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.

Resistant hypertension: medical management and alternative therapies.

Resistant hypertension affects 20% to 30% of patients with high blood pressure (BP). It is defined as failure to achieve goal BP despite using at least 3 antihypertensive drugs of different classes, at maximal tolerated doses, one of which must be a diuretic. Persistent suboptimal BP is the most common attributable risk for death worldwide and its prevalence will most likely increase over the next decade. We review the epidemiologic aspects and diagnostic challenges of resistant hypertension, barriers to achieving proper BP control, and causes of secondary hypertension. Lifestyle modification and pharmacologic and device approaches to treatment are discussed.

Unusual complications of percutaneous epicardial access and epicardial mapping and ablation of cardiac arrhythmias.

BACKGROUND: Percutaneous epicardial access and mapping/ablation of cardiac arrhythmias are being increasingly performed. Although complications such as pericardial effusion are relatively common, other unusual complications may occur due to the complex anatomic architecture of the heart and surrounding tissues. In this report, we report a series of rare and unusual complications related to percutaneous epicardial procedures. METHODS AND RESULTS: Between 2006 and 2011, 334 patients underwent attempts at percutaneous, subxiphoid access for epicardial mapping/ablation at 5 experienced centers. Seven selected complications are highlighted in this case series. Patient 1 had a 1-cm right ventricular pseudoaneurysm after several unsuccessful attempts at epicardial access. This was successfully managed conservatively. Patient 2 had intra-abdominal bleeding related to puncture of the left lobe of the liver during access that required surgical repair. Patient 3 had a subcapsular hepatic hematoma that was probably related to percutaneous access and was successfully managed conservatively. Patient 4 had severe pericardial bleeding followed by ventricular fibrillation, immediately after obtaining percutaneous epicardial access. A lacerated middle cardiac vein was repaired surgically. However, the patient ultimately died of complications. Patient 5 had a history of cardiothoracic surgery and developed a right ventricle-abdominal fistula after multiple attempts at percutaneous access. This was surgically repaired without major sequelae. Patient 6 had cardiac tamponade caused by a lacerated coronary sinus branch during epicardial catheter ablation and required surgical repair. Patient 7 had severe left coronary vasospasm and ventricular fibrillation during catheter manipulation in the pericardium. This complication was successfully managed with intracoronary nitrates. CONCLUSIONS: Though generally safe, percutaneous epicardial access and mapping/ablation can result in uncommon complications. Awareness of these rare complications may facilitate early detection and successful management.

Coronary artery endothelial protection after local delivery of 17beta-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function.

OBJECTIVES: The goal of this research was to study the effect of locally delivered 17beta-estradiol (17beta-E) during angioplasty on endothelial function after percutaneous transluminal coronary angioplasty (PTCA) at four weeks. BACKGROUND: The endothelium plays a major role in the structural and functional integrity of coronary arteries and is damaged by PTCA. METHODS: Juvenile swine were subjected to PTCA, after which each artery was randomly-assigned to 600-microg 17beta-E delivered locally, an equal volume of vehicle (V) or PTCA alone. After four weeks, the improvement in endothelial function was assessed by angiography using intracoronary acetylcholine (Ach) infusion and by immunohistochemistry. RESULTS: At 10(-5) mol/l and 10(-4) mol/l Ach, significant vasoconstriction was noted in arteries treated with PTCA alone (p < 0.01 and p < 0.0001, respectively) and with PTCA plus V (p < 0.02 and p < 0.001, respectively). No significant vasoconstrictive response to Ach was observed in arteries treated with PTCA plus 17beta-E. Immunohistochemistry of vessels four weeks after PTCA revealed enhanced re-endothelialization (p < 0.0005) and endothelial nitric-oxide synthase (eNOS) expression (p < 0.0005) in PTCA plus 17beta-E-treated arteries compared with the other two treatment groups. Arteries treated with 17beta-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression. CONCLUSIONS: Locally delivered 17beta-E significantly enhances re-endothelialization and endothelial function after PTCA, possibly by improving the expression of eNOS. Since endothelial dysfunction can promote both restenosis and coronary spasm, local 17beta-E administration is a promising new approach to improve long-term results after PTCA.

Coronary artery spasm induced by carotid sinus massage.

A 60 year old man with a history of frequent episodes of chest pain and dizziness was referred for evaluation of coronary artery disease. He had no significant coronary artery stenosis at baseline coronary angiography. A carotid sinus massage was performed for evaluation of carotid sinus hypersensitivity in the patient. Both heart rate and blood pressure decreased a little, and returned to baseline level immediately after carotid sinus massage. However, 2.5 minutes after carotid sinus massage, ECG showed ST segment elevation in leads II, III, and aVF. Four minutes after carotid sinus massage, he had chest pain with a progressive elevation in the ST segment in the same leads, when he had 99% focal spasm in the right coronary artery. The vasospasm induced by carotid sinus massage was reproducible over several minutes and resolved spontaneously. Coronary artery spasm may be provoked by the enhanced vagal activation due to carotid sinus massage.

Acute myocardial infarction induced by alternating exposure to heat in a sauna and rapid cooling in cold water.

We describe a patient with acute myocardial infarction, which was thought to result from plaque rupture or thrombosis because of coronary artery spasm. The vasospasm was most likely induced by stimulation of the alpha-adrenergic receptors during alternating heat exposure during sauna bathing and rapid cooling during cold water bathing. This report emphasizes the dangers of rapid cooling after sauna bathing in patients with coronary risk factors.

[The correction of disorders in arachidonic acid metabolism in coronary spasm of an immune origin]. / Korektsiia porushen' metabolizmu arakhidonovoï kysloty pry koronarospazmi imunnoho henezu.

The effect of phosphocreatine and hydroxamate-linoleate (an inhibitor of lipoxigenase) on development of the pathologic process in coronary vessels with immune (cytotoxic) injury of the heart was studied in the experiments on narcotized dogs. Development of the immune response after administration of cardiac serum resulted in development of large transmural damage of the left ventricle myocardium, increased resistance of coronary vessels and changed coronary vascular reactions, which correlates with changes in arachidonic acid metabolism. Experimental data described in this report demonstrate the efficiency of membrane coronary vessels stabilization and inhibition of a lipoxygenase pathway in arachidonic acid metabolism in protection of immune damage of the heart and coronary vessels.

Successful treatment of coronary artery spasm following coronary artery bypass grafting.

A case of coronary artery spasm developed 6 hours after myocardial revascularization inducing both hemodynamic and electrocardiographic changes, is reported. The spasm was documented by coronary angiography, and it was not reversed by intracoronary infusion of isosorbide dinitrate. Intravenous infusion of nifedipine (initial dose of 0.0104 mg/min to final dose of 0.0208 mg/min), along with infusion of glyceronitrate (1.0 micrograms/kg/min) was able to significantly improve hemodynamic impairment and to reverse electrocardiographic changes in 12 hours. Coronary angiography, repeated in postoperative day 3, after 48 hours of continuous nifedipine infusion, showed a resolution of coronary spasm. There was no evidence of myocardial infarction as resulted from total CPK and MB isoenzyme release. Nifedipine infusion was gradually reduced as oral administration of slow release nifedipine (40 mg twice daily) was started. The combined intravenous infusion of glyceronitrate and nifedipine seems to be able to control and overcome coronary artery spasm following coronary surgery.

Coronary artery spasm following coronary artery bypass grafting. Treatment with intracoronary ISDN followed by systemic intravenous nifedipine infusion.

Coronary artery spasm following coronary artery bypass grafting (CABG) has been described previously. The cause and underlying risk factors are mainly speculative and treatment therefore symptomatic. We present the successful management of this condition by administration of an intravenous Nifedipine infusion after intracoronary Isosorbide dinitrate (ISDN) had failed to relieve the spasm.

[A combination of nifedipine and diltiazem in the treatment of refractory spastic angina]. / Association de la nifédipine et du diltiazem dans le traitement de l'angor spastique réfractaire.

Both diltiazem (D) and nifedipine (N) have been shown to be effective in the treatment of spastic angina, but they sometimes prove inadequate, even in high doses. These two drugs have been given in combination on the grounds of a possible synergistic action, but the results obtained were limited by side-effects. We decided to administer the combined treatment in half doses to patients with spastic angina and normal coronary vessels in order to assess its effectiveness and acceptance. The trial was conducted on 13 patients: 11 men and 2 women aged from 37 to 71 years (mean 53 years) with normal or subnormal coronary arteriography. In the absence of any treatment, these patients responded to the ergonovine test by a coronary spasm which we were subsequently unable to prevent with either D or N. Each patient underwent, at the same hours, 4 ergonovine tests, the product being injected intravenously every 3 minutes in incremental doses of 1, 2, 3 and 6 micrograms/kg. These tests were performed without treatment, after 3 days of treatments with D alone (360 mg/kg), after 3 days of treatment with N alone (60 mg/kg) and after 3 days of treatment with D (180 mg/kg) plus N (30 mg/kg). Without treatment, ergonovine triggered the coronary spasm in all 13 patients at a mean threshold dose of 2.7 micrograms/kg. Under treatment with D or N given separately, no test became negative, but the threshold doses of ergonovine rose to 4.5 and 4.6 micrograms/kg respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Spasm of small coronary arteries and ischemic myocardial injury induced by hypothalamic stimulation in the rat.

Electrical stimulation of the lateral hypothalamus resulted in electrocardiographic evidence of acute myocardial ischemia in 35% of normal adult rats under anesthesia. Mean arterial blood pressure was also elevated. Study of vascular corrosion casts disclosed that spasm of smaller branches of the coronary circulation, rather than the major epicardial arteries, was the main cause of the ischemic response. The histologic changes of the same experimental treatment in a separate group of animals revealed multiple focal areas of tissue damage throughout the myocardium, which were quantitatively assessed. The results may be relevant for the clinical problem of various forms of ischemic heart disease in which little evidence is found for organic (atherosclerosis) or dynamic (spasm) stenosis involving the major coronary arteries.

Intraoperative coronary artery spasm successfully treated with nitroglycerin and nifedipine.

Coronary artery spasm is recognized as a major cause of angina and may coexist with fixed coronary artery disease. This report presents the case of a patient who developed recurrent coronary artery spasm in the operating room following effective coronary artery bypass grafting. The coronary artery spasm was manifested by sudden ST segment elevation, hypotension, and decreased cardiac output. Direct injection of nitroglycerin into each coronary artery graft was necessary to reverse the coronary artery spasm. Peripheral intravenous nitroglycerin plus nifedipine administered through a nasogastric tube prevented further recurrence of coronary artery spasm.