title: Atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrosis is an important component of the arrhythmogenic substrate in patients with atrial fibrillation (AF). We studied the effect of interstitial fibrosis on conduction velocity (CV) in the left atrial appendage of patients with AF.
  
  
  RESULTS
  Thirty-five left atrial appendages were obtained during AF surgery. Preparations were superfused and stimulated at 100 beats per minute. Activation was recorded with optical mapping. Longitudinal CV (CVL), transverse CV (CVT), and activation times (> 2 mm distance) were measured. Interstitial collagen was quantified and graded qualitatively. The presence of fibroblasts and myofibroblasts was assessed immunohistochemically. Mean CVL was 0.55 ± 0.22 m/s, mean CVT was 0.25 ± 0.15 m/s, and the mean activation time was 9.31 ± 5.45 ms. The amount of fibrosis was unrelated to CV or patient characteristics. CVL was higher in left atrial appendages with thick compared with thin interstitial collagen strands (0.77 ± 0.22 versus 0.48 ± 0.19 m/s; P = 0.012), which were more frequently present in persistent patients with AF. CVT was not significantly different (P = 0.47), but activation time was 14.93 ± 4.12 versus 7.95 ± 4.12 ms in patients with thick versus thin interstitial collagen strands, respectively (P = 0.004). Fibroblasts were abundantly present and were associated with the presence of thick interstitial collagen strands (P = 0.008). Myofibroblasts were not detected in the left atrial appendage.
  
  
  CONCLUSIONS
  In patients with AF, thick interstitial collagen strands are associated with higher CVL and increased activation time. Our observations demonstrate that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry.
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Sébastien P J
authors: SP
authors: Krul
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Wouter R
authors: WR
authors: Berger
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Nicoline W
authors: NW
authors: Smit
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Shirley C M
authors: SC
authors: van Amersfoorth
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Antoine H G
authors: AH
authors: Driessen
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Wim Jan
authors: WJ
authors: van Boven
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Jan W T
authors: JW
authors: Fiolet
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Antoni C G
authors: AC
authors: van Ginneken
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Allard C
authors: AC
authors: van der Wal
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Jacques M T
authors: JM
authors: de Bakker
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.).
authors: Ruben
authors: R
authors: Coronel
authors: From the Heart Center, Departments of Clinical and Experimental Cardiology (S.P.J.K., W.R.B., N.W.S., S.C.M.v.A., J.W.T.F., J.M.T.d.B., R.C., J.R.d.G.) and Cardiothoracic Surgery (A.H.G.D., W.J.v.B.), Departments of Anatomy, Embryology, and Physiology (A.C.G.v.G.) and Pathology (A.C.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.M.T.d.B.); and L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université de Bordeaux, Bordeaux, France (R.C.). j.r.degroot@amc.uva.nl.
authors: Joris R
authors: JR
authors: de Groot
mesh_terms: D000200:Action Potentials; D000368:Aged; D020517:Atrial Appendage / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D017115:Catheter Ablation / Q000379:methods*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000473:pathology; D058628:Myofibroblasts / Q000737:chemistry / Q000473:pathology; D011667:Pulmonary Veins / Q000503:physiopathology / Q000601:surgery*; D013906:Thoracoscopy; D013997:Time Factors; D016896:Treatment Outcome; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D003094:Collagen
keywords: action potential optical mapping; atrial appendage; atrial fibrillation; atrial remodeling; electrophysiology; fibrosis