Intrinsic Cardiac Autonomic Stimulation Induces Pulmonary Vein Ectopy and Triggers Atrial Fibrillation in Humans

Lim, Phang Boon; Malcolme-Lawes, Louisa; Stüber, Thomas; Wright, Ian; Francis, Dárrel P.; Davies, D. Wyn; Peters, Nicholas S.; Kanagaratnam, Prapa

doi:10.1111/j.1540-8167.2010.01992.x

Cited by 68 publications

(59 citation statements)

References 42 publications

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“…Pacing frequency was set at 20 Hz, pacing output at 20 mA with a pulse duration of 2 ms, based on earlier research. 13,[16][17][18][19] Stimulation duration was 60 s or shorter when SBP increased beyond 180 mm Hg. We waited for the BP to return to baseline values before proceeding to the next stimulation site.…”

Section: Methodsmentioning

confidence: 99%

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

et al. 2016

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R enal denervation (RDN) has been reported as a successful treatment of resistant hypertension in multiple trials studying the efficacy of RDN. [1][2][3][4][5][6] The sham-controlled Symplicity Hypertension-3 (HTN-3) trial, however, failed to show significant RDN-induced changes in blood pressure (BP) versus control, 7 raising serious doubts about the efficacy of RDN. 8-11Variable effects of RDN on BP have been reported, with a wide spectrum ranging between nonresponse to marked reduction in BP. 12 The absence of an ablation procedural end point for RDN is a potential explanation for variable responses, and the successful implementation of a reliably predictable end point could improve procedural success and clinical response.Recently, we reported on the feasibility of high-frequency electric renal nerve stimulation (RNS) in patients with resistant hypertension and demonstrated that RNS-induced BP increase was significantly blunted after RDN. 13 We hypothesized that the difference between RNS-induced BP rise before and after RDN could be used as a procedural end point for RDN and may prove a reliable functional test to predict BP response to RDN. The main goal of the current analysis was to investigate the 24-hour ambulatory BP changes after RDN and the relation to RNS before and after RDN. Methods PatientsAll patients with treatment-resistant hypertension referred for RDN between May 2014 and February 2015 were screened for inclusion in the RNS study. Patients were eligible if they were on a stable Abstract-Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27

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Section: Methodsmentioning

confidence: 99%

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

et al. 2016

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“…Approximately 50% of GP sites that produce ectopic triggering by sync-HFS do not produce an AV nodal response by cont-HFS; however, 90% of sites with an AV nodal response will trigger ectopics. 1 Canine studies suggest that the network has a common pathway into the AV node via the right lower (RL) GP (RLGP) and ablation here abolishes the AV nodal effects from other left atrial (LA) GP sites. 7 Similarly, a common input to the SA node via the right upper (RU) GP (RUGP) exists in dogs, whereby ablation at the RUGP significantly attenuates sinus rate slowing in response to GP stimulation.…”

Section: Editorial See P 458 Clinical Perspective On P 640mentioning

confidence: 99%

“…1,2 In canine studies, epicardial ganglionated plexi (GP) ablation was able to abolish both AF induction and maintenance completely. 3 Although clinical AF ablation has focused on pulmonary vein isolation (PVI), there is a high PV electric reconnection rate even in patients who remain symptomfree.…”

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confidence: 99%

Characterization of the Left Atrial Neural Network and its Impact on Autonomic Modification Procedures

Malcolme-Lawes

Lim

Wright

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background-Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation. High frequency stimulation is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown. Methods and Results-Thirty patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent atrial fibrillation, endocardial continuous high frequency stimulation identified GP sites producing AV block. After right lower GP ablation (N=5), 2 of 15 sites remained positive, whereas after ablation of other GPs (N=5), leaving right lower GP intact, all 19 sites remained positive (right lower GP versus other GP, P<0.005), indicating that neural pathways between LAGPs and the AV node are via the right lower GP. In 20 patients with paroxysmal atrial fibrillation, synchronized high frequency stimulation identified sites initiating pulmonary vein (PV) ectopy. After PV isolation (N=8), no sites remained positive. After local GP ablation (N=9), 3 of 14 sites remained positive, suggesting neural connections to the PV were disrupted by both PV isolation and GP ablation. Heart rate variability indices reduced significantly after right upper GP ablation alone, suggesting that neural pathways from the LA to the SA node travel via the right upper GP. Conclusions-We have demonstrated neural pathways connecting LA GPs with the PVs, AV node, and SA node. The effects of high frequency stimulation at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents atrial fibrillation and highlights important caveats for autonomic modification end points.

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“…79,80 GP connect the extrinsic autonomic nervous system (brain, spinal cord, and ganglia/nerves outside of the heart) to the intrinsic autonomic nervous system within the heart, and are important mediators by which autonomic stimuli influence AF and other arrhythmias. 81 Autonomic signals to the heart via GP exert important electrophysiological effects including altering atrial refractory periods, 81,82 increasing the frequency of triggered atrial premature beats that can subsequently initiate AF, 83 and increasing the vulnerability of atrial tissue to the induction of AF. 81,84,85 Animal studies have demonstrated that stimulation of GP located around the pulmonary veins can reduce the number of atrial extrastimuli required to initiate AF, and that neuronal/autonomic blockade with drugs or GP ablation can prevent AF induction.…”

Section: The Influence Of the Autonomic Nervous System And Ganglionatmentioning

confidence: 99%

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

Waks

Josephson²

2014

Arrhythmia &Amp; Electrophysiology Review

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Atrial fibrillation (AF), the most common sustained arrhythmia, is a leading cause of stroke, and is associated with significant morbidity and mortality worldwide. Despite its frequency, clinical importance, and advances in technology and our knowledge of the molecular, ionic and physiological fundamentals of cardiac electrophysiology, our limited understanding of the mechanisms that initiate and sustain AF has prevented us from being able to truly cure this arrhythmia with antiarrhythmic drugs and/or ablation. This contrasts with other arrhythmias, such as AV nodal tachycardia or circus movement tachycardia using an accessory pathway, which have well-defined mechanisms and circuits that can be safely targeted with high rates of cure. The observations that AF may have different mechanisms in different patients, and that paroxysmal, persistent and permanent forms of AF may differ in how they are initiated and sustained, only serves to reinforce our lack of understanding of this ubiquitous arrhythmia. Historical Mechanisms of Atrial Fibrillation and the Multiple Wavelet HypothesisInterest and understanding of the mechanism of AF began to take form in the early 1900s. Given the chaotic and irregular nature of AF on the surface electrocardiogram, rapid firing of automatic atrial foci was considered a potential mechanism. However, after the seminal work of Mayer 1 , Mines 2 and Garrey 3 in laying the foundation for describing and understanding reentrant arrhythmias, atrial reentrant circuits emerged as the likely drivers of AF.4-7 Although these theories were conceptually sound, it was impossible to prove a specific mechanism with the technology of the time. Moe et al. demonstrated that it was probabilistically unlikely that a large number of simultaneous wavefronts would all die out simultaneously, and AF would therefore perpetuate. However, if the number of simultaneous wavelets were small and/or below a critical value (between 15 and 30 in Moe's computer model), 9 at some point all reentrant wavefronts would be simultaneously extinguished, and AF would therefore terminate. 8,9 Allessie et al. provided experimental evidence supporting this mechanism in a canine heart model of AF where four to six simultaneous reentrant wavelets were needed to sustain arrhythmia. 10 Further evidence supporting multiple wavelets in AF was demonstrated in a separate model, which evaluated the effect of various antiarrhythmic drugs on canine myocardium. This model demonstrated that termination of AF was associated with a reduction AbstractAtrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, yet our understanding of the mechanisms that initiate and sustain this arrhythmia remains quite poor. Over the last 50 years, various mechanisms of AF have been proposed, yet none has been consistently observed in both experimental studies and in humans. Recently, there has been increasing interest in understanding how spiral waves or rotors -which are specific, organised forms of functional reentry -su...

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Intrinsic Cardiac Autonomic Stimulation Induces Pulmonary Vein Ectopy and Triggers Atrial Fibrillation in Humans

Abstract: This study has demonstrated a direct link between activation of the intrinsic cardiac autonomic nervous system and pulmonary vein ectopy in humans.

Cited by 68 publications

References 42 publications

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

Renal Nerve Stimulation–Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation

Characterization of the Left Atrial Neural Network and its Impact on Autonomic Modification Procedures

Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

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