S36 Atrial Electrical and Structural Remodeling: Implications for Racial Differences in Atrial Fibrillation CHU-PAK LAU, M.D., * HUNG-FAT TSE, M.D., Ph.D.,† CHUNG-WAH SIU, M.D.,† and DAVID GBADEBO, M.D., F.H.R.S.‡ From the * Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong SAR, China; †Research Center of Heart, Brain, Hormone and Healthy Ageing, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China; and ‡University of Tennessee Erlanger Cardiology, UT College of Medicine, Chattanooga, Tennessee, USA Racial Disparity in AF Electrophysiology. Racial differences in prevalence and incidence rates of atrial fibrillation (AF) are known to exist even after accounting for ascertainment bias, as well as differences in the prevalence of known risk factors. Thus, a different susceptibility to traditional risk factors in different ethnic groups that lead to AF clearly exists. Initiation and maintenance of AF are dependent on triggers, autonomic influence and atrial substrate, and progression to persistent AF occurs by electromechanical remodeling. Genetic differences among the racial group contribute to such differences. This article reviews the electrophysiologic mechanisms for AF, evidence for racial differences in susceptibility to AF, and suggests possible electromechanical reasons for the susceptibility. (J Cardiovasc Electrophysiol, Vol. 23, pp. S36-S40, November 2012) atrial fibrillation, epidemiology, ethnicity, electrophysiology, remodeling, race Introduction Despite being the most common sustained arrhythmia worldwide, a substantial body of evidence has accumulated to suggest a significant disparity in the expected incidence of atrial fibrillation (AF) in different countries and in differ- ent races (Fig. 1). 1 The mechanism for AF development is complex and incompletely understood. Race is emerging as an independent risk factor for AF. Traditional risk factors for AF are unevenly distributed among racial groups, and also appear to have differential impact on AF development. Addi- tionally, genetic and ethnic variations in haplotype structures and candidate genes for arrhythmias have been reported. Episodic attacks of AF are likely to result from triggering impulses arising from within pulmonary veins (PV) and/or other atrial tissues that can initiate and sustain the arrhyth- mia, especially when there is a conductive and vulnerable substrate. On the other hand, sustained AF often requires multiple reentrant wavelets in the atrium. The atrial sub- strate for AF typically results from the cumulative effects of risk factors that contribute to atrial electrical and struc- tural remodeling. In addition, rapid atrial rate as occurring in AF perpetuates further electrophysiological changes in atrial myocardium, including calcium homeostasis, atrial effective refractory period (ERP), conduction velocity (CV), and can also contribute to development of structural changes with atrial fibrosis and dilatation. Moreover, influence from the No disclosures. Address for correspondence: Chu-Pak Lau, M.D., Honorary Clinical Pro- fessor, Cardiology Division, Department of Medicine, The University of Hong Kong Cardiac Health Heart Centre, Suite 1303, Central Building, 1 Pedder Street, Central, Hong Kong, China. Fax: +852-2179-5114; E-mail: cplau@hkucc.hku.hks Manuscript received 4 September 2012; Revised manuscript received 12 September 2012; Accepted for publication 17 September 2012. doi: 10.1111/jce.12022 autonomic nervous system also plays an important role in AF initiation and perpetuation. It is conceivable that there are identifiable differences in the components of atrial reentry between the races. This re- view examines the differences in the incidence of AF, and any differences in atrial substrates, autonomic influences and triggers of AF that may account for the observed racial dif- ferences in rates of AF. Mechanism of AF Triggers and Autonomic Influence AF is initiated and perpetuated by triggers, autonomic influence, and substrate abnormalities. In humans, a focal source of AF from the residual atrial myocardium in the PV serves as the trigger. 2,3 Some types of AF are highly related to the autonomic tone, 4 and ablation of autonomic ganglia 5 have been shown to reduce recurrence of both paroxysmal and persistent AF. Electromechanical Remodeling In a chronically instrumented goat model, Wijffels et al. 6 showed that repeated triggering events (through high rate atrial pacing) lead to longer duration and more frequent episodes of AF. With shortening of atrial ERP, the AF wave- length is reduced. With time, atrial dilatation occurred, thus accommodating more wavelets, and AF then became sus- tained. 6,7 Calcium overloading is the likely cellular elec- trophysiological mechanism for shortening of ERP, 8 which occurred in rapid atrial pacing models of AF. But conduction velocity slowing was the predominant mechanism respon- sible for AF in a heart failure model. 8 Studies in humans suggest heterogeneous changes in atrial ERP and slowing of CV especially in the left atrium (LA) occurred. 9,10 Suppression of the sinus node function due to sinus node disease is a potent trigger for bradycardia-dependent AF. Si- nus node suppression due to AF has been reported to recover after successful ablation of AF. 11 Stretching of the atria is also a potent stimulus for AF, and this effect has been tested