Catheter Ablation of Paroxysmal Atrial Fibrillation Originating from Non-pulmonary Vein Areas

Abstract

Pulmonary veins (PVs) are a major source of ectopic beats that initiate AF. PV isolation from the left atrium is an effective therapy for the majority of paroxysmal AF. However, investigators have reported that ectopy originating from non-PV areas can also initiate AF. Patients with recurrent AF after persistent PV isolation highlight the need to identify non-PV ectopy. Furthermore, adding non-PV ablation after multiple AF ablation procedures leads to lower AF recurrence and a higher AF cure rate. These findings suggest that non-PV ectopy is important in both the initiation and recurrence of AF. This article summarises current knowledge about the electrophysiological characteristics of non-PV AF, suitable mapping and ablation strategies, and the safety and efficacy of catheter ablation of AF initiated by ectopic foci originating from non-PV areas.

Catheter ablation of AF has become an established therapy and may have the potential to cure this most commonly encountered sustained arrhythmia. Previous studies have demonstrated that pulmonary veins (PVs) are a major source of the ectopic beats that initiate AF. PV isolation in patients with symptomatic paroxysmal AF refractory to antiarrhythmic drugs is effective; however, it is difficult to eliminate all instances of AF.[1–3] If ectopic foci consistently come from a non-PV area and a pattern of spontaneous onset of AF is onset confirmed, the earliest ectopic site is defined as the non-PV trigger initiating AF.[2,4–7] Ectopy originating from non-PV areas can initiate AF and can cause it to recur after PV isolation.[4–31] Non-PV ablation after multiple AF ablation procedures decreases the risk of recurrence and increases the cure rate.[10,19–21,23,25,28,29] Although several ablation strategies have been developed, the outcomes of ablation are not improved unless substrate modification targets AF triggers.[30] Taking all of these considerations into account, non-PV ectopy plays important role in both AF initiation and recurrence.[2,4–7,20,29,30,32–34]

Mapping studies of non-PV foci have revealed that triggers are often found in anatomically predictable regions, such as the left atrial wall, thoracic veins and crista terminalis, and can be sustained or non-sustained triggers of AF. These areas can be mapped by specific multielectrode catheters positioned in key regions and ablated after the AF is induced and localised, or they can be ablated empirically without the induction of ectopy.[1–34] This review focuses on catheter ablation of AF initiated by non-PV triggers, summarising the electrophysiological characteristics, mapping and ablation strategies, their safety and efficacy.

Electrophysiological Features of AF Originating from Non-pulmonary Vein Areas

Incidence of Initiators

Several important concepts have been proposed regarding the role of non-PV ectopy in initiating AF.[2,4–7] AF is initiated by non-PV disturbance of the cardiac rhythm in up to 39 % of cases.[3,8–10,32–38] The left atrium (LA) (25.3 %), superior vena cava (SVC) (22.2 %), coronary sinus (CS) (18.0 %), right atrium (RA) including the crista terminalis (17.4 %), interatrial septum (7.9 %), and ligament of Marshall (LOM) (3.9 %) are the areas in which non-PV triggers of de novo AF are most commonly found (Table 1), whereas the SVC, interatrial septum and LA are the most common non-PV trigger sites in recurrent AF (Table 2).[6–30] Furthermore, there is a higher incidence of non-PV triggers initiating AF in females and in patients with an enlarged LA.[39]

Table 1: De Novo AF Originating from Non-pulmonary Vein Areas.

Publication	Number of patients		Mean age (years)	Gender	Number of Ectopic Foci		Mapping Modality	Origin of Ectopy (No of Foci)
	Total	Non-PV ectopy			Total	Non-PV ectopy		RA	SVC	CS	IAS	LA	LOM	SVT	Others
Lin et al. 2003[6]	240	68 (28 %)	61±13	43 M/25 F	358	73 (20 %)	C, basket, ICE	CT 10	27	1	1	PW (28)	6
Shah et al. 2003[8]	160	36 (23 %)	NA	NA	NA	86	C	5	3*	4		PW (30), PV os (39), others (5)			16**
Beldner et al. 2004[9]	401	68 (17 %)	NA	NA	NA	83	C, ICE, CARTO	CT 11, TA 4, ER 13	4	3	FO (4)	PW (15), MA (7)		20‡	2
Suzuki et al. 2004[10]	127	18 (14 %)	NA	NA	NA	20	C	CT 4	5	1	7	2	1
Yamada et al. 2007[11]	147	31 (21 %)	NA	NA	NA	38	Basket	CT 5	12	2	5	9			5§
Valles et al. 2008[12]	45	NA	NA	NA	57	6 (11 %)	C	CT 2	2	1		1
Lo et al. 2009[13]	85†	17 (20%)	NA	NA	NA	17	NavX		6	2	2	PW (3)	4
Yamaguchi et al. 2010[14]	65	17 (26 %)	62±8	13 M/4 F	95	19 (20 %)	Array	CT 1	5	2	2	8	1
Chang et al. 2013[15]	660†	132 (20 %)	51±12	86 M/46 F	779	146 (19 %)	NavX	CT 15	53	22	13	23	20
Zhang et al. 2014[16]	300	29 (10 %)	NA	NA	NA	29	C	CT 1	27			PV os (1)
Cheng et al. 2014[17]	76	13 (17 %)	NA	NA	NA	13	C		5	5		1			2**
Kuroi et al. 2015[18]	446	26 (6 %)	NA	NA	NA	28	CARTO	9	10		2	7
Hayashi et al. 2015[19]	304	59 (19 %)	NA	NA	178	43 (24 %)	CARTO/NavX	8	19 (PLSVC2)*	3	5	7	1
Lo et al. 2015[20]	530	70 (13 %)	NA	NA	612	85 (14 %)	NavX	CT 4	31	13	10	17	10
Hayashi et al. 2016[21]	216	43 (20 %)	NA	NA	147	58 (39 %)	C	CT 4, RAF 3	17 (PLSVC2)*	1	10	10	1		12**
Hasebe et al. 2016[22]	39	7 (18 %)	51±13	6 M/1 F	53	11 (21 %)	C	CT 5, TA 1, RAF 4	1
Zhao et al. 2016[23]	720	266 (37 %)	NA	NA	NA	423	C	62	23	195		143
Santangeli et al. 2016[24]	1531	165 (11 %)	NA	NA	NA	195‖	CARTO/NavX	70	26	23	27	7		42‡
Hung et al. 2017[25]	579	95 (16 %)	NA	NA	NA	99	NavX	14	42	2	11	14	16
Narui et al. 2017[26]	255†	34 (13 %)	NA	NA	NA	34	C	7	21			6
Allamsettey et al. 2017[27]	32†	11 (34 %)	NA	NA	85	15 (18 %)	Velocity		2			10¶	3
Takigawa et al. 2017[28]	865	68 (8 %)	NA	NA	NA	76	C	CT 16	14	8	27	11
Total	7,823	1,273 (16.3 %)				1597		278 (17.4 %)	355 (22.2 %)	288 (18.0 %)	126 (7.9 %)	404 (25.3 %)	63 (3.9 %)	62 (3.9 %)	37 (2.3 %)

*Includes persistent left superior vena cava. ^†33 paroxysmal and 52 non-paroxysmal AF patients in Lo et al.,[13] 526 and 134 in Chang et al.,[15] 150 and 105 in Narui et al.,[26] and 26 and 6 in Allamsetty et al.[27] ^‡Atrioventricular nodal re-entrant tachycardia and atrioventricular re-entrant tachycardia triggered AF. ^§Five foci were speculated to have an epicardial origin. ^**16, 2 and 12 foci were unmappable non-PV foci, respectively. ^‖Numbers of non-PV ectopic foci were estimated based on the percentage of patients with non-PV ectopic foci. ^¶Non-PV triggers were observed in 34 % of the total population (26 paroxysmal and 6 nonparoxysmal AF). A total of 45 % of non-PV triggers (16 % of the total population) were observed in the aortic encroachment area. Array = EnSite™ Array™ noncontact mapping system (Abbott); Basket = basket catheter; C = conventional mapping; CARTO = CARTO^® system (Biosense Webster); CS = coronary sinus; CT = crista terminalis; ER = Eustachian ridge; F = female; FO = fossa ovalis; IAS = interatrial septum; ICE = intracardiac echocardiography; LA = left atrium; LOM = ligament of Marshall; M = male; MA = mitral annulus; NA = data not available; NavX = EnSite™ NavX™ system (Abbott); PLSVC = persistent left superior vena cava; PV = pulmonary vein; PVos = ostia of an ablated pulmonary vein including the zone between ipsilateral veins; PW = left atrial posterior wall; RA = right atrium; RAF = right atrial free wall; SVC = superior vena cava; SVT = supraventricular tachycardia; TA = tricuspid annulus; Velocity = EnSite™ Velocity™ cardiac mapping system (Abbott). Some data reproduced with permission from Higa et al., 2011.34

Table 2: Recurrent AF Originating from Non-pulmonary Vein Areas.

Publication	Number of patients		Mean age (years)	Gender	Number of Ectopic Foci		Mapping Modality	Origin of Ectopy (No of Foci)
	Total	Non-PV ectopy			Total	Non-PV ectopy		RA	SVC	CS	IAS	LA	LOM	SVT	Others
Takigawa et al. 2005[29]	207	95 (46 %)*	63±11	69 male/26 female	NA	92	C		34		16	12			38†
Lo et al. 2015[20]	94	11 (12 %)*	NA	NA	102	12 (12 %)	NavX	8	25		8	42	17
Lo et al. 2015[20]	52	15 (29 %)‡	NA	NA	75	24 (32 %)	NavX	17	25	4		42	13
Mahonty et al. 2017[30]	84	74 (88 %)§	NA	NA	NA	NA	CARTO		9‖	64	22	69

*Incidence of non-PV foci during a second session of catheter ablation of paroxysmal AF. ^†In this study,35 foci (38 %) were unmappable non-PV foci. ^‡Incidence of non-PV foci during the third to fifth catheter ablation of paroxysmal AF. ^§Incidence of non-PV foci during a second session of catheter ablation of paroxysmal AF with severe left atrial scarring. The non-PV triggers were mostly (90.5 %) located in areas outside the scar region. ^‖9 % of non-PV foci were located on the crista terminalis/superior vena cava. C = conventional mapping; CARTO = CARTO^® system (Biosense Webster); CS = coronary sinus; IAS = interatrial septum; LA = left atrium; LOM = ligament of Marshall; NA = data not available; NavX = EnSite™ NavX™ system (Abbott); RA = right atrium; SVC = superior vena cava; SVT = supraventricular tachycardia. Some data reproduced with permission from Higa et al., 2011.34

Pathophysiology

Histological analysis of the embryonic sinus venosus has identified areas capable of spontaneous depolarisation at the junctions between different embryonic tissues, such as the RA–SVC junction, crista terminalis and CS ostium.[40–42] The SVC is a major origin of non-PV triggers of AF.[5,8,32–34,43–47] Heterogeneity of the SVC sleeve and arrhythmogenicity of cardiomyocytes isolated from the SVC have been reported.[41,42] An excitation from the SVC can conduct to the RA through the myocardial extensions of the SVC sleeve.[48–50] Diseased human atria are hypopolarised in comparison to normal atria, which may account for the abnormal automaticity and/or activity originating from the LA wall.[51–53] The crista terminalis, which is an area exhibiting abnormal automaticity, anisotropy and slow conduction, may serve as an arrhythmogenic substrate for AF initiation and perpetuation.[54,55] Catecholamine-sensitive ectopy arising from the crista terminalis exhibits high-frequency depolarisations with fibrillatory conduction.[6] The LOM is an embryological remnant of the left SVC and contains arrhythmogenic myocardial fibres with sympathetic innervation. Several reports have demonstrated the existence of catecholamine-sensitive tissue within the LOM that has abnormal automaticity, and which could be a potential source of AF initiation.[6,56–58]

The musculature within the CS also has arrhythmogenic activity, with spontaneous depolarisations induced by catecholamine loading.[59,60] Abnormal dilatation due to an unroofed CS can be an arrhythmogenic focus of AF initiation.[61] A recent study found that 45 % of non-PV triggers of AF were in the area of aortic encroachment, which equates to 16 % of the total population with AF. There is also an arrhythmogenic substrate exhibiting low voltage and fractionated electrograms with a prolonged duration in the anterior part of the LA at the site of aortic encroachment.[27]

Diagnosis

Provoking Ectopy

To successfully provoke ectopy with AF initiation, antiarrhythmic drugs should be discontinued for a period of at least five half-lives before the patient undergoes electrophysiological study. Spontaneous initiation of ectopic beats preceding AF should be observed at baseline or after isoproterenol loading.[32–34] In the case of deep sedation or general anaesthesia, it is necessary to give the patient a high dose of isoproterenol to induce ectopy with AF initiation. Adenosine or adenosine triphosphate can also be used, especially in young patients with vagal AF and with a family history of AF.[18]

If ectopy does not occur, short-burst atrial pacing can be delivered with intermittent pauses or, failing that, atrial burst pacing to induce sustained AF. Careful monitoring for spontaneous reinitiation of AF is required after internal or external cardioversion. The induction of spontaneous AF initiation should be attempted at least twice to confirm the location of ectopy, the initiation pattern of spontaneous AF, and the earliest activation site (the AF initiator).[2,4–7,32–34]

Mapping

Localisation of AF triggers is important for the catheter ablation of AF. If it is suspected that the trigger is based in the LA, a decapolar catheter should be inserted into the CS via the internal jugular vein and a circular mapping catheter placed in the LA using a transseptal approach. If the initiator is likely to be in the RA, a duodecapolar catheter can be placed from the crista terminalis to the distal SVC for the simultaneous mapping of the right PVs, crista terminalis and SVC. Endocardial activation timing from the high RA, His bundle and distal/proximal portion of the CS can be used to predict non-PV ectopy (Figure 1).[2,4–7,32–34] It is 100 % accurate in discriminating ectopy from the SVC or upper portion of the crista terminalis from PV ectopy.[32–34,62] The interatrial septum should be the suspected initiator in cases with a monophasic positive narrow P wave in lead V₁ or a relatively short activation time (≤15 ms) preceding P wave onset during ectopy. Simultaneous mapping of the right- and left-sided interatrial septum should be performed to avoid any misdiagnosis.[32–34,63,64]

Figure 1: Stepwise Algorithm for the Localisation of Non-pulmonary Vein AF Initiators.

Δ (high right atrium – His) represents the time interval from the high right atrial electrogram onset to the onset of the His atrial electrogram during sinus beats minus the same interval measured during ectopic atrial activity. CSp – CSd represents the difference in the atrial activation time between the proximal (p) and distal (d) CS atrial electrograms during an ectopic atrial beat. Source: Higa et al., 2006.[32] Reproduced with permission from Elsevier. CS = coronary sinus; LOM = ligament of Marshall; LPV = left pulmonary vein; PV = pulmonary vein; RPV = right pulmonary vein; SVC = superior vena cava.

AF Initiators with Right Atrial Origin

Careful observation of P wave morphology is useful for predicting the approximate location of AF ectopy.[32–34,65] A negative P wave or the presence of a negative component in V₁ is predictive of an RA origin of AF initiation. Ectopy originating from the SVC or upper portion of the crista terminalis exhibits upright P waves in the inferior leads; ectopy from the CS ostium produces negative P wave polarity in the inferior leads; and ectopy from the middle portion of the crista terminalis results in biphasic P waves. Negative P waves with a long duration in V₁ may be associated with RA free-wall ectopy, including the tricuspid annulus.

If RA AF ectopy is suspected, the use of a duo-decapolar catheter is useful for mapping along the crista terminalis to the SVC.[2,4–7,32–34] Bipolar signals from the proximal portion of the SVC usually exhibit a blunted atrial signal followed by a discrete sharp SVC signal during sinus rhythm.[32–34] The activation sequence of these double potentials is reversed during SVC ectopy. Bipolar signals from the distal part of the SVC usually exhibit double potentials: the first component represents a SVC near-field sharp potential; and the second component, a right superior PV far-field blunted signal. During SVC ectopy, the activation sequence of these double potentials remains unchanged. The activation sequence is reversed during right PV ectopy.

Intracardiac recordings along the crista terminalis also exhibit double potentials during sinus rhythm, with a high-to-low activation sequence.[32–34] During crista terminalis ectopy, the atrial activation sequence of the double potentials is reversed. Noncontact mapping using an EnSite™ Array™ (Abbott) can accurately localise the ectopic foci with discrete depolarisations and clarify crista terminalis gap conduction-related small radius re-entry.[32–34,66]

AF Initiators with Left Atrial Origin

The time interval between the atrial activation of the decapolar catheter in the proximal CS and that in the distal CS is useful for predicting ectopic foci located near the right (>0 ms) or left PV antrum (<0 ms) (Figure 1).[32–34,62] During sinus rhythm, the fusion potentials of a blunt signal and a rapid, deflecting sharp signal can be observed in the areas between the LA posterior wall and the PV antrum. The fusion potential consists of atrial and PV signals and can be found at the earliest activation site during LA posterior or PV antral ectopy. An alternating pattern of atrial and PV potentials can also be seen during ectopy.[6,32–34]

The Marshall ligament has multiple electrical connections to the musculature of the CS, LA posterior free wall and left PV; therefore, it is essential to differentiate a Marshall potential from a left PV or LA posterior free wall potential. A differential pacing method and/or direct recording of the LOM potential by a microelectrode catheter cannulated into the vein of Marshall can distinguish a PV potential from a Marshall potential (Tables 3 and 4).[7,32–34,56,67,68]

According to expert consensus statements, complex fractionated atrial electrogram (CFAE)-targeted ablation after PV isolation is feasible for substrate modification.[69] Interestingly, our laboratory reported a close anatomical relationship between the distribution of CFAEs and non-PV AF initiators. All of the non-PV AF initiators were associated with continuous CFAE sites.[70,71] Recently, the efficacy of a novel self-reference mapping technique using a PentaRay® catheter (Biosense Webster) to localise non-PV triggers originating from the LA has been reported.[72]

Limitations of Mapping

AF ablation can be a challenging and sometimes cumbersome task in cases of unmappable infrequent beats originating from uncommon areas. Activation mapping using fixed multipolar catheters and point-by-point mapping are not efficient for the identification of target ectopies in such cases. Single-beat analysis by noncontact mapping using the Array™ system (Figure 2) or non-invasive body-surface mapping using the CardioInsight™ Mapping Vest system (Medtronic) can be useful tools in these situations.[73]

Figure 2: Mapping of Non-pulmonary Vein Triggers.

(A) An isochronal map during an ectopy-initiated AF. During the ectopy, a focal activation originates from the left atrial middle posterior wall with unidirectional conduction block on the left side of the posterior wall, and the activation wavefront preferentially conducts toward the right pulmonary veins and spreads out to the rest of the left atrium (yellow arrows) followed by AF. (B) The unipolar virtual signals demonstrate “QS” morphology at the origin (virtual 6, from the second beat) and “rS” morphology (virtual 8, from the second beat) at the breakout site. Source: Higa et al., 2008.[73] Reproduced with permission from Dr Jonathan S Steinberg. LAA = left atrial appendage; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RSPV = right superior pulmonary vein.

Ablation

The earliest bipolar electrogram site with unipolar QS pattern recorded from the origin is the ablation target for non-PV ectopy.[2,4–7,32–34] Ablation of an ectopic focus and/or electrical isolation of an arrhythmogenic thoracic vein can be achieved with the application radiofrequency energy for around 30 seconds with a non-irrigated tip at 50–55 °C or with an irrigated tip at <25–30 W.[2,4–6,32–34] A contact force catheter can be used to create durable transmural lesions. This method has a lower arrhythmia recurrence and a lower incidence of atrial tachyarrhythmias resulting from incomplete ablation due to proarrhythmic lesion gaps. However, caution should be taken to avoid the application of excessive energy and/or contact pressure at the posterior LA wall close to the oesophagus.

Balloon-based cryoablation of the PV antral area, LA posterior wall and persistent left SVC can also be used to isolate arrhythmogenic myocardium. Complications can be minimised by using a cryocatheter at −30 °C to ice map the area near the atrioventricular node following the cryofreezing (−80 °C) of a para-Hisian or CS ostium trigger. Ice mapping can also be used during ablation near the sinus node when targeting SVC or the upper portion of the crista terminalis. Repeated AF induction protocols should be performed after ablation to assess the non-inducibility of the ablated ectopy.[2,4–7,32–34]

Vena Cava Triggers

Electrical disconnection between the arrhythmogenic SVC and RA at the level of the RA–SVC junction is the preferred approach for minimising AF recurrence and SVC stenosis in patients with SVC triggers.[32–34] The aim is to establish bidirectional (entrance and exit) conduction block between the RA and SVC.[5,32–34,47] Circular and basket catheters, and 3D mapping systems including the CARTO® (Biosense Webster), EnSite™ NavX™ Velocity (Abbott), EnSite™ Array™ noncontact mapping system, and Rhythmia HDx™ mapping system with IntellaMap Orion™ catheter (Boston Scientific) can guide SVC isolation.[6,32–34,44–46,74–77]

Persistent left SVC is also a well-recognised trigger site for AF.[19,21,78–85] The connecting musculature means that multiple electrical signals are conducted to the posterolateral LA and middle portion of the CS from the left SVC trigger site. Complete left SVC isolation may be challenging, as it is close to the oesophagus and left phrenic nerve. There have been rare reports of inferior vena cava triggers.[86,87] In these cases, the IVC triggers were successfully eliminated with a focal/isolation strategy.

Interatrial Septal Triggers

Focal ablation of the earliest activation site preceding the onset of AF should be performed until a complete elimination of the ectopy is achieved in patients with interatrial septal triggers. Near-simultaneous atrial activation of the multielectrode catheters located in the high RA, His bundle region and CS ostium can be observed in such cases. Simultaneous mapping of the right and left atrial septum is crucial to successfully locate and ablate this trigger.

Crista Terminalis Triggers

Focal ablation of the earliest activation site in the crista terminalis during ectopy preceding AF onset should be performed until complete elimination of the ectopy initiating AF or >50 % reduction in the amplitude of the initial local electrogram at the ablation site.[6,32–34] A region with transverse gap conduction in the crista terminalis can be an arrhythmogenic source of re-entry and also ectopy initiating AF. Linear ablation of the transverse gap should address both of these problems.[32–34,66] Intracardiac echocardiography can provide real-time monitoring of the anatomical relationship between the crista terminalis and the catheter position during the procedure.

Coronary Sinus Triggers

For patients with a CS trigger, electrical isolation of the arrhythmogenic CS musculature from the atrium by endocardial and/or epicardial ablation under the guidance of a 3D mapping system is preferable.[32–34,71] The aim is to eliminate (entrance block) and/or dissociate (exit block) the CS potential.[88–91] Care must be taken if an inappropriate impedance rise occurs during CS ablation, and the application of radiofrequency energy should be stopped immediately to prevent any steam pops.

Marshall Ligament Triggers

For patients with Marshall ligament triggers, the earliest site with a LOM potential preceding the onset of AF is targeted using an endocardial and/or epicardial approach.[32–34,92] The isolation of both the LOM and left PVs from the LA can be monitored with simultaneous mapping of the LOM and left PV ostia, maximising the chance of a successful procedure.[32–34,56,67,93] Ethanol infusion into an arrhythmogenic vein of Marshall through angioplasty guidewire and balloon catheter in addition to PV isolation has recently been reported to have beneficial outcomes.[94,95]

Left Atrial Triggers

For ectopy from the LA posterior wall, focal ablation of the earliest activation site should be performed (Figure 2). If unsuccessful, a box-shaped linear ablation needs to be added around the ectopy.[6,32–34] Box isolation of the LA posterior wall in combination with PV isolation may be a therapeutic option in cases refractory to extensive focal ablation. The endpoint is complete elimination of the ectopy initiating AF, >50 % reduction in the electrogram amplitude of the ectopic focus, or isolation of the posterior LA wall.[32–34,73]

The left atrial appendage (LAA) has been reported to be a trigger of AF.[96] Due to its large structure, triggers may arise from the LAA ostium, body or tip. Simultaneous mapping of the left superior PV and LAA can differentiate between a near-field sharp and a far-field blunt signals and identify true LAA triggers. Focal ablation can be applied to avoid LAA isolation. LAA isolation is only indicated when the patient can tolerate long-standing anticoagulation or a LAA occlusion device is indicated.

Table 3: Diagnostic Criteria for Non-pulmonary Vein Ectopy Initiating AF.

Location	Criteria
AF initiators from the right atrium	in the time interval between the atrial activation at the high right atrium and His bundle area during sinus rhythm and ectopy of <0 msec
Inferior vena cava, superior vena cava	Positive (superior vena cava) and negative (inferior vena cava) P waves in the inferior leads and positive or biphasic P waves in V1 (superior vena cava) Earliest ectopic activity in the vena cava during simultaneous mapping of the vena cava and right pulmonary vein (PV) Reversal of the double-potential sequence during ectopy (vena cava potentials with a rapid deflection-far-field atrial potential sequence; distal-to-proximal venous activation sequence)
Crista terminalis (CT)	Polarity of the P waves in the inferior leads: upper portion of the CT, positive; middle portion, biphasic; lower portion, negative Earliest ectopic activity along the CT during simultaneous mapping of the CT, vena cava and right PV
Coronary sinus ostium	Negative P waves in the inferior leads Earliest ectopic activity in the coronary sinus ostium
AF initiators from left atrium	Difference in time interval between the atrial activation at the high right atrium and His bundle area during sinus rhythm and ectopy of >0 msec
Left atrial free wall or left atrial appendage	Atrial potentials with a rapid deflection-PV potential found after the earliest atrial activation
Ligament of Marshall LOM)	Earliest activation site along the vein of Marshall, posterolateral portion of the mitral annulus or left PV ostium Reversal of the triple-potential sequence; the LOM potential is earlier than the left atrium or left PV potentials (LOM–left atrium–PV potentials sequence)

CT = crista terminalis; LOM = ligament of Marshall; PV = pulmonary vein. Source: Higa et al., 2006.[33] Reproduced with permission from Elsevier.

Table 4: Targets for Ablation of AF Originating from Non-pulmonary Vein Areas.

AF Initiators	Target Sites	Mapping Tools
Right Side
Inferior vena cava, superior vena cava	Breakthrough sites around right atrium–vena cava junction for an isolation	Circular catheter, Array, Grid, PentaRay or Rhythmia
Crista terminalis	Earliest crista terminalis activation site for a focal ablation	Unipolar recording with a multipolar catheter, Array, Grid, PentaRay or Rhythmia
Coronary sinus	Connection sites between the coronary sinus and atrial musculature for an isolation	Array, PentaRay or Rhythmia
Left Side
Left atrial free wall, septum, appendage, mitral annulus	Earliest activation site for a focal ablation	Unipolar recording with a multipolar catheter, Array, Grid, PentaRay or Rhythmia
Ligament of Marshall (LOM)	Earliest LOM potential for a focal ablation	Multipolar recording of triple potentials during ectopy and direct mapping of LOM potentials by microelectrode catheter, Array, Grid, PentaRay or Rhythmia
	Connection sites between the left atrium and LOM for an isolation	Multipolar recording of triple potentials during ectopy and direct mapping of LOM potentials by a microelectrode catheter, Array, Grid, PentaRay or Rhythmia

Array = EnSite™ Array™ Noncontact Mapping System (Abbott); Grid = Advisor™ HD Grid Mapping Catheter (Abbott); LOM = ligament of Marshall; PentaRay = PentaRay® Catheter (Biosense Webster); Rhythmia = Rhythmia Mapping System and InntellaMap Orion™ Mapping Catheter (Boston Scientific). Source: Higa et al., 2006.[33] Reproduced with permission from Elsevier.

Efficacy and Safety of Catheter Ablation

Ablation Outcomes

A relatively high success rate has been demonstrated following the ablation of RA triggers of AF.[6] There is a comparatively higher recurrence rate following the ablation of LA triggers. The average success, recurrence and complication rates are 99.3 %, 18.5 %, and 1.9 %, respectively, for AF originating from the vena cava.[8,43–45,74,78–87,97–111] These rates are 78.0 %, 16.7 %, and 2.4 %, respectively, for AF originating from the Marshall ligament.[6,56,67,68,94,112,113]

A higher incidence of recurrent AF and non-PV AF sources has been reported in patients with metabolic syndrome and obstructive sleep apnoea.[114] Patients who have a greater extent of left atrial delayed enhancement on MRI have a higher recurrence rate after PV isolation, suggesting the existence of AF triggers in non-PV areas.[115]

Managing Complications

Overall complication rates are now relatively low as a result of vast improvements in our understanding of the nature and ablation of non-PV ectopy AF triggers. Injury to the sinus node, atrioventricular node, and phrenic nerve, thoracic vein stenosis, peri-oesophageal damage, gastric hypomotility, and pyloric spasms can all be caused by a non-PV trigger ablation.[116–124]

Complications can be minimised by using a titrated and minimum power setting, short duration of radiofrequency energy, and by monitoring for any sinus rate accelerations, PR or RR interval prolongations and for oesophageal temperature rises. An upstream pacing technique to monitor the phrenic nerve and/or compound muscle action potential can minimise phrenic nerve injury. To reduce the risk of atrio-oesophageal fistula formation, which carries a 60–75 % chance of mortality, surgeons should avoid extensive high-power ablation on the LA posterior and CS walls.[119,121,122,125]

The use of several luminal oesophageal temperature monitoring systems – SensiTherm™ (Abbott) and CIRCA S-Cath™ (CIRCA Scientific) – and protection systems, including oesophageal warming/cooling devices and deviators to avoid thermal injury, has recently been reported.[126–130] Massive air emboli and newly developed thrombi that occur during the ablation procedure can be aspirated.[131]

Conclusion

Evidence suggests that inducing the non-PV ectopic trigger responsible for initiating AF both before and after PV isolation is an indispensable step in both initial and repeat ablation/isolation procedures. Advances in mapping and alternative energy modalities with 3D navigation are likely to play an important role in the ablation of non-PV ectopy. Together, these advances and the systematic identification of the trigger foci and their successful elimination will improve overall AF ablation outcomes.

Clinical Perspective

• The mechanisms of paroxysmal AF originating from non-pulmonary vein areas are automaticity, triggered activity, and microreentry.

• The diagnosis is made on the basis of a spontaneous onset of the ectopic beats initiating AF during baseline or after provocative manoeuvres.

• The earliest activation sites are the targets for focal ablation.

• The myocardial sleeve surrounding the ostium of the vena cava is the target for isolation.

• Success rates are >99 % for the vena cava and 78 % for the ligament of Marshall.