focal spasm narrowed a normal coronary artery, or one with a mild fixed obstruction (< or = 50%) to more than 70%, or when a 70% stenosis became occluded. The development of angina and/or electrocardiographic changes were not taken as a criteria of positivity. Thirteen tests (11.2%) were considered positive.(ABSTRACT TRUNCATED AT 250 WORDS)