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Cardiac arrest and sudden unexpected death in variant angina: complications of coronary spasm that can occur in the absence of severe organic coronary stenosis.

Experiences in 81 patients with variant angina were reviewed with the goal of determining which clinical features were associated with the greatest risk of angina-linked cardiac arrest (13 patients) or sudden unexpected death (9 patients). The risk of occurrence of one of these actually or potentially fatal events was approximately tripled by the presence of either a history of angina-linked syncope or documentation of serious arrhythmia complicating attacks. An unexpected finding was that the risk was increased 1.5-fold by the absence of high-grade organic coronary stenosis. Cardiac arrest and sudden death are important risks of variant angina, which can occur without the presence of severe organic coronary stenosis. These risks can be reduced by adequate vasodilator therapy that includes a calcium channel blocker.

Angina Pectoris, Variant↗

Circadian variation of plasma fibrinopeptide A level in patients with variant angina.

Plasma levels of fibrinopeptide A (FPA), beta-thromboglobulin (BTG), and platelet factor 4 (PF4) were examined on venous plasma samples taken every 4 hours for 24 hours in 20 patients with variant angina and 20 patients with stable exertional angina together with 24-hour Holter recordings. The mean plasma FPA levels (ng/ml) at 2:00 PM, 6:00 PM, 10:00 PM, 2:00 AM, 6:00 AM, and 10:00 AM were 4.6 +/- 1.0, 3.1 +/- 0.5, 6.1 +/- 1.6, 9.9 +/- 2.4, 8.7 +/- 1.4, and 4.2 +/- 0.8 in patients with variant angina (p less than 0.01) and 1.8 +/- 0.2, 2.3 +/- 0.3, 1.9 +/- 0.3, and 2.3 +/- 0.2 in those with stable exertional angina. In seven patients with variant angina, we also examined the effects of heparin (3,000 units), given subcutaneously at 6:00 PM, 10:00 PM, and 2:00 AM, on the plasma FPA levels and the anginal attacks. Although heparin suppressed the elevation and circadian variation of plasma FPA levels, it did not suppress the attacks and their circadian variation in these patients. Plasma FPA levels increased significantly from 3.7 +/- 0.5 to 12.5 +/- 2.7 ng/ml during or immediately after an attack in the seven patients with no heparin. On the other hand, the plasma levels of BTG and PF4 were increased in patients with variant angina as compared with those with stable exertional angina but did not show a significant circadian variation in both groups. We conclude that 1) plasma levels of FPA, BTG, and PF4 were increased in patients with variant angina as compared with those with stable exertional angina; 2) there was a significant circadian variation in the plasma levels of FPA in parallel with that of the frequency of the attacks with the peak level occurring from midnight to early morning in patients with variant angina; and 3) elevated levels of plasma FPA are the result and not the cause of coronary spasm.

Angina Pectoris↗

Thromboxane A2 as an enhancing factor of coronary vasospasticity in variant angina.

To clarify the role of thromboxane A2 (TXA2) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B2 (TXB2: a stable catabolite of TXA2) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 (8 mg/kg, i.v.), a TXA2 synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB2 levels (424 +/- 138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB2 levels (223 +/- 38 pg/ml), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB2 levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB2 levels. In 3 patients, an EM rechallenge at symptomatically quiescent stage resulted in negative test with augmented TXB2 levels being markedly decreased. These findings indicate that increased TXA2 in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA2 production in the enhancement of coronary vascular spasticity.

Adult↗

Role of percutaneous transluminal coronary angioplasty in patients with variant angina and coexistent coronary stenosis refractory to maximal medical therapy.

Percutaneous transluminal coronary angioplasty (PTCA) was performed with initial success in 7 patients with variant angina and significant (greater than 60%) coronary stenosis. The mean degree of stenosis was reduced from 77 +/- 12% to 29 +/- 15% and the mean systolic pressure gradient from 78 +/- 18 to 25 +/- 9 mmHg. Apart from a reversible spasm in one patient, PTCA was free of acute complications. Despite long-term treatment with nifedipine, nitrates, and warfarin (patients 1 to 5) or aspirin (patients 6 and 7) restenoses occurred in 4 of 7 patients. An aortocoronary bypass was necessary in 2 patients, 3 respectively 6 weeks after PTCA because of tighter restenoses than before PTCA. Another patient underwent successful repeat angioplasty after 6 weeks and remained improved. During a mean follow-up observation of 21 months (6 to 30 months), 4 patients were asymptomatic, even without medication. In one of these patients, the follow-up angiography (6 months after PTCA) demonstrated a restenosis. These results suggest that PTCA demonstrated a restenosis. These results suggest that PTCA can be performed without a higher risk of acute complications in patients with variant angina. Although the recurrence rate is high in these patients, sustained clinical improvement was achieved in a substantial percentage of patients in our study.

Adult↗

Angiographic documented coronary arterial spasm in absence of critical coronary artery stenoses in a patient with variant angina episodes during exercise and dobutamine stress echocardiography.

Dobutamine stress echocardiography is widely performed as a useful diagnostic tool in patients with known or suspected coronary artery disease. Dobutamine induced myocardial ischaemia is frequently associated with ST segment depression. ST segment elevation is uncommon and is almost always associated with prior myocardial infarction or transient total coronary occlusion. Dobutamine induced ST segment elevation in absence of significant coronary artery disease is a rare condition and is supposed to be a consequence of severe coronary artery spasm. The case of a 58 year old man with variant angina episodes at rest, during exercise test, and dobutamine stress echocardiography is reported, in whom coronary spasm without significant coronary artery stenoses was documented angiographically.

Angina Pectoris, Variant↗

Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm.

Thirteen patients with Prinzmetal's variant angina performed treadmill exercise tests in the early morning and in the afternoon of the same day. The attacks with ST elevation were induced repeatedly in all 13 patients in the early morning, but in only two patients in the afternoon. Propranolol did not suppress the exercise-induced attacks in all 13 patients. Diltiazem suppressed the attacks in all 13 patients and phentolamine in eight of the nine patients. Coronary arteriograms demonstrated that spasm occluding completely or almost completely the large coronary artery supplying the area of myocardium showing ST elevation appeared during the attacks and disappeared along with the attacks after nitroglycerin administration in all four patients in whom the attacks were induced by arm exercise in the catheterization laboratory. We conclude that there is circadian variation of exercise capacity in patients with Prinzmetal's variant angina caused by coronary arterial spasm induced by exercise in the early morning but not in the afternoon.

Adult↗

Long-term prognosis for patients with variant angina and influential factors.

Two hundred forty-five patients with variant angina were followed for an average of 80.5 months (range, 36-184 months). Survival rate at 1, 3, 5, and 10 years was 98%, 97%, 97%, and 93%, respectively. Survival rate without myocardial infarction at 1, 3, 5, and 10 years was 86%, 85%, 83%, and 81%, respectively. By univarite analysis, ST segment elevation in both the anterior and inferior electrocardiographic leads was the most important factor influencing survival, followed by use of calcium antagonists, left ventricular function, smoking, and alcohol intake. The variables that significantly correlated with survival without myocardial infarction were use of calcium antagonists, left ventricular function, extent and severity of coronary artery disease, coronary artery bypass surgery, and disease activity. Multivariate analysis using the Cox proportional hazards model showed that intake of calcium antagonists, extent and severity of coronary artery disease, and ST segment elevation in both the anterior and inferior leads were significant independent predictors of survival without myocardial infarction. We conclude that long-term prognosis for patients with variant angina is relatively good and that use of calcium antagonists improves it.

Adult↗

Transient U wave inversion during variant angina.

We studied the prevalence and clinical significance of transient U wave inversion in 43 patients with variant angina. Twenty-four patients (group A) had ST segment elevation in the anterolateral and 19 patients (group B) had this finding in the inferoposterior leads of the ECG during spontaneous angina. In none of these patients was U wave inversion present on the resting 12-lead ECG in the absence of anginal attack. During anginal attacks, U wave inversion developed in association with ST segment elevation in 16 patients (66.7%) of group A but in no patient of group B. To exclude the possibility that a transient rise of systolic blood pressure during angina caused U wave inversion, treadmill exercise testing was done in the 16 patients after the discontinuation of antianginal drugs. In 12 of the 16 patients, exercise testing did not produce angina or U wave inversion despite a marked elevation of systolic blood pressure. These results indicate that transient U wave inversion frequently develops with anterolateral ischemia but not with inferoposterior ischemia during attacks of variant angina. It is likely that transient U wave inversion was caused by myocardial ischemia but not by a rise of blood pressure during angina.

Adult↗

[Characteristics of traditional Chinese medicine syndromes in both spontaneous and variant angina. An analysis of 21 cases].

An analysis of TCM syndromes is reported in 21 cases with both spontaneous and variant angina as compared with 147 cases with effort angina. The results showed that 3 characteristic features were present, which were as follows: the Biao-Shi syndrome of cold condensation was more than that of the control group in ratio of 42.86% to 3.40%; the Ben-Xu syndrome of Yang deficiency was more and that of Qi deficiency less than those in the control group, and they were in ratio of 33.33% to 6.12% and 33.33% to 72.11% respectively. An absolute reduction of blood supply resulted from coronary spontaneous spasm in both spontaneous and variant angina causes severe chest pain during attacks as a cold condensation type. Hyperfunction of parasympathetic nerves often occurring in coronary heart disease with Yang deficiency is liable to vasoconstriction of the large coronary arteries leading to episodes of both spontaneous and variant angina. The presence of less Qi deficiency type may be related to the less impairment of cardiac function resulted from the short course in these cases and only relatively mild state of an illness, even no marked lesion in coronary arteries in a part of patients with both spontaneous and variant angina. No significant difference in TCM syndromes occurred between spontaneous and variant angina. Both Yang and Yin deficiency, as the Ben-Xu syndromes, were more present in angina of cold condensation type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of diltiazem in patients with variant angina: a randomized double-blind trial.

Effects of diltiazem of frequency of angina and nitroglycerin (NTG) consumption were studied in 12 patients with variant angina (rest pain with ST elevation). Either diltiazem in two dosage schedules (120 mg/day and 240 mg/day), or placebo was administered in a randomized double-blind program over 10 weeks. Significant decreases in angina frequency and TNG consumption were observed when diltiazem treatment periods were compared to placebo periods. Furthermore, when placebo periods following diltiazem were compared to placebo periods following placebo, significant "carry-over" effect with respect to reduced angina frequency was observed. No patient had an increase in angina frequency or TNG consumption on diltiazem compared to placebo. No "rebound effects" or changes in blood pressure or heart rate were observed. One patient complained of dry mouth on diltiazem. These findings, although in a limited number of patients, suggest that diltiazem is effective in decreasing angina frequency and TNG consumption in patients with variant angina. These encouraging results warrant evaluation of diltiazem in a larger patient population over a longer time period.

Adult↗

Factors influencing the clinical course and the long-term prognosis of patients with variant angina.

The purpose of this study was to clarify the factors influencing the clinical course and prognosis in variant angina. Also, the mechanism of acute myocardial infarction in variant angina is reviewed. The subjects were 110 patients with variant angina who, after the initial visit or admission, were observed for a period of at least 2 months, the average observation period being 68 +/- 49 months (range: 2 months-16 years). The incidence of acute myocardial infarction was 21.8% of these patients and 87.5% of the infarctions occurred within 1 month of the initial visit or admission. In variant angina, the average rate over 1 year was 2.2%; however, in classical angina the rate was 3.7% and in postinfarction angina 5.0%. The mortality rate was 5.5%, with death in the majority of cases occurring within 1 month, as in myocardial infarction. When treatment was stopped, spontaneous remission occurred in at least 26 of the 110 cases (23.6%). Beyond 3 months, the remission continued in 19 of these 26 cases. Seven cases had acute myocardial infarction in spite of the suppression of anginal attacks with administration of calcium antagonists. Apparently coronary spasm is the cause of anginal attacks, and the cause of acute myocardial infarction in patients with variant angina appears to be coronary thrombus formation.

Adult↗

Assessment of autonomic nervous activity by heart rate spectral analysis in patients with variant angina.

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Adult↗

Nifedipine therapy for coronary-artery spasm. Experience in 127 patients.

We report clinical experience with the coronary vasodilator nifedipine in 127 patients with symptoms of myocardial ischemia associated with electrocardiographic or angiographic evidence, or both, of coronary-artery spasm. In the majority of patients conventional antianginal therapy including nitrates and beta-adrenergic blockers failed, and in one third of the patients at least one episode of ventricular tachycardia developed during an attack of angina. Nifedipine (40 to 160 mg every 24 hours) significantly reduced the mean weekly rate of anginal attacks from 16 to two (P less than 0.001). Similar marked reductions in the nitroglycerin requirement were noted. In 63 per cent of the patients complete control of anginal attacks was achieved, and in 87 per cent the frequency of angina was reduced by at least 50 per cent. Nifedipine was generally well tolerated, with only 5 per cent of the patients requiring termination of the drug because of intolerable side effects. This experience with nifedipine suggests that it is a highly effective drug for the treatment of coronary-artery spasm and variant angina.

Adult↗

The exercise test in variant angina: results in 114 patients.

One hundred fourteen patients with variant angina performed bicycle exercise stress tests, and were divided into three groups. Group 1 included 37 patients with a normal exercise test. Coronary arteriography revealed absence of significant coronary stenoses in 18 patients, one-vessel disease in 17 and involvement of two or more vessels in two. Group 2 consisted of 40 patients who had ST-segment elevation during or just after exercise. Coronary arteriography in these cases revealed absence of significant coronary stenoses in nine patients, one-vessel disease in 18 and disease of two or more vessels in 13. Group 3 included 37 patients who had ST-segment depression during exercise. Absence of coronary artery disease was found in only two patients, one-vessel disease was found in 19 and disease of two or more vessels was found in 16. Sixty-one patients repeated the exercise test after a mean of 18 months after hospital discharge. Exercise-induced ST-segment elevation was no longer present in surgically or medically treated patients; ST-segment depression was still evident in all the medically treated patients, but was absent in eight of 13 patients who underwent aortocoronary bypass surgery. Exercise testing can be useful in the follow-up of patients with variant angina and in selecting patients most likely to be helped by bypass surgery.

Adult↗

Spontaneous remission is a frequent outcome of variant angina.

To assess the prevalence of spontaneous remission in variant angina, 100 patients with this diagnosis who had undergone coronary arteriography in the hospital and a follow-up of at least 1 year were studied. Patients with coronary bypass surgery or myocardial infarction were excluded. Remission was diagnosed in 45 of the 100 patients who had been angina-free and had had no treatment for more than 3 months (mean 18.3). The other 55 patients were receiving medical treatment; 37 had been angina-free for at least 6 months (mean 22.5) and angina persisted in 18. The persistent angina group had a lower prevalence of organic coronary stenoses 70% or greater: 4 of 18 versus 22 of 45 and 22 of 37 for the other two groups (p less than 0.05), and a longer history of rest angina before admission. The remission group contained more patients (17 of 45 versus 4 of 55 [p less than 0.001]) whose attacks had been documented only by provocative testing. Rest angina recurred when calcium antagonist drugs were discontinued in 15 of 51 instances, within 1 month in 11 patients and later in 4 patients. Remission was eventually attained in 35 of the 38 patients in whom these drugs were stopped. These results indicate that remission is a frequent outcome of variant angina. This fact should be considered in the evaluation of the long-term results of treatment and in the planning of care for an individual patient.

Adult↗

Intermittent coronary spasm during graded exercise.

We report a patient with Prinzmetal's angina with nearly normal coronary angiogram who not only developed severe myocardial ischemia during exercise, documented both electrocardiographically (ST elevation) and scintigraphically (with thallium-201), but also did so intermittently as the graded exercise progressed. Diagnostic coronary angiography showed spontaneous focal spasm of the proximal left anterior descending coronary artery. This unique response to exercise in a patient with variant angina suggests that factors other than catecholamine stimulation alone are active and rapidly attenuated in some patients. This phenomenon could be overlooked without appropriate electrocardiographic monitoring.

Angina Pectoris, Variant↗