Review Editorial For reprint orders, please contact: [email protected]
The left atrial neural network: more complicated than we thought? “More studies are needed to refine the technique of ganglionated plexi ablation, and to understand the potential role of extra-cardiac autonomic modification procedures...” Phang Boon Lim*,1 & Prapa Kanagaratnam1 The autonomic nervous system (ANS) has been implicated in arrhythmogenesis for decades. Both animal and human studies have clearly demonstrated autonomic changes preceding spontaneous onset of arrhythmias [1,2] . The autonomic nervous system plays an important physiologic role to modulate changes in chronotropic (rate), dromotropic (conduction/excitation), inotropic (contractility) function and coronary perfusion that are necessary to maintain normal cardiac function [3] . The anatomical distribution of the autonomic nervous system is complex, and comprises two major divisions, the sympathetic and parasympathetic nervous system [4] . Although the origin of these two major divisions is distinct with the sympathetic nervous system originating from the thoraco-lumbar outflow of preganglionic neurons, and the parasympathetic nervous system originating as portions of the outflows of the cranial nerves (III, VII, IX, X and XI), both these divisions are intricately linked by the time it arrives to the heart. Armour and Ardell [5] , on the basis of extensive anatomic and functional studies, established a dichotomy of cardiac
autonomic innervation. The extrinsic cardiac ANS includes the ganglia within the brain and vagosympathetic trunks, and the intrinsic cardiac ANS includes nerves and ganglionated plexi (GP) on the heart itself and on the large vessels adjacent to the heart. The GP, with its efferent, afferent and interconnecting nerves form a local network for the integration and modification of sensory input and efferent cardiac output. Rather than being a simple relay station, the intrinsic cardiac GP appear to function through a complex interconnecting neural network to maintain physiologic function of the heart [6] . These GP, which have a predilection for sites adjacent to the pulmonary veins (PVs) on the left atrium, contain thousands of nerve cell bodies and axons, with numerous ramifications and functional interaction: the left atrial neural network.
Keywords
• atrial fibrillation • autonomic nervous system • ganglionated plexi • high-frequency stimulation • pulmonary vein
“Rather than being a simple relay
station, the intrinsic cardiac ganglionated plexi appear to function through a complex interconnecting neural network to maintain physiologic function of the heart.”
The role of the left atrial neural network in triggering pulmonary vein ectopy & atrial fibrillation It is clear that spontaneous PV ectopy and tachycardia is the predominant mechanism for initiation of paroxysms of atrial
1 Imperial College Healthcare NHS Trust & Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK *Author for correspondence: Tel.: +44 203 313 2115; Fax: +44 203 313 4232; [email protected]
10.2217/FCA.15.21 © Phang Boon Lim
Future Cardiol. (2015) 11(3), 251–254
part of
ISSN 1479-6678
251
Editorial Lim & Kanagaratnam
“...we have been able to
demonstrate in humans that the ganglionated plexi located adjacent to the right upper pulmonary vein directly modulates sinus node function...”
252
fibrillation (AF), which underscores the current global consensus strategy of PV isolation to eliminate the triggers of paroxysmal AF [7] . However, what is the mechanism for spontaneous PV ectopy triggering AF? Using synchronized high-frequency stimulation (HFS), in which short bursts of HFS were delivered within the local atrial refractory period at presumed GP sites adjacent to the PVs, we demonstrated clear initiation of PV ectopy initiating AF in patients undergoing ablation for paroxysmal AF [8,9] . Ablation of these GP – typically located at antral PV sites – as well as conventional cryoablation to achieve PV isolation abolished the PV ectopic responses, suggesting a mechanism of success following ablation which may be independent of PV isolation. Cappato et al. demonstrated that 32% of patients maintained good clinical outcomes following a PV isolation procedure, despite having PV reconnection at 4 months, which may support the idea that ‘inadvertent’ GP ablation abolishing the PV ectopic-triggering response may be a potential mechanism underscoring a successful ablation procedure, independent of PV isolation. These observations are in keeping with the Euro Heart Survey finding that one in three patients with paroxysmal AF have an autonomic trigger based on the history [10] , as well as heart rate variability studies demonstrating that immediately prior to spontaneous AF onset in humans, there was an increase in adrenergic tone followed by marked modulation toward vagal predominance [1] . Using implantable nerve recording electrodes to record from both the extrinsic cardiac ANS (stellate ganglion and vagal nerve) and the intrinsic ANS (direct GP recording), Choi et al. showed in ambulatory dogs that the onset of spontaneous AF was invariably preceded, in the prior 5s before onset, by increased activity within the GP, and in 28% of cases both the extrinsic and intrinsic cardiac ANS activated together prior to AF onset [2] . Other canine studies have also shown that GP stimulation led to PV firing and increased inducibility of AF [11,12] , and that acetylcholine was needed to produce rapid and stable re-entrant PV tachycardias, suggesting that elevated parasympathetic tone could be a mechanism for perpetuation of AF [13] . Together these data provide compelling evidence for the role of the left atrial neural network in both triggering PV ectopy and sustaining PV tachycardia that initiates AF.
Future Cardiol. (2015) 11(3)
The left atrial neural network: an interconnected & interactive functional neural network of GP Through assessing acute changes in heart rate variability, a marker of autonomic influence on the sinus node, we have been able to demonstrate in humans that the GP located adjacent to the right upper pulmonary vein directly modulates sinus node function [8,14] , corroborating previous animal work by Hou et al. [6] . Similarly we demonstrated that that AV nodal effects (i.e., AV conduction delay or block) are mediated by the GP site adjacent to the right lower pulmonary vein by using continuous HFS. Ablation of this GP site rendered the rest of the GP sites in the atria (previously positive to HFS) unable to produce any further AV block in response to HFS, suggesting that the common pathway to the AV node is via the right lower GP site. This finding may explain why previous studies performing continuous HFS to target GP sites for AF ablation have shown mixed results. Endocardial and epicardial GP ablation was performed until no further AV nodal vagal responses could be elicited with HFS, but AF could still be induced in 17 of 18 patients studied, leading the authors to conclude that GP ablation did not significantly affect the ability to induce and maintain AF [15] . Other autonomic characterization and denervation studies have not specifically commented on the sequence of identification and ablation of left atrial GP sites using HFS, which raises the possibility of ablation of the right lower GP initially precluding the ability to effectively localize the other GP sites in the left atria [16–18] . If an AV nodal response is to be used to identify and ablate GP sites using HFS, the right lower GP, which serves as a final common pathway to the AV node, should be targeted last. Furthermore, we have shown that approximately 50% of GP sites that induce PV ectopy in response to synchronized HFS do not produce an AV nodal response when continuous HFS is applied, which may render functional localization of potential ectopytriggering GPs ineffective using the continuous HFS method. Ablation of the left atrial neural network: limitations & technical considerations The left atrial neural network remains incompletely understood. To date there have been no studies to systematically characterize the
future science group
The left atrial neural network GP sites across the whole atria using HFS. Despite this lack of understanding of the anatomical distribution and functional responses of GPs, studies have been performed targeting GPs, either as an adjunctive strategy or a standalone approach, for treatment of both paroxysmal and persistent AF with promising initial results [19,20] . In these studies, anatomically based targeting of the GP sites around the antra of all PVs was performed. However, without a clear functional end point, it is difficult to understand how much ablation is sufficient to perform before stopping. Furthermore, the conventional approach of a wide area circumferential ablation to achieve PV isolation is likely to cause ‘inadvertent’ GP ablation along the line of ablation, which may make randomized studies between GP ablation and PV isolation procedures difficult to interpret, given they both almost certainly result in a degree of autonomic denervation. The technique of PV ectopy-triggering synchronized HFS may offer a functional target for ablation, and could potentially be used as an end point for GP ablation in treatment of paroxysmal AF. However, a limitation of this technique is that once AF is induced during synchronized HFS, retesting may not be possible unless repeated cardioversions are performed. The hardware and technique needed to perform HFS is not routinely available across electrophysiology labs, precluding large multicenter-based studies, with the most of the emerging data on
1
Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation 105(23), 2753–2759 (2002).
2
Choi EK, Shen MJ, Han S et al. Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs. Circulation 121(24), 2615–2623 (2010).
3
Adams DJ, Cuevas J. Electrophysiological Properties of Intrinsic Cardiac Neurons. In: Basic and Clinical Neurocardiology Armour JA, Ardell JL (Eds). Oxford University Press, NY, USA (2004).
4
Burnstock G. Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacol. Rev. 21(4), 247–324 (1969).
5
Armour JA, Murphy DA, Yuan BX, Macdonald S, Hopkins DA. Gross and
future science group
the role of GP ablation in AF arising from only a handful of centers worldwide. Conclusion Despite the compelling evidence suggesting an important role of the ANS in initiation and maintenance of AF, there is no clearly-defined strategy to identify and ablate the GP in a systematic way. The long-term safety of cardiac autonomic denervation remains unknown. More studies are needed to refine the technique of GP ablation, and to understand the potential role of extra-cardiac autonomic modification procedures, such as renal denervation or direct cervical nerve stimulation, in arrhythmogenesis. Financial & competing interests disclosure PB Lim was supported by British Heart Foundation grant no. FS/06/089. The work conducted by the authors was supported by the NIHR Imperial Biomedical Research Centre. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Open access This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
(ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 9(6), 335–379 (2007).
microscopic anatomy of the human intrinsic cardiac nervous system. Anat. Rec. 247(2), 289–298 (1997).
References
Editorial
6
Hou Y, Scherlag BJ, Lin J et al. Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation. J. Am. Coll. Cardiol. 50(1), 61–68 (2007).
7
Calkins H, Brugada J, Packer DL et al. HRS/ EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology
8
Malcolme-Lawes LC, Lim PB, Wright I et al. Characterization of the left atrial neural network and its impact on autonomic modification procedures. Circ. Arrhythm. Electrophysiol. 6(3), 632–640 (2013).
9
Lim PB, Malcolme-Lawes LC, Stuber T et al. Intrinsic cardiac autonomic stimulation induces pulmonary vein ectopy and triggers atrial fibrillation in humans. J. Cardiovasc. Electrophysiol. 22(6), 638–646 (2011).
www.futuremedicine.com
253
Editorial Lim & Kanagaratnam 10 de Vos CB, Nieuwlaat R, Crijns HJ et al.
Autonomic trigger patterns and antiarrhythmic treatment of paroxysmal atrial fibrillation: data from the Euro Heart Survey. Eur. Heart J. 29(5), 632–639 (2008). 11 Scherlag BJ, Nakagawa H, Jackman WM
et al. Electrical stimulation to identify neural elements on the heart: their role in atrial fibrillation. J. Interv. Card. Electrophysiol. 13(Suppl. 1), 37–42 (2005). 12 Zhou J, Scherlag BJ, Edwards J, Jackman
WM, Lazzara R, Po SS. Gradients of atrial refractoriness and inducibility of atrial fibrillation due to stimulation of ganglionated plexi. J. Cardiovasc. Electrophysiol. 18(1), 83–90 (2007). 13 Po SS, Li Y, Tang D et al. Rapid and stable
re-entry within the pulmonary vein as a mechanism initiating paroxysmal atrial fibrillation. J. Am. Coll. Cardiol. 45(11), 1871–1877 (2005).
254
14 Lim PB, Malcolme-Lawes LC, Stuber T et al.
Feasibility of multiple short, 40-s, intraprocedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias. J. Interv. Card. Electrophysiol. 32(2), 163–171 (2011). 15 Danik S, Neuzil P, D’Avila A et al.
Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation. Am. J. Cardiol. 102(5), 578–583 (2008). 16 Lemery R, Birnie D, Tang AS, Green M,
Gollob M. Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation. Heart Rhythm 3(4), 387–396 (2006). 17 Verma A, Saliba WI, Lakkireddy D et al.
Vagal responses induced by endocardial left atrial autonomic ganglion stimulation before and after pulmonary vein antrum
Future Cardiol. (2015) 11(3)
isolation for atrial fibrillation. Heart Rhythm 4(9), 1177–1182 (2007). 18 Edgerton JR, Brinkman WT, Weaver T
et al. Pulmonary vein isolation and autonomic denervation for the management of paroxysmal atrial fibrillation by a minimally invasive surgical approach. J. Thorac. Cardiovasc. Surg. 140(4), 823–828 (2010). 19 Katritsis DG, Giazitzoglou E, Zografos T,
Pokushalov E, Po SS, Camm AJ. Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study. Heart Rhythm 8(5), 672–678 (2011). 20 Pokushalov E, Romanov A, Katritsis DG
et al. Ganglionated plexus ablation vs linear ablation in patients undergoing pulmonary vein isolation for persistent/long-standing persistent atrial fibrillation: a randomized comparison. Heart Rhythm 10(9), 1280–1286 (2013).
future science group
The left atrial neural network: more complicated than we thought? “More studies are needed to refine the technique of ganglionated plexi ablation, and to understand the potential role of extra-cardiac autonomic modification procedures...” Phang Boon Lim*,1 & Prapa Kanagaratnam1 The autonomic nervous system (ANS) has been implicated in arrhythmogenesis for decades. Both animal and human studies have clearly demonstrated autonomic changes preceding spontaneous onset of arrhythmias [1,2] . The autonomic nervous system plays an important physiologic role to modulate changes in chronotropic (rate), dromotropic (conduction/excitation), inotropic (contractility) function and coronary perfusion that are necessary to maintain normal cardiac function [3] . The anatomical distribution of the autonomic nervous system is complex, and comprises two major divisions, the sympathetic and parasympathetic nervous system [4] . Although the origin of these two major divisions is distinct with the sympathetic nervous system originating from the thoraco-lumbar outflow of preganglionic neurons, and the parasympathetic nervous system originating as portions of the outflows of the cranial nerves (III, VII, IX, X and XI), both these divisions are intricately linked by the time it arrives to the heart. Armour and Ardell [5] , on the basis of extensive anatomic and functional studies, established a dichotomy of cardiac
autonomic innervation. The extrinsic cardiac ANS includes the ganglia within the brain and vagosympathetic trunks, and the intrinsic cardiac ANS includes nerves and ganglionated plexi (GP) on the heart itself and on the large vessels adjacent to the heart. The GP, with its efferent, afferent and interconnecting nerves form a local network for the integration and modification of sensory input and efferent cardiac output. Rather than being a simple relay station, the intrinsic cardiac GP appear to function through a complex interconnecting neural network to maintain physiologic function of the heart [6] . These GP, which have a predilection for sites adjacent to the pulmonary veins (PVs) on the left atrium, contain thousands of nerve cell bodies and axons, with numerous ramifications and functional interaction: the left atrial neural network.
Keywords
• atrial fibrillation • autonomic nervous system • ganglionated plexi • high-frequency stimulation • pulmonary vein
“Rather than being a simple relay
station, the intrinsic cardiac ganglionated plexi appear to function through a complex interconnecting neural network to maintain physiologic function of the heart.”
The role of the left atrial neural network in triggering pulmonary vein ectopy & atrial fibrillation It is clear that spontaneous PV ectopy and tachycardia is the predominant mechanism for initiation of paroxysms of atrial
1 Imperial College Healthcare NHS Trust & Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK *Author for correspondence: Tel.: +44 203 313 2115; Fax: +44 203 313 4232; [email protected]
10.2217/FCA.15.21 © Phang Boon Lim
Future Cardiol. (2015) 11(3), 251–254
part of
ISSN 1479-6678
251
Editorial Lim & Kanagaratnam
“...we have been able to
demonstrate in humans that the ganglionated plexi located adjacent to the right upper pulmonary vein directly modulates sinus node function...”
252
fibrillation (AF), which underscores the current global consensus strategy of PV isolation to eliminate the triggers of paroxysmal AF [7] . However, what is the mechanism for spontaneous PV ectopy triggering AF? Using synchronized high-frequency stimulation (HFS), in which short bursts of HFS were delivered within the local atrial refractory period at presumed GP sites adjacent to the PVs, we demonstrated clear initiation of PV ectopy initiating AF in patients undergoing ablation for paroxysmal AF [8,9] . Ablation of these GP – typically located at antral PV sites – as well as conventional cryoablation to achieve PV isolation abolished the PV ectopic responses, suggesting a mechanism of success following ablation which may be independent of PV isolation. Cappato et al. demonstrated that 32% of patients maintained good clinical outcomes following a PV isolation procedure, despite having PV reconnection at 4 months, which may support the idea that ‘inadvertent’ GP ablation abolishing the PV ectopic-triggering response may be a potential mechanism underscoring a successful ablation procedure, independent of PV isolation. These observations are in keeping with the Euro Heart Survey finding that one in three patients with paroxysmal AF have an autonomic trigger based on the history [10] , as well as heart rate variability studies demonstrating that immediately prior to spontaneous AF onset in humans, there was an increase in adrenergic tone followed by marked modulation toward vagal predominance [1] . Using implantable nerve recording electrodes to record from both the extrinsic cardiac ANS (stellate ganglion and vagal nerve) and the intrinsic ANS (direct GP recording), Choi et al. showed in ambulatory dogs that the onset of spontaneous AF was invariably preceded, in the prior 5s before onset, by increased activity within the GP, and in 28% of cases both the extrinsic and intrinsic cardiac ANS activated together prior to AF onset [2] . Other canine studies have also shown that GP stimulation led to PV firing and increased inducibility of AF [11,12] , and that acetylcholine was needed to produce rapid and stable re-entrant PV tachycardias, suggesting that elevated parasympathetic tone could be a mechanism for perpetuation of AF [13] . Together these data provide compelling evidence for the role of the left atrial neural network in both triggering PV ectopy and sustaining PV tachycardia that initiates AF.
Future Cardiol. (2015) 11(3)
The left atrial neural network: an interconnected & interactive functional neural network of GP Through assessing acute changes in heart rate variability, a marker of autonomic influence on the sinus node, we have been able to demonstrate in humans that the GP located adjacent to the right upper pulmonary vein directly modulates sinus node function [8,14] , corroborating previous animal work by Hou et al. [6] . Similarly we demonstrated that that AV nodal effects (i.e., AV conduction delay or block) are mediated by the GP site adjacent to the right lower pulmonary vein by using continuous HFS. Ablation of this GP site rendered the rest of the GP sites in the atria (previously positive to HFS) unable to produce any further AV block in response to HFS, suggesting that the common pathway to the AV node is via the right lower GP site. This finding may explain why previous studies performing continuous HFS to target GP sites for AF ablation have shown mixed results. Endocardial and epicardial GP ablation was performed until no further AV nodal vagal responses could be elicited with HFS, but AF could still be induced in 17 of 18 patients studied, leading the authors to conclude that GP ablation did not significantly affect the ability to induce and maintain AF [15] . Other autonomic characterization and denervation studies have not specifically commented on the sequence of identification and ablation of left atrial GP sites using HFS, which raises the possibility of ablation of the right lower GP initially precluding the ability to effectively localize the other GP sites in the left atria [16–18] . If an AV nodal response is to be used to identify and ablate GP sites using HFS, the right lower GP, which serves as a final common pathway to the AV node, should be targeted last. Furthermore, we have shown that approximately 50% of GP sites that induce PV ectopy in response to synchronized HFS do not produce an AV nodal response when continuous HFS is applied, which may render functional localization of potential ectopytriggering GPs ineffective using the continuous HFS method. Ablation of the left atrial neural network: limitations & technical considerations The left atrial neural network remains incompletely understood. To date there have been no studies to systematically characterize the
future science group
The left atrial neural network GP sites across the whole atria using HFS. Despite this lack of understanding of the anatomical distribution and functional responses of GPs, studies have been performed targeting GPs, either as an adjunctive strategy or a standalone approach, for treatment of both paroxysmal and persistent AF with promising initial results [19,20] . In these studies, anatomically based targeting of the GP sites around the antra of all PVs was performed. However, without a clear functional end point, it is difficult to understand how much ablation is sufficient to perform before stopping. Furthermore, the conventional approach of a wide area circumferential ablation to achieve PV isolation is likely to cause ‘inadvertent’ GP ablation along the line of ablation, which may make randomized studies between GP ablation and PV isolation procedures difficult to interpret, given they both almost certainly result in a degree of autonomic denervation. The technique of PV ectopy-triggering synchronized HFS may offer a functional target for ablation, and could potentially be used as an end point for GP ablation in treatment of paroxysmal AF. However, a limitation of this technique is that once AF is induced during synchronized HFS, retesting may not be possible unless repeated cardioversions are performed. The hardware and technique needed to perform HFS is not routinely available across electrophysiology labs, precluding large multicenter-based studies, with the most of the emerging data on
1
Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation 105(23), 2753–2759 (2002).
2
Choi EK, Shen MJ, Han S et al. Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs. Circulation 121(24), 2615–2623 (2010).
3
Adams DJ, Cuevas J. Electrophysiological Properties of Intrinsic Cardiac Neurons. In: Basic and Clinical Neurocardiology Armour JA, Ardell JL (Eds). Oxford University Press, NY, USA (2004).
4
Burnstock G. Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacol. Rev. 21(4), 247–324 (1969).
5
Armour JA, Murphy DA, Yuan BX, Macdonald S, Hopkins DA. Gross and
future science group
the role of GP ablation in AF arising from only a handful of centers worldwide. Conclusion Despite the compelling evidence suggesting an important role of the ANS in initiation and maintenance of AF, there is no clearly-defined strategy to identify and ablate the GP in a systematic way. The long-term safety of cardiac autonomic denervation remains unknown. More studies are needed to refine the technique of GP ablation, and to understand the potential role of extra-cardiac autonomic modification procedures, such as renal denervation or direct cervical nerve stimulation, in arrhythmogenesis. Financial & competing interests disclosure PB Lim was supported by British Heart Foundation grant no. FS/06/089. The work conducted by the authors was supported by the NIHR Imperial Biomedical Research Centre. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Open access This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
(ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 9(6), 335–379 (2007).
microscopic anatomy of the human intrinsic cardiac nervous system. Anat. Rec. 247(2), 289–298 (1997).
References
Editorial
6
Hou Y, Scherlag BJ, Lin J et al. Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation. J. Am. Coll. Cardiol. 50(1), 61–68 (2007).
7
Calkins H, Brugada J, Packer DL et al. HRS/ EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology
8
Malcolme-Lawes LC, Lim PB, Wright I et al. Characterization of the left atrial neural network and its impact on autonomic modification procedures. Circ. Arrhythm. Electrophysiol. 6(3), 632–640 (2013).
9
Lim PB, Malcolme-Lawes LC, Stuber T et al. Intrinsic cardiac autonomic stimulation induces pulmonary vein ectopy and triggers atrial fibrillation in humans. J. Cardiovasc. Electrophysiol. 22(6), 638–646 (2011).
www.futuremedicine.com
253
Editorial Lim & Kanagaratnam 10 de Vos CB, Nieuwlaat R, Crijns HJ et al.
Autonomic trigger patterns and antiarrhythmic treatment of paroxysmal atrial fibrillation: data from the Euro Heart Survey. Eur. Heart J. 29(5), 632–639 (2008). 11 Scherlag BJ, Nakagawa H, Jackman WM
et al. Electrical stimulation to identify neural elements on the heart: their role in atrial fibrillation. J. Interv. Card. Electrophysiol. 13(Suppl. 1), 37–42 (2005). 12 Zhou J, Scherlag BJ, Edwards J, Jackman
WM, Lazzara R, Po SS. Gradients of atrial refractoriness and inducibility of atrial fibrillation due to stimulation of ganglionated plexi. J. Cardiovasc. Electrophysiol. 18(1), 83–90 (2007). 13 Po SS, Li Y, Tang D et al. Rapid and stable
re-entry within the pulmonary vein as a mechanism initiating paroxysmal atrial fibrillation. J. Am. Coll. Cardiol. 45(11), 1871–1877 (2005).
254
14 Lim PB, Malcolme-Lawes LC, Stuber T et al.
Feasibility of multiple short, 40-s, intraprocedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias. J. Interv. Card. Electrophysiol. 32(2), 163–171 (2011). 15 Danik S, Neuzil P, D’Avila A et al.
Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation. Am. J. Cardiol. 102(5), 578–583 (2008). 16 Lemery R, Birnie D, Tang AS, Green M,
Gollob M. Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation. Heart Rhythm 3(4), 387–396 (2006). 17 Verma A, Saliba WI, Lakkireddy D et al.
Vagal responses induced by endocardial left atrial autonomic ganglion stimulation before and after pulmonary vein antrum
Future Cardiol. (2015) 11(3)
isolation for atrial fibrillation. Heart Rhythm 4(9), 1177–1182 (2007). 18 Edgerton JR, Brinkman WT, Weaver T
et al. Pulmonary vein isolation and autonomic denervation for the management of paroxysmal atrial fibrillation by a minimally invasive surgical approach. J. Thorac. Cardiovasc. Surg. 140(4), 823–828 (2010). 19 Katritsis DG, Giazitzoglou E, Zografos T,
Pokushalov E, Po SS, Camm AJ. Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study. Heart Rhythm 8(5), 672–678 (2011). 20 Pokushalov E, Romanov A, Katritsis DG
et al. Ganglionated plexus ablation vs linear ablation in patients undergoing pulmonary vein isolation for persistent/long-standing persistent atrial fibrillation: a randomized comparison. Heart Rhythm 10(9), 1280–1286 (2013).
future science group
