The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most frequently encountered sustained cardiac arrhythmia in clinical practice and a major cause of morbidity and mortality. Effective treatment of AF still remains an unmet medical need. Treatment of AF is based on drug therapy and ablative strategies. Antiarrhythmic drug therapy is limited by a relatively high recurrence rate and proarrhythmic side effects. Catheter ablation suppresses paroxysmal AF in the majority of patients without structural heart disease but is more difficult to achieve in patients with persistent AF or with concomitant cardiac disease. Stroke is a potentially devastating complication of AF, requiring anticoagulation that harbors the risk of bleeding. In search of novel treatment modalities, targeted pharmacological treatment and gene therapy offer the potential for greater selectivity than conventional small-molecule or interventional approaches. This paper summarizes the current understanding of molecular mechanisms underlying AF. Established drug therapy and interventional treatment of AF is reviewed, and emerging clinical and experimental therapeutic approaches are highlighted.

Keywords: antiarrhythmic therapy; anticoagulation; atrial fibrillation; catheter ablation; stroke.

Figure 1

Electrical mechanisms of atrial fibrillation (AF). Rapid ectopic activity and re-entry are key electrophysiological mechanisms of AF. The development of functional re-entrant circuits requires a trigger (eg, an ectopic beat) that initiates the arrhythmia. Atrial remodeling creates a structural substrate for re-entry by altering ion channel function or by inducing fibrosis. The leading circle concept and the spiral wave hypothesis represent models of re-entry. Remodeling may induce ectopic electrical discharges through changes in Ca²⁺ ion desposition or K⁺ current levels, resulting in trigger activity. Abbreviations: EAD, early after depolarization; DAD, delayed after depolarization.

Figure 2

Overview: treatment options for patients with atrial fibrillation. Abbreviations: LAA, left atrial appendage; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker.