Recent Insights Into the Role of the Autonomic Nervous System in the Creation of Substrate for Atrial Fibrillation

Arora, Rishi

doi:10.1161/circep.112.972273

Cited by 89 publications

(76 citation statements)

References 93 publications

(112 reference statements)

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“…46 Changes in autonomic tone, also known as sympathovagal imbalance, are important triggers in some forms of paroxysmal AF and also in the generation and maintenance of persistent AF. [41][42][43] With the expression of Na v 1.8 channels in vagal fibers and their absence in sympathetic fibers, it is possible that the observed effects on Na v 1.8 function of the different variants alters the sympathovagal balance.…”

Section: Discussionmentioning

confidence: 99%

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

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2=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. Methods and Results-SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1 ). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function. Conclusions-The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF. (Circ Cardiovasc Genet. 2015;8:64-73.

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Section: Discussionmentioning

confidence: 99%

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

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“…[4][5][6] Modulation of the autonomic nervous system by several strategies like ganglion stellatum ablation, 7 high thoracic epidural anesthesia, 8 low level vagal nerve stimulation, 9 or ablation of ganglionated plexi 10 has been shown to attenuate the development of electric, autonomic, and structural atrial remodeling during AF. Another strategy to influence sympathetic nervous system activity is renal denervation (RDN).…”

mentioning

confidence: 99%

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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“…Autonomic remodeling or interplay between the sympathetic and parasympathetic systems can also generate ectopic foci within the left atrium (LA) to create and propagate AF (17). Both animal and human models alike have shown an association between AF and abnormal autonomic system function.…”

Section: Autonomic Remodelingmentioning

confidence: 99%

“…Approximately 30% of ganglionic cells have both adrenergic and cholinergic properties (18). Vagal discharge by parasympathetic system and sympathetic activation leading to a heterogeneous increase in transmembranous and intracellular calcium and ultimately the release of norepinephrine, which can trigger focal areas in the LA and differentially decrease the atrial effective refractory period across the posterior LA, contribute to the initiation and preservation of AF (17).…”

Section: Autonomic Remodelingmentioning

confidence: 99%

Ablation of long-standing persistent atrial fibrillation

Mody¹,

Raza²,

Jacobson³

et al. 2017

Ann. Transl. Med.

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Atrial fibrillation (AF) is the most commonly encountered arrhythmia in the clinical setting affecting nearly 6 million people in United States and the numbers are only expected to rise as the population continues to age. Broadly it is classified into paroxysmal, persistent and longstanding persistent AF.Electrical, structural and autonomic remodeling are some of the diverse pathophysiological mechanisms that contribute to the persistence of AF. Our review article emphasizes particularly on long standing persistent atrial fibrillation (LSPAF) aspect of the disease which poses a great challenge for electrophysiologists. While pulmonary vein isolation (PVI) has been established as a successful ablation strategy for paroxysmal AF, same cannot be said for LSPAF owing to its long duration, complexity of mechanisms, multiple triggers and substrate sites that are responsible for its perpetuation. The article explains different approaches currently being adopted to achieve freedom from atrial arrhythmias. These mainly include ablation techniques chiefly targeting complex fractionated atrial electrograms (CFAE), rotors, linear lesions, scars and even considering hybrid approaches in a few cases while exploring the role of delayed enhancement magnetic resonance imaging (deMRI) in the pre-procedural planning to improve the overall short and long term outcomes of catheter ablation.

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Recent Insights Into the Role of the Autonomic Nervous System in the Creation of Substrate for Atrial Fibrillation

Cited by 89 publications

References 93 publications

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

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

Ablation of long-standing persistent atrial fibrillation

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