Circadian variation of autonomic nervous activity in patients with multivessel coronary spasm.

The present study investigated whether the circadian rhythm of sympathovagal activity is related to the severity of coronary spasm or multivessel coronary spasm. Heart rate variability was examined in 22 consecutive patients with vasospastic angina provoked by intracoronary injection of acetylcholine, who had either multivessel spasm (Group M, n=11 ) or single vessel spasm (Group S, n= 11), in 20 subjects without coronary artery disease (Group C) and 20 patients with effort angina who had organic coronary artery stenosis (Group E). The frequency domain indices were analyzed, including low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4Hz), the latter being an index of efferent parasympathetic activity, and the ratio (L/H) as an index of sympathovagal balance. The circadian variation of the parameters was analyzed by its pattern and was quantified by the difference of the mean values between daytime and nighttime. Although the HF power increased during nighttime in Groups C and S, this increase was attenuated in Groups E and M. The circadian variation of the L/H ratio (ie, a drop during nighttime) was smaller in the S and M groups than in Groups C and E. Accordingly, in Group M, the circadian variation of both sympathetic and parasympathetic nervous activity was attenuated, but in Group S, the variation of sympathetic nervous activity, but not parasympathetic nervous activity, was decreased. These data suggest that relatively enhanced sympathetic nervous activity at night may be involved in the mechanism underlying multivessel coronary spasm.     

Wavelet transform analysis of heart rate variability to assess the autonomic changes associated with spontaneous coronary spasm of variant angina

We used Wavelet transform (WT) to investigate whether variation in autonomic tone was associated with spontaneous coronary spasm in patients with variant angina by analysis of heart rate variability (HRV). Twenty-one episodes preceding ST-segment elevation were selected under Holter monitoring in 12 men and 3 women with variant angina. HRV indices were calculated at 10 second intervals with the continuous WT, and analyzed within 30 minutes preceding ST-segment elevation. High frequency (HF; 0.15 approximately 2.00 Hz) increased significantly during the 4 minutes prior to ST-segment elevation, low frequency (LF; 0.04 approximately 0.15 Hz) decreased significantly during the period from 10 to 5 minutes and increased significantly during the 2 minutes prior to ST-segment elevation, the LF/HF ratio decreased significantly during the period from 10 to 3 minutes and increased significantly during the 2 minutes prior to ST-segment elevation. The RR interval decreased significantly during the 2 minutes prior to ST-segment elevation. These results suggest that the acute variation in autonomic tone was associated with spontaneous coronary spasm in patients with variant angina. A reduction in sympathetic activity, then enhancement of vagal activity may play a key role in triggering the spontaneous coronary spasm, and the secondary activation of sympathetic activity may worsen the coronary spasm resulting in the attack.     

Alterations of autonomic nervous activity in recurrence of variant angina

OBJECTIVE: To investigate whether autonomic nervous activity is involved in the recurrence of spontaneous coronary spasm in variant angina. DESIGN: Retrospective analysis. SETTING: Cardiology department of a university hospital. PATIENTS: 18 patients with variant angina were divided into single attack group (SA; nine patients) and multiple attack group (MA; nine patients) according to the frequency of ischaemic episodes with ST segment elevation during 24 hour Holter monitoring. METHODS: Heart rate variability indices were calculated using MemCalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for fitting analysis, at 30 second intervals for 30 second periods, from 40 minutes before the attack to 30 minutes after the attack. High frequency (HF; 0.04-0.15 Hz) was defined as a marker of parasympathetic activity, and the ratio of low frequency (LF; 0.15-0.40 Hz) to high frequency (LF/HF) as an indicator of sympathetic activity. The averaged value during the 40 to 30 minute period before an attack was defined as the baseline. RESULTS: Compared with baseline, the HF component decreased in both groups at two minutes before the attack (p < 0.01), and the LF/HF ratio decreased at three minutes before the attack (p < 0.01). The baseline LF/HF was lower in the MA group than in the SA group (p < 0. 01). CONCLUSIONS: A reduction of sympathetic activity may play a key role in determining the recurrence of transient ischaemic events caused by spontaneous coronary spasm in patients with variant angina.     

Catheter-induced spasm during spontaneous attack of variant angina

The simultaneous occurrences of spontaneous spasm and catheter-induced spasm during coronary angiography were obtained in 3 patients. Catheter-induced spasm was seen in the right coronary artery in 3 patients: 1 patient had spontaneous spasm in the distal right coronary artery and 2 patients had spontaneous spasm in the proximal left anterior descending coronary artery. These findings suggest that patients with variant angina may be susceptible to mechanical induction of spasm.     

Cardiac arrest related to coronary spasm in patients with variant angina: a three-case study

We present three patients with variant angina pectoris and episodes of cardiac arrest. All of them had typical clinical symptoms, ST-segment changes in electrocardiogram, and coronary artery spasm confirmed by arteriography. They were treated with high doses of calcium antagonists and nitrates. An automatic cardioverter-defibrillator was implanted in the patient who developed ventricular fibrillation despite therapy with calcium antagonists. In another patient a DDD pacemaker was implanted because of high-degree atrioventricular block.     

Provocation of coronary spasm by dopamine in patients with active variant angina pectoris

The effects of dopamine on arteries are different depending on the dose, route of administration, and receptor population. Its administration can cause vasodilation by stimulation of dopaminergic receptors, vasoconstriction by stimulation of alpha-adrenergic and serotonergic receptors, and even spasm of cerebral arteries when given intracisternally in dogs. The ability of dopamine to provoke coronary spasm was assessed in 18 patients with active vasospastic angina in whom this amine was infused at rates of 5, 10, and 15 micrograms/kg/min for periods of 5 min each. The 12-lead electrocardiogram and blood pressure (cuff) were monitored throughout the whole test. In nine patients dopamine caused angina and ischemic electrocardiographic changes suggestive of coronary spasm: ST segment elevation in six patients and ST segment depression in the absence of important coronary stenoses in the remaining three. Infusion of dopamine was repeated during coronary angiography in three patients with positive test results: this provoked occlusive coronary spasm with ST segment elevation in two patients and nonocclusive spasm with ST segment depression in the remainder. In conclusion, infusion of dopamine provokes coronary spasm in a sizeable proportion of patients with active vasospastic angina. Its administration may be detrimental in patients susceptible to coronary spasm, such as those with acute myocardial infarction.     

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.     

Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 micrograms ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of the 25 of the 27 patients. The injection of 20 to 100 micrograms ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection of ACh is a useful test for provocation of coronary spasm.     

Coronary hemodynamic responses during spontaneous angina in patients with and patients without coronary artery spasm

The mechanisms of spontaneous angina were evaluated during cardiac catheterization in 13 patients who had angina occurring without provocation at rest. Left ventricular and systemic hemodynamics, coronary venous flows (thermodilution technique), electrocardiogram and coronary angiograms were recorded before and during spontaneous angina. Angiography during spontaneous angina showed that 5 patients had coronary spasm (group I) and 8 patients did not (group II). In group II there was a preponderance of multivessel coronary artery disease. Left ventricular end-diastolic pressure increased in all patients in both groups during spontaneous angina. In group I, 4 patients had transient ST elevation and 1 patient had peaked T waves during angina. Transient ST depression occurred during spontaneous angina in all group II patients. Group I patients had decreased coronary sinus flow (4 of 5 patients) or decreased regional flow (5 of 5) during spontaneous angina. Coronary resistance and ratio of double product to coronary blood flow increased in all patients. In group II, coronary hemodynamic responses during spontaneous angina varied. Coronary venous flows, coronary resistance and ratio of double product to coronary blood flow showed no uniform pattern. Thus, patients with severe coronary artery disease can have spontaneous angina without angiographic findings of coronary spasm. After analysis of angiograms and coronary hemodynamics in these patients, no apparent uniform mechanism for spontaneous angina was found.     

Persistent coronary artery spasm documented by follow-up coronary angiography in patients with symptomatic remission of variant angina

For patients with variant angina it is very important to start medical therapy using calcium-channel blockers. However, the decision of physicians regarding whether to decrease the dose of the drug or discontinue it is controversial. We investigated whether the nature of spasm is remissive and whether the termination of medications is safe. The subjects studied were included in the Vasospastic Angina in Catholic Medical Center Registry from March 2001 to December 2009. We analyzed 37 patients (62 lesions) with variant angina, diagnosed using coronary angiography (CAG) and he acetylcholine provocation test, without any organic coronary stenosis, whose symptoms were well controlled after medication. The follow-up CAG with provocation test was performed at a median interval of 44 months. The characteristics of spasm were analyzed on each pair of CAGs. The study group consisted of 23 men (62.2 %) and 14 women (37.8 %) with a mean age of 59 ± 11.1 years. The follow-up CAG with provocation test showed that the characteristics of the spasmodic nature were consistent with the first test in all patients. Although the patients with variant angina had no chest pain after medical treatment, the spasmodic nature of coronary arteries still remained. We may decrease the drug dosage after carefully checking the patient’s symptoms but recommend not discontinuing therapy, even if the patient is asymptomatic.     

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)     

Three-vessel coronary artery spasm in a patient with variant angina and normal coronary arteries

Variant angina with two or more electrocardiographic or angiographic localizations has seldom been reported [1-4]. We present a case of variant angina pectoris and normal coronary arteries with three different and independent electrocardiographic localizations.     

Hyperventilation-induced simultaneous multivessel coronary spasm in patients with variant angina: an echocardiographic and arteriographic study

Left ventricular wall motion abnormalities during an attack of coronary spasm induced by hyperventilation were examined with use of two-dimensional echocardiography in 27 patients with variant angina. Transient abnormal wall motion (asynergy) confined to one coronary artery region was found in 18 of the 27 patients and transient abnormal motion extending over more than one coronary artery region in the remaining 9 patients. Spasm of more than one major coronary artery was demonstrated separately by coronary arteriography during an attack induced by injection of acetylcholine or ergonovine in seven of the nine patients who manifested asynergy in more than one coronary artery region. In one patient, spasm was demonstrated in one major coronary artery, and the other coronary arteries were severely stenosed or occluded organically. In the remaining patient, acetylcholine was not injected into both arteries; however, the attack was sometimes associated with ST segment elevation in the anterior leads and at other times in the inferior leads. Therefore, simultaneous multivessel coronary spasm seems to have occurred in eight of the nine patients who exhibited asynergy in more than one coronary artery region. The 8 patients with simultaneous multivessel coronary spasm had a higher degree and longer duration of ST segment elevation and a higher incidence of arrhythmias during the attack induced by hyperventilation than did the 19 patients with single vessel coronary spasm, and all of them had no significant organic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine

Acetylcholine (20 to 100 micrograms) was infused directly into coronary arteries in 10 patients with variant angina (group A), 13 subjects without coronary artery disease (group B) and 8 patients with significant organic coronary artery stenosis (greater than or equal to 50%) but without variant angina (group C) during coronary arteriography, to clarify the action of this agent on coronary arteries. Temporary pacing was performed at a demand heart rate of 40 beats/min while bradyarrhythmia developed. Coronary arteriography after administration of acetylcholine showed coronary vasoconstriction in all 10 patients (100%) of group A. Angina accompanied by electrocardiographic ischemic changes in 9 of 10 (90%, 7 ST-segment elevation and 2 depression) was provoked during this test. In the patients of group B, acetylcholine also induced vasoconstriction in 8 of 22 (36%) coronary arterial systems examined, chest pain in 3 (14%) and ST-segment deviation in none (0%). In the patients of group C, acetylcholine induced vasoconstriction in 3 of 9 (33%), chest pain in 2 (22%) and ST-segment depression in 1 (11%). No definite coronary artery dilation induced by acetylcholine was noted. Coronary vasoconstriction (p less than 0.05), electrocardiographic ischemic findings (p less than 0.01) and chest pain (p less than 0.01) were induced significantly more frequently in group A than in both groups B and group C. No significant difference was found between group B and group C. The coronary arteries in the patients with variant angina seem to be more susceptible to acetylcholine than those of patients without variant angina irrespective of the presence of significant atherosclerosis.     

Prinzmetal's variant form of angina with arteriographic evidence of coronary arterial spasm

Spasm of the proximal right coronary artery was arteriographically demonstrated during an episode of chest pain in a patient with Prinzmetal's variant form of angina. A right aortocoronary saphenous vein bypass procedure was performed but, despite a patent graft, the angina recurred and the patient died. The only significant finding at autopsy was an eccentric atherosclerotic plaque that narrowed the right coronary artery by 75 percent at the site of the spasm. These findings support Prinzmetal's hypothesis that this variant form of angina is produced by spasm of a coronary artery with a seriously compromised lumen.