Prognostic Impact of Chronic Vasodilator Therapy in Patients With Vasospastic Angina.

Background Chronic vasodilator therapy with long-acting nitrate is frequently used to treat vasospastic angina. However, the clinical benefits of this approach are controversial. We investigated the prognostic impact of vasodilator therapy in patients with vasospastic angina from the multicenter, prospective VA-KOREA (Vasospastic Angina in KOREA) registry. Methods and Results We analyzed data from 1895 patients with positive intracoronary ergonovine provocation test results. The patients were divided into 4 groups: no vasodilator (n=359), nonnitrate vasodilator (n=1187), conventional nitrate (n=209), and a combination of conventional nitrate and other vasodilators (n=140). The primary end point was a composite of cardiac death, acute coronary syndrome, and new-onset arrhythmia at 2 years. Secondary end points were the individual components of the primary end point, all-cause death, and rehospitalization due to recurrent angina. The groups did not differ in terms of the risk of the primary end point. However, the acute coronary syndrome risk was significantly higher in the conventional nitrate (hazard ratio [HR], 2.49; 95% CI, 1.01-6.14; P=0.047) and combination groups (HR, 3.34; 95% CI, 1.15-9.75, P=0.027) compared with the no-vasodilator group, as assessed using the inverse probability of treatment weights. Subgroup analyses revealed prominent adverse effects of nitrate in patients with an intermediate positive ergonovine provocation test result and in those with low Japanese Coronary Spasm Association scores. Conclusions Long-acting nitrate-based chronic vasodilator therapy was associated with an increased 2-year risk of acute coronary syndrome in patients with vasospastic angina, especially in low-risk patients.

Pericarditis as a trigger for Prinzmetal angina - a case report.

Prinzmetal angina is one of the causes of acute coronary syndromes, the exact etiology of which is still unknown. Here we introduce a 27-year-old man with no history of cardiovascular disease, with a history of hospitalization due to acute pericarditis in the previous month, who was discharged with a good response to ibuprofen treatment but had clinical and electrocardiographically recurrence of pericarditis with compressive retrosternal chest pain and electrocardiogram (ECG) changes in favor of acute infero-postero-right ventricular (RV) myocardial infarction (MI). Treatment with vasodilator improved compressive retrosternal chest pain and reversed acute myocardial infarction changes completely and left pleuritic chest pain and pericarditis changes in the ECG. Due to the typical chest pain, he was admitted to the emergency room; ECG revealed generalized ST-segment elevation with acute pericarditis pattern again. Acute infero-posterior and right ventricular acute myocardial infarction pattern was also evident. After treatment with nitroglycerin in the Critical Cardiac Unit (CCU), all ECG ischemic changes returned to baseline, and pericarditis remained in all leads. The patient was discharged with non-steroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and a good general condition.

A case of vasospastic angina. Vasospasm physiopathology: a new therapeutic role for ranolazine?

We report the case of a 40-year-old man, transferred from another hospital to our ICU because of acute coronary syndrome. Coronarography did not show coronary stenosis. Twenty-four hours monitoring EKG allowed diagnosis of Prinzmetal angina and appropriate therapy was administered. Six months after discharge due recurrence of symptoms, ranolazine was added to therapy. After one year the patient is symptoms free.

Clopidogrel plus Aspirin Use is Associated with Worse Long-Term Outcomes, but Aspirin Use Alone is Safe in Patients with Vasospastic Angina: Results from the VA-Korea Registry, A Prospective Multi-Center Cohort.

Anti-platelet agents are commonly used in vasospastic angina (VA) patients with comorbidity like coronary artery disease. However, long-term clinical outcomes in the use of aspirin, clopidogrel or the two agents together have rarely been investigated in VA patients. In a prospective study, we enrolled 2960 patients who received coronary angiography and ergonovine provocation test at 11 university hospitals in Korea. Among them, 1838 patients were diagnosed either with definite (n = 680) or intermediate (n = 1212) VA, using the criteria of chest pain, ECG changes and ergonovine provocation test results. They were analyzed according to their use of aspirin, clopidogrel or both, or no anti-platelet agent at all. The primary outcome was time to composite events of death from any cause, acute coronary syndrome (ACS) and symptomatic arrhythmia during a 3-year follow-up. A primary composite outcome was significantly more common in the aspirin plus clopidogrel group, at 10.8% (14/130), as compared with the non-antiplatelet group, at 4.4% (44/1011), (hazard ratio [HR] 2.41, 95% confidence interval [CI], 1.32-4.40, p = 0.004). With regard to the person-time event rate, similar results were shown, with the highest rate in the aspirin plus clopidogrel user at 4.72/1000 person months (95% CI, 2.79-7.96, log-rank test for primary outcome p = 0.016). The person-time event of the ACS rate was also highest in that group, at 2.81 (95% CI, 1.46-5.40, log-rank test for ACS p = 0.116). Kaplan-Meier survival analysis demonstrated poor prognosis in primary outcomes and ACS in aspirin plus clopidogrel users (log-rank test, p = 0.005 and p = 0.0392, respectively). Cox-proportional hazard regression analysis, adjusting for age, sex, history of coronary heart disease, hypertension, diabetes, presence or not of definite spasm, use of calcium channel blocker, demonstrated that the use of aspirin plus clopidogrel is an independent risk for the primary outcome (HR 2.01, CI: 1.07-3.81, p = 0.031). The aspirin-alone group had a similar primary and individual event rate compared to the no-antiplatelet agent group (HR 0.96, CI, 0.59-1.55, p = 0.872). Smokers using aspirin plus clopidogrel had poorer outcomes than non-smokers, with HR 6.36 (CI 2.31-17.54, p = 0.045 for interaction). In conclusion, among VA patients, aspirin plus clopidogrel use is associated with a poor clinical outcome at 3 years, especially in ACS. Aspirin alone appears to be safe for use in those patients.

Vasospastic Angina Presenting With Syncope and Chest Pain: A Case Report and Brief Literature Review.

A 65-year-old male presented to the hospital with chest pain associated with recurrent syncope. He had a history of coronary artery disease and a long-standing history of smoking. While he was hospitalized, he had an episode of chest pain during which he was found to have transient ST segment elevation in the inferior leads. He was also noted to have a brief cardiac tachyarrhythmia. Coronary arteriography revealed vasospasm of the left anterior descending artery and right coronary artery, which were relieved to a significant extent after administration of intracoronary nitroglycerin. Subsequent angiograms and fractional flow reserve studies, demonstrated underlying non-obstructive coronary artery disease at the sites of spasm. No percutaneous coronary intervention was pursued. The patient was started on a calcium channel blocker on dismissal from the hospital. Upon follow up several months later, he remained free of symptoms that brought him to the hospital.

Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test.

BACKGROUND: When drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction. METHODS AND RESULTS: We examined 245 consecutive patients with suspected vasospastic angina who had undergone acetylcholine provocation test. Of those patients, 29 patients had been on amlodipine, an ultra-long term acting CCB (group A), 34 on other CCBs (group O), and 182 patients on no CCB (group N). After CCBs had been withheld > 48h, we performed acetylcholine provocation, which resulted in 152 positive, 36 intermediate, and 57 negative reactions. We evaluated coronary artery tone calculated as follows: (luminal diameter after nitrate-baseline luminal diameter)÷(luminal diameter after nitrate)×100 (%). In group A patients, coronary artery tone was lower (A:9.1±6.9% vs. O:11.7±8.3% vs. N:12.1±8.5%, p=0.0011) and the positive rate of acetylcholine provocation test was lower than group O and group N (A:41% vs. O:68% vs. N:64%, p=0.047). Multivariate logistic analysis showed that taking amlodipine until 2days before acetylcholine provocation test was a significant inverse predictor for acetylcholine-provoked coronary spasm (odds ratio 0.327; 95% confidence interval 0.125-0.858, p=0.023). CONCLUSIONS: Residual vasodilatory effects of ultra-long acting CCB may decrease coronary artery tone and the vasoconstrictive reaction to acetylcholine suggesting that a 2-day pre-test drug holiday may not be long enough.

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.

Impact of Renin-Angiotensin System Inhibitors on Long-Term Clinical Outcomes of Patients With Coronary Artery Spasm.

BACKGROUND: Coronary artery spasm (CAS) is a well-known endothelial dysfunction, and a major cause of vasospastic angina (VSA). The renin-angiotensin system (RAS) is known to be closely associated with endothelial function. However, there are only a few studies that investigated the impact of RAS inhibitor on long-term clinical outcomes in VSA patients. METHODS AND RESULTS: A total of 3349 patients with no significant coronary artery disease, diagnosed with CAS by acetylcholine provocation test were enrolled for this study. Significant CAS was defined as having ≥70% narrowing of the artery after incremental injections of 20, 50, and 100 µg of acetylcholine into the left coronary artery. Patients were divided into 2 groups according to whether the prescription included RAS inhibitor or not (RAS inhibitor group: n=666, non-RAS inhibitor group; n=2683). To adjust for any potential confounders that could cause bias, propensity score matching (PSM) analysis was performed using a logistic regression model. After PSM analysis, 2 matched groups (524 pairs, n=1048 patients, C-statistic=0.845) were generated and their baseline characteristics were balanced. During the 5-year clinical follow-up, the RAS inhibitor group showed a lower incidence of recurrent angina (8.7% versus 14.1%, P=0.027), total death (0.0% versus 1.3%, P=0.045), and total major adverse cardiovascular events (1.0% versus 4.1%, P=0.026) than the non-RAS inhibitor group. CONCLUSIONS: Chronic RAS inhibitor therapy was associated with lower incidence of cardiovascular events in VSA patients in the 5-year clinical follow-up.

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.

[A CASE OF ASPIRIN-EXACERBATED RESPIRATORY DISEASE COMPLICATED BY REFRACTORY VARIANT ANGINA, WHICH SHOWED EXCELLENT RESPONSE TO STEROID TREATMENT].

A 47-year-old woman with aspirin-exacerbated respiratory disease visited our hospital complaining of persistent chest pain that manifested in the evenings and early mornings. Holter monitoring revealed ST elevation during chest pain and coronary angiography showed coronary vasospasm, which led to the diagnosis of variant angina. Chest pain persisted despite administration of a coronary vasodilator. The patient experienced an increase in peripheral blood eosinophils during the clinical course and received prednisolone for the same, which resulted in the resolution of her chest pain. Prednisolone was therefore seen to be effective for treating variant angina that manifested as a non-respiratory tract symptom of aspirin-exacerbated respiratory disease.

[Many possible causes of variant angina]. / Veel mogelijke oorzaken voor vasospastische angina pectoris.

BACKGROUND: Variant angina, or vasospastic angina, is a form of angina caused by vasospasm of the coronary arteries, probably caused by endothelial dysfunction. This form of angina is provoked by non-classical risk factors such as stress, alcohol use, use of sympathomimetics and low environmental temperatures, but also by smoking. Treatment is based on elimination of risk factors and vasodilator therapy with nitrates and long-acting calcium antagonists. CASE DESCRIPTION: We present a 68-year-old woman with recurring thoracalgia at rest and during exercise, suggestive of severe variant angina in more than one coronary artery. Despite elimination of risk factors and administration of vasodilatory therapy the treatment was initially insufficient. It eventually emerged that the probable cause was frequent use of a vasoconstrictive nasal spray, although this was not described in literature, and not originally mentioned by the patient. CONCLUSION: A thorough case history is of vital importance in a patient presenting with a history suggestive of variant angina. Even undescribed and apparently less important risk factors can be responsible for persistence of symptoms, and can lead to an applied treatment not producing the desired result.

Recurrent myocardial infarction secondary to Prinzmetal's variant angina.

Prinzmetal's variant angina describes chest pain secondary to reversible coronary artery vasospasm in the context of both diseased and non-diseased coronary arteries. Symptoms typically occur when the patient is at rest and are associated with transient ST-segment elevation. Acute episodes respond to glyceryl trinitrate, but myocardial infarction and other potentially fatal complications can occur, and long-term management can be challenging. Although it is not well understood, the underlying mechanism appears to involve a combination of endothelial damage and vasoactive mediators. In this case, a 35-year-old woman with myocardial infarction secondary to coronary artery vasospasm experienced recurrent chest pain. Coronary angiography revealed severe focal stenosis in the mid left anterior descending artery, which completely resolved after administration of intracoronary glyceryl trinitrate. The patient was discharged on nitrates and calcium channel blockers. The patient re-presented with another myocardial infarction, requiring up-titration of medical therapy.