Early repolarization in the inferolateral leads predicts the presence of vasospastic angina: a novel predictor in patients with resting angina.

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.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

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 (ß = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

ST-segment elevation and the Tpeak-Tend/QT ratio predict the occurrence of malignant arrhythmia events in patients with vasospastic angina.

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.

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

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.

Vasospastic angina: A literature review of current evidence.

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.

Alternative causes of myocardial ischemia in women: An update on spontaneous coronary artery dissection, vasospastic angina and coronary microvascular dysfunction.

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.

Prinzmetals angina presenting with non critical lesion with normal FFR -to stent or not to stent.

Variant angina also called Prinzmetals angina is an enigma characterized by transient circadian symptoms of chest pain associated with ECG changes. The patient is symptom free with normal ECG and echo during symptom free periods. We present a case associated with transient ST-segment elevation with non critical lesion with normal FFR.

Fluctuations in the amplitude of ST-segment elevation in vasospastic angina: Two case reports.

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.

Clinical implications of low-dose aspirin on vasospastic angina patients without significant coronary artery stenosis; a propensity score-matched analysis.

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.

Pharmacotherapy of Vasospastic Angina.

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.

Differential incidence and type of spasm according to coronary arterial location.

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.

The Usefulness of Spinal Cord Stimulation for Chronic Pain Due to Combined Vasospastic Prinzmetal Angina and Diabetic Neuropathic Pain of the Lower Limbs.

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.