Alcohol-induced variant angina and considerations of its mechanism: a case report]

A 64-year-old man had episodes of angina pectoris several hours after ingestion of alcohol. Otherwise, anginal attacks never occurred. He was diagnosed as having variant angina based on the typical ST elevation in leads II, III and aVF during the anginal attacks. We performed an alcohol challenge test on his 4th admission day. He was given 540 ml of "sake" at 6:00 p.m. and anginal attacks with ST elevations occurred 9.5 hours after its ingestion. The peak value of plasma ethanol was 136 mg/dl at 9:00 p.m. and it returned to 0 when angina occurred. By alcohol ingestion, urinary excretion of Mg increased in association with a slight decrease in serum Mg. The ratio of serum Ca to Mg was increased from 4.0 at the control state before taking alcohol to 4.5 at the occurrence of anginal attack. Mg content in red blood cells and in plasma catecholamines did not differ between before and after ingesting alcohol. We concluded that the change in the extracellular Ca-Mg equilibrium may contribute to the mechanism of alcohol-induced variant angina.     

Increased fibrinopeptide A during anginal attacks in patients with variant angina

It is not known whether coronary vasospasm is associated with coronary thrombosis. In this study, plasma levels of fibrinopeptide A during anginal attacks in 24 patients with variant angina were examined. A hyperventilation test was used to induce angina. Hyperventilation induced angina and ST segment elevation (AST: 0.32 +/- 0.14 mV, p less than 0.01) in eight patients with variant angina. Fibrinopeptide A increased from 0.75 +/- 0.27 at control to 7.8 +/- 4.4 ng/ml (p less than 0.01) during anginal attacks in these eight patients. In addition, four patients had spontaneous attacks of angina; they also had elevated levels of fibrinopeptide A during attacks (from 2.0 +/- 1.2 at control to 21.9 +/- 18.0 ng/ml [p less than 0.01] during attacks). Hyperventilation did not induce either angina or ST segment elevation in 12 of the patients with variant angina. Fibrinopeptide A levels did not change with hyperventilation in these patients. To determine whether elevated plasma levels of fibrinopeptide A were associated with angina, the plasma levels of fibrinopeptide A were examined during exercise-induced angina in seven additional patients with stable effort angina. They all developed angina with treadmill exercise; however, plasma fibrinopeptide A did not change. Therefore, only the patients with variant angina demonstrated elevated levels of fibrinopeptide A during anginal attacks. These findings suggest that coronary vasospasm associated with myocardial ischemia may induce stasis of blood, resulting in fibrinogen-fibrin conversion in the coronary vessels.     

Prinzmetal's variant angina: Hemodynamic and angiographic observations during pain

Hemodynamic and angiographic data obtained during pain from four patients with Prinzmetal's variant angina are reported. The left ventricular pressure-time index did not increase before or during attacks of angina in three of the four patients; left ventricular systolic performance was impaired during pain in all three. In one of these three patients left ventricular pressure-volume data obtained during angina suggested a reduction in diastolic compliance; in another, pain and S-T segment elevation were present during coronary arterial spasm. The fourth patient had an increase in both arterial blood pressure and heart rate before an attack; in this patient coronary arterial spasm could not be demonstrated during the period of pain and S-T elevation. The data presented suggest that hemodynamic factors that increase the myocardial Oxygen requirements are absent and that coronary arterial spasm is present in some, but not all, patients with variant angina.     

Continuous electrocardiographic recording in Prinzmetal's variant angina pectoris. A report of four cases

Four patients with Prinzmetal's variant angina pectoris were subjected to continuous electrocardiographic recording. In three of them several episodes of ST segment elevation unaccompanied by pain were recorded. In one patient, identical electrocardiographic alterations were observed both in presence or in absence of pain, while in the others a good correlation was evident between pain and severity of the electrocardiographic abnormalities. In two patients transmural myocardial infarction complicated the course of the angina. In contrast to the classical findings, in these patients the attacks of chest pain did not cease after the infarction, but became more frequent and severe. The electrocardiographic alterations of the anginal episodes occurred in the same myocardial areas involved by the infarction, so that a reversible superposition of electrocardiographic signs of acute ischaemia on those of recent necrosis was observed.Continuous electrocardiographic recording provided the best means of investigation of these patients with the variant form of angina pectoris.     

Inhibition of vasospastic angina by alcohol ingestion

A 66-year-old man having a long history of angina on effort has started to show frequent episodes of angina at rest since 6 months ago. He noticed that chest pain was uncommon after taking alcohol. A variant form of angina pectoris (variant angina) was diagnosed by documentation of typical ST elevation during anginal attack and also by inducing coronary arterial spasm with intracoronary administration of ergonovine maleate. Ambulatory ECG monitoring revealed frequent ST elevation during sleep. Since the history suggested that alcohol ingestion could be effective for preventing variant angina, this effect was examined by giving 540 ml of "sake" in the evening. Variant angina was inhibited, while plasma ethanol was detected. The plasma ethanol reached its peak value as 152 mg/dl at 10 o'clock pm and returned to zero after 12 hours. When ethanol disappeared in the plasma, variant angina recurred again. Although the precise mechanism for inhibition of variant angina by alcohol ingestion is not clear, alcohol or its metabolite such as acetaldehyde seems to be able to inhibit coronary arterial spasm.     

Books received

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.     

Changes in bradykinin level in coronary sinus blood after the experimental occlusion of a coronary artery

In order to study whether bradykinin is responsible for anginal pain, its level in the coronary sinus blood was determined in the dogs after experimental ligation of the anterior descending artery. A marked elevation of bradykinin level and a slight decrease of bradykininogen occurred after the ligation, while bradykininase increased to some extent. The bradykinin content in the ischemic area, estimated from its level in the coronary sinus blood and coronary sinus blood flow, was in the range reportedly sufficient to produce pain. The elevated bradykinin level continued for about 10 minutes, almost coinciding with the duration of the attack of angina pectoris. The results obtained showed also that the increase of bradykinin is induced directly or indirectly by lowering of pH and Po₂ in the ischemic area.     

The relation of the systolic blood pressure and heart rate to attacks of angina pectoris precipitated by effort

Attacks of angina pectoris were induced in thirty-five patients by exercise under standardized conditions. The systolic blood pressure and heart rate were determined at half-minute intervals during and following such exercise. In this manner it was possible to determine the systolic blood pressure and heart rate not only during attacks of angina pectoris but also immediately before and at the very onset of the paroxysms of pain.     

Effect of a new calcium antagonist, nilvadipine, on variant angina pectoris evaluated by 24-hour Holter electrocardiography

The clinical effect of nilvadipine, a new calcium antagonist, was investigated in a single blind trial in 19 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during observation periods and during two treatment periods when the drug was given in doses of 4 mg twice a day or 4 mg 3 times a day. The frequency of anginal attacks and the consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with those in the observation period before treatment, but in the observation period after treatment tended to increase in comparison with those during the second treatment period. The frequency and duration of ST-segment elevation and the maximum ST-segment elevation confirmed by Holter electrocardiography also improved significantly in both treatment periods, compared with those in the observation period before treatment. Our findings show that nilvadipine is effective for variant angina pectoris at doses of 4 mg twice a day.     

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.     

Comparative study of myocardial ischemia during angina at rest and on exertion using thallium-201 scintigraphy

To compare the results of thallium-201 myocardial scintigraphy during angina at rest with those observed during effort angina, 81 patients were selected in whom the existence of acute myocardial ischemia was indicated both by typical transient S-T segment or T wave changes and by typical anginal pain. In these patients, scintigrams were obtained during 58 attacks of angina on effort (group 1) and during 40 attacks of angina at rest (group 2); 16 patients were studied during both types of angina. The attack at rest was spontaneous in 20 patients and induced by ergonovine maleate in 20 patients.In the presence of S-T segment elevation or transient normalization of inverted T waves, scintigrams were positive in all 24 studies at rest and in 19 of 20 studies during exercise. By contrast, in the presence of S-T segment depression scintigrams were positive in 14 (95 percent) of 15 studies during angina at rest, but in only 20 (53 percent) of 38 during angina on effort. Neither the degree of S-T segment changes nor their duration after injection of thallium was significantly different in resting studies relative to exercise studies, but the heart rate and double product were consistently higher during exercise.The marked difference in sensitivity in detecting ischemia in angina at rest with S-T segment depression compared with detection during exertional angina, even in the same patients, suggests that different pathogenetic mechanisms are responsible for the attack. Conversely, a similar mechanism operating in angina at rest and on exertion during S-T segment elevation and normalization of T waves is suggested by the similarity of thallium-201 scintigraphic findings in this situation. The findings are compatible with the hypothesis of a regional reduction in myocardial blood flow in angina at rest, independently of the direction of S-T segment change, and in exertional angina with S-T segment elevation or normalization of inverted T waves; they suggest an inadequate increase in myocardial blood flow in angina on effort with S-T segment depression.     

Pure arrhythmic form of the pre-infarction syndrome or spasm responsible for myocardial necrosis

A 74 years old man was admitted as an emergency for syncopal attacks due to recurrent ventricular fibrillation (VF). These attacks were observed at the height of myocardial ischaemia as shown by ST elevation in Leads II, III and RV without associated anginal pain. Inferior myocardial infarction occurred during recurrent VF on the 4th day; the outcome was favourable. Coronary angiography was performed on the 10th day and showed double vessel disease; ergometrine (0.2 mg) induced anginal pain and ST elevation in Leads II, III and AVF. A good clinical result was obtained by calcium antagonists with an 18 months follow-up. Coronary spasm, documented in this case by the ergometrine provocation test, is now recognised as a cause of resting angina, effort angina and also some cases of myocardial infarction. This report suggests that coronary spasm may also induce apparently isolated severe ventricular arrhythmias without associated chest pain, which raises the question as to whether arrhythmias induced by spasm could play a primary role in aggravating myocardial ischaemia, leading to myocardial infarction.     

Continuous electrocardiographic recording in Prinzmetal's variant angina pectoris: A report of four cases

Four patients with Prinzmetal''s variant angina pectoris were subjected to continuous electrocardiographic recording. In three of them several episodes of ST segment elevation unaccompanied by pain were recorded. In one patient, identical electrocardiographic alterations were observed both in presence or in absence of pain, while in the others a good correlation was evident between pain and severity of the electrocardiographic abnormalities. In two patients transmural myocardial infarction complicated the course of the angina. In contrast to the classical findings, in these patients the attacks of chest pain did not cease after the infarction, but became more frequent and severe. The electrocardiographic alterations of the anginal episodes occurred in the same myocardial areas involved by the infarction, so that a reversible superposition of electrocardiographic signs of acute ischaemia on those of recent necrosis was observed.Continuous electrocardiographic recording provided the best means of investigation of these patients with the variant form of angina pectoris.     

心肌缺血的叠加在心绞痛中的作用

本文依据对冠心病患者心绞痛发作前后的动态心电图的分析,提出心肌缺血的叠加是一种较常见的临床现象,其中由阈下心肌缺血间的叠加诱发心绞痛可分为三种类型:(1)先有劳力诱发的阈下心肌缺血后与冠脉供血减少所致心肌缺血相叠加。(2)先有冠脉供血减少所致阈下心肌缺血后与劳力诱发心肌缺血相叠加。(3)劳力诱发阈下心肌缺血间的叠加。结果提示,阈下心肌缺血及其叠加效应是造成心绞痛阈值多变的主要原因之一。     

ST-segment depressions correlate in patients with hypertensive heart disease with spontaneous changes in blood pressure]

In 15 patients with essential hypertension, anginal pain, and angiographically excluded coronary artery disease 24-h monitoring of the ST-segment and blood pressure was performed. 26 episodes with ST-segment depressions 0400.1 mV were recorded in 11/15 patients. In 10/26 episodes with ST-segment depressions blood pressure was elevated above 150/95 mm Hg or by more than 20% as compared to three successive measurements before the ST-segment depressions. Heart rate was increased by more than 20% in 20/26 ST-segment depressions. During 9 periods with ST-segment depressions angina pectoris was reported; in addition 27 anginal attacks without ST-segment depressions were observed. A significant, positive correlation between the diastolic (p less than 0.005) and systolic (p less than 0.02) blood pressure and the extent of the ST-segment depression was observed. These correlations imply a patho-physiological meaning of ST-segment depressions in hypertensive patients.     

The effect of timolol vs placebo on angina pectoris

The effect of timolol vs placebo on the frequency of anginal episodes, nitroglycerin consumption and exercise performance was investigated in a double-blind, randomized, crossover study in 23 patients with angina pectoris. The optimal dose of timolol (10-30 mg twice daily) for each patient was titrated by exercise studies. Compared with placebo, timolol decreased the weekly number of anginal attacks and the weekly number of nitroglycerin tablets consumed, reduced the resting heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate, decreased the heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate at the onset of angina pectoris or marked fatigue, prolonged exercise duration, and diminished electrocardiographic evidence of myocardial ischemia. Timolol is an excellent antianginal agent when prescribed twice daily, with the optimal dose titrated by exercise studies.     

Hemodynamic observations in patients with unstable angina pectoris

Brachial and pulmonary arterial pressures were monitored for 48 hours in 26 patients with unstable angina pectoris and documented occlusive coronary artery disease. The circulatory response during 56 episodes of spontaneous anginal pain permitted the division of responses into three distinctive hemodynamic subsets. Patients in group I had an increased heart rate only with the spontaneous attack of angina; patients in group II had associated increases in brachial arterial pressure and slight increases in heart rate during the episodes of pain; patients in group III demonstrated increases in both brachial and pulmonary arterial diastolic pressures with minimal changes in heart rate. Resting hemodynamic data during pain-free periods were normal in 25 of 26 patients. Patients in all groups who had more than one episode of pain had similar hemodynamic responses to the first and later episodes. Although myocardial hypoxemia appears to be responsible for the spontaneous attack of angina, the hemodynamic responses to the attack varied but were highly specific for any one patient.Our observations suggest that there may be various pathogenic mechanisms for “spontaneous” or resting angina in patients with occlusive coronary artery disease but that the mechanism and associated hemodynamic changes may be specific for individual patients.     

Vasospastic ischemic mechanism of frequent asymptomatic transient ST-T changes during continuous electrocardiographic monitoring in selected unstable angina patients

Asymptomatic episodes of ST segment and/or T wave changes are often reported during Holter monitoring in patients with angina pectoris. However, the interpretation of such changes is debated relative to silent myocardial ischemia. We studied 11 patients admitted to the CCU because of frequent episodes of unstable anginal attacks who had undergone repeated periods of Holter monitoring, characterized by predominantly occurring asymptomatic episodes of ST segment and/or T wave changes associated with less frequent typical anginal attacks. In a total of 89 days of Holter monitoring, the patients evidenced 520 episodes of transient ECG changes including 180 of ST elevation, 73 of ST depression, and 267 of T wave alterations. Only 12% of episodes were symptomatic. Coronary injection during asymptomatic ST-T changes was performed in eight patients. In six it was possible to document spontaneous coronary spasm. In seven patients ergonovine administration induced anginal pain, ST-T changes, and coronary spasm. In all patients the anginal attacks completely disappeared with medical treatment and the asymptomatic episodes were abolished in six and reduced in four. Our findings support the hypothesis that in certain selected unstable anginal patients, transient asymptomatic ECG changes are caused by acute myocardial ischemia.     

Pseudostabilization of unstable angina pectoris: disappearance of symptoms in persistence of silent myocardial ischemia

We studied a patient hospitalized with unstable angina pectoris; ST-segment analysis during Holter ECG revealed several silent ischemic attacks despite complete disappearance of anginal symptoms under medical treatment. Prior to cardiac catheterization the patient went into acute myocardial infarction. Immediate intravenous thrombolysis and subsequent angioplasty of a high-grade stenosis abolished the ischemic events. ST-segment analysis during Holter ECG offers a method to detect ischemic events despite the disappearance of anginal symptoms in the clinical course of unstable angina pectoris. This technique might therefore identify patients with unstable angina pectoris at higher risk for further cardiac events.     

Changes in angina threshold induced by administration of ergonovine maleate during pacing in patients with chronic exertional angina

It is widely accepted that the occurrence of chest pain and/or ST segment elevation during ergonovine testing is a hallmark of abnormal coronary constriction. However, the negativity of this test cannot be considered as an incontrovertible proof of the absence of coronary sensitivity to vasoconstriction. Indeed, it could only indicate that the resulting effect is inadequate to critically reduce coronary blood flow. To test this hypothesis we studied 12 patients with proven coronary artery disease and negative ergonovine test who had complained of chronic exertional angina pectoris and referred variable threshold for the occurrence of pain. They were submitted to atrial pacing (starting from 90 bpm, with 10 bpm increments every 2 min) before (control) and after ergonovine administration (total dose = 0.675 mg). Time, heart rate and rate pressure product were evaluated at the onset of angina and significant ischemia (0.1 mV ST segment depression). After ergonovine, angina was achieved earlier (405 +/- 173 vs 526 +/- 180 sec, p less than 0.005) than during control and at a lower heart rate (116 +/- 15 vs 131 +/- 15 bpm, p less than 0.001) and rate pressure product (15.8 +/- 2.0 vs 18.8 +/- 2.3 X 10(3) U, p less than 0.001). Changes in anginal threshold were widely variable among cases being that the time to onset of pain was dramatically reduced in certain patients but unchanged in one. Similar results were obtained when substituting the ischemic to the anginal threshold. Thus, negativity to ergonovine testing does not imply the absence of coronary constriction which may be revealed when increasing myocardial oxygen demand by atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)