The electrophysiological properties of ranolazine: a metabolic anti-ischemic drug or an energy-efficient antiarrhythmic agent?

Ranolazine, a newer anti-ischemic agent that appears to induce a more efficient utilization of adenosine triphosphate at the cellular level, has been shown to be clinically beneficial in patients with chronic stable angina. More recently, the antiarrhythmic effects of the drug have been described in patients with acute coronary syndromes, as well as in those with atrial fibrillation, when combined with other agents. Experimentally, the predominant inhibitory effects on late I(Na), I(Ca), I(Na-Ca), and I(Ks), with little or no effect on I(to) or I(K1), have been demonstrated.

Celivarone in patients with an implantable cardioverter-defibrillator: adjunctive therapy for the reduction of ventricular arrhythmia-triggered implantable cardioverter-defibrillator interventions.

Background: Implantable cardioverter-defibrillators (ICDs) remain the treatment of choice for the prevention of life-threatening arrhythmias. However, many patients with ICDs require additional antiarrhythmic therapy to reduce the morbidity associated with recurrent arrhythmia-triggered ICD interventions.

Objective: Our study aimed to evaluate the safety and efficacy of celivarone in reducing these interventions.

Augmenting maintenance of sinus rhythm in the control of atrial fibrillation by antiarrhythmic drug combinations.

In recent years, a major development in the treatment of atrial fibrillation (AF) is the use of catheter ablation, and a significant number of patients may benefit from this mode of therapy. On a global scale, it may not be feasible to deal with most patients solely on the basis of ablation. Therefore, it is likely that much of the therapy for AF will continue to rely on antiarrhythmic agents for maintaining sinus rhythm.

A new agent for atrial fibrillation: electrophysiological properties of dronedarone.

Although originally synthesized as an antianginal compound, amiodarone has emerged as an effective antiarrhythmic for both supraventricular and ventricular arrhythmias. Over the decades, the properties, the effectiveness, the merits as well as the shortcomings of the compound have been well established. The major limitations of this agent are mainly due to the systemic side effects seen with prolonged therapy.

Levosimendan and calcium sensitization of the contractile proteins in cardiac muscle: impact on heart failure.

Levosimendan increases the sensitivity of the cardiac fibrils to calcium, favorably affects hemodynamics in patients with heart failure. It is a positive inotrope and a peripheral vasodilator. The elimination half-life of the compound is about 1 hour.

Amiodarone as paradigm for developing new drugs for atrial fibrillation.

Introduced as an anti-anginal compound in 1962, amiodarone emerged in the 1970s as a uniquely effective antiarrhythmic and antifibrillatory drug with a multiplicity of properties, the most striking being the lengthening of the repolarization in the atria and ventricles associated with bradycardia but without a significant propensity for inducing torsade de pointes. Amiodarone is now the most frequently used agent for maintaining sinus rhythm in patients with AF. Its effectiveness for maintaining sinus rhythm remains unrivalled.

Rhythm control versus rate control for atrial fibrillation and heart failure.

Background: It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied.

Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation.

Background: Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort.

Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.

Background: Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.

Methods: In two identical multicenter, double-blind, randomized trials, one conducted in Europe (ClinicalTrials.

Dose-dependent effects of oral dronedarone on the circadian variation of RR and QT intervals in healthy subjects: implications for antiarrhythmic actions.

Dronedarone, a non-iodinated benzofuran derivative, was developed as a potentially less toxic alternative to amiodarone. This study describes Holter data of dronedarone in humans. Five groups of healthy subjects were given 1 of 5 oral doses of dronedarone in a twice-daily regimen or placebo.

Amiodarone: a multifaceted antiarrhythmic drug.

Synthesized as an antianginal compound 40 years ago, amiodarone has emerged as a uniquely effective antiarrhythmic compound in recent years. It has numerous properties, the most prominent being the ability to lengthen repolarization in the atria and ventricles associated with bradycardia without the significant potential for torsades de pointes. Amiodarone effectively controls a wide spectrum of atrial and ventricular antiarrhythmic disorders, but its limiting side effects, such as thyroid dysfunction, pulmonary fibrosis, and dermatologic changes, may limit its long-term use in some patients.

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

Objectives: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF.

Background: Restoration of SR in patients with AF improving QOL and EP remains controversial.

Methods: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo.

Beta-Adrenergic blockers as antiarrhythmic and antifibrillatory compounds: an overview.

Beta-Adrenergic blockers have a wide spectrum of action for controlling cardiac arrhythmias that is larger than initially thought. Data from the past several decades indicate that, as an antiarrhythmic class, beta-blockers remain among the very few pharmacologic agents that reduce the incidence of sudden cardiac death, prolong survival, and ameliorate symptoms caused by arrhythmias in patients with cardiac disease. As a class of compounds, beta-blockers have a fundamental pharmacologic property that attenuates the effects of competitive adrenergic receptors.

Amiodarone versus sotalol for atrial fibrillation.

Background: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial.

Methods: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years.

Antiarrhythmic and proarrhythmic properties of QT-prolonging antianginal drugs.

In recent years there has been a major reorientation of drug therapy for cardiac arrhythmias, its changing role, and above all, a radical change in the class of arrhythmia drugs because of their impact on mortality. The decline in the use of sodium-channel blockers has led to an ex panding use of beta-blockers and simple or complex class III agents for controlling cardiac arrhythmias. Success with these agents in the context of their side effects has spurred the development of compounds with simpler ion-channel blocking properties that have less complex adverse reactions.

Control of heart rate versus rhythm in rheumatic atrial fibrillation: a randomized study.

Background: Patients with rheumatic heart disease with atrial fibrillation incur significant morbidity and mortality. Which approach, ventricular rate control or maintenance of sinus rhythm, in this setting might be superior is not known. The role of amiodarone in this patient population for maintaining sinus rhythm has not been evaluated.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001.