Similarly, in the SAFE\T study of amiodarone and sotalol in 665 patents with persistent AF, the 2 2 drugs were equally effective in converting AF to sinus rhythm, but amiodarone was superior for maintaining it (median time to recurrence of AF was 487 days and 74 days, respectively; 0.001).45 However, the potential of amiodarone to cause serious adverse effects in the long term might preclude its use as a first\choice drug. AF recurrence is not usually LSN 3213128 achievable; however, total restoration of sinus rhythm may not be necessary for patients to achieve clinically meaningful benefits. Copyright ? 2011 Wiley Periodicals, Inc. The editorial assistance provided for this manuscript was funded by Sanofi\Aventis. The authors were fully responsible for all content and editorial decision, and received no financial support or other form of compensation related to the development of the paper. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Introduction Atrial fibrillation (AF) is usually a common supraventricular tachyarrhythmia characterized by disorganized atrial activity, reduced cardiac function, and hemodynamic impairment.1 As the population of the United States ages, the number of individuals with AF is expected to reach 5.6 million by 2050. Clinicians have long acknowledged the importance of judicious management of AF to prevent unfavorable cardiovascular sequelae. AF increases the risk of stroke approximately 5\fold and, LSN 3213128 in the United States, it is responsible for 25% of all strokes among the elderly.2, 3 Other effects of AF include worsening of congestive heart failure (CHF), increased risk of hospitalization, impaired quality of life, and increased mortality.4 Recently, there has been increasing interest not only in preventing the negative effects of AF, but also in preventing progression of the disease itself. This interest reflects a better understanding of the mechanisms that cause AF and an increased awareness of the high prevalence of disease progression. Nearly 25% of patients who in the beginning present with paroxysmal disease eventually progress to prolonged or permanent AF.5 Herein we describe current theories regarding the pathophysiology of AF and discuss arrhythmia\induced cardiac changes that are thought to sustain the arrhythmia and facilitate its progression. The potential benefits of achieving and maintaining sinus rhythm are explored, and treatment options and anticipations are discussed. Mechanisms of AF Development and Progression The precise pathophysiology of AF development and progression remains incompletely comprehended. The principal electrophysiological mechanism responsible for AF development likely entails both focal activation (1 or more ectopic foci) and multiple wavelet re\access.6, 7, 8 The progressive nature of AF has been attributed to changes in the electrical, structural, and contractile properties of atrial tissue that arise from your arrhythmia itself.8 Electrical remodeling typically begins soon after AF onset and is characterized by shortened action potentials and effective refractory periods and a loss of rate dependence.8, 9 These irregularities reflect multiple abnormalities in ion channel expression and ion circulation, including changes in the movement of calcium and sodium across atrial cell membranes. Specific changes include inactivation of (short term) and downregulation of expression (long term), in response to increased calcium influx associated with quick firing, and downregulation of the fast sodium current.10, 11, 12, 13 Electrical remodeling appears to be reversible upon restoration of sinus rhythm.11 Structural remodeling is LSN 3213128 more insidious in onset (occurring over periods of weeks to months). Generally observed changes in animal models include increased cell size, myolysis, and the accumulation of glycogen round the nucleus.11 Fibrotic changes in peripulmonary vein tissue have been observed in patients with AF who undergo mitral valve surgery.14 Although the causes of these structural changes are not completely understood, they may include AF\induced changes in the expression of collagen and matrix metalloproteinase.15, 16, 17 Atrial Rabbit Polyclonal to TNFSF15 stretch and compensatory elevations of catecholamine and angiotensin II concentrations, triggered by the loss of atrial systole and suboptimal ventricular filling, also may play a role.5, 11, 18 Changes in atrial structure LSN 3213128 presumably contribute to AF progression by altering refractoriness and conduction. 19 Whereas some of these structural changes may be irreversible,8 the reversal of left ventricular dysfunction following ablation (proximal isolation of arrhythmogenic pulmonary veins and removal of non\postventricular triggers) has been.