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.     

Severe coronary artery spasm can be associated with hyperthyroidism

BACKGROUND: Coronary artery spasm is not infrequently seen in Korea. Most of the patients with coronary spasm show a focal spasm in coronary angiography. However, the cause of the disease is not well known. There have been a few anecdotal case reports of coronary artery spasm associated with hyperthyroidism, but there has not been a report concerning a large series of such patients. Over a period of 5 years and 8 months, we experienced eight patients having the diffuse or severe type of coronary artery spasm in association with hyperthyroidism. METHODS: We investigated the characteristics of the patients with coronary artery spasm, which was diagnosed by coronary angiography or by provocation with an intracoronary injection of acetylcholine or ergonovine. The demographic data, coronary angiographic findings, thyroid function test results, and the follow-up clinical data of the eight patients having coronary artery spasm associated with hyperthyroidism were analyzed. RESULTS: All eight patients had Graves' disease. In six patients, the coronary arterial vasoconstriction developed during the coronary angiography without an injection of ergonovine. In three patients, the left main stem coronary artery was involved in the spasm. Among these eight patients, five were female, and all of these female patients were < or = 51 years old. All of the patients were treated with anti-thyroid medications, calcium channel blockers, and long-acting nitroglycerines; they all remained free of chest pain during the median follow-up period of 5 years. CONCLUSIONS: A severe form of coronary artery spasm could be associated with hyperthyroidism. A high level of suspicion and the thyroid function study should be mandatory for patients with coronary artery spasm, especially for the young female patients.     

Angina in thyrotoxicosis. Thyroid-related coronary artery spasm

Ischemic heart disease is a common complication of thyrotoxicosis, although the exact mechanism has not been defined. A case is reported of angina and thyrotoxicosis in which the angina was reproduced by coronary artery spasm induced by ergonovine maleate, relieved by thyroid ablation, and reactivated by postablative thyroid replacement. Coronary arteriography did not show significant stenoses prior to ergonovine injection. Possible mechanisms of coronary artery spasm in thyrotoxicosis are briefly discussed. Hyperthyroidism should be considered as a cause of angina in any patient with rest pain and normal coronary arteries.     

Importance of coronary artery spasm in alcohol-related unexplained syncope.

To examine the role of coronary artery spasm in patients with syncope after alcohol ingestion, we performed an intracoronary ergonovine provocation test in 7 male patients (39 to 73 years old, mean 54 years) with alcohol-related syncope which remained unexplained despite noninvasive cardiovascular and neurological examinations. No patients had structural heart disease or significant coronary artery stenosis. Ergonovine was continuously infused into each coronary artery at a rate of 10 micrograms/min for up to 5 min. Coronary artery spasm with ST-segment elevation was induced in 4 of 7 patients. Chest pain before syncope or history of chest pain were not present in 3 of 4 patients with a positive ergonovine test. Multivessel coronary artery spasm was induced in 3 patients. One patient presented with triple vessel coronary artery spasm progressing to near syncope as a result of profound hypotension and ventricular tachycardia during provocation. Coronary artery spasm was promptly relieved by intracoronary isosorbide dinitrate infusion. All patients with a positive ergonovine test were treated with calcium antagonist and did not experience syncope during follow-up. These results suggest that coronary artery spasm is one of the important causes of syncope after alcohol ingestion.     

Generalized spasm of the right coronary artery after successful stent implantation provoked by intracoronary administration of ergonovine

Coronary spasm may be one of the reasons for the appearance of chest pain after successful percutaneous coronary interventions, and is potentially hazardous when myocardial ischemia occurs. Coronary spasm can be diagnosed by intracoronary administration of ergonovine as a selective spasm provocative test. We report here the case of a patient who had chest pain and ST segment elevation 10 days after successful right coronary artery stent implantation. Repeat angiography was performed, with results of no in-stent stenosis and no stenosis in other segments. Since coronary artery spasm was considered as a possible reason, a spasm provocative test was attempted. Following ergonovine administration (total dose, 50 mug) into the right coronary artery, severe spasm with 99% stenosis developed over the whole artery except the stented segment. Isosorbide dinitrate was injected immediately, and the provoked spasm was soon relieved. Intravascular ultrasound revealed no neointima at the stented segment and diffuse and mild low-echogenic concentric plaque at the distal as well as proximal segment of the stent. Most reports regarding coronary artery spasm provocative tests have focused on focal lesions before interventional therapy, or during interventional procedures. Although it is quite rare, potential coronary spasm should be considered when chest symptoms recur after percutaneous coronary interventions without angiographic representation.     

Nifedipine blockade of ergonovine-lnduced coronary arterial spasm: Angiographic documentations

To determine whether calcium-flux blockade with nifedipine blunts coronary vasospasm, four patients with angiographically demonstrable coronary arterial spasm in the absence of Significant fixed coronary arterial stenosis were evaluated with coronary arteriography before and after treatment with nifedipine. After initial coronary arteriography, ergonovine was administered in successive doses of 0.05, 0.1 and (when necessary) 0.2 mg intravenously at 3 minute intervals. Three patients had symptomatic high grade focal coronary arterial spasm with electrocardiographic changes, and the fourth exhibited asymptomatic 60 percent constriction of the left anterior descending coronary artery. A maximal ergonovine challenge was repeated 30 minutes later after each patient had been pretreated with a 20 mg sublingual dose of nifedipine. Under these conditions, no patient had chest pain or electrocardiographic changes. Furthermore, neither focal nor diffuse coronary arterial spasm was demonstrable angiographically after the second challenge. Thus, in each case, a single dose of nifedipine precluded the angiographie expression of ergonovine-provoked coronary arterial spasm.     

Reduction of coronary blood flow during coronary artery spasm occurring spontaneously and after provocation by ergonovine maleate

A 50-year-old man suffering from recurrent chest pain accompanied by transient ST-segment elevation developed spasm of the left anterior descending coronary artery after receiving ergonovine maleate. During spontaneous chest pain, thermodilution coronary sinus blood flow fell from 96 ml/min to 46 ml/min, while the coronary sinsu arteriovenous oxygen difference widened from 9.82 volumes percent to 11.3 volumes percent. During spontaneous relief of pain, coincident with resolution of the ST-segment changes, coronary sinus blood flow gradually rose to 135 ml/min, while coronary sinus arteriovenous oxygen difference narrowed to 6.82 volumes percent. Similar aterations in coronoary sinus blood flow accompanied chest pain provoked by ergonovine maleate. A thallium-201 scan confirmed a perfusion defect in the distribution the left anterior descending coronary artery. Thus, coronary artery spasm can produce a marked deficity in coronary blood flow that is associated with increased myocardial oxygen extraction; release of spasm creates a hyperemic response.     

Acetylcholine- and ergonovine-induced coronary microvascular spasm reflected by increased coronary vascular resistance and myocardial lactate production

Diagnosis of coronary microvascular spasm remains largely speculative because it has been mostly based on chest pain and electrocardiographic ST-segment shift with slow filling of contrast medium into the coronary artery. A patient with resting chest pain and normal coronary angiograms underwent provocative tests with intracoronary acetylcholine (ACh) and ergonovine. During the tests, coronary diameter and flow velocity in the left anterior descending (LAD) coronary artery were measured with quantitative coronary angiography and intracoronary Doppler guide wire, respectively. Vascular resistance of the LAD and lactate production were determined separately. With injections of 100 microg of ACh and 20 microg of ergonovine, chest pain occurred with ST-segment elevation in the precordial leads in the absence of epicardial coronary spasm. Coronary vascular resistance increased by 2.2- and 1.6-fold of the baseline value with ACh and ergonovine, respectively. Myocardial lactate production was noted during the ST-segment elevation. Coronary microvascular spasm was verified by the increment in coronary vascular resistance and myocardial lactate production with concomitant ST-segment elevation in the presence of normal coronary angiograms.     

Congenital absence of left circumflex coronary artery presented with vasospastic angina and myocardial bridge in single left coronary artery

Congenital absence of left circumflex coronary artery (LCX) is a very rare congenital anomaly of the coronary circulation, and few cases have been reported in the literature. We report a case of a 48-year-old male who had congenital absence of LCX presented with vasospastic angina. Routine coronary angiography showed congenital absence of the LCX, typical myocardial bridge in the mid left anterior descending coronary artery (LAD) and super-dominant right coronary artery (RCA). The dominant LAD showed a spastic appearance at the baseline coronary angiography and significant spasm was induced by incremental intracoronary acetylcholine (ACh) provocation test at mid LAD where the myocardial bridge site was observed and was extended to the distal LAD. Typical anginal chest pain was documented during the Ach provocation test and the patient was stabilized with conventional anti-anginal medication. Precise morphological and functional evaluation of the anomalous coronary artery is important for selecting the best treatment modality and better prognosis.     

Vasospastic total occlusion at the left main tract in a single coronary artery.

A 64-year-old man was admitted to hospital under the suspicion of unstable angina pectoris. Coronary angiography showed that he has a single coronary artery originating from the right coronary artery (RCA) without significant fixed stenosis. Acetylcholine was superselectively infused into the left main coronary artery (LMCA), and confirmed the coronary vasospastic occlusion associated with chest pain and elevation of the ST-segment in the precordial leads. This is the first report of the induction of a totally occlusive spasm of the LMCA of a patient with a RCA type single coronary artery, and this case suggests that spasm of the aberrant coronary artery is a potential mechanism for sudden death in patients with a single coronary artery.     

Unusual vasomotor coronary arterial responses after reversal of ergonovine induced spasm with glyceryl trinitrate.

Unusual vasomotor responses in the coronary arteries occurred in two patients after the administration of glyceryl trinitrate to relieve spasm induced by ergonovine maleate. In one patient after treatment with glyceryl trinitrate and despite dilatation of the adjoining segments a new severe reduction in diameter occurred distally to the segments of the right coronary artery where the ergonovine induced spasm developed. In the other patient the left anterior descending artery filled very slowly after the completely occlusive spasm of the right coronary artery had resolved with glyceryl trinitrate though the circumflex did not. These vasomotor changes were associated with chest discomfort and electrocardiographic abnormalities in both cases. These findings indicate that caution is needed when performing provocative tests even after the ergonovine induced spasm has been reversed with glyceryl trinitrate.     

Ergonovine testing for coronary artery spasm in patients with angiographic mitral valve prolapse

Coronary artery spasm (CAS) has been postulated to be a pathophysiologic mechanism in the production of ischemic-like chest pain and ECG changes in patients with idiopathic mitral valve prolapse syndrome. To evaluate the possible role of symptomatic CAS evoked by ergonovine maleate, this agent was administered (0.05 to 0.4 mg IV) to 24 patients with chest pain and mitral valve prolapse who had no significant (<50%) coronary artery obstruction. Symptoms, ECG and blood pressure changes were monitored in all patients following ergonovine administration. No significant changes were observed in heart rate, systolic blood pressure, or double product. Six patients developed their typical chest pain. In two of these six with chest pain, ST segment shifts >1 mm were seen. Post-ergonovine left ventricular end-diastolic pressure (LVEDP) and coronary angiographic changes were also studied in a subgroup of 12 of these patients, including five of the six chest pain responders. In the five chest pain responders, pain was associated with a significant rise in LVEDP, whereas no significant change occurred in those patients not experiencing chest pain (p<0.01). Chest pain was also associated with significant CAS (>50% lumen reduction) in two patients, each with ST segment shifts >1 mm. In summary, ergonovine stimulation failed to evoke symptoms, ECG or blood pressure changes in three quarters of mitral valve prolapse patients studied. Six patients developed chest pain. Chest pain was associated with ECG changes characteristic of CAS in two of these patients, each with angiographic CAS. Thus, symptomatic CAS induced by ergonovine was absent in the majority of these 24 patients with idiopathic mitral valve prolapse syndrome.     

Comparison of electrocardiography and thallium-201 myocardial scintigraphy for the detection of ergonovine-induced coronary artery spasm: angiographic correlation

This study was performed to determine the sensitivity of thallium imaging vs ECG monitoring for detecting coronary artery spasm noninvasively following intravenous ergonovine administration as compared to simultaneous coronary angiography. Thirty-two patients with insignificant coronary artery disease and chest pain underwent 12-lead ECG monitoring, thallium imaging, and coronary arteriography following the administration of 0.05, 0.1, 0.2, and 0.3 mg of ergonovine given 5 minutes apart or until chest pain occurred. One minute following the last dose of ergonovine, 2.5 mCi of thallium-201 was injected intravenously, and a final ECG was recorded and repeat coronary arteriography performed. Within 10 minutes following the injection of thallium, imaging was performed in the 40-degree and 70-degree left anterior oblique and anterior projections. The ECG, thallium study, and coronary arteriogram were read blindly and results were compared. The ECG, angiogram, and thallium study were read as positive if the following occurred, respectively: greater than or equal to 1 mm ST segment elevation, depression, or T wave reversal; greater than 50% vessel narrowing,; and reversible perfusion defect. Five patients were excluded from analysis because of either catheter-induced spasm, suboptimal thallium studies, or protocol violations. Of the 27 patients included for analysis, six had chest pain, five had a positive angiogram, five had a positive thallium study, and one had a positive ECG. The sensitivity of thallium vs ECG monitoring was 80% vs 25%, and the accuracy was 92% vs 80%. We conclude that thallium imaging greatly increases the noninvasive detection of ergonovine-induced coronary spasm as compared with the ECG with no loss of accuracy.     

Successful management of intractable coronary spasm with a coronary stent

Although the long-term survival of patients suffering from coronary spasm is usually excellent, serious complications can develop, such as disabling pain, myocardial infarction, ventricular tachyarrhythmias, atrioventricular block and sudden cardiac death. A 40-year-old man who had intractable chest pain from coronary artery spasm suffered ventricular fibrillation and an acute anterior myocardial infarction upon first admission. The patient underwent a coronary angiogram, which revealed a spontaneous focal spasm at the proximal left anterior descending coronary artery (LAD). He was treated by the combination of nitrate and calcium channel blocker, but continued to complain of severe chest pain despite intensive medical therapy and he had to be treated in the emergency room 5 times during an 8-month follow-up period. An ergonovine coronary angiogram was performed and an intracoronary ultrasound examination, which revealed a focal spasm at the same site of the proximal LAD with a small amount of localized eccentric atheromatous plaque. A coronary artery stent was placed in the proximal LAD and his symptoms resolved. A follow-up coronary angiogram was performed 3 years after stenting and the stent remained patent without any in-stent restenosis or spasm.     

Postmyocardial infarction angina and coronary spasm

Coronary spasm can cause chest pain, and may even culminate in a myocardial infarction, but it is not often considered a cause of chest pain in the early postinfarction period. Three patients who had chest pain early (1 day to 3 weeks) after myocardial infarction were shown to have coronary spasm with ergonovine maleate provocation. Two patients had spasm in the coronary artery associated with the acute infarction; the third had spasm in a remote vessel. Two required intracoronary nitroglycerin to establish patency in the affected vessel. It is concluded that coronary vasospasm can result in postinfarction angina.     

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.     

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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.     

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.     

High prevalence of coronary artery spasm in survivors of cardiac arrest with no apparent heart disease.

The pathogenesis of cardiac arrest in the absence of any apparent heart disease remains unclear. Based on the hypothesis that coronary spasm may be a cause of cardiac arrest in the absence of apparent heart disease, ergonovine testing and/or electrophysiologic studies (EPS) were performed to evaluate the cause of cardiac arrest. Fourteen patients resuscitated from cardiac arrest had no apparent heart disease. A spontaneous episode of angina with ST-segment elevation occurred in 4 patients while under observation. Ergonovine testing was performed in 9 patients, and coronary spasm was induced in 5. EPS were performed in 8 patients, including 3 patients with coronary spasm. No electrophysiologic abnormalities were found in the 3 patients with coronary spasm. Ventricular fibrillation was induced by programmed ventricular stimulation in 2 patients with documented ventricular fibrillation at the time of resuscitation. All but one of the patients with coronary spasm had chest pain preceding cardiac arrest or at least a history of chest pain at rest, while 4 of 5 patients without coronary spasm had no prodromal symptoms. Patients with coronary spasm had a good prognosis when treated with a Ca-antagonist and/or long-acting nitrate. In conclusion, coronary spasm is the most frequent cause of cardiac arrest in cardiac arrest survivors with no apparent heart disease. Ergonovine testing should be performed to evaluate the cause of cardiac arrest when patients have no apparent heart disease.     

Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine

Multivessel coronary spasm has been described but its incidence in patients with variant angina still remains unclear. Thirty-three patients with variant angina were studied during coronary angiographic examination with selective intracoronary injection of acetylcholine (ACh). In all but three patients, the location of ischemia during attack was determined by the electrocardiographic findings, by exercise 201Tl myocardial scintigraphy, and by two-dimensional echocardiography during a hyperventilation test, and the coronary artery (or arteries) responsible for the attack was predicted before the study. ACh induced spasm of at least one coronary artery in all but one patient. ACh induced spasm of both the left and right coronary arteries (i.e., multivessel coronary spasm) in 24 patients: in two of the four patients who were predicted to have spasm of the left coronary artery, in six of the 11 predicted to have spasm of the right coronary artery, in 13 of the 15 predicted to have spasm of both the left and right coronary arteries, and in three of the three in whom coronary artery responsible for attack had not been predicted. This ACh-induced spasm of the left and right coronary arteries occurred separately and no patients showed hemodynamic instability during attack. In one patient in whom multivessel coronary spasm had been predicted and ACh failed to induice coronary spasm, ergonovine maleate (0.2 mg) induced spasm of both the left and right coronary arteries simultaneously, resulting in severe prolonged hypotension. Nineteen of the 25 patients in whom multivessel coronary spasm was documented showed angiographically normal or nearly normal coronary arteries after administration of nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)