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Abstract

The clinical and physiopathological clinical entity known as spastic angina or variant angina has been long documented. It remains, however, an under-estimated condition, which is insufficiently diagnosed and explored. This pathology is associated with severe complications such as heart rhythm disorders, which may potentially result in ventricular fibrillation and cause sudden death. In Japan, this condition occurs more frequently and is better documented. Stimulation tests are also carried out more often and have a higher positivity rate than in France where vasospastic angina is less frequently reported and where provocation tests are associated with negative results and are, consequently, performed less often. In order to improve the detection of this pathology, its potential presence should be explored in patients with rest angina who experience chest pain in the second half of the night and also in instances of acute coronary syndrome with sudden death and no angiographically visible coronary artery disease. The diagnosis should be confirmed by means of ergonovine provocation tests. In order to enhance the sensitivity of these tests without increasing the risk of complications, injection of ergonovine should be preferably carried out via the intracoronary route. By increasing the frequency and sensitivity of these tests, this pathology, which responds well to medical treatment in many cases, could be amenable to therapeutic management as any other form of coronary artery disease. Copyright © 2019. Published by Elsevier Masson SAS.

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... Authors who have performed studies on cAVB complicating MI, we cite UJ Gang, Hymie H, Harpaz D, Nguyen [6][7][8][9] have worked on what appear to be patients with cAVB present during the early phase of an MI even before revascularization either by thrombolysis or by PR to judge the effectiveness of the two methods on the patient's prognosis. In the course of our research, we issued opinions, possible hypotheses, which could explain, if applicable, our patient: a) Either by stenosis of the Stent with spontaneous reperfusion by fibrinolysis which allows the lysis of the fibrinoerythro-platelet clot, and the maintenance of vascular permeability [10,11] (The in situ formation of a coronary thrombus can lead to the occlusion responsible for 'an MI, followed by spontaneous lysis of the thrombus, which may explain the discovery of normal angiography [12]); which is unlikely given that the patient received a 600 mg bolus of Clopidogrel, just prior to PR, to prevent activation of platelets by inhibiting adenosine Di-phosphate; b) Or by prolonged vasospasm of the anterior interventricular artery [11][12][13][14][15][16][17][18]. ...
Article
Background: Patients presenting with chest pain may or may not be experiencing a panic attack. Is chest pain caused by a panic attack or myocardial infarction with non-obstructive coronary arteries (MINOCA) syndrome? Aim: In this study, we evaluated both MINOCA syndrome and HEART score in patients who presented to the emergency department with panic attacks and chest pain. Method: Patients who applied to the emergency department with panic disorder and chest pain complaints were included. Patients who met the MINOCA diagnostic criteria were identified. The study was completed with 143 eligible patients out of a total of 217 patients evaluated. The patients were divided into two groups. The first group was those whose symptoms and test results were consistent with MINOCA. The second group was composed of those whose chest pain was considered non-specific. The HEART score of all patients was calculated. The demographic characteristics, symptoms, and HEART scores were compared between the groups. Results: Of the 143 patients evaluated in the study, 62 (43.3%) were male and 81 (56.7%) were female. While the mean HEART score was 4.7 ± 1.5 in the MINOCA group, it was 2.0 ± 1.0 in the non-cardiac group, a statistically significant difference. Conclusion: Clinicians should pay attention to the patient's age, gender, number of attacks per week, HEART score, and which symptoms (palpitations, shortness of breath, and fear of death) are present in patients who meet the panic attack diagnostic criteria. Clinicians should be alert to the MINOCA syndrome in panic attack patients.
Article
Coronary artery vasospasm (CAVS) plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries. Pathophysiology of the disease remains incompletely understood, with autonomic and endothelial dysfunction thought to play an important role. Due to the dynamic nature of the disease, its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population. Cigarette smoking remains a prominent risk factor, although CAVS does not follow traditional coronary artery disease risk factors. Many triggers continue to be identified, with recent findings identifying chemotherapeutics, allergens, and inflammatory mediators as playing some role in the exacerbation of CAVS. Provocative testing with direct visualization is currently the gold-standard for diagnosis, but non-invasive tests, including the use of biomarkers, are being increasingly studied to aid in the diagnosis. Treatment of the CAVS is an area of active research. Apart from risk factor modification, calcium channel blockers are currently the first line treatment, with nitrates playing an important adjunct role. High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator (ICD), although timing criteria for escalated therapy require further investigation. The role of pharmaceuticals targeting oxidative stress remains incompletely understood.
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A 43-year-old man was diagnosed with acute myocardial infarction (AMI) due to multivessel coronary vasospasm. Accordingly, two coronary vasodilators were administered, and he was discharged without an angina attack. However, from the following day, he reported frequent chest pain and was re-hospitalized. Despite adding multiple coronary vasodilators, it was difficult to completely suppress the angina attack. He also demonstrated hypereosinophilia from the onset of AMI, and his eosinophil count gradually increased up to 6,238 /μL. After corticosteroid administration was started, the vasospasm was completely controlled, and his eosinophil count normalized. He remained free from angina attacks for two years with corticosteroid therapy.
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A 60-year-old man was prescribed oral desmopressin (1-deamino-8-D-arginine vasopressin acetate trihydrate; DDAVP) for nocturnal polyuria. One week after starting to take desmopressin, he frequently felt chest pain while resting. Coronary angiography revealed no organic stenosis; however, an acetylcholine provocation test showed severe coronary spasm with ST elevation. He was diagnosed with coronary spastic angina, and we stopped the oral desmopressin and added diltiazem. While DDAVP should dilate the coronary vessels in healthy subjects, it may provoke coronary vasospasm in patients with endothelial dysfunction. We should be careful to avoid triggering coronary spasm when administering DDAVP to patients that may have potential endothelial dysfunction.
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Ischemic heart disease involves both "structural" and/or "functional" disorders of the coronary circulation. Structural atherosclerotic coronary artery disease (CAD) is well recognized, with established diagnostic and treatment strategies. In contrast, "functional CAD" has received limited attention and is seldom actively pursued in the investigation of ischemic heart disease. Vasospastic angina encompasses "functional CAD" attributable to coronary artery spasm and this "state of the art" consensus statement reviews contemporary aspects of this disorder. Patients with vasospastic angina typically present with angina at rest that promptly responds to short-acting nitrates and is associated with transient ischemic ECG changes. Although spontaneous episodes may be documented, provocative spasm testing may be required to confirm the diagnosis. It is important to diagnose vasospastic angina because it may be associated with major adverse events that can be prevented with the use of appropriate vasodilator therapy (eg, calcium-channel blockers) and the avoidance of aggravating stimuli (eg, smoking). Future studies are required to clarify the underlying pathophysiology, natural history and effective treatments for patients refractory to conventional therapy.
Article
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ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain), Stephan Achenbach (Germany), Helmut Baumgartner (Germany), Jeroen J. Bax (Netherlands), He ' ctor Bueno (Spain), Veronica Dean (France), Christi Deaton (UK), Cetin Erol (Turkey), Robert Fagard (Belgium), Roberto Ferrari (Italy), David Hasdai (Israel), ArnoW. Hoes (Netherlands), Paulus Kirchhof (Germany/UK), JuhaniKnuuti (Finland), PhilippeKolh (Belgium), Patrizio Lancellotti (Belgium), Ales Linhart (CzechRepublic), Petros Nihoyannopoulos (UK), Massimo F. Piepoli (Italy), Piotr Ponikowski (Poland), Per Anton Sirnes (Norway), Juan Luis Tamargo (Spain), Michal Tendera (Poland), AdamTorbicki (Poland), WilliamWijns (Belgium), StephanWindecker (Switzerland). Document Reviewers: Juhani Knuuti (CPG Review Coordinator) (Finland), Marco Valgimigli (Review Coordinator) (Italy), Hector Bueno (Spain), Marc J. Claeys (Belgium), Norbert Donner-Banzhoff (Germany), Cetin Erol (Turkey), Herbert Frank (Austria), Christian Funck-Brentano (France), Oliver Gaemperli (Switzerland), JoseR. Gonzalez-Juanatey (Spain), Michalis Hamilos (Greece), David Hasdai (Israel), Steen Husted (Denmark), Stefan K. James (Sweden), Kari Kervinen (Finland), Philippe Kolh (Belgium), Steen Dalby Kristensen (Denmark), Patrizio Lancellotti (Belgium), Aldo Pietro Maggioni (Italy), Massimo F. Piepoli (Italy), Axel R. Pries (Germany), Francesco Romeo (Italy), Lars Ryden (Sweden), Maarten L. Simoons (Netherlands), Per Anton Sirnes (Norway), Ph. Gabriel Steg (France), Adam Timmis (UK), William Wijns (Belgium), StephanWindecker (Switzerland), Aylin Yildirir (Turkey), Jose Luis Zamorano (Spain).
Article
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Vasospastic angina is a frequent and well-recognized pathology with a high risk of life-threatening ventricular arrhythmias and sudden cardiac death. The diagnosis of vasospastic angina requires the combination of clinical and electrocardiographic variables and the results of provocation tests, such as ergonovine administration. Smoking cessation is the first step in the management of vasospastic angina. Optimal medical treatment using calcium-channel blockers and/or nitrate derivatives can provide protection, but life-threatening ventricular arrhythmias may occur despite optimal medical treatment and several years after the start of treatment. In this review, we evaluate the role of implantable defibrillators as a complement to optimal medical management in patients with life-threatening ventricular arrhythmias due to vasospastic angina; this role is not well characterized in the literature or guidelines. We discuss the role of implantable defibrillators in secondary prevention in light of three recent cases managed in our departments and a review of the literature. An implantable defibrillator was implanted in two of the three cases of vasospastic angina with ventricular arrhythmias that we managed. We considered secondary prevention by implantable defibrillator to be justified even in the absence of any obvious risk factor. Ventricular arrhythmias recurred during implantable defibrillator follow-up in the two patients implanted. In patients with life-threatening ventricular arrhythmias due to vasospastic angina, an implantable defibrillator should be considered because of the risk of recurrence despite optimal medical management.
Article
Objectives: We examined the clinical usefulness of treadmill exercise tests (TETs) in diagnosing coronary spastic angina (CSA). Methods: We performed the TETs and 24-h Holter monitoring in 300 CSA patients consisting of 152 patients with rest angina, 77 patients with effort angina, and 71 patients with rest and effort angina. Organic stenosis (>75%) was observed in 44 patients. Multiple spasms were recognized in 204 patients (68%). Results: Positive TETs were recognized in 113 patients (38%) and borderline was observed in 30 patients (10%). Positive response was significantly higher in patients with organic stenosis than those without fixed stenosis (63.6% vs. 33.2%, p<0.001). Moreover, ST elevation was more frequent in patients with organic stenosis than those without fixed stenosis (27.3% vs. 1.2%, p<0.001). Positive response in patients with effort angina (46.8%) was higher than those in patients with rest angina (33.6%) and rest and effort angina (36.6%), but not significant. Positive response was not different between single spasm and multiple spasms. In all 300 patients, ST segment elevation was observed in only four patients (1.3%) on the 24-h Holter monitoring. Conclusions: TET was useful in documenting ischemia in patients with CSA. More than a third of patients with CSA had positive TETs. Moreover, we obtained the pathologic TET response in approximately half of patients with CSA.
Article
The aim of this study was to define the morphological features of coronary artery spasm sites using optical coherence tomography (OCT) in patients with vasospastic angina (VSA). Plaque characteristics at coronary artery spasm sites have not been investigated systematically. Sixty-nine consecutive patients (80 spasm sites) presenting with VSA who underwent OCT imaging were included in this study. Fibrous cap disruption was identified by the discontinuation of fibrous cap with or without intraplaque cavity formation. OCT-defined erosion was established by the presence of thrombus with or without lumen irregularity overlying an intact fibrous cap on multiple adjacent OCT frames. Other morphological features such as the absence of thrombus with or without lumen irregularity and those not in the previously mentioned criteria were also documented. Plaque was seen on OCT in 79 of the 80 spasm sites. Fibrous cap disruption was detected at 3 sites (4%). OCT-defined erosion was observed at 21 spasm sites (26%). Thrombus with lumen irregularity was observed in 20 sites, whereas 1 site had thrombus without lumen irregularity. Lumen irregularity without thrombus was observed at 49 spasm sites (61%). Spontaneous spasm was seen more frequently in patients with acute myocardial infarction and out-of-hospital cardiac arrest than in patients without these conditions (50.0% vs. 19.3%, p = 0.025). Our results show that OCT-defined erosion at spasm sites occurred in more than one-fourth of patients in this study. Luminal irregularity was observed in nearly two-thirds of the patients without overlying thrombus. These findings suggest the potential role of antiplatelet therapy in VSA. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Article
The prevalence of vasospastic angina is said to be low in Europe, but maybe because of a lack of diagnosis in the daily practice. However, coronary spasm is a common cause of cardiac arrest, especially among patients free of cardiac illness, and it should be systematically investigated after an unexplained cardiac arrest. Intracoronary spasm provocation test exposes patients to a lower risk compared to the risk of spontaneous spastic angina. Accurate modalities and diagnostic criteria have to be clarified for European population. Avoiding external causes of coronary spasm (such as cigarette smoking or more generally consuming coronary spasm inducing drugs) and prescribing antispastic medicine (first of all calcium channel blockers) are the basis of vasospastic angina treatment. However, recurrent coronary spasms have been reported despite an appropriate treatment and implantable automatic defibrillator has been implanted after case discussion when the onset of illness was cardiac arrest. We report the case of a patient recovering from cardiac arrest who had a positive spasm coronary provocation test, and was treated with calcium channel blockers and had been an automatic defibrillator implanted, with a coronary spasm provocation test performed afterward still contentious. While discussing this case, we are making a literature review of the diagnosis and treatment of spastic angina revealed by cardiac arrest. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Article
Coronary spasm is an important and often overlooked etiology of chest pain. While coronary spasm, or Prinzmetal's angina, has been thought of as benign, contemporary studies have shown serious associated adverse outcomes including acute coronary syndrome, arrhythmia, and death. Definitive diagnosis of coronary spasm can at times be difficult given the transience of symptoms. Numerous agents have been historically described for provocative testing. We provide a review of literature for the role of provocation testing in the diagnosis of coronary spasm.
Article
The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n=1,429; median 66 years; median follow-up of 32 months) was utilized for score derivation. Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-elevation during angina and β-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0-2, n=598), intermediate (score 3-5, n=639) and high (score 6 or more, n=192). The incidence of MACE in the low-, intermediate- and high-risk patients were 2.5%, 7.0% and 13.0%, respectively (P<0.001). Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.
Article
Patients with acute coronary syndrome (ACS) and nonobstructive coronary artery disease (CAD) have a substantial risk of subsequent coronary events within 1 year. The aim of the present study was to evaluate the prevalence, long-term outcomes, and adherence to oral antiplatelet therapy in patients with ACS and nonobstructive CAD compared with patients with ACS and obstructive CAD who had undergone percutaneous coronary intervention. Nonobstructive CAD was defined as an angiographic finding of <50% diameter stenosis in any major epicardial artery. These patients were further stratified into 2 groups: those with normal coronary arteries (0% angiographic stenosis) and those with mild CAD (0% to 50% angiographic stenosis). Major adverse cardiac events, defined as death, myocardial infarction, ACS leading to hospitalization, and nonfatal stroke, were recorded and compared with a historical control group of patients with ACS and obstructive CAD who had undergone percutaneous coronary intervention. Of 2,438 consecutive patients with ACS undergoing coronary angiography, 318 (13%) had nonobstructive CAD. Of the 318 with nonobstructive CAD, 160 had normal coronary arteries and 158 had mild CAD. Patients with obstructive CAD had experienced greater rates of major adverse cardiac events at 26 ± 16 months (16.6% vs 9.1%, p = 0.001), driven by a greater rate of myocardial infarction compared with those without (5.3% vs 0%, p <0.001). However, the rate of death, ACS leading to hospitalization, and stroke was similar. After adjusting for baseline characteristics, no difference was found in the risk of major adverse cardiac events across the groups. Only 50% of patients with nonobstructive CAD were prescribed dual antiplatelet therapy. In conclusion, patients with ACS and nonobstructive CAD remain at high risk of long-term recurrent ischemic events.
Article
AimsProvocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association.Methods and resultsA total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not.Conclusion The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients.
Article
Spastic angina is considered rare but its prevalence is probably underestimated especially in case of atherosclerotic coronary lesions. Its diagnosis remains important due to its poor prognosis and therapeutic characteristics. We report three clinical cases illustrating two different clinical presentations and the problem of diagnosis of spastic angina. We performed a review of the literature essentially concerning commonly used diagnosis means and especially provocative testing for coronary spasm. This test needs to be adapted to the evolution of techniques and uses of coronary angiography in 2011, particularly the wide spread use of radial approach. Therefore new recommendations are needed, specifying the terms of provocative testing and establishing clear diagnosis criteria including clinical, electrocardiographic and angiographic data. Such guidelines would probably help to better diagnose and treat these patients in our practice. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Article
The existence of myocardial infarction despite angiographically normal coronary arteries was recognized more than 30 years ago. Since then, various series of such patients have been described, but the aetiology and pathogenesis of the condition are still a source of debate. Evidence exists for a role of coronary vasospasm, thrombosis, embolization and inflammation, per se or combined, in determining the occurrence of myocardial infarction in the presence of angiographically normal coronary arteries. Endothelial dysfunction, possibly superimposed to nonangiographically evident atherosclerosis, may be an underlying common feature predisposing to the acute event. Additionally, myocarditis may explain some of these occurrences. Myocardial infarction with normal coronary arteries is therefore likely the result of multiple pathogenetic mechanisms. Although most reports emphasize the good prognosis of this condition, in general much better than myocardial infarction with coronary artery disease, prognosis is likely variable according to the underlying mechanism. This review summarizes current knowledge on this condition and examines areas of recent progress.
Article
We sought to determine the prognosis of patients with acute coronary syndrome without culprit lesion and proof of coronary spasm during 3 years of follow-up. Coronary artery spasm has been identified as an alternative cause for acute coronary syndrome (ACS) in patients without culprit lesion. In the CASPAR (Coronary Artery Spasm as a Frequent Cause for Acute Coronary Syndrome) study, we recently showed that ∼50% of ACS patients without culprit lesion, in whom intracoronary acetylcholine provocation was performed, had coronary spasm. However, data on prognosis in these patients are sparse. After 3 years of follow-up, data regarding the following end points were obtained: death (cardiac and noncardiac), nonfatal myocardial infarction, and recurrent angina leading to repeated coronary angiography. The analysis focused on patients with a culprit lesion (n = 270) and patients without a culprit lesion (n = 76) but with acetylcholine provocation (total n = 346). In patients without culprit lesion, there was no cardiac death or nonfatal myocardial infarction during follow-up; 1 patient died due to a noncardiac cause. However, 38 of 76 patients reported persistent angina requiring repeated angiography in 3 cases (3.9%). Thirty of 270 patients with culprit lesion died due to a cardiac cause (11.1%) and 13 due to a noncardiac cause (4.8%). Eleven patients had nonfatal myocardial infarction (4.1%) and 27 repeated angiography due to persistent or recurrent angina (10%). Patients with a culprit lesion had a higher mortality and more coronary events compared with those without (p < 0.0005, log-rank test). ACS patients without culprit lesion and proof of coronary spasm have an excellent prognosis for survival and coronary events after 3 years compared with patients with obstructive ACS. However, persistent angina represents a challenging problem in these patients, leading in some cases to repeated coronary angiography.
Article
This study was conducted to clarify the incidence of coronary spasm in emergency patients with suspected acute coronary syndrome (ACS) and acute chest pain at rest. Chest pain at rest is a frequent symptom in the emergency room. Acute coronary syndrome is suspected in patients with elevation of cardiac markers, ischemic electrocardiographic changes, or simply typical clinical symptoms of unstable (usually resting) angina. However, of all patients with suspected ACS who undergo coronary angiography, up to 30% have nonobstructed coronary arteries. We sought to clarify how many of these patients suffer from coronary spasm as a possible cause of their chest pain. In a prospective study from June to December 2006, all patients with suspected ACS who underwent coronary angiography and had no culprit lesion underwent intracoronary provocation with acetylcholine. The ACH testing was considered positive at a vasoconstriction of >/=75% relative to the diameter after intracoronary nitroglycerine when the initially reported symptoms could be reproduced. Of 488 consecutive patients, 138 had no culprit lesion (28%). Twenty-two were found to have another diagnosis. The ACH testing was performed in 86 of the remaining 116 patients. In 42 patients, coronary spasm was verified (49%). Every fourth patient with ACS had no culprit lesion. Coronary spasm could be documented in nearly 50% of the patients tested by ACH. Coronary spasm is a frequent cause of ACS and should regularly be considered as a differential diagnosis.
Article
To investigate whether ergonovine acts directly on coronary arteries or via remote neurohumoral reflexes, we administered small titrated increments of intracoronary ergonovine up to a maximum cumulative dose of 50 micrograms to 15 patients. In six patients with variant angina (group 1), ischemic electrocardiographic ST changes, angina, and localized coronary spasm (local coronary diameter reduction of 87.8 +/- 18.9% [mean +/- SD]) followed after 6 to 50 micrograms (mean 20.7) cumulative intracoronary ergonovine. In nine patients with atypical chest pain, normal baseline coronary arteriograms, and no evidence of variant angina (group 2), there was no ischemic ST segment change or localized coronary spasm after 6 to 50 micrograms (mean 31.6) intracoronary ergonovine. Coronary diameter of proximal vessels of patients in group 2 was reduced by 16.2 +/- 6.5% and did not differ from the response of nonspastic vessels of comparable size of group 1 (20.5 +/- 13.8%; p = .7). There was no significant difference in the median effective dose values in the dose-response curves of the spastic and nonspastic segments between groups 1 and 2. Ergonovine causes coronary spasm by a direct local effect, which seems to be caused by localized arterial hyperreactivity rather than supersensitivity. Intracoronary delivery may be safer than intravenous administration because negligible drug recirculation may prevent perpetuation of spasm and selective coronary administration can avoid branches with critical stenoses.
Article
Among 63 patients with Prinzmetal's variant angina, coronary arterial spasm responsible for attacks of variant angina was documented arteriographically in 9 patients. In each observed episode (11 attacks in nine patients), coronary spasm producing myocardial ischemia occurred at and was superimposed on a site of preexisting organic stenosis. Measurements of normal portions of "spastic" and "nonspastic" vessels suggested a generalized uniform constriction of all major coronary arteries during attacks, with "spasm" limited to the site of an organic lesion in most cases. In two cases the magnitude of constriction in all vessels was consistent with generalized coronary hypercontractility or spasm. Among 104 patients with organic coronary artery disease and documented single vessel coronary spasm (foregoing 9 patients combined with 95 others from published reports), there were 70 patients with essentially single vessel organic coronary disease in 90 percent of whom the spasm involved the diseased vessel. Of 60 cases abstracted from the literature in which the relation of coronary spasm to the site of organic disease was described, 88 percent had the spasm causing ischemia localized to the site of an organic lesion. Hypotheses attempting to describe the pathophysiologic aspects of coronary spasm in variant angina must account for the intimate association of spasm with sites of organic stenosis in the majority of cases.
Article
The clinical manifestations of symptomatic coronary arterial spasm were analyzed in 30 patients whose coronary arteriograms demonstrated no fixed severe obstructions. The study group consisted of 14 men and 16 women (average age, 47 years). Angina at rest was invariable and it was usually typical in quality, location, duration and response to nitroglycerin. Exertional angina occurred in 23 percent and syncope with angina in 33 percent. Spontaneous remission of angina for at least 1 month occurred in 57 percent of patients. Prinzmetal's variant angina occurred in 77 percent of patients and only S-T segment depression or T wave changes during angina occurred in 23 percent. Major arrhythmias during ischemia developed in 47 percent. Exericse tests were positive in 24 percent. Myocardial infarction, probably due to coronary spasm, occurred in 7 percent of patients. Isosorbide dinitrate and propranolol were effective therapy in only 39 percent and 6 percent of patients, respectively. Nifedipine, a calcium flux antagonist, was effective in 80 percent of patients. Patients with normal coronary arteriograms who have clinical features suggestive of coronary arterial spasm should be considered for further investigation, including long-term electrocardiographic monitoring and provocative testing for spasm.
Article
We established the incidence of coronary artery spasm provoked by 0.4 mg of methergine in 1089 consecutive patients undergoing coronary angiography. The test was performed after routine coronary arteriography. Subjects included patients with angina, both typical and atypical, patients who had recently had myocardial infarction and patients with either valvular disease or congestive cardiomyopathy. Patients with spontaneous spasm, left main narrowing or severe three-vessel disease were excluded. One hundred thirty-four patients experienced focal spasm. Focal spasm was uncommon in patients with atypical precordial pain (1.2%), angina of effort (4.3%), valvular disease (1.95%) or cardiomyopathy (0%). It occurred most often in patients with angina at rest and less often in patients with angina both at rest and induced by exercise. Spasm was provoked in 20% of patients with recent transmural infarction, but in only 6.2% of patients studied later after infarction. Spasm was superimposed on fixed atherosclerotic lesions in 60% of the patients. No serious complications were encountered. Although the patients who underwent provocation tests in this study are not representative of all patients with coronary artery disease, spasm occurred in 20% of patients who experienced a coronary event and in 15% of patients who complained of chest pain.
Article
The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levels were increased significantly in the coronary sinus (32.8 +/- 3.6 to 52.8 +/- 5.9 ng/mL, P < .001) and in the aortic root (34.6 +/- 3.7 to 41.9 +/- 4.4 ng/mL, P < .05) after the attacks in the coronary spastic angina group but remained unchanged in the stable exertional angina group after the attacks and in the control group after the administration of acetylcholine. Furthermore, the coronary sinus-arterial difference of soluble P-selectin increased significantly after the attacks in the coronary spastic angina group (-1.8 +/- 2.2 to 10.9 +/- 2.7 ng/mL, P < .001). Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.
Article
Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm. Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone. The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result. The patients' mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm. A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.
Article
Japanese investigators have provided a substantial contribution in the understanding of coronary vasomotor reactivity. On occasions, their findings have been at variance with those undertaken on caucasian patients, raising speculation that vasomotor differences between races may exist. In a comparative review of the published literature, we evaluated the vasoreactive differences among Japanese and caucasian patients with variant angina or myocardial infarction. In variant angina, Japanese patients appear to have diffusely hyperreactive coronary arteries compared with caucasian people, manifested by their segmental rather than focal spasm, hyperreactive nonspastic vessels and multivessel spasm. These differences may reflect the increased basal tone among Japanese variant angina patients and may relate to controversial differences in endothelial nitric oxide production or autonomic nervous system activity. Provocative vasomotor studies of Japanese patients with a recent myocardial infarction report a higher incidence of inducible spasm than caucasian studies, an observation recently supported by a controlled study. Furthermore, the hyperreactivity was diffuse, occurring in both non-infarct- and infarct-related vessels. These observations support the existence of racial coronary vasomotor reactivity differences but require confirmation in further prospectively conducted studies.
Article
Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial. The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non-infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183+/-59 versus 247+/-53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs than in NIRAs in both populations (67% versus 39% and 23% versus 11%, respectively). Multivessel spasm was more common (64% versus 17%, P<0.02) and vasoconstriction of nonspastic segments was greater in Japanese patients (-23.4+/-14.9% versus -20.1+/-15.7%, P<0.02) in the presence of similar average basal coronary tone with respect to post-nitroglycerin dilation and of nonsignificant differences of coronary atherosclerotic score. Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.
Article
This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.
Article
The experimental data here reported indicate that ST deviation is related largely to a change in the balance between intra- and extracellular electrolytes. This change in intra- and extracellular electrolyte balance occurs in ischemic heart disease as well as in a wide variety of noncardiac conditions.
Article
There are no data concerning the incidence of provoked coronary arterial spasms via intracoronary administration of ergonovine (ER). This study sought to establish the incidence of spasms due to intracoronary injection of ER in Japanese patients who underwent coronary angiography. The subjects were 596 consecutive patients (369 men, mean age 64.2 +/- 10.3 years) who were studied with a selective ER test. ER was administered in total doses of 40 microg into the right coronary artery and 64 microg into the left coronary artery. A positive spasm was defined as a total or subtotal occlusion. Coronary vasospasms were determined in 173 patients (29.0%). Spasms occurred often in patients with ischemic heart disease (43.3%); during effort and rest in patients with angina (46.3%), exertional angina (27.7%), recent myocardial infarction (36.7%), healed myocardial infarction (34.1%), and especially in patients with rest angina (55.5%), but were relatively uncommon in patients with nonischemic heart disease (3.7%). The incidence of provoked coronary spasms in this study was 2.2-2.6 times higher than in previous reports with intravenous ER administration. More spasms were superimposed on significant atherosclerotic lesions than on nonfixed atherosclerotic lesions (42.8% vs 24.0%, p < 0.01). No serious or irreversible complications were observed in this study. In conclusion, intracoronary administration of ER was a safe and reliable test. Compared with Caucasian patients, in Japanese patients, coronary arterial spasms occurred 2-3 times more frequently with various cardiac disorders.
Article
There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh was injected in incremental doses of 20, 50 and 80 microg into the right coronary artery and 20, 50 and 100 microg into the left coronary artery. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. Thus, both selective ACh and ER tests were useful as spasm provocation tests.
Article
The majority of patients with acute coronary syndromes (ACS) present with unstable angina, acute myocardial infarction, and sudden coronary death. The most common cause of coronary thrombosis is plaque rupture followed by plaque erosion, whereas calcified nodule is infrequent. If advances in coronary disease are to occur, it is important to recognize the precursor lesion of ACS. Of the three types of coronary thrombosis, a precursor lesion for acute rupture has been postulated. The non-thrombosed lesion that most resembles the acute plaque rupture is the thin cap fibroatheroma (TCFA), which is characterized by a necrotic core with an overlying fibrous cap measuring <65 microm, containing rare smooth muscle cells but numerous macrophages. Thin cap fibroatheromas are most frequently observed in patients dying with acute myocardial infarction and least common in plaque erosion. They are most frequently observed in proximal coronary arteries, followed by mid and distal major coronary arteries. Vessels demonstrating TCFA do not usually show severe narrowing but show positive remodeling. In TCFAs the necrotic core length is approximately 2 to 17 mm (mean 8 mm) and the underlying cross-sectional area narrowing in over 75% of cases is <75% (diameter stenosis <50%). The area of the necrotic core in at least 75% of cases is < or =3 mm2. These lesions have lesser degree of calcification than plaque ruptures. Thin cap fibroatheromas are common in patients with high total cholesterol (TC) and high TC/high-density lipoprotein cholesterol ratio, in women >50 years, and in those patients with elevated high levels of high sensitivity C-reactive protein. It has only recently been recognized that their identification in living patients might help reduce the incidence of sudden coronary death.
Article
Clinical characteristics and outcome of patients with variant angina were assessed in the 1970-1980s of the past Century. The recent progress in prevention, diagnosis and treatment of coronary artery disease may have significantly modified clinical characteristics and prognosis of these patients. From January 1991 to December 2002, 202 patients (57.1+/-12 years; 166 men) were diagnosed to have variant angina at our Institute. Detailed clinical findings and clinical events were prospectively collected for each patient. The median time from the first angina attack to diagnosis was 2 months (range 1-276), with diagnosis requiring >6 months in 31.7% of patients. Coronary angiography (n=183) showed normal coronary arteries in 42.1% of patients and significant coronary stenoses (>50%) in 44.3%, with multi-vessel disease in 8.7%. Diagnosis of variant angina was done during coronary angiography in 3% of cases during the first half of the study period, but in 42% of patients in the second half of the study period. Major cardiac events (MCE, i.e., death, resuscitation from cardiac arrest, myocardial infarction) occurred in 41 patients (20.3%), with 43.9% of events occurring within 1 month of symptom onset. The only variable significantly associated with MCE was the detection during angina of ST segment elevation in both anterior and inferior ECG leads (odds ratio 3.24; 95% confidence interval 1.43-7.36; P=0.005). Our data suggest that variant angina is still a frequently overlooked diagnosis, and a timely diagnosis would be crucial to prevent early life-threatening events. Patients with diffuse ST segment elevation on ECG are those at the highest risk of MCE, independently of angiographic findings.