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 Antoons; Andreas Lueger; Christian Muhlfeld; Gernot Plank; Ulrich Schotten; Heiner Post; Daniel Scherr

doi:10.1016/j.hrthm.2018.05.016

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

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1328-1336
Number of pages	9
Journal	Heart Rhythm
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.hrthm.2018.05.016
Publication status	Published - 1 Sept 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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10.1016/j.hrthm.2018.05.016

Cite this

Manninger, M., Zweiker, D., van Hunnik, A., Alogna, A., Prassl, A. J., Schipke, J., Zeemering, S., Zirngast, B., Schonleitner, P., Schwarzl, M., Herbst, V., Thon-Gutschi, E., Huber, S., Rohrer, U., Ebner, J., Brussee, H., Pieske, B. M., Heinzel, F. R., Verheule, S., ... Scherr, D. (2018). Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation. Heart Rhythm, 15(9), 1328-1336. https://doi.org/10.1016/j.hrthm.2018.05.016

@article{8f0d0c2a614c4caaada813647692163e,

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

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.",

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",

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

year = "2018",

month = sep,

day = "1",

doi = "10.1016/j.hrthm.2018.05.016",

language = "English",

volume = "15",

pages = "1328--1336",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "Elsevier Science",

number = "9",

}

Manninger, M, Zweiker, D, van Hunnik, A, Alogna, A, Prassl, AJ, Schipke, J, Zeemering, S, Zirngast, B, Schonleitner, P, Schwarzl, M, Herbst, V, Thon-Gutschi, E, Huber, S, Rohrer, U, Ebner, J, Brussee, H, Pieske, BM, Heinzel, FR, Verheule, S, Antoons, G, Lueger, A, Muhlfeld, C, Plank, G, Schotten, U, Post, H & Scherr, D 2018, 'Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation', Heart Rhythm, vol. 15, no. 9, pp. 1328-1336. https://doi.org/10.1016/j.hrthm.2018.05.016

TY - JOUR

T1 - Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation

AU - Manninger, Martin

AU - Zweiker, David

AU - van Hunnik, Arne

AU - Alogna, Alessio

AU - Prassl, Anton J.

AU - Schipke, Julia

AU - Zeemering, Stef

AU - Zirngast, Birgit

AU - Schonleitner, Patrick

AU - Schwarzl, Michael

AU - Herbst, Viktoria

AU - Thon-Gutschi, Eva

AU - Huber, Stefan

AU - Rohrer, Ursula

AU - Ebner, Jakob

AU - Brussee, Helmut

AU - Pieske, Burkert M.

AU - Heinzel, Frank R.

AU - Verheule, Sander

AU - Antoons, Gudrun

AU - Lueger, Andreas

AU - Muhlfeld, Christian

AU - Plank, Gernot

AU - Schotten, Ulrich

AU - Post, Heiner

AU - Scherr, Daniel

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - Arterial hypertension

KW - Atrial dilatation

KW - Atrial fibrillation

KW - Atrial fibrosis

KW - Electrical remodeling

KW - Structural remodeling

KW - HEART-FAILURE

KW - PRIMARY ALDOSTERONISM

KW - CANINE MODEL

KW - OVINE MODEL

KW - MECHANISMS

KW - SUBSTRATE

KW - GOATS

KW - SIZE

KW - ELECTROPHYSIOLOGY

KW - ABNORMALITIES

U2 - 10.1016/j.hrthm.2018.05.016

DO - 10.1016/j.hrthm.2018.05.016

M3 - Article

C2 - 29803020

SN - 1547-5271

VL - 15

SP - 1328

EP - 1336

JO - Heart Rhythm

JF - Heart Rhythm

IS - 9

ER -