Impact of left atrial appendage exclusion using an epicardial ligation system (LARIAT) on atrial fibrillation burden in patients with cardiac implantable electronic devices Muhammad R. Afzal, MD,* Arun Kanmanthareddy, MD, MS,* Matthew Earnest, MD,* Madhu Reddy, MD, FHRS,* Donita Atkins, BS,* Sudharani Bommana, MPhil,* Krystof Bartus, MD, FHRS,† Abdi Rasekh, MD, FHRS,‡ Fred Han, MD,§ Nitish Badhwar, MD,¶ Jie Cheng, MD,‡║ Luigi Dibiase, MD, FHRS,** Christopher R. Ellis, MD,†† Buddhadeb Dawn, MD,* Andrea Natale, MD, FHRS,** Randall J. Lee, MD, FHRS,¶ Dhanunjaya Lakkireddy, MD, FHRS* From the *Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital and Medical Center, Kansas City, Kansas, †John Paul II, Krakow, Poland, ‡Texas Heart Institute, St. Lukes Hospital, Houston, Texas, §University of Utah, Salt Lake City, Utah, ¶University of San Francisco, San Francisco, California, ║University of Texas, Houston, Texas, **Texas Cardiac Arrhythmia Institute, Austin, Texas, and ††Vanderbilt University Medical Center, Nashville, Tennessee. BACKGROUND The left atrial appendage (LAA) is a well-known source of atrial arrhythmia and atrial fibrillation (AF).
significantly reduced at 3 months (52% ⫾ 35%) and 12 months (42% ⫾ 19%) compared to respective baseline (84 ⫾ 31%, P o .0001).
OBJECTIVE The purpose of this study was to determine whether LAA exclusion using the LARIAT device would decrease AF burden.
CONCLUSION LAA exclusion appears to reduce AF burden. The presence of AF triggers in the LAA appears to be the strongest predictor of AF reduction. The study underscores the role of the LAA in arrhythmogenesis for AF and highlights the complementary role of LAA exclusion in restoration of normal sinus rhythm.
METHODS A total of 50 patients with AF and cardiac implantable electronic devices who underwent successful LAA exclusion were enrolled in this prospective observational study. AF burden before LAA exclusion (baseline) and 3 and 12 months after exclusion was assessed by device interrogation.
KEYWORDS Atrial fibrillation; Left atrial appendage; Suture exclusion; Pericarditis
RESULTS AF burden at 3-month follow-up (42% ⫾ 34%) was significantly lower compared to baseline (76% ⫾ 33%, P o .0001). The reduction in AF burden was sustained at 12 months (59% ⫾ 26%, P o .001). Subgroup analysis revealed that AF burden at 3-month follow-up was similarly reduced in both paroxysmal AF (n ¼ 19) and nonparoxysmal AF (n ¼ 31). However, there was no reduction in AF burden in patients with paroxysmal AF at 12 months. AF burden in patients with known AF triggers in the LAA (n ¼ 9) was
ABBREVIATIONS AF ¼ atrial fibrillation; CIED ¼ cardiac implantable electronic device; CT ¼ computed tomography; GP ¼ ganglionated plexus; LAA ¼ left atrial appendage; PAF ¼ paroxysmal atrial fibrillation; PV ¼ pulmonary vein; RF ¼ radiofrequency; TEE ¼ transesophageal echocardiography
Introduction
prevalence of 1% to 2%. Current estimates from 2010 indicate that approximately 33.5 million individuals worldwide have AF, with close to 5 million new cases occurring each year.1 Thromboembolic stroke is the most dreadful complication of AF. Ninety percent of non-rheumatic AFrelated left atrial (LA) thrombi were isolated to, or originated from, the left atrial appendage (LAA), accounting for a significant thromboembolic burden in these patients.2 Recent studies using the Watchman device (Boston Scientific) have shown the feasibility and noninferiority of LAA exclusion in
Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice, with an estimated Address reprint requests and correspondence: Dr. Dhanunjaya Lakkireddy, Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of EP Research–KU Cardiovascular Research Institute, Bloch Heart Rhythm Center, Mid America Cardiology, University of Kansas Hospital and Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
(Heart Rhythm 2015;12:52–59) rights reserved.
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2015 Heart Rhythm Society. All
http://dx.doi.org/10.1016/j.hrthm.2014.09.053
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Reduction in AF Burden with LAA Exclusion
preventing thromboembolic complications.3,4 LAA has also been implicated as a significant source of atrial tachycardia and AF.5–9 In a study by Di Biase et al,10 close to 30% of AF triggers in persistent AF were found to be non-pulmonary venous (non-PV), especially LAA, in origin. Successful ablation or isolation of the LAA seems to significantly impact arrhythmia control in these patients.10,11 Successful endocardial isolation of the LAA with radiofrequency (RF) ablation often is difficult because of the complex regional anatomy and problems with catheter stability. Furthermore, the arrhythmia source can be deep inside the LAA or sometimes even epicardial in location. Ablation of these foci can be challenging and associated with higher rates of complications, such as cardiac perforation. Recent studies have shown the feasibility and safety of LAA exclusion devices.12,13 Depending on the design of these devices and the technique of deployment, they can result in either mechanical exclusion or both mechanical and electrical exclusion. Endocardially deployed LAA devices (Watchman [Boston Scientific] and Amplatzer cardiac plug [St Jude Medical]) typically occlude the LAA ostium and result in varying degrees of mechanical exclusion, whereas techniques that use an epicardial approach (LARIAT device [SentreHEART, Redwood, CA], AtriClip [AtriCure, West Chester, OH], surgical ligation) typically result in both mechanical and electrical isolation because they tend to compress the tissue, resulting in ischemic necrosis of the LAA distal to the site of exclusion. A recent article by Han et al16 showed that snare closure of the LAA using the LARIAT device produces an acute reduction in LAA voltage and inhibits capture of the LA during LAA pacing. This indicates tissue ischemia and possible necrosis of the LAA tissue distal to the ligation site. Application of a clip (AtriClip) was shown to cause entrance and exit block in LAA consistent with effective electrical isolation.7,14,15 Based on these observations, we hypothesized that LAA exclusion using the LARIAT device potentially could decrease the overall burden of AF. In this study, we assessed the role of epicardial LAA ligation with the LARIAT device in reducing AF burden in patients with an cardiac implantable electronic device (CIED).
Methods and materials Patient population This was a prospective multicenter observational study of the consecutive patients with AF and a CIED (6 [12%] cardiac resynchronization therapy-defibrillator, 10 [20%] dualchamber ICD, 34 [68%] dual-chamber pacemaker) undergoing LAA exclusion enrolled between July 2010 and April 2013. All devices had a functional atrial lead. Eligible patients met the following inclusion criteria: (1) age Z18 years; (2) nonvalvular AF; (3) at least 1 risk factor for embolic stroke (CHADS2 Z1); and (4) poor candidate or ineligible for warfarin therapy (eg, labile international normalized ratio level, noncompliant, contraindicated) and/ or warfarin failure (ie, transient ischemic attack or stroke
53 while on warfarin therapy). Patients were excluded from the study if they met any of the following exclusion criteria: (1) history of cardiac surgery; (2) severe pectus excavatum; (3) recent myocardial infarction within 3 months; (4) prior embolic event within the last 30 days; (5) New York Heart Association functional class IV heart failure symptoms; and (6) history of thoracic radiation. All patients underwent a screening contrast cardiac computed tomographic (CT) scan. Additional exclusion criteria based on LAA anatomy included (1) LAA width 440 mm; (2) superiorly oriented LAA with the LAA apex directed behind the pulmonary trunk; (3) bilobed LAA or multilobed LAA in which lobes were oriented in different planes exceeding 40 mm; and (4) posteriorly rotated heart. The institutional review boards at all participating institutions approved the protocol. Informed consent was obtained from all patients.
Measurement of LAA electrograms Forty-four patients had recording of endocardial and epicardial voltage before and after LARIAT deployment. Measurement of LAA electrograms was performed as described previously.16 Voltage data for 12 of the patients included in this study have been reported in a previous study.16
Percutaneous suture exclusion of LAA using the LARIAT device LAA exclusion was performed using a LARIAT device as described previously.17
Clinical follow-up Interrogation of CIEDs was performed at baseline before LAA exclusion and at 3- and 12-month follow-up to determine AF burden. At each visit, the device was reset to determine the AF burden in the interim period. An updated medication list was obtained at every visit to ensure the stability of antiarrhythmic drug therapy.
Statistical analysis Normally distributed continuous variables are expressed as mean ⫾ SD. Continuous variables were compared using the t test for normally distributed data or the Mann–Whitney U test for non-normally distributed data as deemed appropriate.
Results Baseline data A total of 50 patients were enrolled in the current study. Baseline characteristics of the study patients are given in Table 1. Mean age was 70 ⫾ 8.4 years, and mean AF duration was 54 ⫾ 40 months . Mean CHADS2 score was 2.8 ⫾ 0.4, and mean CHA2DS2-VASc score was 4.3 ⫾ 0.7. Mean HAS-BLED score was 3.4 ⫾ 0.5. Mean duration from time of device placement was 36 months. Thirty-one patients (62%) had persistent or longstanding persistent AF collectively termed non-paroxysmal atrial fibrillation (non-PAF), and 19 (38%) had paroxysmal atrial fibrillation (PAF). Mean
54 Table 1 Selected baseline characteristics of study participants (N ¼ 50) Clinical variable Male 33/50 (66%) Age (years) 70 ⫾ 8.4 Race (white/African-American) 48/2 Height (cm) 178 ⫾ 6.2 Weight (kg) 99 ⫾ 18 Body mass index 31 ⫾ 4 Coronary artery disease 25 (50%) Hypertension 39 (78%) Diabetes 9 (18%) Congestive heart failure 26 (52%) History of cerebrovascular attack/transient 30 (60%) ischemic attack History of gastrointestinal bleed 13 (26%) Chronic renal insufficiency 18 (36%) Cardiac device in place Cardiac resynchronization therapy-defibrillator 6 (12%) Dual-chamber implantable cardioverter-defibrillator 10 (20%) Dual-chamber pacemaker 34 (68%) 2.8 ⫾ 0.4 CHAD2 score 4.3 ⫾ 0.7 CHADS2-VASc score HAS-BLED score 3.4 ⫾ 0.5 Antiarrhythmic drug Class I 4 (8%) Class III 21 (42%) Beta-blockers 39 (78%) Calcium channel blockers 10 (20%) AF duration (months) 54 ⫾ 40 AF type Paroxysmal 19 (38%) Nonparoxysmal 31 (62%) Left ventricular ejection fraction (%) 45.6 ⫾ 5 Left atrial size (cm) 5 ⫾ 0.8 Mitral regurgitation Trace 12 (24%) Mild 17 (34%) Moderate 8 (16%) Values are given as mean ⫾ SD or n/N (%), where n ¼ number of available patients. AF ¼ atrial fibrillation.
ejection fraction was 45.6% ⫾ 5%. Mean LA size was 5 ⫾ 0.8 cm . The most common valvular abnormality was mitral regurgitation, with 12 (24%) patients having trace, 17 (34%) mild, and 8 (14%) moderate regurgitation.
LAA exclusion Exclusion success was defined as successful closure of the LAA with absence of contrast leak on left atriogram and r1mm jet as visualized by color Doppler on transesophageal echocardiography (TEE). At 3-month follow-up TEE, 47 patients had complete closure of the LAA, and 3 patients had a small leak o3 mm assessed by TEE performed at 3-month follow-up. Representative fluoroscopy, TEE, and cardiac CT images are shown in Figure 1. A representative image of preprocedural and postprocedural CT with 3-dimensional reconstructions shows sloughing of the LAA (see Online Supplementary Figure 1). A recent study has reported a comparable incidence of incomplete LAA closure leak assessed by TEE performed at completion of the LARIAT procedure.18
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Postprocedural complications Pericardial drain was removed after 18 ⫾ 9.1 hours. No embolic events or deaths occurred during the follow-up period. Four patients had pericardial drainage 4500 mL; however, none of them developed cardiac tamponade. Pericardial effusion in these patients developed over a period of 24 hours and was serous in consistency. The most likely cause of this serous effusion is local irritation from catheter manipulation in the pericardial space. Two patients had femoral arteriovenous fistula. The lower bleeding complications in our cohort compared to the recent study by Price et al18 could be due to differences in operator experience at different institutions. There was a significant decrease of blood pressure and increase in heart rate after the LARIAT procedure (see Online Supplementary Table 1).
Arrhythmia follow-up All 50 patients completed 3- and 12-month follow-up after the LARIAT procedure. Interrogation of CIEDs showed a significant reduction in AF burden at 3 months (42% ⫾ 34%) and 12 months (59% ⫾ 26%) compared to baseline (76% ⫾ 33%, P o .0001 for both; Figure 2A). Subgroup analysis revealed that patients with PAF had a significant reduction in AF burden at 3-month follow-up (25% ⫾ 16%) compared to baseline (46% ⫾ 26%, P o .0001); however, there was no significant change at 12-month follow-up (47% ⫾ 24%, P ¼ NS; Figure 2B). Patients with non-PAF had a sustained reduction in AF at both 3-month (51% ⫾ 37%, P o .0001) and 12-month (66% ⫾ 24%, P o .0001) follow-up compared to baseline (94% ⫾ 19%; Figure 2C). The individual data of AF burden for patients with PAF are shown in Figure 3 and for patients with non-PAF in Figure 4. The reduction in AF burden in patients with incomplete LAA closure (n ¼ 3) was significantly lower at 3-month (33%) and 12-month (61%) follow-up compared to baseline (100%). No episodes of defibrillation occurred during the follow-up period. Patients with cardiac resynchronization therapy (n ¼ 6) had stable biventricular pacing at follow-up visits after LAA exclusion. There was no change in the antiarrhythmic drug therapy at follow-up in all patients.
Reduction in AF burden in patients with LAA triggers Subgroup analysis revealed that the reduction in AF was significant in patients who had known triggers in the LAA. In the current study, there were 9 (18%) patients in whom the LAA was identified as the source of triggered activity/atrial tachycardia or as the only source of any meaningful electrical activity in the LA during previous AF ablation. AF burden in these patients was significantly reduced at 3-month (52% ⫾ 35%) and 12-month (42% ⫾ 19%) follow-up compared to baseline (84 ⫾ 31, P o .0001 for both; Figure 5A). AF burden in individual patients is shown in Figure 5B. A representative image of CIED interrogation is shown in Figure 6.
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55
Figure 1 Imaging of the left atrial appendage (LAA) before and after LAA exclusion with the LARIAT device. LAA is seen on fluoroscopy (A) and transesophageal echocardiography (C) immediately before ligation with the LARIAT. LAA is seen on cardiac CT (E) performed a few days before the procedure. LAA is seen on fluoroscopy (B) and transesophageal echocardiography (D) immediately after ligation with the LARIAT. LAA is seen on cardiac CT (F) performed at a follow-up visit after the procedure. Red arrow is pointing toward the LAA.
LAA voltage measurements before and after exclusion
Patients (n ¼ 44) who had recording of endocardial and epicardial voltage before and after the LARIAT procedure
showed significant acute reduction in LAA voltage after the procedure. Endocardial voltage decreased from 6.0 ⫾ 2.1 mV to 2.3 ⫾ 0.7 mV (P o .001). Epicardial voltage decreased from 6.0 ⫾ 2.1 mV to 2.1 ⫾ 0.6 mV (P o .001; Figure 7)
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Figure 2 Reduction in atrial fibrillation (AF) burden after left atrial appendage (LAA) exclusion with the LARIAT device. A: Overall reduction in AF burden in all patients. B: Reduction of AF burden in patients with paroxysmal AF. C: Reduction of AF burden in patients with nonparoxysmal AF.
Figure 3 Individual atrial fibrillation (AF) burden at different time-points in patients with paroxysmal AF. First row in table below the graph gives the patient ID in this group. Rows 2-4 give the AF burden in percentage at 3 different time-points.
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Reduction in AF Burden with LAA Exclusion
57
Figure 4 Individual atrial fibrillation (AF) burden at different time-points in patients with nonparoxysmal AF. First row in table below the graph gives the patient ID in this group. Rows 2–4 give the AF burden in percentage at 3 different time-points.
Discussion Major findings
This is the first study to show that LAA exclusion with the LARIAT device reduces AF burden and continues to have a
sustained effect even at 12-month follow-up in patients with non-PAF. The presence of AF triggers in the LAA is the strongest predictor of AF reduction after LAA exclusion.
Role of LAA in arrhythmogenesis
Figure 5 Reduction in atrial fibrillation (AF) burden after the LARIAT procedure in patients with known triggers in the left atrial appendage (LAA). A: Reduction in AF burden in patients with a history of radiofrequency ablation and known triggers of AF in the LAA. B: Individual AF burden at different time-points in patients with known triggers in the LAA. First row in table below the graph gives the patient ID in this group. Rows 2–4 give the AF burden in percentage at 3 different time-points.
The arrhythmogenic role of the LAA has been described in several recent studies. The LAA has extensive pectinate muscles and a heterogeneous fiber orientation. The trabeculated muscles in the LAA influence wave propagation and favor the formation of conduction block/slow conduction and initiation of reentry.5,6 Two recent studies proposed automaticity as the underlying mechanism for atrial tachycardia originating from the LAA.8,19 These findings were further supported by the observation in patients undergoing LAA exclusion. Epicardial exclusion of the LAA with a minimally invasive occlusion device (AtriClip) implanted from outside the heart through a thoracoscopic approach has been shown to be successful in achieving electrical isolation and thus elimination of focal atrial tachycardia.7 In a series of 10 consecutive patients undergoing coronary artery bypass grafting, epicardial LAA clip occlusion led to complete electrical isolation of the LAA, resulting not only in the elimination of an important source of systemic thromboembolism but also the electrical exclusion of potential triggers for the recurrence of AF.15 In a large series of patients, Di Biase et al10 reported that 27% of patients undergoing redo catheter ablation for AF showed firing from the LAA, and in 9% the LAA was found to be the only source of arrhythmia without any evidence of PV or extrapulmonary sources. Hocini et al9 systematically studied the role of the LAA in organized atrial arrhythmias arising in the context of AF ablation. The study described a cohort of patients with localized reentrant tachycardia harbored within the LAA after AF ablation suggesting that the LAA may contribute directly to maintenance of AF. Studies with power spectral analysis and mapping to localize dominant frequency sites of activation have shown
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Figure 6 Cardiac implantable electronic device (CIED) interrogation before and after left atrial appendage (LAA) exclusion with the LARIAT device. Representative image of CIED interrogation in a patient with atrial fibrillation (AF) shows termination of AF (downward pointing arrow) after LAA exclusion with the LARIAT device. AT ¼ atrial tachycardia; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia.
that PVs harbor the highest-frequency sites in patients with PAF, and AF can be terminated successfully by targeting RF ablation at those sites in up to 87% of patients. However, the recent data in persistent AF patients provide compelling evidence that the sources are, in fact, reentrant and located outside of the PVs. Similarly, in longstanding persistent AF patients, it is rare to find dominant frequency sites at the PV region, and this agrees well with the relatively poor success rate of RF ablation in such patients. The data suggest that in patients with longstanding persistent AF, atrial remodeling somehow augments the number of AF drivers and shifts their location away from the PV/ostial region.20,21 Based on these observations, it is possible that the LAA harbors some of the triggers. Clusters of autonomic ganglionated plexuses (GPs) are found in abundance along the groove between the left superior pulmonary vein and the LAA. The fat pad around
Figure 7 Reduction of endocardial and epicardial voltage after left atrial appendage (LAA) exclusion with the LARIAT device. Graph shows immediate reduction in endocardial and epicardial voltage after LAA ligation with the LARIAT.
the LAA also could have additional GPs that are poorly defined. LAA exclusion could affect GP activity and thereby reduce triggers by altering autonomic tone. This possibly could be the contributing factor in the reduction of AF after the LARIAT procedure. Our group and others in the past have described a phenomenon of “atriomyopathy” in which patients have extensive atrial scarring on endocardial voltage maps that is disproportionate to chamber size and duration/type of AF.22 Often the only structure that was electrically active was the LAA with focal triggers arising from it. Thus, the observation in the current study is in congruence with the previous literature.
Impact of LAA exclusion on LAA electrical activity LAA exclusion using a suture or a clip causes an acute infarct of the tissue and results in a significant voltage reduction. Over time, the LAA tissue becomes atretic, resulting in complete mechanical and electrical isolation of the LAA from the rest of the LA (see Online Supplementary Figure 1). Ligation of the LAA possibly can remove the reentrant and triggered arrhythmias that arise from this structure. Typically there is a 10% to 40% reduction in LA volume and surface area after LAA exclusion, which essentially decreases the available LA substrate for AF propagation and perpetuation. Also, the peri-appendageal fat pad probably has a significant number of GPs that could be impacted by ligation. LAA is also known to have a significant impact on neuroendocrine modulation through atrial natriuretic peptide (ANP) and other related homeostatic factors, including the renin–angiotensin– aldosterone system. In summary, the LAA seems to play an important role in atrial arrhythmia, and LAA exclusion using an epicardial
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Reduction in AF Burden with LAA Exclusion
ligation system seems to result in a significant reduction in AF burden.
Clinical implications This study clearly highlights the value of LAA electrical exclusion in decreasing the overall arrhythmia burden. This method could be used as a potential adjunctive strategy in improving the efficacy of AF ablation for rhythm control while mechanically excluding the source of thrombus formation in the LA.
Study limitations This current study is a very small prospective observational study. We have limited data on whether the LAA was the true source of atrial arrhythmias in all patients. A large randomized controlled trial looking at the added benefit of LAA ligation along with AF ablation would be the future direction.
Conclusion LAA exclusion appears to reduce AF burden in patients with non-PAF. The presence of AF triggers in the LAA appears to be the strongest predictor of AF reduction. The study underscores the role of the LAA in arrhythmogenesis for AF and highlights the complementary role of LAA exclusion in restoration of normal sinus rhythm.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.hrthm. 2014.09.053.
References 1. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation 2013. 2. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–759. 3. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P, Investigators PA. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534–542. 4. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D, Investigators PA. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial. Circulation 2013;127:720–729.
59 5. Cabrera JA, Ho SY, Climent V, Sanchez-Quintana D. The architecture of the left lateral atrial wall: a particular anatomic region with implications for ablation of atrial fibrillation. Eur Heart J 2008;29:356–362. 6. Ho SY, Sanchez-Quintana D, Cabrera JA, Anderson RH. Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation. J Cardiovasc Electrophysiol 1999;10:1525–1533. 7. Benussi S, Mazzone P, Maccabelli G, Vergara P, Grimaldi A, Pozzoli A, Spagnolo P, Alfieri O, Della Bella P. Thoracoscopic appendage exclusion with an AtriClip device as a solo treatment for focal atrial tachycardia. Circulation 2011;123:1575–1578. 8. Yang Q, Ma J, Zhang S, Hu JQ, Liao ZL. Focal atrial tachycardia originating from the distal portion of the left atrial appendage: characteristics and long-term outcomes of radiofrequency ablation. Europace 2012;14:254–260. 9. Hocini M, Shah AJ, Nault I, et al. Localized reentry within the left atrial appendage: arrhythmogenic role in patients undergoing ablation of persistent atrial fibrillation. Heart Rhythm 2011;8:1853–1861. 10. Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation 2010;122:109–126. 11. Yamada T, McElderry HT, Alison JS, Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm 2008;5: 766–767. 12. Bartus K, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Yakubov SJ, Lee RJ. Feasibility of closed-chest ligation of the left atrial appendage in humans. Heart Rhythm 2011;8:188–193. 13. Sick PB, Schuler G, Hauptmann KE, Grube E, Yakubov S, Turi ZG, Mishkel G, Almany S, Holmes DR. Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J Am Coll Cardiol 2007;49:1490–1495. 14. Bartus K, Morelli RL, Szczepanski W, Kapelak B, Sadowski J, Lee RJ. Anatomic analysis of the left atrial appendage after closure with the LARIAT device. Circ Arrhythmia Electrophysiol 2014;7:764–767. 15. Starck CT, Steffel J, Emmert MY, Plass A, Mahapatra S, Falk V, Salzberg SP. Epicardial left atrial appendage clip occlusion also provides the electrical isolation of the left atrial appendage. Interact Cardiovasc Ther 2012;15: 416–418. 16. Han FT, Bartus K, Lakkireddy D, Rojas F, Bednarek J, Kapelak B, Bartus M, Sadowski J, Badhwar N, Earnest M, Valderrabano M, Lee RJ. The effects of LAA ligation on LAA electrical activity. Heart Rhythm 2014;11:864–870. 17. Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, Lee RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation initial clinical experience. J Am Coll Cardiol 2013;62:108–118. 18. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. Transcatheter LAA Ligation Consortium. J Am Coll Cardiol 2014;64:565–572. 19. Yamada T, McElderry HT, Allison JS, Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm 2008;5: 766–767. 20. Lin YJ, Tsao HM, Chang SL, Lo LW, Hu YF, Chang CJ, Tsai WC, Suenari K, Huang SY, Chang HY, Wu TJ, Chen SA. Role of high dominant frequency sites in nonparoxysmal atrial fibrillation patients: insights from high-density frequency and fractionation mapping. Heart Rhythm 2010;7:1255–1262. 21. Sanders P, Berenfeld O, Hocini MZ, et al. Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans. Circulation 2005;112:789–797. 22. Reddy M, Di Biase L, Vallakati A, Swarup V, Umbarger L, Bakdunes W, Bommana S, Atkins D, Natale A, Lakkireddy D. Predictors of severe left atrial scarring in patients with paroxysmal atrial fibrillation: unveiling a new syndrome of atriomyopathy. Heart Rhythm 2013;10:S126.
CLINICAL PERSPECTIVES The current study highlights the contribution of electrical activity in the LAA for the genesis and maintenance of AF. Electrical isolation of the LAA using a device such as the LARIAT potentially could eliminate the arrhythmia contribution from the LAA. The outcomes of AF ablation in both the short term and the long term have been less than optimal, and we believe that by using LAA exclusion as adjunctive strategy in addition to pulmonary vein isolation, we may be able to improve the overall success rate of rhythm control and improve patient care. This is an observational study that lays the foundation for larger prospective randomized studies looking at the contribution of the LAA in the genesis and maintenance of AF for eventual translation into clinical practice.
significantly reduced at 3 months (52% ⫾ 35%) and 12 months (42% ⫾ 19%) compared to respective baseline (84 ⫾ 31%, P o .0001).
OBJECTIVE The purpose of this study was to determine whether LAA exclusion using the LARIAT device would decrease AF burden.
CONCLUSION LAA exclusion appears to reduce AF burden. The presence of AF triggers in the LAA appears to be the strongest predictor of AF reduction. The study underscores the role of the LAA in arrhythmogenesis for AF and highlights the complementary role of LAA exclusion in restoration of normal sinus rhythm.
METHODS A total of 50 patients with AF and cardiac implantable electronic devices who underwent successful LAA exclusion were enrolled in this prospective observational study. AF burden before LAA exclusion (baseline) and 3 and 12 months after exclusion was assessed by device interrogation.
KEYWORDS Atrial fibrillation; Left atrial appendage; Suture exclusion; Pericarditis
RESULTS AF burden at 3-month follow-up (42% ⫾ 34%) was significantly lower compared to baseline (76% ⫾ 33%, P o .0001). The reduction in AF burden was sustained at 12 months (59% ⫾ 26%, P o .001). Subgroup analysis revealed that AF burden at 3-month follow-up was similarly reduced in both paroxysmal AF (n ¼ 19) and nonparoxysmal AF (n ¼ 31). However, there was no reduction in AF burden in patients with paroxysmal AF at 12 months. AF burden in patients with known AF triggers in the LAA (n ¼ 9) was
ABBREVIATIONS AF ¼ atrial fibrillation; CIED ¼ cardiac implantable electronic device; CT ¼ computed tomography; GP ¼ ganglionated plexus; LAA ¼ left atrial appendage; PAF ¼ paroxysmal atrial fibrillation; PV ¼ pulmonary vein; RF ¼ radiofrequency; TEE ¼ transesophageal echocardiography
Introduction
prevalence of 1% to 2%. Current estimates from 2010 indicate that approximately 33.5 million individuals worldwide have AF, with close to 5 million new cases occurring each year.1 Thromboembolic stroke is the most dreadful complication of AF. Ninety percent of non-rheumatic AFrelated left atrial (LA) thrombi were isolated to, or originated from, the left atrial appendage (LAA), accounting for a significant thromboembolic burden in these patients.2 Recent studies using the Watchman device (Boston Scientific) have shown the feasibility and noninferiority of LAA exclusion in
Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice, with an estimated Address reprint requests and correspondence: Dr. Dhanunjaya Lakkireddy, Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of EP Research–KU Cardiovascular Research Institute, Bloch Heart Rhythm Center, Mid America Cardiology, University of Kansas Hospital and Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
(Heart Rhythm 2015;12:52–59) rights reserved.
I
2015 Heart Rhythm Society. All
http://dx.doi.org/10.1016/j.hrthm.2014.09.053
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Reduction in AF Burden with LAA Exclusion
preventing thromboembolic complications.3,4 LAA has also been implicated as a significant source of atrial tachycardia and AF.5–9 In a study by Di Biase et al,10 close to 30% of AF triggers in persistent AF were found to be non-pulmonary venous (non-PV), especially LAA, in origin. Successful ablation or isolation of the LAA seems to significantly impact arrhythmia control in these patients.10,11 Successful endocardial isolation of the LAA with radiofrequency (RF) ablation often is difficult because of the complex regional anatomy and problems with catheter stability. Furthermore, the arrhythmia source can be deep inside the LAA or sometimes even epicardial in location. Ablation of these foci can be challenging and associated with higher rates of complications, such as cardiac perforation. Recent studies have shown the feasibility and safety of LAA exclusion devices.12,13 Depending on the design of these devices and the technique of deployment, they can result in either mechanical exclusion or both mechanical and electrical exclusion. Endocardially deployed LAA devices (Watchman [Boston Scientific] and Amplatzer cardiac plug [St Jude Medical]) typically occlude the LAA ostium and result in varying degrees of mechanical exclusion, whereas techniques that use an epicardial approach (LARIAT device [SentreHEART, Redwood, CA], AtriClip [AtriCure, West Chester, OH], surgical ligation) typically result in both mechanical and electrical isolation because they tend to compress the tissue, resulting in ischemic necrosis of the LAA distal to the site of exclusion. A recent article by Han et al16 showed that snare closure of the LAA using the LARIAT device produces an acute reduction in LAA voltage and inhibits capture of the LA during LAA pacing. This indicates tissue ischemia and possible necrosis of the LAA tissue distal to the ligation site. Application of a clip (AtriClip) was shown to cause entrance and exit block in LAA consistent with effective electrical isolation.7,14,15 Based on these observations, we hypothesized that LAA exclusion using the LARIAT device potentially could decrease the overall burden of AF. In this study, we assessed the role of epicardial LAA ligation with the LARIAT device in reducing AF burden in patients with an cardiac implantable electronic device (CIED).
Methods and materials Patient population This was a prospective multicenter observational study of the consecutive patients with AF and a CIED (6 [12%] cardiac resynchronization therapy-defibrillator, 10 [20%] dualchamber ICD, 34 [68%] dual-chamber pacemaker) undergoing LAA exclusion enrolled between July 2010 and April 2013. All devices had a functional atrial lead. Eligible patients met the following inclusion criteria: (1) age Z18 years; (2) nonvalvular AF; (3) at least 1 risk factor for embolic stroke (CHADS2 Z1); and (4) poor candidate or ineligible for warfarin therapy (eg, labile international normalized ratio level, noncompliant, contraindicated) and/ or warfarin failure (ie, transient ischemic attack or stroke
53 while on warfarin therapy). Patients were excluded from the study if they met any of the following exclusion criteria: (1) history of cardiac surgery; (2) severe pectus excavatum; (3) recent myocardial infarction within 3 months; (4) prior embolic event within the last 30 days; (5) New York Heart Association functional class IV heart failure symptoms; and (6) history of thoracic radiation. All patients underwent a screening contrast cardiac computed tomographic (CT) scan. Additional exclusion criteria based on LAA anatomy included (1) LAA width 440 mm; (2) superiorly oriented LAA with the LAA apex directed behind the pulmonary trunk; (3) bilobed LAA or multilobed LAA in which lobes were oriented in different planes exceeding 40 mm; and (4) posteriorly rotated heart. The institutional review boards at all participating institutions approved the protocol. Informed consent was obtained from all patients.
Measurement of LAA electrograms Forty-four patients had recording of endocardial and epicardial voltage before and after LARIAT deployment. Measurement of LAA electrograms was performed as described previously.16 Voltage data for 12 of the patients included in this study have been reported in a previous study.16
Percutaneous suture exclusion of LAA using the LARIAT device LAA exclusion was performed using a LARIAT device as described previously.17
Clinical follow-up Interrogation of CIEDs was performed at baseline before LAA exclusion and at 3- and 12-month follow-up to determine AF burden. At each visit, the device was reset to determine the AF burden in the interim period. An updated medication list was obtained at every visit to ensure the stability of antiarrhythmic drug therapy.
Statistical analysis Normally distributed continuous variables are expressed as mean ⫾ SD. Continuous variables were compared using the t test for normally distributed data or the Mann–Whitney U test for non-normally distributed data as deemed appropriate.
Results Baseline data A total of 50 patients were enrolled in the current study. Baseline characteristics of the study patients are given in Table 1. Mean age was 70 ⫾ 8.4 years, and mean AF duration was 54 ⫾ 40 months . Mean CHADS2 score was 2.8 ⫾ 0.4, and mean CHA2DS2-VASc score was 4.3 ⫾ 0.7. Mean HAS-BLED score was 3.4 ⫾ 0.5. Mean duration from time of device placement was 36 months. Thirty-one patients (62%) had persistent or longstanding persistent AF collectively termed non-paroxysmal atrial fibrillation (non-PAF), and 19 (38%) had paroxysmal atrial fibrillation (PAF). Mean
54 Table 1 Selected baseline characteristics of study participants (N ¼ 50) Clinical variable Male 33/50 (66%) Age (years) 70 ⫾ 8.4 Race (white/African-American) 48/2 Height (cm) 178 ⫾ 6.2 Weight (kg) 99 ⫾ 18 Body mass index 31 ⫾ 4 Coronary artery disease 25 (50%) Hypertension 39 (78%) Diabetes 9 (18%) Congestive heart failure 26 (52%) History of cerebrovascular attack/transient 30 (60%) ischemic attack History of gastrointestinal bleed 13 (26%) Chronic renal insufficiency 18 (36%) Cardiac device in place Cardiac resynchronization therapy-defibrillator 6 (12%) Dual-chamber implantable cardioverter-defibrillator 10 (20%) Dual-chamber pacemaker 34 (68%) 2.8 ⫾ 0.4 CHAD2 score 4.3 ⫾ 0.7 CHADS2-VASc score HAS-BLED score 3.4 ⫾ 0.5 Antiarrhythmic drug Class I 4 (8%) Class III 21 (42%) Beta-blockers 39 (78%) Calcium channel blockers 10 (20%) AF duration (months) 54 ⫾ 40 AF type Paroxysmal 19 (38%) Nonparoxysmal 31 (62%) Left ventricular ejection fraction (%) 45.6 ⫾ 5 Left atrial size (cm) 5 ⫾ 0.8 Mitral regurgitation Trace 12 (24%) Mild 17 (34%) Moderate 8 (16%) Values are given as mean ⫾ SD or n/N (%), where n ¼ number of available patients. AF ¼ atrial fibrillation.
ejection fraction was 45.6% ⫾ 5%. Mean LA size was 5 ⫾ 0.8 cm . The most common valvular abnormality was mitral regurgitation, with 12 (24%) patients having trace, 17 (34%) mild, and 8 (14%) moderate regurgitation.
LAA exclusion Exclusion success was defined as successful closure of the LAA with absence of contrast leak on left atriogram and r1mm jet as visualized by color Doppler on transesophageal echocardiography (TEE). At 3-month follow-up TEE, 47 patients had complete closure of the LAA, and 3 patients had a small leak o3 mm assessed by TEE performed at 3-month follow-up. Representative fluoroscopy, TEE, and cardiac CT images are shown in Figure 1. A representative image of preprocedural and postprocedural CT with 3-dimensional reconstructions shows sloughing of the LAA (see Online Supplementary Figure 1). A recent study has reported a comparable incidence of incomplete LAA closure leak assessed by TEE performed at completion of the LARIAT procedure.18
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Postprocedural complications Pericardial drain was removed after 18 ⫾ 9.1 hours. No embolic events or deaths occurred during the follow-up period. Four patients had pericardial drainage 4500 mL; however, none of them developed cardiac tamponade. Pericardial effusion in these patients developed over a period of 24 hours and was serous in consistency. The most likely cause of this serous effusion is local irritation from catheter manipulation in the pericardial space. Two patients had femoral arteriovenous fistula. The lower bleeding complications in our cohort compared to the recent study by Price et al18 could be due to differences in operator experience at different institutions. There was a significant decrease of blood pressure and increase in heart rate after the LARIAT procedure (see Online Supplementary Table 1).
Arrhythmia follow-up All 50 patients completed 3- and 12-month follow-up after the LARIAT procedure. Interrogation of CIEDs showed a significant reduction in AF burden at 3 months (42% ⫾ 34%) and 12 months (59% ⫾ 26%) compared to baseline (76% ⫾ 33%, P o .0001 for both; Figure 2A). Subgroup analysis revealed that patients with PAF had a significant reduction in AF burden at 3-month follow-up (25% ⫾ 16%) compared to baseline (46% ⫾ 26%, P o .0001); however, there was no significant change at 12-month follow-up (47% ⫾ 24%, P ¼ NS; Figure 2B). Patients with non-PAF had a sustained reduction in AF at both 3-month (51% ⫾ 37%, P o .0001) and 12-month (66% ⫾ 24%, P o .0001) follow-up compared to baseline (94% ⫾ 19%; Figure 2C). The individual data of AF burden for patients with PAF are shown in Figure 3 and for patients with non-PAF in Figure 4. The reduction in AF burden in patients with incomplete LAA closure (n ¼ 3) was significantly lower at 3-month (33%) and 12-month (61%) follow-up compared to baseline (100%). No episodes of defibrillation occurred during the follow-up period. Patients with cardiac resynchronization therapy (n ¼ 6) had stable biventricular pacing at follow-up visits after LAA exclusion. There was no change in the antiarrhythmic drug therapy at follow-up in all patients.
Reduction in AF burden in patients with LAA triggers Subgroup analysis revealed that the reduction in AF was significant in patients who had known triggers in the LAA. In the current study, there were 9 (18%) patients in whom the LAA was identified as the source of triggered activity/atrial tachycardia or as the only source of any meaningful electrical activity in the LA during previous AF ablation. AF burden in these patients was significantly reduced at 3-month (52% ⫾ 35%) and 12-month (42% ⫾ 19%) follow-up compared to baseline (84 ⫾ 31, P o .0001 for both; Figure 5A). AF burden in individual patients is shown in Figure 5B. A representative image of CIED interrogation is shown in Figure 6.
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55
Figure 1 Imaging of the left atrial appendage (LAA) before and after LAA exclusion with the LARIAT device. LAA is seen on fluoroscopy (A) and transesophageal echocardiography (C) immediately before ligation with the LARIAT. LAA is seen on cardiac CT (E) performed a few days before the procedure. LAA is seen on fluoroscopy (B) and transesophageal echocardiography (D) immediately after ligation with the LARIAT. LAA is seen on cardiac CT (F) performed at a follow-up visit after the procedure. Red arrow is pointing toward the LAA.
LAA voltage measurements before and after exclusion
Patients (n ¼ 44) who had recording of endocardial and epicardial voltage before and after the LARIAT procedure
showed significant acute reduction in LAA voltage after the procedure. Endocardial voltage decreased from 6.0 ⫾ 2.1 mV to 2.3 ⫾ 0.7 mV (P o .001). Epicardial voltage decreased from 6.0 ⫾ 2.1 mV to 2.1 ⫾ 0.6 mV (P o .001; Figure 7)
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Figure 2 Reduction in atrial fibrillation (AF) burden after left atrial appendage (LAA) exclusion with the LARIAT device. A: Overall reduction in AF burden in all patients. B: Reduction of AF burden in patients with paroxysmal AF. C: Reduction of AF burden in patients with nonparoxysmal AF.
Figure 3 Individual atrial fibrillation (AF) burden at different time-points in patients with paroxysmal AF. First row in table below the graph gives the patient ID in this group. Rows 2-4 give the AF burden in percentage at 3 different time-points.
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57
Figure 4 Individual atrial fibrillation (AF) burden at different time-points in patients with nonparoxysmal AF. First row in table below the graph gives the patient ID in this group. Rows 2–4 give the AF burden in percentage at 3 different time-points.
Discussion Major findings
This is the first study to show that LAA exclusion with the LARIAT device reduces AF burden and continues to have a
sustained effect even at 12-month follow-up in patients with non-PAF. The presence of AF triggers in the LAA is the strongest predictor of AF reduction after LAA exclusion.
Role of LAA in arrhythmogenesis
Figure 5 Reduction in atrial fibrillation (AF) burden after the LARIAT procedure in patients with known triggers in the left atrial appendage (LAA). A: Reduction in AF burden in patients with a history of radiofrequency ablation and known triggers of AF in the LAA. B: Individual AF burden at different time-points in patients with known triggers in the LAA. First row in table below the graph gives the patient ID in this group. Rows 2–4 give the AF burden in percentage at 3 different time-points.
The arrhythmogenic role of the LAA has been described in several recent studies. The LAA has extensive pectinate muscles and a heterogeneous fiber orientation. The trabeculated muscles in the LAA influence wave propagation and favor the formation of conduction block/slow conduction and initiation of reentry.5,6 Two recent studies proposed automaticity as the underlying mechanism for atrial tachycardia originating from the LAA.8,19 These findings were further supported by the observation in patients undergoing LAA exclusion. Epicardial exclusion of the LAA with a minimally invasive occlusion device (AtriClip) implanted from outside the heart through a thoracoscopic approach has been shown to be successful in achieving electrical isolation and thus elimination of focal atrial tachycardia.7 In a series of 10 consecutive patients undergoing coronary artery bypass grafting, epicardial LAA clip occlusion led to complete electrical isolation of the LAA, resulting not only in the elimination of an important source of systemic thromboembolism but also the electrical exclusion of potential triggers for the recurrence of AF.15 In a large series of patients, Di Biase et al10 reported that 27% of patients undergoing redo catheter ablation for AF showed firing from the LAA, and in 9% the LAA was found to be the only source of arrhythmia without any evidence of PV or extrapulmonary sources. Hocini et al9 systematically studied the role of the LAA in organized atrial arrhythmias arising in the context of AF ablation. The study described a cohort of patients with localized reentrant tachycardia harbored within the LAA after AF ablation suggesting that the LAA may contribute directly to maintenance of AF. Studies with power spectral analysis and mapping to localize dominant frequency sites of activation have shown
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Figure 6 Cardiac implantable electronic device (CIED) interrogation before and after left atrial appendage (LAA) exclusion with the LARIAT device. Representative image of CIED interrogation in a patient with atrial fibrillation (AF) shows termination of AF (downward pointing arrow) after LAA exclusion with the LARIAT device. AT ¼ atrial tachycardia; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia.
that PVs harbor the highest-frequency sites in patients with PAF, and AF can be terminated successfully by targeting RF ablation at those sites in up to 87% of patients. However, the recent data in persistent AF patients provide compelling evidence that the sources are, in fact, reentrant and located outside of the PVs. Similarly, in longstanding persistent AF patients, it is rare to find dominant frequency sites at the PV region, and this agrees well with the relatively poor success rate of RF ablation in such patients. The data suggest that in patients with longstanding persistent AF, atrial remodeling somehow augments the number of AF drivers and shifts their location away from the PV/ostial region.20,21 Based on these observations, it is possible that the LAA harbors some of the triggers. Clusters of autonomic ganglionated plexuses (GPs) are found in abundance along the groove between the left superior pulmonary vein and the LAA. The fat pad around
Figure 7 Reduction of endocardial and epicardial voltage after left atrial appendage (LAA) exclusion with the LARIAT device. Graph shows immediate reduction in endocardial and epicardial voltage after LAA ligation with the LARIAT.
the LAA also could have additional GPs that are poorly defined. LAA exclusion could affect GP activity and thereby reduce triggers by altering autonomic tone. This possibly could be the contributing factor in the reduction of AF after the LARIAT procedure. Our group and others in the past have described a phenomenon of “atriomyopathy” in which patients have extensive atrial scarring on endocardial voltage maps that is disproportionate to chamber size and duration/type of AF.22 Often the only structure that was electrically active was the LAA with focal triggers arising from it. Thus, the observation in the current study is in congruence with the previous literature.
Impact of LAA exclusion on LAA electrical activity LAA exclusion using a suture or a clip causes an acute infarct of the tissue and results in a significant voltage reduction. Over time, the LAA tissue becomes atretic, resulting in complete mechanical and electrical isolation of the LAA from the rest of the LA (see Online Supplementary Figure 1). Ligation of the LAA possibly can remove the reentrant and triggered arrhythmias that arise from this structure. Typically there is a 10% to 40% reduction in LA volume and surface area after LAA exclusion, which essentially decreases the available LA substrate for AF propagation and perpetuation. Also, the peri-appendageal fat pad probably has a significant number of GPs that could be impacted by ligation. LAA is also known to have a significant impact on neuroendocrine modulation through atrial natriuretic peptide (ANP) and other related homeostatic factors, including the renin–angiotensin– aldosterone system. In summary, the LAA seems to play an important role in atrial arrhythmia, and LAA exclusion using an epicardial
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ligation system seems to result in a significant reduction in AF burden.
Clinical implications This study clearly highlights the value of LAA electrical exclusion in decreasing the overall arrhythmia burden. This method could be used as a potential adjunctive strategy in improving the efficacy of AF ablation for rhythm control while mechanically excluding the source of thrombus formation in the LA.
Study limitations This current study is a very small prospective observational study. We have limited data on whether the LAA was the true source of atrial arrhythmias in all patients. A large randomized controlled trial looking at the added benefit of LAA ligation along with AF ablation would be the future direction.
Conclusion LAA exclusion appears to reduce AF burden in patients with non-PAF. The presence of AF triggers in the LAA appears to be the strongest predictor of AF reduction. The study underscores the role of the LAA in arrhythmogenesis for AF and highlights the complementary role of LAA exclusion in restoration of normal sinus rhythm.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.hrthm. 2014.09.053.
References 1. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation 2013. 2. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–759. 3. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P, Investigators PA. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534–542. 4. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D, Investigators PA. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial. Circulation 2013;127:720–729.
59 5. Cabrera JA, Ho SY, Climent V, Sanchez-Quintana D. The architecture of the left lateral atrial wall: a particular anatomic region with implications for ablation of atrial fibrillation. Eur Heart J 2008;29:356–362. 6. Ho SY, Sanchez-Quintana D, Cabrera JA, Anderson RH. Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation. J Cardiovasc Electrophysiol 1999;10:1525–1533. 7. Benussi S, Mazzone P, Maccabelli G, Vergara P, Grimaldi A, Pozzoli A, Spagnolo P, Alfieri O, Della Bella P. Thoracoscopic appendage exclusion with an AtriClip device as a solo treatment for focal atrial tachycardia. Circulation 2011;123:1575–1578. 8. Yang Q, Ma J, Zhang S, Hu JQ, Liao ZL. Focal atrial tachycardia originating from the distal portion of the left atrial appendage: characteristics and long-term outcomes of radiofrequency ablation. Europace 2012;14:254–260. 9. Hocini M, Shah AJ, Nault I, et al. Localized reentry within the left atrial appendage: arrhythmogenic role in patients undergoing ablation of persistent atrial fibrillation. Heart Rhythm 2011;8:1853–1861. 10. Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation 2010;122:109–126. 11. Yamada T, McElderry HT, Alison JS, Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm 2008;5: 766–767. 12. Bartus K, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Yakubov SJ, Lee RJ. Feasibility of closed-chest ligation of the left atrial appendage in humans. Heart Rhythm 2011;8:188–193. 13. Sick PB, Schuler G, Hauptmann KE, Grube E, Yakubov S, Turi ZG, Mishkel G, Almany S, Holmes DR. Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J Am Coll Cardiol 2007;49:1490–1495. 14. Bartus K, Morelli RL, Szczepanski W, Kapelak B, Sadowski J, Lee RJ. Anatomic analysis of the left atrial appendage after closure with the LARIAT device. Circ Arrhythmia Electrophysiol 2014;7:764–767. 15. Starck CT, Steffel J, Emmert MY, Plass A, Mahapatra S, Falk V, Salzberg SP. Epicardial left atrial appendage clip occlusion also provides the electrical isolation of the left atrial appendage. Interact Cardiovasc Ther 2012;15: 416–418. 16. Han FT, Bartus K, Lakkireddy D, Rojas F, Bednarek J, Kapelak B, Bartus M, Sadowski J, Badhwar N, Earnest M, Valderrabano M, Lee RJ. The effects of LAA ligation on LAA electrical activity. Heart Rhythm 2014;11:864–870. 17. Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, Lee RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation initial clinical experience. J Am Coll Cardiol 2013;62:108–118. 18. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. Transcatheter LAA Ligation Consortium. J Am Coll Cardiol 2014;64:565–572. 19. Yamada T, McElderry HT, Allison JS, Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm 2008;5: 766–767. 20. Lin YJ, Tsao HM, Chang SL, Lo LW, Hu YF, Chang CJ, Tsai WC, Suenari K, Huang SY, Chang HY, Wu TJ, Chen SA. Role of high dominant frequency sites in nonparoxysmal atrial fibrillation patients: insights from high-density frequency and fractionation mapping. Heart Rhythm 2010;7:1255–1262. 21. Sanders P, Berenfeld O, Hocini MZ, et al. Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans. Circulation 2005;112:789–797. 22. Reddy M, Di Biase L, Vallakati A, Swarup V, Umbarger L, Bakdunes W, Bommana S, Atkins D, Natale A, Lakkireddy D. Predictors of severe left atrial scarring in patients with paroxysmal atrial fibrillation: unveiling a new syndrome of atriomyopathy. Heart Rhythm 2013;10:S126.
CLINICAL PERSPECTIVES The current study highlights the contribution of electrical activity in the LAA for the genesis and maintenance of AF. Electrical isolation of the LAA using a device such as the LARIAT potentially could eliminate the arrhythmia contribution from the LAA. The outcomes of AF ablation in both the short term and the long term have been less than optimal, and we believe that by using LAA exclusion as adjunctive strategy in addition to pulmonary vein isolation, we may be able to improve the overall success rate of rhythm control and improve patient care. This is an observational study that lays the foundation for larger prospective randomized studies looking at the contribution of the LAA in the genesis and maintenance of AF for eventual translation into clinical practice.
