Adjuvant therapy for atrial fibrillation.

Atrial fibrillation (AF) is the most common heart rhythm disorder, with increasing prevalence in the aging US population and affecting more than 2.3 million people. Current approaches for managing AF are rate- or rhythm-control strategies, both using anti-thrombotic therapy to prevent thromboembolism. While great advances have been made in understanding the pathophysiology of AF, few new strategies have shown promise in prevention or treatment of AF. Recent data suggest that non-antiarrhythmic medication may be useful in modifying the substrate that allows AF precipitation and perpetuation. This article reviews the data on the role of these agents in the prevention and management of AF as an adjunct to standard therapy.

Drug therapy for atrial fibrillation.

Atrial fibrillation is the most frequently diagnosed arrhythmia. Prevalence increases with age, and the overall incidence is expected to increase as the population continues to age. Choice of pharmacologic therapy for atrial fibrillation depends on whether or not the goal of treatment is maintaining sinus rhythm or tolerating atrial fibrillation with adequate control of ventricular rates. Many new antiarrhythmic drugs are currently being tested in clinical trials. Drugs that target remodeling and inflammation have shown potential in prevention of atrial fibrillation, or as adjunctive therapy.

New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?

Pharmacologic antiarrhythmic therapy is the most commonly used treatment in most patients with atrial fibrillation (AF), but currently available agents are limited by risks that may offset the benefits of sinus rhythm. The development of antiarrhythmic agents with the potential for fewer adverse ventricular effects and less extracardiac toxicity is a primary aim of current investigations. At present, pharmacologic research is actively focused on developing antiarrhythmic agents with multiple or novel ion channel effects. There are 4 agents that act by simultaneously blocking multiple ion channels that are currently under regulatory review: azimilide dihydrochloride, tedisamil, dronedarone, and vernakalant (RSD-1235). In addition, agents with mechanisms of action that differ from those of existing agents (eg, gap junction modulators) are under review, as is the use of nonantiarrhythmic agents (eg, renin-angiotensin system antagonists, statins, n-3 polyunsaturated fatty acids) to alter the cardiac substrate and suppress AF in some patient subtypes.

Drug therapy for atrial fibrillation.

Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia. Prevalence increases with age, and the overall incidence is expected to increase as the population continues to age. Choice of pharmacologic therapy for atrial fibrillation depends on whether or not the goal of treatment is maintaining sinus rhythm or tolerating atrial fibrillation with adequate control of ventricular rates. New antiarrhythmic drugs are being tested in clinical trials. Drugs that target remodeling and inflammation are being tested for their use as prevention of AF or as adjunctive therapy.

Future directions in antiarrhythmic drug therapy for atrial fibrillation.

Atrial fibrillation is the most commonly sustained cardiac arrhythmia. Drugs currently approved by the US FDA for the treatment of this arrhythmia are imperfect owing to either side effects or limited efficacy. Drug development strategies have focused on two areas: the modification of existing agents--such as Class III drugs aimed at improving their safety and efficacy profile--and targeting newly postulated mechanisms of atrial fibrillation. In this article, we review new drugs currently in development and promising drug strategies for atrial fibrillation prevention and treatment.

Ventricular repolarization components on the electrocardiogram: cellular basis and clinical significance.

Ventricular repolarization components on the surface electrocardiogram (ECG) include J (Osborn) waves, ST-segments, and T- and U-waves, which dynamically change in morphology under various pathophysiologic conditions and play an important role in the development of ventricular arrhythmias. Our primary objective in this review is to identify the ionic and cellular basis for ventricular repolarization components on the body surface ECG under normal and pathologic conditions, including a discussion of their clinical significance. A specific attempt to combine typical clinical ECG tracings with transmembrane electrical recordings is made to illustrate their logical linkage. A transmural voltage gradient during initial ventricular repolarization, which results from the presence of a prominent transient outward K(+) current (I(to))-mediated action potential (AP) notch in the epicardium, but not endocardium, manifests as a J-wave on the ECG. The J-wave is associated with the early repolarization syndrome and Brugada syndrome. ST-segment elevation, as seen in Brugada syndrome and acute myocardial ischemia, cannot be fully explained by using the classic concept of an "injury current" that flows from injured to uninjured myocardium. Rather, ST-segment elevation may be largely secondary to a loss of the AP dome in the epicardium, but not endocardium. The T-wave is a symbol of transmural dispersion of repolarization. The R-on-T phenomenon (an extrasystole originating on the T-wave of a preceding ventricular beat) is probably due to transmural propagation of phase 2 re-entry or phase 2 early after depolarization that could potentially initiate polymorphic ventricular tachycardia or fibrillation.