Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation

Martin Manninger*, David Zweiker, Arne van Hunnik, Alessio Alogna, Anton J. Prassl, Julia Schipke, Stef Zeemering, Birgit Zirngast, Patrick Schonleitner, Michael Schwarzl, Viktoria Herbst, Eva Thon-Gutschi, Stefan Huber, Ursula Rohrer, Jakob Ebner, Helmut Brussee, Burkert M. Pieske, Frank R. Heinzel, Sander Verheule, Gudrun AntoonsAndreas Lueger, Christian Muhlfeld, Gernot Plank, Ulrich Schotten, Heiner Post, Daniel Scherr

*Corresponding author for this work

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Abstract

BACKGROUND Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms. OBJECTIVE We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP) induced AF combined with desoxycorticosterone acetate (DOCA) induced HT. METHODS Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed. RESULTS DOCA implantation led to secondary HT (median [inter-quartile range] aortic pressure 109.9 [100-137] mm Hg in AF+ HT vs 82.2 [79-96] mm Hg in AF; P <.05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P <.05), concentric left ventricular hypertrophy, atrial dilatation (119 +/- 31 cm(2) in AF+HT vs 78 +/- 23 cm(2) in AF; P <.05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non intermyocyte areas (1.62 +/- 0.38 cm(3) in AF+HT vs 0.96 +/- 0.3 cm(3) in AF; P <.05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size. CONCLUSION In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.
Original languageEnglish
Pages (from-to)1328-1336
Number of pages9
JournalHeart Rhythm
Volume15
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Keywords

  • Arterial hypertension
  • Atrial dilatation
  • Atrial fibrillation
  • Atrial fibrosis
  • Electrical remodeling
  • Structural remodeling
  • HEART-FAILURE
  • PRIMARY ALDOSTERONISM
  • CANINE MODEL
  • OVINE MODEL
  • MECHANISMS
  • SUBSTRATE
  • GOATS
  • SIZE
  • ELECTROPHYSIOLOGY
  • ABNORMALITIES

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