Role of endo-epicardial dissociation of electrical activity and transmural conduction in the development of persistent atrial fibrillation

Verheule, Sander; Eckstein, Jens; Linz, Dominik; Maesen, Bart; Bidar, Elham; Gharaviri, Ali; Schotten, Ulrich

doi:10.1016/j.pbiomolbio.2014.07.007

Cited by 86 publications

(83 citation statements)

References 67 publications

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“…22 Structural atrial remodeling results in the progressive loss of endo-epicardial electric connections increasing atrial endoepicardial dissociation and thereby enhances the likelihood for transmural conduction and producing a 3-dimensional substrate for AF. 20 In the RDN group, LA AF complexity was lower than in SHAM-AF animals with the same AF duration. The complexity of AF activation patterns is determined by the incidence of conduction block, which is critically determined by structural alterations.…”

Section: Rdn and Atrial Structural Remodeling And Complexity Of Afmentioning

confidence: 86%

“…[20][21][22][23] Animal procedures conformed to international standards on Research Animal Use and approved by the local ethical committee. All animals received a right atrial endocardial pacemaker lead (Medtronic Capsurefix).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported that AF in goats with AF duration of 3 weeks was characterized by a higher number of simultaneous waves (both peripheral waves and epicardial breakthroughs) and a larger incidence of conduction block, leading to a more dissociated and complex fibrillation pattern compared with acute AF in goats. 20,21 Importantly, AF complexity occurred independent from changes in AFCL and conduction velocity. AF complexity most likely represents the functional consequence of atrial structural remodeling.…”

Section: Rdn and Atrial Structural Remodeling And Complexity Of Afmentioning

confidence: 96%

“…18 The effect of RDN on the development of an atrial structural remodeling and AF has not been investigated sufficiently. 19 In particular, the influence of RDN on the complexity of AF propagation patterns, 20 representing the functional consequence of atrial structural remodeling, 21,22 has not yet been studied. This study is aimed to determine the effect of sympathetic nervous system modulation by RDN on structural and neural remodeling in the atrium and AF complexity in a goat model of persistent AF without hypertension or structural heart disease.…”

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confidence: 99%

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Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats

Linz

Hunnik

Hohl

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background-Atrial fibrillation (AF) leads to structural and neural remodeling in the atrium, which enhances AF complexity and perpetuation. Renal denervation (RDN) can reduce renal and whole-body sympathetic activity. Aim of this study was to determine the effect of sympathetic nervous system modulation by RDN on atrial arrhythmogenesis. Methods and Result-Eighteen goats were instrumented with an atrial endocardial pacemaker lead and a burst pacemaker.Percutaneous catheter-based RDN was performed in 8 goats (RDN-AF). Ten goats undergoing a sham procedure served as control (SHAM-AF). AF was induced and maintained by burst pacing for 6 weeks. High-resolution mapping was used to record epicardial conduction patterns of the right and left atrium. RDN reduced tyrosine hydroxylase-positive sympathetic nerve staining and resulted in lower transcardiac norepinephrine levels. This was associated with reduced expression of nerve growth factor-β, indicating less atrial nerve sprouting. Atrial endomysial fibrosis content was lower and myocyte diameter was smaller in RDN-AF. Median conduction velocity was higher (75±9 versus 65±10 cm/s, P=0.02), and AF cycle length was shorter in RDN-AF compared with SHAM-AF. Left atrial AF complexity (4.8±0.8 fibrillation waves/AF cycle length versus 8.5±0.8 waves/AF cycle length, P=0.001) and incidence of breakthroughs (2.0±0.3 versus 4.3±0.5 waves/AF cycle length, P=0.059) were lower in RDN-AF compared with SHAM-AF. Blood pressure was normal and not significantly different between the groups. Conclusions-RDN reduces atrial sympathetic nerve sprouting, structural alterations, and AF complexity in goats with persistent AF, independent of changes in blood pressure. (Circ Arrhythm Electrophysiol. 2015;8:466-474.

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Section: Rdn and Atrial Structural Remodeling And Complexity Of Afmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Rdn and Atrial Structural Remodeling And Complexity Of Afmentioning

confidence: 96%

mentioning

confidence: 99%

See 2 more Smart Citations

Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats

Linz

Hunnik

Hohl

et al. 2015

Circ: Arrhythmia and Electrophysiology

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“…Large‐animal structural models, such as sheep15, 16 and goats,17 have been used to investigate myofiber structure and surface geometry of the intact atria and progress has been made in defining the mechanisms of AF in animal models 4, 18. However, the interspecies difference in atrial structure and physiology may diminish the translational applications of these models to human AF 7.…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo

Zhao

Hansen

Wang

et al. 2017

JAHA

122

140

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BackgroundStructural remodeling of human atria plays a key role in sustaining atrial fibrillation (AF), but insufficient quantitative analysis of human atrial structure impedes the treatment of AF. We aimed to develop a novel 3‐dimensional (3D) structural and computational simulation analysis tool that could reveal the structural contributors to human reentrant AF drivers.Methods and ResultsHigh‐resolution panoramic epicardial optical mapping of the coronary‐perfused explanted intact human atria (63‐year‐old woman, chronic hypertension, heart weight 608 g) was conducted during sinus rhythm and sustained AF maintained by spatially stable reentrant AF drivers in the left and right atrium. The whole atria (107×61×85 mm3) were then imaged with contrast‐enhancement MRI (9.4 T, 180×180×360‐μm3 resolution). The entire 3D human atria were analyzed for wall thickness (0.4–11.7 mm), myofiber orientations, and transmural fibrosis (36.9% subendocardium; 14.2% midwall; 3.4% subepicardium). The 3D computational analysis revealed that a specific combination of wall thickness and fibrosis ranges were primarily present in the optically defined AF driver regions versus nondriver tissue. Finally, a 3D human heart–specific atrial computer model was developed by integrating 3D structural and functional mapping data to test AF induction, maintenance, and ablation strategies. This 3D model reproduced the optically defined reentrant AF drivers, which were uninducible when fibrosis and myofiber anisotropy were removed from the model.ConclusionsOur novel 3D computational high‐resolution framework may be used to quantitatively analyze structural substrates, such as wall thickness, myofiber orientation, and fibrosis, underlying localized AF drivers, and aid the development of new patient‐specific treatments.

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References

2019

Understanding Atrial Fibrillation

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Role of endo-epicardial dissociation of electrical activity and transmural conduction in the development of persistent atrial fibrillation

Cited by 86 publications

References 67 publications

Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats

Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats

Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo

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