Genes and atrial fibrillation: a new look at an old problem.

Atrial fibrillation (AF) is an abnormality of the heart’s rhythm that is characterized by rapid and irregular activation of the atria. AF was first described in humans in 19061 and is now recognized to be the most common sustained cardiac arrhythmia and a major public health burden.2 The loss of coordinated atrial contraction results in reduced ventricular filling and blood stasis in the atria, which predispose to heart failure and thromboembolic stroke, respectively.3,4 AF accounts for 15% of all strokes and one third of strokes in individuals >65 years of age.4 AF is also an independent risk factor for death, with a relative risk over all age groups of 1.5 for men and 1.9 for women.5 The prevalence of AF increases with age, ranging from 80 years old.6 Given our aging population, together with contemporary increases in the incidence of risk factors for AF, the numbers affected and the hospitalization and treatment costs are predicted to increase markedly in the future.2 These observations underscore the need for a better understanding of the pathophysiological basis of AF and for the development of new approaches to prevention and management. AF is frequently observed as a complication of diverse cardiac and systemic disorders, including hypertension, coronary artery disease, valvular heart disease, and cardiomyopathies. Hence, AF has traditionally been regarded as a sporadic, nongenetic disorder. In approximately 10% to 20% of cases, an underlying cause cannot be identified, and AF is termed “idiopathic” or “lone.”7 One hundred years on, there is now accumulating evidence that genetic factors have a role in the pathogenesis of AF in a significant proportion of cases. The genes involved and the mechanisms by which defects in these genes alter atrial electrophysiological properties …