Patients with symptomatic ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death remain at high risk for arrhythmia recurrence. In recent years, strategies to treat these patients have changed. Concerns about the proarrhythmia risk and uncertain efficacy of class I agents have resulted in a shift in interest to non-class I antiarrhythmic drugs such as sotalol and amiodarone. Both drugs have class III antiarrhythmic properties (i.e., both lengthen repolarization and refractoriness); however, each also has its own additional electrophysiologic effects. Prospectively designed, randomized studies have shown that both sotalol and amiodarone have more potent antiarrhythmic actions than class I agents. However, even as the advantages of sotalol and amiodarone have been recognized, enthusiasm for nonpharmacologic modes of treatment, particularly the implantable cardioverter-defibrillator (ICD), has also markedly increased. The ICD has been shown to decrease dramatically the incidence of sudden death, which may lead to the reduction of total mortality. Whether patients with life-threatening ventricular tachyarrhythmias should be treated first with antiarrhythmic agents or with an ICD is an important question. The results of recent studies suggest that treatment with an ICD is more effective than electrophysiologically guided treatment with class I agents. However, results of prospectively designed randomized studies comparing the efficacy of the ICD with that of sotalol and amiodarone must become available before definitive recommendations can be made concerning the use of the ICD as first-line therapy in patients with ventricular tachycardia/ventricular fibrillation or aborted sudden cardiac death. In addition, there may be a significant role for the use of antiarrhythmic drugs in conjunction with ICDs.
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The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation.
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Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current.
Flecainide, mexiletine, propafenone, and amiodarone are antiarrhythmic drugs that are used primarily in the treatment of cardiac arrhythmias. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with loxapine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix matched calibration curve is used for quantitation.
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We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers.
Simvastatin is lipophilic statin with a short half-life that is primarily metabolized by CYP450 3A4. At doses of 5 - 80 mg, simvastatin lowers LDL cholesterol by 25 - 50%. Simvastatin has been shown to reduce the risk of cardiovascular disease by 35% and overall mortality by up to 30% over 5 years. The recommended starting dose of simvastatin 40 mg is approved as a lipid-lowering agent and for all high-risk patients, including those with cardiovascular disease and diabetes, regardless of the baseline LDL level. Simvastatin dose should be adjusted in those receiving CYP3A4 inhibitors, gemfibrozil, or ciclosporin, amiodarone, or in those with severe renal insufficiency. Coformulation of simvastatin with ezetimibe is now available, and coformulation with extended release niacin is under development.
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In the present study, the incidence of AIH was similar to that reported in iodine-replete areas. The incidence of AIT was higher that previously reported, a fact underlining the importance of the proper screening and monitoring of patients. Cases with previous thyroid morphologic and/or immunologic abnormalities require frequent monitoring.
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Eight patients (3 women and 5 men, aged 14 to 60 years) with repetitive, uniform atrial tachycardias were studied. In six patients the arrhythmia had been refractory to at least three antiarrhythmic agents (class 1A and C sodium channel blockers, amiodarone, beta-adrenergic blocking agents, verapamil, digoxin). Conventional electrocardiograms, Holter recordings and B mode echocardiograms were performed in each patient. Intravenous lidocaine and verapamil were tested in the eight patients. Six patients underwent an electrophysiologic study.
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We present the latest changes in the guidelines for resuscitation from the International Liaison Committee on Resuscitation (ILCOR). Defibrillation performed by non-medical personnel is more strongly endorsed than before. In unintubated patients the ventilation-to-compression ratio should always be 2:15. With a foreign body in the airway of an unconscious patient, compressions should be performed instead of the Heimlich manoeuvre. Amiodarone 300 mg intravenously is the first choice in refractory ventricular fibrillation or ventricular tachycardia in adults. Intubation of children is only recommended when performed by experienced personnel. The use of drugs is less recommended than previously; albumin is not recommended for the newly born.
Depending on the severity of the disease, patients with dilative cardiomyopathy (DCM) have a poor prognosis. No definite data are available to show that complex ventricular ectopy, the presence of ventricular late potentials, or programmed electrical stimulation in patients without symptoms with DCM identify patients at risk of sudden cardiac death. Although poor left ventricular function seems to be the most potent predictor of total cardiac death, the prediction of sudden death in patients without symptoms with DCM is poor. Studies with either class I antiarrhythmic drugs or amiodarone have not yet demonstrated a reduction in total mortality rates or sudden death. The usefulness of an implantable cardioverter defibrillator (ICD) in patients without symptoms with DCM is currently under investigation. The usefulness of serial electropharmacologic testing for patients with documented sustained ventricular tachycardia or ventricular fibrillation and DCM is still controversial. Because most patients with DCM and VT or out-of-hospital cardiac arrest have either no inducible ventricular tachyarrhythmia at baseline or the reproducibility of ventricular tachycardia/ventricular fibrillation induction is poor, implantation of an ICD should be considered in most of these patients. The indication for implantation of an ICD should be made on clinical judgment of the patient's functional status and other prognosis-limiting factors, such as rapid progression of heart failure, end-stage heart failure, and age.
Between March 2002 and December 2004, 61 patients (mean age 65.4 +/- 10 years) underwent isolated endo-left atrial AF ablation using a unipolar RF device (Cardioblate; Medtronic, USA) in conjunction with 34 MV repairs and 27 MV replacements. AF was paroxysmal in 13 patients (21%), and permanent in 48 (79%), with a mean duration of 3.6 +/- 3.5 years. The etiology was degenerative in 35 patients (57%), rheumatic in 17 (28%), and ischemic in nine (17%). All patients received amiodarone postoperatively.
The purpose of this prospective study was to characterize the clinical profile of patients with atrial fibrillation (AF) in the urban population of a sub-Saharan African country and to assess how successfully current guidelines are applied in that context.
We searched MEDLINE (1966 through 2000) for English-language publications providing specific monitoring recommendations for amiodarone. A cross-sectional retrospective chart review of 99 outpatients receiving amiodarone therapy between Jan 1, 2000, and Jan 1, 2001, at a large tertiary-care hospital was performed to assess monitoring practices. Adverse drug events were identified by use of structured implicit reviews. The main outcome measure was the proportion of patients receiving the monitoring recommended in the literature and having amiodarone-related adverse drug events.
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Dronedarone is a novel multichannel blocker with antiadrenergic and vasodilatory properties. The aim of this study was to investigate the effects of dronedarone on functional capacity in patients with severe left ventricular (LV) dysfunction and compensated stable heart failure (HF).
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ARFI seems to be a useful method for the assessment of diffuse thyroid gland pathology.
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To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability.
A case of lung disease due to amiodarone is described based on epidemiological, clinical and evolution criteria, bronchoalveolar lavage (BAL) analysis, X-ray and pathological study by optic and electron microscopy. Iodine on pulmonary tissue quantified spectrophotometrically was 2 p.p.m. This was not observed in normal lung tissue. The best diagnostic criteria for amiodarone pneumopathy are discussed highlighting lymphocytosis in the BAL and the presence of dense lamellar bodies in the ultrastructural study of the affected lung tissue.
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Surgical therapy with mapping-guided subendocardial resection was used in 30 patients with drug-refractory ventricular tachycardia. Results of preoperative, intraoperative and postoperative electrophysiologic evaluation and long-term clinical follow-up are reported. Left ventricular aneurysm was located in the inferior wall in 8 patients and in the anterior wall in 22. Left ventricular mapping was performed in 15 patients preoperatively and in all 30 patients intraoperatively. Subendocardial resection was supplemented with cryoablation in 26 patients and with laser photocoagulation in 4. Coronary bypass surgery was performed in 27 patients. The surgical mortality rate was 10%; the three deaths were due to cardiogenic shock, pneumonia and sepsis, respectively. At postoperative electrophysiologic study, ventricular tachycardia was inducible in 8 (30%) of 27 patients. Previously ineffective antiarrhythmic drugs were effective in preventing the induction of ventricular tachycardia in four of these eight patients. Two of the remaining four patients received an automatic implantable cardioverterdefibrillator; the other two were treated with amiodarone. At a mean follow-up period of 18 +/- 17 months (range 1 to 52), there has been one sudden death and one nonfatal recurrence of ventricular tachycardia in the 18 patients without inducible arrhythmias postoperatively. Among the eight patients with inducible ventricular tachycardia after subendocardial resection, there has been one nonfatal ventricular tachycardia recurrence. Thus, among the 27 patients surviving surgery, 17 (63%) were cured with surgery alone, and another 7 (26%) had their ventricular tachycardia controlled with drugs (n = 5) or the defibrillator (n = 2). Inability to completely map the tachycardia, a clinical history of cardiac arrest requiring resuscitation and the presence of myocardial infarction within 2 months predicted postoperative arrhythmia inducibility and recurrence.
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The short QT syndrome (SQTS) is associated with cardiac arrhythmias and sudden death. The SQT1 form of SQTS results from an inactivation-attenuated, gain-of-function mutation (N588K) to the human ether-à-go-go-related gene (hERG) potassium channel. Pharmacological blockade of this mutated hERG channel may have therapeutic value. However, hERG-blocking potencies of canonical inhibitors such as E-4031 and D-sotalol are significantly reduced for N588K-hERG. Here, five hERG-blocking drugs were compared to determine their relative potencies for inhibiting N588K channels, and two other inactivation-attenuated mutant channels were tested to investigate the association between impaired inactivation and altered drug potency.
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In general, antiarrhythmic agents that prolong the action potential duration (APD) have attenuated effects on repolarization at short cycle lengths (reverse frequency dependence), and this may limit their efficacy for controlling ventricular arrhythmias. The frequency-dependent effects of amiodarone on repolarization may differ from those of other antiarrhythmic agents and have not been determined in humans.
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Elderly patients are more susceptible to the adverse effects of antiarrhythmic medications as a result of multiple factors, including decreased clearance and metabolism of medications as well as interactions caused by comorbid conditions and medications. Pharmacists can play a key role in a multidisciplinary team to monitor and educate patients on their antiarrhythmic therapy.
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1. The cardiac actions of amiodarone, a benzofuran derivative used in the treatment of angina pectoris, have been compared with those of (+/-)-propranolol in anaesthetized dogs.2. After three successive intravenous injections of propranolol, 0.5 mg/kg, had reduced the heart rate by 25%, a fourth dose had no further negative chronotropic action, but amiodarone, 10 mg/kg intravenously, at this point reduced the heart rate by 23%.3. Amiodarone, 10 mg/kg intravenously, reduced, but did not abolish, cardiac responses to isoprenaline, 2 mug/kg intravenously. Subsequent successive injections of 10 mg/kg of amiodarone did not further block the responses to isoprenaline, but propranolol, 1 mg/kg intravenously, abolished them.4. Amiodarone reduced cardiac chronotropic and inotropic responses to glucagon, which were not affected by propranolol.5. Cardiac output was increased 5 min after amiodarone, 10 mg/kg intravenously, but at 10 min and thereafter it did not differ from control values. Propranolol, 1 mg/kg intravenously, reduced cardiac output by 17% at 5 min, and by 30% after 30 min.6. From this and other evidence which is discussed, it is concluded that the cardiac actions of amiodarone are not produced by competitive blockade of beta-adrenoceptors.
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Iodine plays an important role in thyroid physiology resulting from its importance as a requisite substrate for the synthesis of thyroid hormones and from its action as a regulator of thyroid function. Following intestinal absorption, inorganic iodide is largely confined to the extracellular fluid. Serum concentrations of inorganic iodide well reflect the amount of iodine present in the extracellular compartment. Since serum inorganic iodide levels are important determinants of thyroid iodine uptake, serum iodide measurement offers a valuable tool for the investigation of many basic and clinical aspects of thyroid iodine metabolism. Here we summarize important aspects of iodine metabolism and focus selectively on technical aspects of serum inorganic iodide measurement and on the kinetics of inorganic iodide in various states of iodine excess. Presently, paired-ion, reversed-phase HPLC with electrochemical detection is obviously the best method for measurement of serum inorganic iodide being highly sensitive, easy to perform, and almost completely insensitive to interfering substances. Using this method, we could demonstrate an acute increase of serum inorganic iodide during the administration of large amounts of iodide as Lugol's solution given preoperatively in patients with Graves' hyperthyroidism. In patients under treatment with the iodine containing drug amiodarone (n=37), serum inorganic iodide levels were highly elevated (range 3.5-208.2 microg/dl, median 36.6 microg/dl). Serum concentrations of inorganic iodide were correlated neither to the daily amiodarone dose, nor to the serum levels of amiodarone.
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The antidysrhythmic drug amiodarone may be given during general anesthesia. We examined the single and combined direct cardiac effects of amiodarone and halothane in the isolated guinea pig heart. Guinea pig hearts were isolated and perfused retrogradely through the aorta with oxygenated Krebs-Ringer solution at 37 degrees C at constant pressure (55 mm Hg). Variables measured in 61 hearts included spontaneous heart rate (HR), atrioventricular conduction time (AVCT), isovolumetric left ventricular pressure (LVP), and coronary flow (CF). Amiodarone was administered as a single bolus into the retrogradely perfused aortic root and halothane was vaporized into the perfusing solution. Mean control values of pooled data before treatment were as follows: HR, 228 +/- 4 (SEM) beats/min; AVCT (during atrial pacing at 240 beats/min), 82 +/- 2 ms; LVP, 97 +/- 4 mm Hg; and CF, 6.1 +/- 0.2 mL.min-1.g-1. Amiodarone, 100 micrograms and 200 micrograms, decreased HR by 8% +/- 2% and 8% +/- 2%, increased AVCT by 5 +/- 2 and 15 +/- 3 ms, decreased LVP by 22% +/- 3% and 27% +/- 3%, and increased CF by 20% +/- 1% and 40% +/- 2%, respectively; all these changes were sustained for 60 min and, except for HR, were dose dependent. Halothane, 0.5% and 1%, transiently and dose-dependently decreased HR by 6% +/- 2% and 12% +/- 2% increased AVCT by 4 +/- 2 and 8 +/- 2 ms, decreased LVP by 15% +/- 3% and 31% +/- 3%, and increased CF by 2% +/- 1% and 6% +/- 2%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Twelve consecutive patients referred by physicians with chronic atrial fibrillation which had not responded appropriately to pharmacological agents.
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1. The acute effects of amiodarone (AM), a potent antiarrhythmic drug, on tetrodotoxin (TTX)-sensitive component of action potentials of Purkinje fibers from guinea pig were studied by use of conventional microelectrode techniques, and compared the findings with the results obtained in the papillary muscle. 2. The present study showed that the action potentials of Purkinje fibers (PF) were more sensitive to AM, compared to those of papillary muscle. 3. Acute exposure (30 min) to 4.4 x 10(-5) M AM led to a depression of plateau potential of PF action potential, but the drug did not affect the total action potential duration. 4. TTX (2-4 x 10(-6) M) shortened the PF action potential duration at all levels of repolarization. 5. The depression of PF plateau potential in the presence of AM was, at least in part, involved in a decrease in TTX-sensitive plateau sodium current, because no further depression of the plateau potential was observed by addition of TTX in the presence of AM.