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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sotalol is a unique compound with several potential antiarrhythmic mechanisms, including beta blockade (class II activity), action potential duration prolongation (class III activity), and possibly reduction of QT dispersion. In recent years, trials such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial reported disappointing results with the use of class I agents in the management of ventricular arrhythmias in patients with coronary artery disease. These results have led to increased interest in class III antiarrhythmic agents, including sotalol. Sotalol is effective in suppressing ventricular premature complexes as well as nonsustained and sustained ventricular tachyarrhythmias. The interaction between sotalol and implantable cardioverter-defibrillators (ICDs) is generally favorable. As is the case with other antiarrhythmic drugs, there is no placebo-controlled trial assessing the effect of sotalol on mortality. It is not known if sotalol is more effective than placebo, conventional beta blockade, amiodarone, or ICDs in reducing mortality from life-threatening ventricular arrhythmias. In addition, the optimal method of selecting patients for sotalol therapy has yet to be determined. The safety profile of sotalol has been well established in > 3,000 patients worldwide. Proarrhythmia occurs in approximately 4% of patients, and torsades de pointes occurs in approximately 2.5%. The majority of episodes of torsades de pointes occurs within 3 days of commencing sotalol therapy, and the risk of torsades de pointes increases sharply at dosages > 320 mg daily. It is recommended that initiation of sotalol therapy or dosage increases be performed in a monitored setting. Overall, only 1% of patients enrolled in clinical trials of sotalol discontinued therapy as a result of drug-related congestive heart failure. However, these trials have excluded patients with poor left ventricular systolic function and/or overt heart failure. The optimal management of these patients, who are at greatest risk of sudden cardiac death, and of patients with substrates other than coronary artery disease remains to be elucidated.
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PMID:Evolving role of sotalol in the management of ventricular tachyarrhythmias. 878 Mar 29

Class III antiarrhythmic agents are characterized by their ability to prolong action potential and increase refractoriness. The use of these drugs namely, sotalol hydrochloride and amiodarone hydrochloride, is rising. Both agents are effective for treating a range of ventricular arrhythmias, and amiodarone in particular has been linked with improved mortality in certain patient populations compared with class I agents. Sotalol and amiodarone have individual, complex pharmacologic profiles. As a result, there are also differences in their side effects and proarrhythmic actions. Sotalol is associated with side effects related to beta-adrenergic blockade and an incidence of proarrhythmia similar to that of class Ia agents. Amiodarone is associated with pulmonary toxicity and other adverse events, but rarely induces torsades de pointes. These agents must be differentiated from pure class III potassium channel blockers, such as the dextro isomer form of sotalol, which is linked to increased mortality compared with placebo in post-myocardial infarction patients with reduced ventricular function or a history of heart failure.
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PMID:Class III antiarrhythmic agents: the next wave. 908 43

We performed a randomized, double-blind, placebo-controled, parallel-group comparison study of the efficacy and safety of sotalol in the prophylaxis of paroxysmal supraventricular tachyarrhythmias (PSVTs) (including paroxysmal atrial fibrillation and paroxysmal reentrant SVTs). The frequency of PSVT episodes while not receiving drug therapy was monitored during a baseline phase, the length of which depended on the frequency of PSVT events. In the double-blind phase, the duration of which depended on the baseline frequency of episodes of PSVT, patients received placebo, sotalol 80 mg twice daily, or sotalol 160 mg twice daily. PSVT events were documented by electrocardiogram and diary. The time to recurrence of PSVT was significantly less compared with placebo when receiving sotalol 80 mg (p = 0.018) and sotalol 160 mg (p = 0.0009). On subanalysis, sotalol was shown to be effective in the prophylaxis of both paroxysmal atrial fibrillation and paroxysmal reentrant arrhythmias. Sotalol was well tolerated, with no deaths, proarrhythmia, or cardiac failure. Because of adverse effects, drug therapy was discontinued in six patients.
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PMID:Multicenter comparative study of the efficacy and safety of sotalol in the prophylactic treatment of patients with paroxysmal supraventricular tachyarrhythmias. 912 66

The negative inotropic effect of nearly all antiarrhythmic drugs, especially important in patients with impaired left ventricular function, represents a major drawback of medical therapy. The aim of this study is to evaluate the atrial and ventricular function and the exercise capacity in patients with mild heart failure treated with d,l-sotalol after electrical conversion of atrial fibrillation. The study included patients with persistent atrial fibrillation (for more than 2 weeks but less than 1 year) and mild heart failure (< or = class II NYHA). All patients had comparable basal echocardiographic findings, and received captopril. After successful cardioversion the patients were randomized in two groups: group 1 treated with sotalol (mean dose 240 mg q.d., max. 320 mg) and group 2--without sotalol. The drop-out criterion was the failure to maintain sinus rhythm. Finally, in the study remained 17 patients (10 men, 7 women, aged 41-60 years); group 1 included 10 patients and group 2-7 patients. They were assessed by quantitative echocardiography + Doppler and by standard ecg exercise test at less than 1 month but more than 2 weeks, and at 1, 3, and 6 months. When first evaluated (2 weeks-1 month), peak A wave velocity and atrial filling ratio were higher in group 2 than in group 1 (37 +/- 10 cm/s vs 20 +/- 5 cm/s and 23% +/- 7 vs 13% +/- 5, respectively) and group 1 had also a lower exercise tolerance (80 +/- 25 W vs 110 +/- 10 W). There were no significant differences between groups 1 and 2 in left atrial and left ventricular dimensions, ejection fraction and E wave deceleration time. After 1 month there were no significant differences in Doppler characteristics, echocardiographic parameters and exercise tolerance between the two groups. Group 1 remained at a lower heart rate and had a lower maximal double product (17250 mmHg/min vs 22100 mmHg/min) corresponding to a lower cardiac work. At 3 and 6 months there were no significant changes in all characteristics between the two groups. In conclusion, sotalol seems to be a well tolerated antiarrhythmic agent in patients with mild heart failure, after conversion of persistent atrial fibrillation. In this setting: 1. Sotalol could reversibly amplify the effect of atrial stunning after electrical cardioversion of atrial fibrillation, but this effect is brief. 2. Sotalol has no relevant negative inotropic effect, at least not in association with captopril. 3. Sotalol improves the effort capacity.
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PMID:Hemodynamic performances in patients treated with sotalol after electrical cardioversion of atrial fibrillation. 956 49

Cardiac failure is a common cause of arrhythmia. Many factors predispose to the genesis of arrhythmias in these patients. A number of non-invasive methods allow stratification of the risk of arrhythmia in cardiac failure. Approximately half the deaths of these patients are due to arrhythmia. Unfortunately, most of the investigations for risk evaluation have a high negative predictive value but a lower positive predictive value. The treatment of supraventricular arrhythmias, mainly atrial fibrillation, is complex in cardiac failure. Class I antiarrhythmics are contraindicated. The only remaining options are Class II, especially Sotalol, and Class III drugs, especially Amiodarone. In some cases, non-pharmacological methods such as ablation, pacing or an implantable atrial defibrillator must be considered. The treatment of ventricular arrhythmias is also difficult. In this indication, Class I antiarrhythmic agents must also be avoided. Non-sustained ventricular tachycardia may be treated by betablockers or amiodarone. The use of an implantable defibrillator is increasingly recommended after the results of several controlled large scale trials. The indication is obvious in patients resuscitated from sudden death and these devices are also beneficial in sustained ventricular tachycardia in patients with cardiac failure. Many studies are currently under way to determine the value of this therapeutic modality in indications now considered to be "prophylactic".
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PMID:[Management of arrhythmias in patients with heart failure]. 986 6

Patients with congestive heart failure frequently have ventricular arrhythmias on ambulatory electrocardiographic recordings and sudden cardiac death is seen in almost 50% of such patients. Many antiarrhythmic agents have been approved to suppress the arrhythmia in an effort to improve survival. Some sodium-channel blockers not only failed to improve survival but have been shown to be harmful. This led to the development of potassium-channel blockers, such as d-sotalol, amiodarone, dofetilide, and azimilide. d-Sotalol was associated with excess mortality in patients with left ventricular dysfunction; amiodarone seems to be potentially beneficial; and dofetilide has a neutral effect on mortality. The Sudden Cardiac Death Heart Failure Trial (SCD HEFT) is testing the implantable cardioverter defibrillator (ICD) against amiodarone and placebo. The ICDs appear to be superior to antiarrhythmic drugs in certain high-risk patients, although not proved in unstratified patients with heart failure.
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PMID:Class III drugs and congestive heart failure: focus on the congestive heart failure-survival trial of antiarrhythmic therapy. 1056 68

In patients with severe chronic heart failure, many deaths are sudden due to life-threatening ventricular arrhythmias. Supraventricular arrhythmias such as paroxysmal or chronic atrial fibrillation may also cause serious complications in those patients due to acute loss of atrial contraction, pump failure during rapid ventricular response and embolic events. Two therapeutic strategies are currently available for therapy and prevention of malignant ventricular arrhythmias and subsequent sudden arrhythmic death: antiarrhythmic drug therapy and implantable defibrillators. However, selection of the most beneficial strategy for the individual patient to reduce the risk of sudden death remains a major challenge in cardiology. Betablockers exert a favorable antiarrhythmic action without increasing proarrhythmia, thus betablockers may serve as a basic medication in patients at risk for sudden death. However, the general use of antiarrhythmic drug therapy for symptomatic ventricular arrhythmias is not recommended, as these drugs have been shown to increase mortality in patients with severe congestive heart failure due to proarrhythmic or negative inotropic effects (e.g. class Ia antiarrhythmics). Even class III antiarrhythmic drugs such as amiodarone, which has been studied sufficiently in patients with left ventricular dysfunction, is not effective enough for significant reduction of cardiac mortality in patients with symptomatic ventricular arrhythmias and depressed ventricular function (e.g. EMIAT, CAMIAT). But as a positive result of available studies, amiodarone does not increase mortality in those patients. Dofetilide has also not been shown to prolong life significantly by suppressing malignant ventricular arrhythmias (DIAMOND-Study). In patients with symptomatic ventricular arrhythmias or aborted sudden death, ICD therapy has been proven to be superior to antiarrhythmic drug therapy in cardiac mortality reduction as a secondary prevention strategy (e.g. AVID, CASH, CIDS). For primary prevention of sudden arrhythmic death in high risk patients, 2 studies (MADIT, MUSST) have already demonstrated favorable results, decreasing mortality by ICD therapy in selected patient populations with partly-reduced ventricular function and unsustained but inducible ventricular tachycardias. This topic is, however, undergoing further evaluation by ongoing trials (e.g. MADIT II, SCD-HeFT). From available data, antiarrhythmic drug therapy in high risk patients is not justified on a routine basis, whereas ICD therapy as a secondary and perhaps primary prevention strategy will significantly reduce cardiac mortality in patients with severe heart failure. Sotalol, a class III antiarrhythmic agent, has recently been shown to reduce ICD-shock delivery which indicates that concomitant drug therapy in patients with an ICD device already implanted may be beneficial in terms of reducing ICD discharges due to ventricular and supraventricular tachycardias. In patients with paroxysmal atrial fibrillation and congestive heart failure, restitution of sinus rhythm is the primary therapeutic goal which can be safely achieved by amiodarone and dofetilide (DIAMOND). In the latter, continuous monitoring of the patient is mandatory because of increased risk of torsade de pointes arrhythmias during the first days of drug administration. In patients with chronic atrial fibrillation rate control and anticoagulation with warfarin is the primary therapeutic option, which can be achieved with either drug treatment (Digoxin, betablockers, amiodarone) or by His bundle ablation with subsequent pacemaker insertion.
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PMID:[Antiarrhythmic therapy in patients with heart failure]. 1085 93

A noteworthy shift from class I to class III antiarrhythmic agents for suppression of atrial fibrillation has occurred. Sotalol, amiodarone, and dofetilide have been evaluated for their ability to maintain sinus rhythm in patients with chronic atrial fibrillation. All of these agents are moderately effective; however, amiodarone appears to be most efficacious. Aside from their common class III actions, these agents have profoundly different pharmacologic, pharmacokinetic, safety, and drug interaction profiles that help guide drug selection. Amiodarone and dofetilide are safe in patients who have had a myocardial infarction and those with heart failure. The safety of commercially available d,l-sotalol in these patients is poorly understood. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide, and risk increases with renal dysfunction. Amiodarone has minimal proarrhythmic risk but has numerous noncardiac toxicities that require frequent monitoring. Overall, an ideal antiarrhythmic agent does not exist, and drug selection should be highly individualized.
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PMID:A review of class III antiarrhythmic agents for atrial fibrillation: maintenance of normal sinus rhythm. 1176 3

Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft surgery (CABG). Post-CABG AF occurs most commonly on the second postoperative day and declines in incidence thereafter. A number of risk factors have been found to be associated with a higher frequency of post-CABG AF. These risk factors include advanced age, a prior history of AF, hypertension, and heart failure. Postoperative complications--including low cardiac output, use of an intra-aortic balloon pump, pneumonia, and prolonged mechanical ventilation--are also associated with higher rates of post-CABG AF. Post-CABG AF increases the risk of stroke, and the length and cost of hospitalization. Prophylactic administration of conventional beta-adrenoceptor antagonists (beta-blockers) or sotalol produces a consistent and significant reduction in the incidence of post-CABG AF; however, results with prophylactic amiodarone or magnesium are less consistent. Termination of post-CABG AF, once it occurs, can be accomplished with a number of antiarrhythmic agents. Ibutilide has been the most widely studied agent for this indication. Sotalol is not indicated for cardioversion of AF and has not been studied in the post-CABG setting. Electrical cardioversion and biatrial pacing have also been used to terminate post-CABG AF. Ventricular rate is best controlled with beta-blockers and calcium channel antagonists. Esmolol has a rapid onset of action and is easily titrated to effect. Digoxin can control the ventricular rate, but has a slow onset of action. There are limited data available to guide decisions regarding the optimal management of post-CABG AF.
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PMID:Pharmacological management of atrial fibrillation following cardiac surgery. 1625 24

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a predominantly genetically determined and heritable form of cardiomyopathy that is characterized pathologically by the replacement of myocytes by adipose and fibrous tissue and leads to right ventricular failure, arrhythmias, and sudden cardiac death. The estimated prevalence of ARVC/D in the general population ranges from 1 in 2,000 to 1 in 5,000, men are more frequently affected than women, with an approximate ratio of 3:1. ARVC/D can be inherited as an autosomal dominant disease with reduced penetrance and variable expression, autosomal recessive inheritance is also described. There have been 12 genes identified which are linked to ARVC/D, encoding several components of the cardiac desmosome. Dysfunctional desmosomes resulting in defective cell adhesion proteins, such as plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP-2), and desmoglein-2 (DSG-2) consequently cause loss of electrical coupling between cardiac myocytes, leading to myocyte cell death, fibrofatty replacement and arrhythmias. Diagnosis is based on the finding a combination of characteristic abnormalities in family history, electrocardiography, cardiac imaging as well as endomyocardial biopsy (original task force criteria). Therapeutic options remain limited because of the progressive nature of ARVC/D. Competitive athletics should be avoided. Patients with ARVC/D with a history of having been resuscitated from sudden cardiac death, patients with syncope, very young patients, and those who have marked right ventricular involvement are at the highest risk for arrhythmic death and also, the presence of left ventricular involvement is a risk factor. Several authors concluded that patients who meet the Task Force criteria for ARVC/D are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. The role of electrophysiologic study and VT catheter ablation in ARVC/D remains poorly defined, and is frequently used as a palliative measure for patients with refractory VT. The progressive nature of ARVC/D suggests that catheter ablation would not be a long-term curative procedure. Sotalol proved to be highly effective in patients with ARVC/D and inducible as well as non-inducible ventricular tachycardia; if it is ineffective in inducible ventricular tachycardia response to other antiarrhythmic drugs is unlikely and therefore non-pharmacological therapy without further drug testing should be considered. Orthotopic heart transplantation is considered in patients with progressive heart failure and intractable recurrent ventricular arrhythmias.
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PMID:Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. 2136 Feb 43


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