Volume 10, Issue 1, Pages (January 2013)

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Volume 10, Issue 1, Pages 90-100 (January 2013) Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation Hany S. Abed, MBBS, B Pharm, Chrishan S. Samuel, PhD, Dennis H. Lau, MBBS, PhD, Darren J. Kelly, PhD, Simon G. Royce, PhD, Muayad Alasady, MBChB, Rajiv Mahajan, MD, Pawel Kuklik, PhD, Yuan Zhang, MD, PhD, Anthony G. Brooks, PhD, Adam J. Nelson, MBBS, Stephen G. Worthley, MBBS, PhD, Walter P. Abhayaratna, MBBS, PhD, Jonathan M. Kalman, MBBS, PhD, Gary A. Wittert, MBChB, MD, Prashanthan Sanders, MBBS, PhD, FHRS Heart Rhythm Volume 10, Issue 1, Pages 90-100 (January 2013) DOI: 10.1016/j.hrthm.2012.08.043 Copyright © 2013 Terms and Conditions

Figure 1 Study outline. CMR = cardiac magnetic resonance; EPS = electrophysiology study. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 2 Cardiac structural and hemodynamic changes with increasing weight. Representative CMRI cines from each cohort are shown. P values were derived from 1-way analysis of variance. Pairwise comparisons were performed by using the Bonferroni method. A: Horizontal long axis. B: Short axis. CMRI data are presented as mean±SD, and hemodynamic data are presented as median and interquartile range. CMR = cardiac magnetic resonance; LA = left atrium; LAP = left atrial pressure; LVEDV = left ventricular end-diastolic volume; MAP = mean arterial pressure; RA = right atrium; RVEDV = right ventricular end-diastolic volume. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 3 A: Effect of progressive obesity on regional slowing in conduction velocity at the 4 pacing sites. This relationship persisted following adjustment for hemodynamic variables. B: Changes in biatrial conduction heterogeneity index with increasing adiposity. CLs of 500 and 200 ms are presented. CL = cycle length; LAA = left atrial appendage; LAFW = left atrial free wall; RAA = right atrial appendage; RAFW = right atrial free wall. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 4 A: Activation isochronal maps of LAA pacing at 400 ms. Demonstrated are representative examples of S1 (top panel) and S2 (middle panel) for an animal at baseline (left column), overweight (middle column), and obese (right column) cohorts. B: Pacing train (S1) and premature extra stimulus (S2) impact on CV decrement with increasing weight. P values refer to group×condition (S1, S2) interaction. CL = cycle length; CV = conduction velocity; LAA = left atrial appendage. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 5 A: Scatter plot of spontaneous and induced AF episodes (log transformed) for each animal, and bar graph of AF duration (minutes) with weight cohort (median and interquartile range; P = .001). B: Example of spontaneous AF observed from the LAA. AF = atrial fibrillation; LAA = left atrial appendage. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 6 Histology from atrial tissue (×200 magnifications). From top panel: Picrosirius red staining, inflammatory infiltrates on hematoxylin and eosin, and myocardial lipidosis on Oil red O. Values are presented as median and interquartile range. All pairwise comparisons were performed by using the Mann-Whitney U method. LA = left atrium; RA = right atrium. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 7 A: Western blots of ETA receptor (63 kDa) and ETB receptor (∼30 kDa) expression and α-tubulin (55 kDa) demonstrates equivalent loading of samples. Two bands are shown per group. B: Top panel shows IHC staining of ETA receptors and middle panel shows IHC staining of ETB receptors on the atrial cardiomyocyte membrane. Lower panel shows IHC staining of the ET-1 ligand in the cardiomyocyte cytoplasm. ET-1 = endothelin-1; ETA = endothelin-A; ETB = endothelin-B; IHC = immunohistochemistry. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions

Figure 8 Immunohistochemical staining of TGF-β1 (top panels), PDGF-BB (middle panels), and CTGF (lowest panels) in atrial tissue and quantitative morphometry. CTGF = connective tissue growth factor; PDGF-BB = platelet-derived growth factor; TGF-β1 = transforming growth factor β1. Heart Rhythm 2013 10, 90-100DOI: (10.1016/j.hrthm.2012.08.043) Copyright © 2013 Terms and Conditions