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Background: An association between early repolarization and ventricular fibrillation has recently been reported in patients with vasospastic angina (VSA). However, no studies have clarified whether the presence of early repolarization can predict VSA., Methods: Participants comprised 286 patients (136 males) with clinically suspected VSA who underwent intracoronary provocation tests using acetylcholine or ergonovine. Patients were divided into a VSA group [n = 94, positive provocation test as induction of coronary arterial spasm (>90% stenosis)] and a non-VSA group (n = 192). Detailed early repolarization data were compared between groups., Results: The VSA group showed a higher frequency of smokers (28.7%) than the non-VSA group (17.2%; P = 0.02). On baseline 12-lead ECG, early repolarization (defined as a J-point elevation ≥0.1 mV from baseline in both or either of inferolateral leads) was found in 39 patients (inferior leads, n = 27; inferolateral leads, n = 12). Early repolarization was found more frequently in the VSA group (28.7%) than in the non-VSA group (6.2%, P < 0.01). Multivariate analysis revealed early repolarization as an independent predictor of VSA (odds ratio, 5.22; 95% confidence interval, 2.41-11.2; P < 0.01). Early repolarization pattern features including inferior lead, higher amplitude, notched type and horizontal/descending ST segments were associated with increased risk of VSA., Conclusion: In patients with resting chest pain, early repolarization was a predictor of VSA that could be particularly related to the inferior lead, higher amplitude, notched type and horizontal/descending ST segment., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (β = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Background: ST-segment elevation (STE) and an increased Tpeak-Tend interval (Tp-e) have prognostic value for malignant arrhythmia events (MAEs) in patients with ST-segment elevation myocardial infarction (STEMI) and Brugada syndrome. Whether STE could predict MAEs and has an electrophysiological relationship with Tp-e in electrocardiogram (ECG) of vasospastic angina (VA) patients needs to be elucidated., Methods: Sixty-five patients with VA and 23 patients with VA complicated by MAEs were enrolled. The relationship of ECG parameters and MAEs (defined as ventricular tachycardia/ventricular fibrillation (VT/VF), syncope, and aborted sudden death) was analyzed by t-test, regression and receiver operating characteristic (ROC) curve analyses., Results: Patients with MAEs showed greater STE (P<0.001) and corrected QT dispersion (cQTd) (P=0.021), a longer corrected Tp-e interval (cTp-e) (P<0.001), and a larger Tp-e/QT ratio (P<0.001) than those in non-MAE groups. Univariate analysis revealed that cQTd (odds ratio (OR)=1.065; P=0.020), cTp-e (OR=1.159; P=0.001), Tp-e/QT (OR=1.344, P=0.002), and STE (OR=5.655, P<0.001) were significantly associated with MAEs. In the multivariate analysis, Tp-e/QT and STE remained predictors of MAEs. ROC curve analysis showed that the areas under curve (AUCs) for Tp-e/QT (AUC=0.944) and STE (AUC=0.974) were not significantly different (P>0.05), but both were significantly different than AUCs for cQTd (AUC=0.724) and cTp-e (AUC=0.841) (all P<0.05). STE was well fitted with the Tp-e/QT ratio in a multivariable linear regression model., Conclusions: STE and increased Tp-e/QT ratio had related electrophysiological properties and were independent prognostic indicators of MAEs in patients with VA., (Copyright © 2019. Published by Elsevier Inc.)

Vasospastic angina (VSA) is a variant form of angina pectoris, in which angina occurs at rest, with transient electrocardiogram modifications and preserved exercise capacity. VSA can be involved in many clinical scenarios, such as stable angina, sudden cardiac death, acute coronary syndrome, arrhythmia or syncope. Coronary vasospasm is a heterogeneous phenomenon that can occur in patients with or without coronary atherosclerosis, can be focal or diffuse, and can affect epicardial or microvasculature coronary arteries. This disease remains underdiagnosed, and provocative tests are rarely performed. VSA diagnosis involves three considerations: classical clinical manifestations of VSA; documentation of myocardial ischaemia during spontaneous episodes; and demonstration of coronary artery spasm. The gold standard diagnostic approach uses invasive coronary angiography to directly image coronary spasm using acetylcholine, ergonovine or methylergonovine as the provocative stimulus. Lifestyle changes, avoidance of vasospastic agents and pharmacotherapy, such as calcium channel blockers, nitrates, statins, aspirin, alpha1-adrenergic receptor antagonists, rho-kinase inhibitors or nicorandil, could be proposed to patients with VSA. This review discusses the pathophysiology, clinical spectrum and management of VSA for clinicians, as well as diagnostic criteria and the provocative tests available for use by interventional cardiologists., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing., Methods: A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion., Results: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921)., Conclusions: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.

Competing Interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

Although coronary obstruction due to atherosclerosis is the most common cause of myocardial ischemia, a significant proportion of patients have myocardial ischemia in the absence of obstructive epicardial coronary artery disease (CAD). This finding is more common among women and alternative causes can mediate myocardial ischemia. Abnormalities in vascular structure, alterations in coronary vasomotion and dysfunction of the coronary microcirculation can all cause ischemia in the absence of obstructive CAD due to atherosclerosis. In this review, we provide an update on three alternative causes of myocardial ischemia: spontaneous coronary artery dissection (SCAD), vasospastic angina (VSA) and coronary microvascular dysfunction (CMVD). We review pathophysiology, clinical presentation, diagnosis, treatment and outcomes related to these important clinical entities. There is increasing interest in better defining this patient population with use of advanced imaging and testing tools. Despite the increased associated risk with future cardiac events, evidence-based treatments for these diagnoses remain under-studied and poorly defined. These alternative diagnoses should be kept in mind when evaluating women with myocardial ischemia without obstructive CAD due to atherosclerosis.

Rationale: ST-segment elevation localizes an ischemic lesion to the coronary artery supplying the area of the myocardium reflected by the electrocardiographic leads. Dynamic ST-segment elevation can be due to severe transmural ischemia secondary to a thrombus, vasospasm, or a tightly fixed coronary artery lesion or a combination of these situations., Patient Concerns: In this study, we report on two patients with angina who had fluctuations in ST-segment amplitude on serial electrocardiograms. The amplitude of ST-segment elevation varied between 1-20 mm., Diagnoses: Vasospastic angina (VSA) was diagnosed based on electrocardiography and coronary angiography., Interventions: Calcium antagonists were prescribed for both patients., Outcomes: No recurrent VSA was noted during outpatient follow-up., Lessons: VSA can be associated with fluctuations in the amplitude of ST-segment elevation, indicating dynamic coronary vasospasm in different locations and extensions in patients with VSA.

Background: High-dose aspirin has been reported to exacerbate coronary artery spasm in patients with vasospastic angina. We investigated clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis., Methods: We included patients without significant coronary artery stenosis on coronary angiography (CAG) and with positive results on intracoronary ergonovine provocation test between January 2003 and December 2014. A total of 777 patients were divided into two groups according to prescription of low-dose aspirin at discharge: aspirin group (n=321) and non-aspirin group (n=456). The major adverse cardiovascular events (MACE), defined as composite outcomes of cardiac death, acute myocardial infarction, revascularization, or rehospitalization requiring CAG or medication change due to recurrent angina were compared., Results: The aspirin group had significantly higher incidence of MACE (22.8% versus 12.1%; p=0.04) and had higher tendency for rehospitalization (20.6% versus 11.2%; p=0.08). All-cause mortality and cardiac death were similar between the two groups. After propensity score matching, the aspirin group had greater risk of MACE (hazard ratio [HR] 1.54; 95% confidence interval [CI], 1.04-2.28; p=0.037) and rehospitalization requiring CAG (HR, 1.33; 95% CI, 1.13-4.20; p=0.03), and a higher tendency for rehospitalization (HR, 1.40; 95% CI, 0.94-2.09; p=0.12)., Conclusion: In vasospastic angina without significant coronary artery stenosis, patients taking low-dose aspirin are at higher risk of MACE, driven primarily by tendency toward rehospitalization. Low-dose aspirin might be used with caution in vasospastic angina patients without significant coronary artery stenosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Vasospastic angina is a diagnosis of exclusion that manifests with signs and symptoms, which overlap with obstructive coronary artery disease, most often ST-segment elevation myocardial infarction. The pharmacotherapy that is available to treat vasospastic angina can help ameliorate angina symptoms. However, the etiology of vasospastic angina is ill-defined, making targeted pharmacotherapy difficult. Most patients receive pharmacotherapy that includes calcium channel blockers and/or long-acting nitrates. This article reviews the efficacy and safety of the pharmacotherapy used to treat vasospastic angina. High-dose calcium channel blockers possess the most evidence, with respect to decreasing angina incidence, frequency, and duration. However, not all patients respond to calcium channel blockers. Nitrates and/or alpha1-adrenergic receptor antagonists can be used in patients who respond poorly to calcium channel blockers. Albeit, evidence for use of nitrates and alpha1-adrenergic receptor antagonists in vasospastic angina is not as robust as calcium channel blockers and can exacerbate adverse effects when added to calcium channel blocker therapy. Despite having a clear benefit in patients with obstructive coronary artery disease, the benefit of beta-adrenergic receptor antagonists, statins, and aspirin remains unclear. More data are needed to elucidate whether or not these agents are beneficial or harmful to patients being treated for vasospastic angina. Overall, the use of pharmacotherapy for the treatment of vasospastic angina should be guided by patient-specific factors, such as tolerability, adverse effects, drug-drug, and drug-disease interactions., (© The Author(s) 2016.)

Background: We encounter a less provoked spasm in the left circumflex artery (LCX) by acetylcholine (ACh) testing compared with left anterior descending artery and right coronary artery (RCA) in the real world., Objectives: We investigated the clinical characteristics of provoked spasm in the LCX by ACh testing., Methods: We retrospectively analyzed consecutive 1392 ACh testing over 20 years (1991-2011). The maximal ACh dose was 100 μg into the left coronary artery and 80 μg into the RCA. Positive spasm was defined as transient of more than or equal to 90% narrowing and usual chest symptoms or ischemic ECG changes., Results: Positive provoked spasm was recognized in 622 patients (44.7%) including 456 RCA spasms, 448 left anterior descending artery spasms, and 176 LCX spasms. LCX-provoked spasm was significantly lower than other vessels (P<0.001). LCX-provoked spasm was observed in 176 patients, of whom 113 patients (64.2%) had triple-vessel spasm, 46 patients (26.1%) had double-vessel spasm, and 17 patients (9.7%) had single-vessel spasm. More than 90% patients with LCX-provoked spasm had multiple spasms. Of 17 patients with LCX single-vessel spasm, 15 patients (88.2%) had focal spasm., Conclusion: Under a maximal ACh dose of 100 μg into the left coronary artery, LCX-provoked spasm was significantly lower than other vessels and more than 90% of patients had multiple spasms.

Objective: To describe an unusual case of combined neuropathic and ischemia-induced chronic pain in a patient who was treated with one high thoracic paddle lead., Background: To the best of our knowledge, the use of spinal cord stimulation (SCS) utilizing a single lead as a treatment strategy for combined Prinzmetal angina, a cardiac ischemia-induced disturbance of nociceptive perception, and diabetic neuropathy of the lower limbs has rarely been described., Case Report: The underlying pain conditions and SCS technique used to treat both types of pain-Prinzmetal angina and lower-limb diabetic neuropathy-in a 73-year-old patient experiencing medical or interventional refractory complex pain syndrome are described. The SCS electrode was placed in the anatomical midline with a T2- to T3-level laminotomy and externalized for postoperative trial stimulation with systemic antibiotic administration., Results: After 8 months, stable pain control was achieved. No complications occurred., Conclusion: We present a chronic pain syndrome due to combined Prinzmetal angina and diabetic neuropathy of the lower limbs with sustained pain relief utilizing a single SCS lead., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Hyperglycemia on admission is associated with increased mortality rates in patients with ST-elevation myocardial infarction (STEMI) who are treated with either fibrinolytic therapy (FT) or primary percutaneous coronary intervention (PCI). However, data regarding the relationship between hyperglycemia and the success of FT are lacking. The aim of this study was to investigate the value of admission blood glucose for the prediction of failed reperfusion following FT., Methods and Results: This is a retrospective study of 304 STEMI patients who received FT and whose admission glucose levels were recorded. The main outcome measure was ST segment resolution≥50%. The median (interquartile range [IQR]) blood glucose level in the entire study group was 112 (95-153). In 92 (30.2%) patients, FT was unsuccessful and rescue PCI was performed. Admission glucose (126 [99-192] vs. 110 [94-144] mg/dL, p<0.001), time from symptom onset to FT (180 [120-270] vs. 150 [120-180] min, p=0.009), and maximum ST elevation amplitude (3 [2-7] vs. 3 [2-6] mm, p=0.05) were higher in the failed reperfusion group than in the reperfusion group. Admission hyperglycemia was an independent predictive factor for failed reperfusion (hazard ratio 4.79 [1.80-12.76], p=0.002), along with time from symptom onset to fibrinolysis and anterior wall myocardial infarction., Conclusions: In patients with STEMI who undergo FT, admission hyperglycemia is an independent predictor of the failure of fibrinolysis.

Coronary spasm is involved in many clinical scenarios, such as stable angina, acute coronary syndrome, sudden cardiac death, non-ischemic cardiomyopathy, arrhythmia and syncope. In recent years, imaging tools such as computerized tomographic angiography, intravascular ultrasound or optical coherence tomography have been applied to study the coronary pathology in patients with vasospastic angina. Patients with vasospastic angina represent a heterogeneous cohort of patients with regard to the extent of concomitant coronary atherosclerosis. They share the common pathophysiological phenomenon of vascular smooth muscle hyperreactivity leading to spasm caused by various factors that may also overlap. Focal coronary spasm is related to epicardial atherosclerosis and in the presence of obstructive coronary artery disease it may be useful to treat the lesion to prevent further spasm. The aim of this article is to review structural and functional coronary artery abnormalities in patients with vasospastic angina.

Background: We will focus our attention in this article in the ECG changes of classical Prinzmetal angina that occur during occlusive proximal coronary spasm usually in patients with normal or noncritical coronary stenosis., Results: The most important ECG change during a focal proximal coronary spasm is in around 50% of cases the appearance of peaked and symmetrical T wave that is followed, if the spasm persist, by progressive ST-segment elevation that last for a few minutes, and later progressively resolve. The most frequent ECG changes associated with ST-segment elevation are: (a) increased height of the R wave, (b) coincident S-wave diminution, (c) upsloping TQ in many cases, and (d) alternans of the elevated ST-segment and negative T wave deepness in 20% of cases. The presence of arrhythmias is very frequent during Prinzmetal angina crises, especially ventricular arrhythmias. The prevalence and importance of ventricular arrhythmias were related to: (a) duration of episodes, (b) degree of ST-segment elevation, (c) presence of ST-T wave alternans, and (d) the presence of >25% increase of the R wave., Conclusions: The incidence of Prinzmetal angina is much lower then 50 years ago for many reasons including treatment with calcium channel blocks to treat hypertension and ischemia heart disease and the decrease of smoking habits., (© 2014 Wiley Periodicals, Inc.)

Prominent T-wave inversions are well recognized electrocardiographic signs that can occur in acute myocardial infarction (AMI). However, the giant negative T waves may be associated with myocardial stunning without AMI.This case report describes 2 patients without AMI who developed rare giant T-wave inversions measuring up to 35 mm in depth and QT prolongation after admission to hospital. While 1 patient presented with acute pulmonary edema, the other patient presented with severe chest pain at rest and transient ST elevation.The giant T-wave inversion with QT prolongation may be caused by myocardial stunning due to the triple vessel diseases and elevated wall stress, high-end diastolic pressure and decreased coronary arterial flow during pulmonary edema in the first patient. The giant T-wave inversion with QT prolongation in the second patient may be caused by myocardial stunning due to the left anterior descending artery spasm (transient ST elevation) leading to transient total occlusion of left anterior descending artery. Percutaneous coronary intervention was successfully undergone for both patients. The patients remained well.The electrophysiologic mechanism responsible for giant T-wave inversion with QT prolongation is presently unknown. The two cases demonstrate that the rare giant negative T waves may be associated with myocardial stunning without AMI.

Background: The prevalence, clinical features, and long-term outcome of patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) associated with coronary spasm are not fully investigated., Methods and Results: This observational multicenter study enrolled 1601 consecutive patients with suspected NSTE-ACS who underwent cardiac catheterization between January 2001 and December 2010. A culprit lesion was found in 1152 (72%) patients. In patients without a culprit lesion, the acetylcholine provocation test was performed in 221 patients and was positive in 175 patients. In the other patients, coronary spasm was verified in 145 patients during spontaneous attack. Spasm-induced NSTE-ACS was diagnosed in 320 (20%) patients. Multivariable analysis identified age <70 years (odds ratio [OR] 2.19, 95% CI 1.58 to 3.04), estimated glomerular filtration rate >60 mL/min per 1.73 m(2) (OR 1.72, 95% CI 1.16 to 2.56), and lack of hypertension (OR 2.55, 95% CI 1.90 to 3.41), dyslipidemia (OR 2.76, 95% CI 2.05 to 3.73), diabetes mellitus (OR 2.49, 95% CI 1.78 to 3.48), previous myocardial infarction (OR 5.37, 95% CI 2.89 to 10.0), and elevated cardiac biomarkers (OR 2.84, 95% CI 2.11 to 3.83) as significant correlates of spasm-induced NSTE-ACS (P<0.01 for all variables). Transient ST-segment elevation during spontaneous attack (variant angina) was observed in 119 patients with spasm-induced NSTE-ACS. Variant angina was more common in nondyslipidemic men among patients with spasm-induced NSTE-ACS., Conclusions: The study showed frequent involvement of coronary spasm in the pathogenesis of NSTE-ACS. Variant angina was observed in one third of patients with spasm-induced NSTE-ACS. Coronary spasm should be considered even in patients with less coronary risk factors and nonobstructive coronary arteries.

Objectives: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS)., Methods: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively., Results: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography., Conclusions: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation., (© 2014 S. Karger AG, Basel.)

Background: The aim of this study was to elucidate the correlation between angiographic coronary vasomotor responses to intracoronary acetylcholine (ACh) injection, clinical features, and long-term prognosis in patients with vasospastic angina (VSA)., Methods and Results: This is a retrospective, observational, single-center study of 1877 consecutive patients who underwent ACh-provocation test between January 1991 and December 2010. ACh-provoked coronary spasm was observed in 873 of 1637 patients included in the present analysis. ACh-positive patients were more likely to be older male smokers with dyslipidemia, to have a family history of ischemic heart disease, and to have a comorbidity of coronary epicardial stenosis than were ACh-negative patients. ACh-positive patients were divided into 2 groups: those with focal (total or subtotal obstruction, n=511) and those with diffuse (severe diffuse vasoconstriction, n=362) spasm patterns. Multivariable logistic regression analysis identified female sex and low comorbidity of coronary epicardial stenosis to correlate with the ACh-provoked diffuse spasm pattern in patients with VSA. Kaplan-Meier survival curve indicated better 5-year survival rates free from major adverse cardiovascular events in patients with diffuse spasm pattern compared with those with focal spasm pattern (P=0.019). Multivariable Cox hazard regression analysis identified diffuse spasm pattern as a negative predictor of major adverse cardiovascular events in patients with VSA., Conclusions: ACh-induced diffuse coronary spasm was frequently observed in female VSA patients free of severe coronary epicardial stenosis and was associated with better prognosis than focal spasm. These results suggest the need to identify the ACh-provoked coronary spasm subtypes in patients with VSA.

We present the case of a 46-year-old woman with Prinzmetal's angina and syncope due to severe bradyarrhythmias. Dynamic electrical changes were documented on 12-lead 24-hour electrocardiographic (ECG) monitoring. We highlight the importance of continuous ECG monitoring in making the diagnosis and the indication for permanent cardiac pacing in this case.

The authors present the case of a 61-year-old woman who was troubled by regular episodes of throat discomfort, headache, dyspnoea and tingling sensation in the upper limbs. These were associated with occasional episodes of transient loss of consciousness accompanied by urinary incontinence over a period of 5 years. As these episodes became increasingly frequent, she was referred to a neurologist. Initial neurological assessment and investigations had a negative diagnostic yield and she was therefore referred for cardiac review. A repeat 24 h Holter revealed intermittent episodes of significant ST-segment elevation associated with a Mobitz type II atrio-ventricular block correlating with her symptoms. Her echocardiography and coronary angiography were normal; hence a diagnosis of Prinzmetal angina was made. She was treated appropriately with nitrates and a calcium channel blocker and followed up in cardiology clinic with no further recurrence of symptoms.

Purpose: The aim of this study was to evaluate the effects of a smoking cessation education on endothelial function and carboxyhemoglobin levels in smokers with variant angina., Methods: A nonequivalent control group pretest-posttest design was used. Participants were 60 male smokers with variant angina admitted to one hospital: the control group (30) between September and December, 2009, and the experimental group (30) between February and May, 2010. Endothelial function, as defined by flow-mediated vasodilation (FMD) of the brachial artery, and serum carboxyhemoglobin (COHb) were determined at baseline and at 3 months after the initiation of education in both groups., Results: Three months after the program, smoking cessation was successful in 22 of the 30 smokers in the experimental group, but only in 4 of 30 smokers in the control group (p<.001). After the education, the experimental group showed a significant increase in FMD, and a significant decreased in serum COHb compared with the control group., Conclusion: The findings indicate that this smoking cessation education program is effective for hospitalized smokers with variant angina.

Acute myocardial infarction resulting from an occlusive thrombus is recognized on an electrocardiogram by ST-segment elevation. The earlier the reperfusion, the greater the benefit, and the time to treatment is now considered to indicate the quality of care. In the current era when percutaneous interventions are carried out so readily, it is important to remember that acute infarction is not the only cause of ST-segment elevation. We hereby report a case of Prinzmetal's angina which mimics presentation of STEMI in many respects.

To illustrate the effect of myocardial bridges on coronary vascular tone, we describe the cases of 2 patients with different clinical presentations in the context of reproducible increased spasticity at the site of myocardial bridging. One had an episode of takotsubo cardiomyopathy, and one developed typical Prinzmetal angina while receiving desmopressin treatment for pituitary insufficiency. In both patients, acetylcholine challenge clearly revealed both the presence and the severity of myocardial bridging while producing several recognizable degrees of abnormal spastic tendency.Both baseline functional states and responses to different medications correlate with spastic tendency and enable the characterization of individual cases. Understanding the spectrum of spastic conditions might help to clarify the causes of atypical ischemic events, especially in patients with myocardial bridging.

We report the case of a 71-year-old woman with previous coronary angioplasty, ovarian cancer with multiple metastases and allergy to iodinated contrast media, who developed vasospastic angina after several treatments with cisplatin and cyclophosphamide, so that we considered this as a case of "allergic angina" or Kounis syndrome (type II variant). The patient underwent standard anti-ischemic therapy with nitrates, calcium blocking agents and enoxaparin so having an uneventful outcome., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

We report a case of recurrent variant angina pectoris which occurred even while receiving antispastic treatment. Coronary angiography revealed no obvious lesion. Behçet's syndrome was diagnosed based on recurrent oral aphthous and genital ulcer as well as skin manifestation. After treatment with immunosuppressant, neither angina nor oral ulcer relapsed. We strongly believe that the variant angina is due to coronary vasospasm induced by Behçet's syndrome in this patient.

Wellens syndrome is characterised by negative or biphasic T waves in V2-V4 leads and critical stenosis of proximal part of the left descending coronary artery. These ECG changes without atherosclerotic changes in coronary angiography, i.e. coronary artery spasm are called pseudo-Wellens syndrome. We describe a patient with acute coronary syndrome and pseudo-Wellens syndrome as a cause of vasospastic angina. These ECG abnormalities need differentiation with acute pulmonary embolism.

Variant angina is a form of angina pectoris that shows transient ST-segment elevation on electrocardiogram during an attack of chest pain. Ischemic episodes of variant angina show circadian variation and often occur at rest from midnight to early morning. Ischemic episodes also occur during mild exercise in the early morning. However, they are not usually induced by strenuous exercise in the afternoon. Other important clinical features of variant angina include the high frequency of asymptomatic ischemic episodes and the syncope that sometimes occur during the ischemic episodes. Syncope is due to severe arrhythmias, including ventricular tachycardia, ventricular fibrillation, and high-degree atrioventricular block. Coronary artery spasm is the mechanism of ischemic episodes in variant angina. The incidence of coronary artery spasm shows a racial difference and is higher in Japanese than in Caucasians. Coronary arteriograms are normal or near-normal in most Japanese patients with variant angina. Deficient basal release of nitric oxide (NO) due to endothelial dysfunction, and enhanced vascular smooth muscle contractility with the involvement of the Rho/Rho-kinase pathway are reported to play important roles in the pathogenesis of coronary artery spasm. Other precipitating factors of coronary artery spasm include imbalance in autonomic nervous activity, increased oxidative stress, chronic low-grade inflammation, magnesium deficiency, and genetic susceptibility. The genetic risk factors associated with coronary artery spasm include gene polymorphisms of endothelial NO synthase (NOS), paraoxonase, and other genes. Calcium channel blockers are extremely effective in preventing coronary spasm. The long-acting nitrate, nicorandil, and Rho-kinase inhibitor are also useful for inhibiting coronary artery spasm. Because variant angina can lead to acute myocardial infarction, fatal arrhythmias, and sudden death, early treatment is important. The prognosis of patients with variant angina is favorable, if early complications can be overcome. However, because coronary artery spasm cannot be suppressed in some patients, even with multiple medications, medications to suppress intractable coronary artery spasm must be developed.

The association of variant angina (VA) and myocardial bridges is a rare finding. We describe a case of VA with recurrent coronary spasm triggered by different stimuli at the site of a myocardial bridge. The interplay of endothelial dysfunction, coronary vasoconstriction and myocardial bridging was detected by intracoronary acetylcholine test and IVUS. We speculate that mechanical stimulation at the bridge site caused endothelial dysfunction and enhanced local susceptibility to vasoconstrictor stimuli. Variant angina should always be suspected in cases of ST-elevation acute coronary syndrome without any significant angiographic coronary stenosis.

Objective: Several studies have shown that significant coronary narrowing makes the prognosis of vasospastic angina pectoris (VAP) worse. However, the effects of various factors on the prognosis of patients without significant arterial narrowing have not yet been shown., Methods and Results: We investigated 1248 consecutive patients with VAP who had no coronary stenosis of more than or equal to 50%. The mean follow-up was 11.7±6.8 years. Ninety-one patients (7.3%) developed unstable angina, acute myocardial infarction, or effort angina with new coronary narrowings. Thirty patients (2.4%) died suddenly. Multivariate analysis showed that the presence of coronary stenosis, even if trivial, made the prognosis worse (P=0.027; odds ratio, 1.66; 95% confidence interval, 1.06-2.61). In addition, unusually, female patients had a better prognosis than male patients (P=0.007; odds ratio, 0.35; 95% confidence interval, 0.16-0.75). Other factors, such as hyperlipemia, diabetes, and hypertension did not affect the prognosis., Conclusion: In patients with VAP, the presence of coronary narrowing, even if mild, was associated with worse prognosis.

Background: It is generally considered that patients with variant angina pectoris (VAP) have a potential disturbance in the coronary endothelium. High-density lipoprotein (HDL) has been shown to mediate vasodilation as a result of its endothelium-enhancing property; however, the significance of low HDL in patients with VAP has not been clarified. We sought to determine the association between a low level of high-density lipoprotein cholesterol (HDL-C) and VAP., Methods: We examined a total of 174 consecutive patients who were suspected of having VAP and underwent spasm provocation test by direct injection of acetylcholine into the coronary arteries. One hundred and three patients (59%) were consequently diagnosed as having VAP. Serum HDL-C, fasting plasma glucose (FPG), and glycohemoglobin levels were measured in all patients., Results: HDL-C in quartiles showed a significant negative correlation with the presence of VAP. Multivariate analysis revealed that the lowest HDL-C quartile (<43 mg/dl), as well as cigarette smoking and impaired fasting glucose/diabetes mellitus, was an independent determinant of VAP (odds ratio=3.39, P=0.010). Patients in the highest FPG quartile (> or =106 mg/dl) or with cigarette smoking habit in combination with the lowest HDL-C quartile showed an increased risk for VAP (relative risk=2.01 and 1.88, respectively)., Conclusions: A low level of HDL-C is an independent determinant for VAP. Endothelial dysfunction caused by a low HDL state may play a role in the development of VAP., (Copyright 2008 Elsevier Ireland Ltd. All rights reserved.)

Coronary artery spasm has an important function in the etiology of variant angina and other acute coronary syndromes. Abnormal activation of Rho-family GTPases has been observed in cardiovascular disorders, but the function of genetic variability in Rho-family GTPases remains to be evaluated in cardiovascular disorders. We examined the genetic variability of Rho-family GTPases and their regulators in coronary artery spasm. We performed a comprehensive candidate gene analysis of 67 single nucleotide polymorphisms with amino-acid substitution in Rho-family GTPases and their regulators in 103 unrelated Japanese patients with acetylcholine-induced coronary artery spasm and 102 control Japanese subjects without acetylcholine-induced coronary artery spasm. We noted an association of the single nucleotide polymorphism of ARHGAP9 (rs11544238, Ala370Ser) with coronary artery spasm (odds ratio =2.67). We found that ARHGAP9 inactivated Rac as RacGAP and that the mRNA level of ARHGAP9 was strongly detected in hematopoietic cells. ARHGAP9 negatively regulated cell migration. The Ala370Ser polymorphism counteracted ARHGAP9-reduced cell migration, spreading and adhesion. The Ala370Ser polymorphism in the ARHGAP9 gene is associated with coronary artery spasm. These data suggest that the polymorphism of ARHGAP9 has a critical function in the infiltration of hematopoietic cells into the endothelium and inflammation leading to endothelial dysfunction.

Background: Endothelial dysfunction and vascular inflammation may be associated with variant angina (VA). Flow-mediated vasodilation (FMD), carotid artery intima-media thickness (IMT), and pulse wave velocity (PWV) are widely used as non-invasive modalities for evaluating atherosclerosis., Methods and Results: A total of 254 patients with chest pain were divided into three groups according to coronary angiogram (CAG) finding. There were 76 patients (VA group: 53.5+/-10.2 years, 41 males) with normal CAG with positive ergonovine-provocation test (EPT), 58 patients (control group: 55.3+/-8.7 years, 30 males) with normal CAG with negative EPT, and 120 patients with angiographically diagnosed coronary artery disease (CAD group: 56.3+/-9.7 years, 79 males). The level of FMD was lower in the VA group than in the control group (7.7+/-3.5% vs. 9.4+/-3.8%, p=0.014). Carotid IMT was higher in the VA group than in the control group (0.58+/-0.1 mm vs. 0.54+/-0.1 mm, p=0.029). The brachial-ankle PWV (baPWV) was higher in the VA group than in the control group (1445.3+/-211.8 cm/s vs. 1396.7+/-394.5 cm/s, p=0.020). The levels of monocyte cell counts was higher in patients of the VA group than in the other two groups (7545.7+/-2611.1/mm(3) vs. 6548.2+/-2156.4/mm(3) vs. 6740.9+/-1730.4/mm(3), p=0.015, respectively; monocyte cell counts: 657.2+/-242.6/mm(3) vs. 442.5+/-219.3/mm(3) vs. 490.0+/-172.0/mm(3), p=0.025)., Conclusion: VA is associated with endothelial dysfunction and increased carotid IMT, baPWV, and inflammatory markers.

The role of endothelial dysfunction in coronary vasospasm is controversial. We hypothesized that reactive oxygen species (ROS) and endothelin-1 (ET-1) are plausible candidates as the mediator of vasospasm is linked to endothelial dysfunction. In a pig model with repetitive endothelial injury in coronary arteries, intracoronary administration of serotonin induced a vasospasm at the endothelial injury site. The level of endothelin-converting enzyme was upregulated at that site where, upon exposure to serotonin, there were also increases in p47(phox), ROS, and ET-1 fluorescence intensities, and myosin light chain phosphorylation and RhoA activation were detected. The nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, had the effect of extinguishing not only ROS but also the appearance of ET-1. The chronic blockade of endothelin type-A receptor prevented a serotonin-triggered vasospasm along with the inhibition of ROS generation and myosin light chain phosphorylation. Under the coronary artery endothelial dysfunction, ET-1 is essential for an ROS-dependent coronary vasospasm. Our findings suggest that endothelial dysfunction plays a critical role in clinically defined human Prinzmetal angina.

Prinzmetal's variant angina (VA) and cardiac syndrome X (CSX) are two distinct, usually easily recognizable, forms of angina syndromes, caused by epicardial spasm, usually responsible for transient transmural myocardial ischemia at rest and by coronary microvascular dysfunction (CMVD), usually responsible for effort induced subendocardial ischemia, respectively. In this article we report clinical evidence in three patients of the simultaneous occurrence of angina episodes typical of both VA and CSX, suggesting that common pathogenetic factors may be responsible for clinical manifestations both of functional macrovascular and microvascular coronary artery abnormalities in some angina patients.