Nathan Angel1,2, L I Li1, Rob S Macleod1,2, Nassir Marrouche1,3, Ravi Ranjan1,2, Derek J Dosdall1,3,2. 1. Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA. 2. Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA. 3. Center for Engineering Innovation, Salt Lake City, Utah, USA.
Abstract
INTRODUCTION: Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF. METHODS AND RESULTS: Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s). CONCLUSIONS: AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset.
INTRODUCTION:Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF. METHODS AND RESULTS: Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s). CONCLUSIONS:AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset.
Authors: T Kawara; R Derksen; J R de Groot; R Coronel; S Tasseron; A C Linnenbank; R N Hauer; H Kirkels; M J Janse; J M de Bakker Journal: Circulation Date: 2001-12-18 Impact factor: 29.690
Authors: L Polontchouk; J A Haefliger; B Ebelt; T Schaefer; D Stuhlmann; U Mehlhorn; F Kuhn-Regnier; E R De Vivie; S Dhein Journal: J Am Coll Cardiol Date: 2001-09 Impact factor: 24.094
Authors: Sébastien P J Krul; Wouter R Berger; Nicoline W Smit; Shirley C M van Amersfoorth; Antoine H G Driessen; Wim Jan van Boven; Jan W T Fiolet; Antoni C G van Ginneken; Allard C van der Wal; Jacques M T de Bakker; Ruben Coronel; Joris R de Groot Journal: Circ Arrhythm Electrophysiol Date: 2015-02-11
Authors: Vias Markides; Richard J Schilling; Siew Yen Ho; Anthony W C Chow; D Wyn Davies; Nicholas S Peters Journal: Circulation Date: 2003-02-11 Impact factor: 29.690
Authors: Amir A Schricker; Gautam G Lalani; David E Krummen; Wouter-Jan Rappel; Sanjiv M Narayan Journal: Circ Arrhythm Electrophysiol Date: 2014-09-12
Authors: Nassir F Marrouche; David Wilber; Gerhard Hindricks; Pierre Jais; Nazem Akoum; Francis Marchlinski; Eugene Kholmovski; Nathan Burgon; Nan Hu; Lluis Mont; Thomas Deneke; Mattias Duytschaever; Thomas Neumann; Moussa Mansour; Christian Mahnkopf; Bengt Herweg; Emile Daoud; Erik Wissner; Paul Bansmann; Johannes Brachmann Journal: JAMA Date: 2014-02-05 Impact factor: 56.272
Authors: Aleksei V Mikhailov; Anuradha Kalyanasundaram; Ning Li; Shane S Scott; Esthela J Artiga; Megan M Subr; Jichao Zhao; Brian J Hansen; John D Hummel; Vadim V Fedorov Journal: J Mol Cell Cardiol Date: 2020-10-29 Impact factor: 5.000
Authors: Joylene E Siland; Bastiaan Geelhoed; Isabelle C van Gelder; Pim van der Harst; Michiel Rienstra Journal: PLoS One Date: 2017-02-03 Impact factor: 3.240
Authors: Caroline H Roney; John Whitaker; Iain Sim; Louisa O'Neill; Rahul K Mukherjee; Orod Razeghi; Edward J Vigmond; Matthew Wright; Mark D O'Neill; Steven E Williams; Steven A Niederer Journal: Comput Biol Med Date: 2018-11-01 Impact factor: 4.589