J Interv Card Electrophysiol (2015) 42:11–19 DOI 10.1007/s10840-014-9963-2
MULTIMEDIA REPORT
Safety and effectiveness of compassionate use of LARIAT® device for epicardial ligation of anatomically complex left atrial appendages Mehul B. Patel & Abdi Rasekh & Mossaab Shuraih & Mihail G. Chelu & Tracy Bartlett & Nilesh Mathuria & Payam Naeini & James Strickland & Ali Massumi & Mehdi Razavi & Jie Cheng
Received: 16 July 2014 / Accepted: 28 November 2014 / Published online: 17 January 2015 # Springer Science+Business Media New York 2015
Abstract Background Percutaneous left atrial appendage (LAA) ligation using an epicardial suture system (LARIAT®, SentreHEART, Palo Alto, CA) has been used in patients with nonvalvular atrial fibrillation (AF) and contraindication to oral anticoagulation. However, complex LAA anatomy may preclude its use. We report the safety and effectiveness of compassionate use of first-generation LARIAT® device for epicardial ligation of large, complex left atrial appendages. Methods Between January 2010 and March 2013, 93 patients with AF, high CHADS2 score, and contraindication(s) for oral anticoagulation therapy were evaluated for LAA ligation. Complex anatomy detected by 3D cardiac computed tomography CT angiography led to preclusion of 25 patients (27%). Of these, nine patients who opted for epicardial LAA ligation on compassionate grounds were studied. Results Mean age was 68.1±8.2 years, four females, all with large LAA width (>40 mm, 45–58 mm) and additional anatomic complexities such as bilobed (two), long C-shaped-like (two), goose neck-like (one), multilobed cauliflower-like (two), cactus-like (one), and chicken wing-like (one) LAA.
LAA ligation with LARIAT® was successfully performed with surgical standby in all patients. Seven patients (78%) were safely treated percutaneously and only two patients required minimally invasive thoracotomy (one due to inability to release the epicardial snare from long C-shaped LAA and other due to preexisting adhesions precluding pericardial entry). There were no major complications. Repeat transesophageal echocardiography at 3 months showed no remnant flow and none had stroke off Coumadin at 19.3±8.2 months of follow-up. Conclusions Despite a high preclusion rate, percutaneous LAA ligation may be safely and effectively performed on compassionate grounds using the first-generation LARIAT® device with surgical standby in patients with large and complex LAA. Keywords LARIAT® . Epicardial suture delivery system . Left atrial appendage ligation . Atrial fibrillation . Stroke
1 Introduction Electronic supplementary material The online version of this article (doi:10.1007/s10840-014-9963-2) contains supplementary material, which is available to authorized users. M. B. Patel : A. Rasekh : M. Shuraih : M. G. Chelu : N. Mathuria : P. Naeini : A. Massumi : M. Razavi : J. Cheng (*) Texas Heart Institute/Baylor CHI St. Luke Health System, 6770 Bertner Street, MC 2-255, Houston, TX 77030, USA e-mail: [email protected] M. B. Patel : A. Massumi : M. Razavi Baylor College of Medicine, Houston, USA T. Bartlett : N. Mathuria : J. Strickland : J. Cheng University of Texas Health Science Center, Houston, TX, USA
Atrial fibrillation (AF) is the most common sustained arrhythmia affecting more than three million people in the USAwith a five times higher risk for an embolic stroke [1, 2]. The deep trabeculated left atrial appendage (LAA) in a low or no flow state is the nidus for more than 90% of thrombus formation in AF [3, 4]. Clots arising from the left appendage may cause catastrophic embolic stroke if dislodged. Although the risk of thromboembolic events is markedly reduced with long-term oral anticoagulation therapy (OAC), it is estimated that only 60% of eligible patients with atrial fibrillation take warfarin, and moreover only 2/3 of these patients have a stable therapeutic international normalized ratio (INR) [5, 6]. The newer
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OAC (NOAC) such as dabigatran, rivaroxaban, and apixaban, though convenient, have no readily available antidote and are especially contraindicated in patients with major bleeding risks. Importantly, up to 17–21 % of the AF patients have varying degrees of intolerance or contraindications to any form of OAC [7]. The advent of surgical techniques and the understanding of LAA as the source of emboli gave momentum to surgical LAA excision for stroke prevention [8–10]. Less invasive catheter-based approaches to occlude the LAA too has evolved over time. There has been increasing evidence of noninferiority, equal efficacy, and even superiority of occlusion devices when compared to OAC [11–21]. However, LAA occlusion is reported to have periprocedural complications such as pericardial effusion, incomplete LAA closure, device dislodgement, and blood clot formation on the exposed device requiring 6 weeks of full oral anticoagulation post procedure, thus exposing the patients to continued risk of bleeding especially in those with contraindications [18]. More recently, percutaneous epicardial suture delivery system (LARIAT®, SentreHEART, Palo Alto, CA) for LAA ligation has been introduced [22–28]. However, the use of this technique is limited by the complexity of LAA and its neighboring anatomy. Given the maximum horizontal diameter of the firstgeneration LARIAT® device of 40 mm, current preclusion criteria for the use of this device include large LAA width more than 40 mm along with complex anatomic features such as bilobed LAA, multilobed LAA, or LAA apex directed behind the pulmonary trunk. We sought to assess the safety and feasibility of a modified approach to LAA ligation using the first-generation LARIAT® device with surgical standby on compassionate grounds in patients with large, challenging LAA anatomies, currently deemed unsuitable for the procedure.
2 Methods The study was approved by the institutional review board and all standard requirements regarding research study on human subjects were met. The LARIAT device is a suture delivery system that received 510(k) marketing clearance from the FDA in 2006. A total of 93 AF patients with high CHADS2, CHA2DS2-VASc, and HAS-BLED scores with contraindication(s) or intolerance for OAC was evaluated for LAA ligation with the LARIAT® device. LAA anatomy was evaluated using cardiac computed tomography (CT) angiography with 3D reconstruction. Among them, patients who had indication for LAA ligation but deemed unsuitable due to anatomic considerations (see above) were studied. All these patients requested for an alternative and effective therapy to prevent stroke, avoiding OAC/NOAC at all times in view of the major/life-threatening bleed that they braved. All possible
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alternatives including totally thoracoscopic LAA clip exclusion were offered to every patient and they opted for LARIAT® device. These patients consented for the LARIAT® device with a clear understanding of its compassionate, high-risk, and off-label use. The exclusion criteria for the study included prior cardiac surgery, myocardial infarction within the previous 3 months, embolic events within 30 days, New York Heart Association function class IV, and patient’s inability or refusal to consent. 2.1 Description of patients in the study Complex anatomic features led to initial preclusion of 25(27%) of the 93 patients for LAA ligation with LARIAT® device; of these, 9 patients who opted for and consented for the procedure underwent LAA ligation with close surgical backup. The remaining 16 patients who did not consent continued medical management. All nine patients in our study had large LAA width (>40 mm, range 45 to 58 mm). Additional anatomic variations included bilobed LAA in two, long C-shaped-like LAA in two (supplemental videos 1 and 2), goose neck-like LAA in one, large multilobed cauliflower-like LAA in two, cactus-like LAA in one, and chicken wing-like LAA in one (Fig. 1). 2.2 Pre-procedure evaluation All patients had paroxysmal, permanent, or persistent AF. Cardiac CT angiography with 3D reconstruction was performed to define the morphology, location, and neighboring anatomy of LAA (Fig. 1). Informed consent with a clear understanding of the “off-the-label” compassionate use and possible open thoracic surgery was explained to all patients. Patients presented in a nonsedated post absorptive state to the hybrid operating room. General anesthesia with ventilator support and intra-operative transesophageal echocardiography (TEE) guidance was used in all patients. 2.3 Hardware components The LARIAT® device consist of five components: (1) a 20mm compliant, low profile, highly echogenic balloon catheter (EndoCATH®); (2) 0.025- and 0.035-in. opposite-pole magnet-tipped guide wires (FindrWIRZ); (3) a 12-F suture delivery device that delivers a 40-mm diameter, pre-tied suture loop contained on a closure snare composed of size 0 Teflon-coated braided polyester suture; (4) suture-release actuator; and (5) specially designed suture cutter. 2.4 Procedure details Pericardial access was obtained under fluoroscopic guidance using a pericardial needle with angled bevel (17-gauge Tuohy
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Fig. 1 Cardiac CT angiogram with 3D reconstruction images showing the complex and varied LAA morphologies of patients 1 (a), 2 (b), 3 (c), 4 (d), 5 (e), 6 (f), 7 (g), 8 (h), and 9 (i)
epidural needle from Hakko Corporation, Naganoken, Japan) as previously described [22]. Epicardial access was directed anteriorly with its trajectory directed toward the tip of the largest or the primary lobe of LAA as seen on cardiac CT images. A 0.035-in. guide wire with a floppy tip was advanced into the pericardial space, and the access was sequentially dilated to 14 F with the track directed toward the LAA. The SentreHEART pericardial sheath with a soft tip was then advanced over the guide wire into the pericardial space toward the tip of the primary lobe of LAA. Transseptal access was obtained using a standard TEE-guided technique for placement of the 8.5-F SL1 guide catheter into the left atrium. Heparin bolus (80 units/kg) and then continuous drip was administered to maintain activated clotting times (ACT) at 300–350 s. Left atrial appendogram was performed in orthogonal views at baseline and with balloon inflation at the LAA ostium to clearly delineate the ostium and the morphology of LAA with all its lobes. A 0.025-in. endocardial FindrWIRE, back-loaded over an EndoCATH® balloon catheter, was positioned at the tip of the left atrial appendage or the primary lobe and confirmed on anteroposterior and lateral views. Once in position, the
FindrWIRE was secured by closure of the rotating hemostasis valve. Another 0.035-in. FindrWIRE back-loaded with the LARIAT® catheter was advanced in the pericardial space. With gentle sweeping motion while advancing the epicardial wire toward the tip of the endocardial wire, the magnets on the tips of each FindrWIRE attract to each other and unite. This endo-epi magnetized union forms a continuous arc stabilizing the thin-walled LAA before the LARIAT® snare can be advanced over it to grasp the LAA ostium. Under the guidance of TEE and fluoroscopy, the LARIAT® snare was advanced over the LAA. At this point, the technique was carefully modified to include the entire LAA with all its lobes/ diverticulii making sure there was no remnant/dead space. 2.5 Modifications of the standard technique for complex LAA anatomies After first capturing of the longest or the largest lobe (primary lobe) where the endocardial FindrWIRE was first parked, the LARIAT® snare was careful maneuvered to capture the secondary lobes while making sure that it does not slip out from the primary lobe. Using slow and careful clockwise/
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counterclockwise motion of the LARIAT® catheter along with opening/closing position of snare, all secondary lobes/ complete LAA were captured (supplemental videos 4 and 5). Gentle forward tension on the endocardial FindrWIRE to longitudinally stretch the LAA along with gentle suction through the EndoCATH® catheter was applied with the LARIAT® partially closed near the LAA ostium as an attempt to reduce the LAA volume, width, and circumference. Capture of the entire LAA with LARIAT device was confirmed with color Doppler TEE showing capture and no flow across the LAA ostium. Reopening and repositioning of the LARIAT® device was repeated if necessary to ensure complete capture of the LAA before its final deployment. The balloon EndoCATH® was then fully deflated and pulled back to the LA along with the endocardial FindrWIRE. The suture was tightened around the ostium of LAA by retracting the suture-release actuator of the tensioning device. Final cinching of the suture was performed at an interval of 5 min to ensure complete closure. Left atrial angiogram was then performed to demonstrate flush LAA ligation confirmed by TEE color Doppler showing no flow. After deploying the suture, the LARIAT® was carefully disengaged from the LAA without using any extra force. The epicardial and transseptal catheters were then removed under fluoroscopic guidance after cutting the suture using the suture cutter. A schematic step-by-step flowchart on the use of LARIAT® device for large LAAs is shown in Fig. 2. 2.6 Transseptal puncture before pericardial access In 6 of the 9 cases, transseptal puncture followed by 5000 units of Heparin and left atrial appendography was performed first before obtaining pericardial access to allow optimal positioning and orientation of the pericardial puncture needle with LA appendogram as the guide (supplemental video 3). This was an important modification to the standard procedure. In the remaining three of nine patients, the initial pericardial access was guided by reviewing the 3D CT angiography before the transseptal access. 2.7 Minimally invasive thoracic surgery A standby minimally invasive lateral thoracotomy surgery was planned in advance in all patients in case of difficulties with epicardial deployment of the LARIAT® device and/or as an emergency rescue for potential percutaneous periprocedural complications. 2.8 Post procedure care Intrapericardial soft drain was left in place and all patients were transferred to CCU for close monitoring. A chest X-ray and transthoracic echocardiogram on post procedure day 1
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were performed in all patients. The indwelling drain was removed in the absence of any significant or expanding pericardial effusion on the next day. All patients received nonsteroidal anti-inflammatory drugs and/or colchicine to reduce pericardial frictional pain.
3 Results The clinical characteristic of patients is provided in Table 1. The average age was 68.1±8.2 years, four females, CHADS2 score of 2.5±1.1, CHA2DS2-VASc score of 3.4±0.8, and HAS-BLED score of 3.1±0.8. The major contraindications for OAC included life-threatening gastrointestinal (GI) bleeding (six out of nine patients), retinal bleeding (one patient), and ataxia with recurrent falls (one patient). One patient had LAA thrombus despite therapeutic INR and was deemed to have failure of OAC therapy. After initiating dual anticoagulation therapy using OAC and NOAC, the clot disappeared after 3 months on TEE. However, understanding the high risk for major bleeds, the patient refused to continue medical therapy and opted for LAA ligation. The mean LAA width was 48±49 mm (range 45–58 mm) in the axis perpendicular to the longitudinal axis of the LAA with additional anatomic variations. The LARIAT® delivery device was able to completely capture the LAA at the ostium and deliver the suture at the LAA ostium in all patients. Seven patients (78%) were safely treated percutaneously and only two patients required minimally invasive thoracotomy (one due to inability to release the epicardial snare from C-shaped LAA and other due to preexisting adhesions precluding pericardial entry) (Table 2). There were no complications with transseptal and epicardial accesses. Endo-epi connection of the FindrWIRZ was successfully achieved in all patients. However, in one of the three patients in whom epicardial access was obtained prior to transseptal access, a second pericardial access was required to optimally align the epicardial and endocardial FindrWIREs. A single LARIAT® device was able to capture the entire LAA in a piecemeal fashion with careful maneuvers as described for capturing multiple lobes/diverticulii. The mean length of stay with the compassionate use study population was 6±2.5 days in contrast to 5.29±5.86 days (p= 0.72) in patients with standard indications performed during the same time frame. This included the length of stay to optimize medications and for management of other comorbidities in all patients. There were no major periprocedural complications. Two patients developed moderate pericardial effusion that required extended pericardial drainage for 48 h without the need for further intervention or transfusion. The total aspirate was less than 500 ml in both cases.
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Fig. 2 Schematic step-by-step flow-chart on the pragmatic use of the LARIAT® device for complex LA anatomies
Patient 5 with preexisting pericardial adhesions had no history of prior cardiac surgery. However, he had two previous percutaneous pulmonary vein isolation procedures, and post procedure pericarditis was speculated to be the etiology for pericardial adhesions. After obtaining pericardial access, there was difficulty in passing the guide wire through the adhesions. A mini lateral thoracotomy with 5-cm incision was thus
performed to obtain free pericardial access and allow completion of the procedure using the standard percutaneous technique for LAA ligation. Patient 2 had difficulty in removing the LARIAT from the LAA after deploying the suture, compelling an urgent minimally invasive lateral thoracotomy to release the LARIAT from the LAA. This led to the thought process of applying
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Table 1
Pt1 Pt2 Pt3 Pt4 Pt5 Pt6 Pt7 Pt8 Pt9
Clinical characteristics of the study population Gender
Age
Contraindication for anticoagulation
CHADS2 score
CHA2DS2-VASc score
HAS-BLED score
M M M F F M F F M
67 79 73 60 82 61 65 67 59
GI bleed GI bleed GI bleed Retinal hemorrhage Ataxia, falls GI bleed GI bleed GI bleed LA thrombus with therapeutic INR
2 3 1 2 2 5 2 2 3
3 4 4 2 3 3 4 5 3
2 4 4 3 4 2 3 3 3
suction through the EndoCATH® catheter with the LARIAT partially closed to reduce the LAA volume and width before disengaging. The LAA was successfully excluded using the LARIAT device in all patients without the use of any additional surgical devices.
the same day of the procedure and never reinitiated in any patient till last follow-up. There was no stroke or transient ischemic attack on last follow-up with one patient lost to follow-up 2 months after the procedure.
3.1 Follow-up 4 Discussion The mean follow-up period was 19.3±8.2 months. All patients were scheduled to follow-up at 3 weeks, 3 months, and then every 6 months; TEE was done at 3 months per protocol, except in one patient where it was done at 2 months after the procedure. There was no suture leak, persistent flow, and residual or new pericardial effusion in any patient. All patients had pericardial pain for a few days after the procedure, which was well controlled by NSAIDS and or colchicine. There was no clinical or echocardiographic evidence of delayed pericardial inflammation or effusion noted in any patient during follow-up. All forms of anticoagulation was discontinued on Table 2
Procedural characteristics of the study population
LAA anatomy
Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 Pt 9
Our main finding is that LAA ligation may be safely and effectively performed even in patients that are currently excluded due to anatomical limitations by pragmatic modifications to the use of first-generation LARIAT® device. Our data indicate that the preclusion rate using 3D CT angiography for the use of LARIAT® device is rather high (nearly 27% in our cohort). Our observation also suggests that percutaneous LAA ligation in these patients may be best attempted with appropriate surgical backup. To our knowledge, this is the first study to report the incidence of patient preclusion due to
Problems encountered during
Large width >40 mm in all TSPa
Pericardial accessa Capturea and snare Cinchinga Releasea
Bilobed Cactus like Cauliflower like Long C shaped Long C shaped Chicken wing like Cauliflower like Long goose neck like Bilobed
None, 2 accessesb None None None Yes (adhesions) None None None None
None None None None None None None None None
None None None None None None None None None
None None None None None None None None None
None Yes None None None None None None None
Success Complications
OTS
Yes Yes Yes Yes Yes Yes Yes Yes Yes
n/a Yes n/a n/a Yes n/a n/a n/a n/a
None Could not release snare None None None None None None None
TSP transseptal puncture, OTS open thoracic surgery a b
Steps in LAA ligation including transseptal puncture, pericardial access, complete capture and snaring of the LAA, cinching, and release of LARIAT®
Double pericardial access performed as initial access was either too laterally or too medially placed. Approximately 10–15 ml of contrast was injected into the pericardial space before the second access was performed to facilitate the visualization of the pericardial space
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unfavorable LAA anatomy using the first-generation device. This is also the first to report initial experience on safety and efficacy of compassionate use of LARIAT® device for epicardial LAA ligation in a largest ever reported cohort of patients with complex LAA anatomies. Non-pharmacological approaches to reduce the risk of stroke in AF have evolved significantly over time, from surgical interventions to percutaneous procedures to occlude/ exclude the LAA [8–17, 29]. Overall surgical closure has longer procedure times with excess tissue manipulation and variable success rates. The first percutaneous left atrial appendage occlusion using the PLAATO occluder (Appriva Medical, Inc. from Sunnyvale, CA) and subsequently the WATCHMAN device (Aritech Inc, Plymouth, Minnesota) demonstrated safety, feasibility, and noninferiority to OAC. Follow-up data from the PROTECT AF study using LAA occlusion devices not only confirmed that “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin but also revealed a lower rate (3.2%) of both ischemic and hemorrhagic stroke in the device arm than in the control arm (4.5%) [14]. Additionally, the 5year results of the use of the percutaneous LAA occlusion device revealed an annual stroke/transient ischemic attack rate of 3.8%, which is less than the annual stroke rate of 6.6% predicted by the CHADS2 scoring system [15–21]. Recently, the results of LAA ligation using the LARIAT® device have generated much interest [22–28, 30]. The LARIAT® device causes flush ligation of the LAA ostium, leaving minimal chances for a remnant dead space or persistent flow. To date, direct comparison between LAA occlusion and ligation is lacking although absence of a foreign or thrombogenic intracardiac material with the LARIAT® device may be highly favorable to those with absolute contraindications to OAC. However, the use of LARIAT® device may be limited by the complexity of the LAA and its neighboring anatomy, and patients with history of cardiac surgery and pericarditis may be unsuitable due to the presence of pericardial adhesions preventing percutaneous epicardial access [26, 27]. Candidate selection for LAA ligation with LARIAT® device usually involves screening with 3D contrast cardiac CT angiography. The current preclusion criteria include [1] maximum LAA width more than 40 mm, [2] LAA apex directed behind the pulmonary trunk, [3] large bilobed LAA or multilobed LAA, or [4] posteriorly rotated heart. With the accumulation of experience over time, we have learned that pragmatic modifications of the standard procedure could improve the success rate, even in patients with such challenging anatomies. These include [1] obtaining transseptal access before epicardial access. This modification is safe and advantageous as such since LA appendogram after transseptal access serves as an important real-time road map using the same imaging modality (fluoroscopy) to direct the epicardial needle and align the trajectory of epicardial dilator/catheter, and [2] gentle
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twisting of the epicardial LARIAT® apparatus may facilitate capturing of multilobed LAA which is best started at the lobe that is inferiorly located and [3] suction through the EndoCATH® with the LARIAT partially closed near the LAA ostium with gentle forward tension on the endocardial FindrWIRE may help to reduce the volume and width of a large LAA and allow for successful and complete LAA capture. In our study, only two patients required complementary surgical intervention to complete the LAA ligation. Thoracoscopic stand-alone appendectomy may have been an option in this population [31]. The study population was primarily eligible only for surgical ligation due to unfavorable anatomy; however, since patients opted for a trial of percutaneous closure, in effect 78% (7 of 9 patients) of patients were successfully closed percutaneously without the need for surgery. We believe that every patient should be given a choice of options with its individual risk to benefit ratios depending on institutional expertise. Given the results of the current study, the risk to benefit ratio seems to tilt more toward benefit for a planned approach of percutaneous ligation with a clear understanding of the compassionate nature and the possibility of switching to surgical ligation. However, such attempts to percutaneously ligate large, complex LAA should only be performed with close surgical backup in the hybrid OR on patients who opt for and clearly understand the compassionate nature of the procedure. All patients should consent for open LAA ligation. A wellplanned collaboration between the operating cardiologists and cardiac surgeons after reviewing the detailed anatomy by 3D CT scan in all patients is important. This on-site surgical standby approach may also be useful in patients with unexpected pericardial adhesions. The results of this study do not alter the standard indications of LARIAT® ligation due to the retrospective nonrandomized nature of our study with small number of patients. Such compassionate procedure should be only performed in experienced centers at this time, and future studies with significantly larger sample sizes are needed. Eligible patients should be given all possible options and prepared for open ligation with the knowledge of a likelihood of surgery. Modification of the LARIAT® device with enlargement of the LARIAT® snare diameter to 55 mm as a secondgeneration device may help to percutaneously ligate complex LAA with ease. Novel noninvasive markers to diagnose preprocedure pericardial adhesions could help immensely in planning ahead and identifying potential need for surgery. 4.1 Limitations The major limitation of our study relates to its retrospective nature with small number of cases. Although only two patients required surgical intervention, there were only nine patients in
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the series. Another major limitation is that only a limited number of patients who consented for the procedure were studied, and thus outcome data from a prospective multicenter study may be helpful. Recent reports on persistent leaks and reopening of the device also warrant long-term follow-up of LAA suture-based ligation [32, 33].
5 Conclusions Current strict exclusion criteria for percutaneous LAA ligation result in a high preclusion rate for the procedure. LAA ligation however may be performed safely and effectively with careful modifications to the standard technique in patients with anatomically complex and large LAA who are prepared for open ligation in centers with experience. However, such cases should be well planned with close surgical backup. Data from further multicentric studies are needed before recommending LARIAT® ligation in patients with complex anatomy. Acknowledgments The authors would like to thank Dr. Sandeep Patel, MD, and Dr. Benjamin Y. Cheong, MD, for their contribution in cardiac 3D CT reconstruction images. Funding There was no industry funding obtained for this study. Conflict of interest There is no conflict of interest either real or perceived of any author in the publication of this manuscript. Disclosure None
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Protection in Patients with Atrial Fibrillation) Trial. Circulation. 2013; Feb 12;127(6):720–9. Sosa, E., Scanavacca, M., D’avila, A., & Pilleggi, F. (1996). A new technique to perform epicardial mapping in the electrophysiology laboratory. Journal of Cardiovascular Electrophysiology, 7, 531–536. D’Avila, A., Scanavacca, M., & Sosa, E. (2006). Transthoracic epicardial catheter ablation of ventricular tachycardia. Heart Rhythm, 3, 1110–1111. Bartus, K., Bednarek, J., Myc, J., et al. (2011). Feasibility of closedchest ligation of the left atrial appendage in humans. Heart Rhythm, 8, 188–93. Lee, R. J., Bartus, K., & Yakubov, S. J. (2010). Catheter-based left atrial appendage (LAA) ligation for the prevention of embolic events arising from the LAA: initial experience in a canine model. Circulation Cardiovascular Interventions, 3, 224–9. 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. 2012 Sep 28. pii: S0735-1097(12)03035-5. Shetty, R., Leitner, J. P., & Zhang, M. (2012). Percutaneous catheterbased left atrial appendage ligation and management of periprocedural left atrial appendage perforation with the LARIAT suture delivery system. Journal of Invasive Cardiology, 24(11), E289–93. Friedman, P. A., Asirvatham, S. J., Dalegrave, C., Kinoshita, M., Danielsen, A. J., Johnson, S. B., Hodge, D. O., Munger, T. M.,
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Paceker, D. L., & Bruce, C. J. (2009). Percutaneous epicardial left atrial appendage closure: preliminary results of an electrogram guided approach. Journal of Cardiovascular Electrophysiology, 20, 908– 915. Massumi, A., Chelu, M. G., Nazeri, A., May, S. A., AfsharKharaghan, H., Saeed, M., Razavi, M., & Rasekh, A. (2013). Initial experience with a novel percutaneous left atrial appendage exclusion device in patients with atrial fibrillation, increased stroke risk, and contraindications to anticoagulation. American Journal of Cardiology, 111(6), 869–73. Singh, S. M., Dukkipati, S. R., d’Avila, A., Doshi, S. K., & Reddy, V. Y. (2010). Percutaneous left atrial appendage closure with an epicardial suture ligation approach: a prospective randomized pre-clinical feasibility study. Heart Rhythm, 7, 370–6. Ohtsuka, T., Ninomiya, M., Nonaka, T., Hisagi, M., Ota, T., & Mizutani, T. (2013). Thoracoscopic stand-alone left atrial appendectomy for thromboembolism prevention in nonvalvular atrial fibrillation. Journal of the American College of Cardiology, 62(2), 103–7. Yeow, W. L., Matsumoto, T., & Kar, S. (2013). Successful closure of residual leak following LARIAT procedure in a patient with high risk of stroke and hemorrhage. Catheterization and Cardiovascular Interventions. Di Biase, L., Burkhardt, J. D., Gibson, D. N., & Natale, A. (2013). 2D and 3D TEE evaluation of an early reopening of the LARIAT epicardial left atrial appendage closure device. Heart Rhythm.
MULTIMEDIA REPORT
Safety and effectiveness of compassionate use of LARIAT® device for epicardial ligation of anatomically complex left atrial appendages Mehul B. Patel & Abdi Rasekh & Mossaab Shuraih & Mihail G. Chelu & Tracy Bartlett & Nilesh Mathuria & Payam Naeini & James Strickland & Ali Massumi & Mehdi Razavi & Jie Cheng
Received: 16 July 2014 / Accepted: 28 November 2014 / Published online: 17 January 2015 # Springer Science+Business Media New York 2015
Abstract Background Percutaneous left atrial appendage (LAA) ligation using an epicardial suture system (LARIAT®, SentreHEART, Palo Alto, CA) has been used in patients with nonvalvular atrial fibrillation (AF) and contraindication to oral anticoagulation. However, complex LAA anatomy may preclude its use. We report the safety and effectiveness of compassionate use of first-generation LARIAT® device for epicardial ligation of large, complex left atrial appendages. Methods Between January 2010 and March 2013, 93 patients with AF, high CHADS2 score, and contraindication(s) for oral anticoagulation therapy were evaluated for LAA ligation. Complex anatomy detected by 3D cardiac computed tomography CT angiography led to preclusion of 25 patients (27%). Of these, nine patients who opted for epicardial LAA ligation on compassionate grounds were studied. Results Mean age was 68.1±8.2 years, four females, all with large LAA width (>40 mm, 45–58 mm) and additional anatomic complexities such as bilobed (two), long C-shaped-like (two), goose neck-like (one), multilobed cauliflower-like (two), cactus-like (one), and chicken wing-like (one) LAA.
LAA ligation with LARIAT® was successfully performed with surgical standby in all patients. Seven patients (78%) were safely treated percutaneously and only two patients required minimally invasive thoracotomy (one due to inability to release the epicardial snare from long C-shaped LAA and other due to preexisting adhesions precluding pericardial entry). There were no major complications. Repeat transesophageal echocardiography at 3 months showed no remnant flow and none had stroke off Coumadin at 19.3±8.2 months of follow-up. Conclusions Despite a high preclusion rate, percutaneous LAA ligation may be safely and effectively performed on compassionate grounds using the first-generation LARIAT® device with surgical standby in patients with large and complex LAA. Keywords LARIAT® . Epicardial suture delivery system . Left atrial appendage ligation . Atrial fibrillation . Stroke
1 Introduction Electronic supplementary material The online version of this article (doi:10.1007/s10840-014-9963-2) contains supplementary material, which is available to authorized users. M. B. Patel : A. Rasekh : M. Shuraih : M. G. Chelu : N. Mathuria : P. Naeini : A. Massumi : M. Razavi : J. Cheng (*) Texas Heart Institute/Baylor CHI St. Luke Health System, 6770 Bertner Street, MC 2-255, Houston, TX 77030, USA e-mail: [email protected] M. B. Patel : A. Massumi : M. Razavi Baylor College of Medicine, Houston, USA T. Bartlett : N. Mathuria : J. Strickland : J. Cheng University of Texas Health Science Center, Houston, TX, USA
Atrial fibrillation (AF) is the most common sustained arrhythmia affecting more than three million people in the USAwith a five times higher risk for an embolic stroke [1, 2]. The deep trabeculated left atrial appendage (LAA) in a low or no flow state is the nidus for more than 90% of thrombus formation in AF [3, 4]. Clots arising from the left appendage may cause catastrophic embolic stroke if dislodged. Although the risk of thromboembolic events is markedly reduced with long-term oral anticoagulation therapy (OAC), it is estimated that only 60% of eligible patients with atrial fibrillation take warfarin, and moreover only 2/3 of these patients have a stable therapeutic international normalized ratio (INR) [5, 6]. The newer
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OAC (NOAC) such as dabigatran, rivaroxaban, and apixaban, though convenient, have no readily available antidote and are especially contraindicated in patients with major bleeding risks. Importantly, up to 17–21 % of the AF patients have varying degrees of intolerance or contraindications to any form of OAC [7]. The advent of surgical techniques and the understanding of LAA as the source of emboli gave momentum to surgical LAA excision for stroke prevention [8–10]. Less invasive catheter-based approaches to occlude the LAA too has evolved over time. There has been increasing evidence of noninferiority, equal efficacy, and even superiority of occlusion devices when compared to OAC [11–21]. However, LAA occlusion is reported to have periprocedural complications such as pericardial effusion, incomplete LAA closure, device dislodgement, and blood clot formation on the exposed device requiring 6 weeks of full oral anticoagulation post procedure, thus exposing the patients to continued risk of bleeding especially in those with contraindications [18]. More recently, percutaneous epicardial suture delivery system (LARIAT®, SentreHEART, Palo Alto, CA) for LAA ligation has been introduced [22–28]. However, the use of this technique is limited by the complexity of LAA and its neighboring anatomy. Given the maximum horizontal diameter of the firstgeneration LARIAT® device of 40 mm, current preclusion criteria for the use of this device include large LAA width more than 40 mm along with complex anatomic features such as bilobed LAA, multilobed LAA, or LAA apex directed behind the pulmonary trunk. We sought to assess the safety and feasibility of a modified approach to LAA ligation using the first-generation LARIAT® device with surgical standby on compassionate grounds in patients with large, challenging LAA anatomies, currently deemed unsuitable for the procedure.
2 Methods The study was approved by the institutional review board and all standard requirements regarding research study on human subjects were met. The LARIAT device is a suture delivery system that received 510(k) marketing clearance from the FDA in 2006. A total of 93 AF patients with high CHADS2, CHA2DS2-VASc, and HAS-BLED scores with contraindication(s) or intolerance for OAC was evaluated for LAA ligation with the LARIAT® device. LAA anatomy was evaluated using cardiac computed tomography (CT) angiography with 3D reconstruction. Among them, patients who had indication for LAA ligation but deemed unsuitable due to anatomic considerations (see above) were studied. All these patients requested for an alternative and effective therapy to prevent stroke, avoiding OAC/NOAC at all times in view of the major/life-threatening bleed that they braved. All possible
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alternatives including totally thoracoscopic LAA clip exclusion were offered to every patient and they opted for LARIAT® device. These patients consented for the LARIAT® device with a clear understanding of its compassionate, high-risk, and off-label use. The exclusion criteria for the study included prior cardiac surgery, myocardial infarction within the previous 3 months, embolic events within 30 days, New York Heart Association function class IV, and patient’s inability or refusal to consent. 2.1 Description of patients in the study Complex anatomic features led to initial preclusion of 25(27%) of the 93 patients for LAA ligation with LARIAT® device; of these, 9 patients who opted for and consented for the procedure underwent LAA ligation with close surgical backup. The remaining 16 patients who did not consent continued medical management. All nine patients in our study had large LAA width (>40 mm, range 45 to 58 mm). Additional anatomic variations included bilobed LAA in two, long C-shaped-like LAA in two (supplemental videos 1 and 2), goose neck-like LAA in one, large multilobed cauliflower-like LAA in two, cactus-like LAA in one, and chicken wing-like LAA in one (Fig. 1). 2.2 Pre-procedure evaluation All patients had paroxysmal, permanent, or persistent AF. Cardiac CT angiography with 3D reconstruction was performed to define the morphology, location, and neighboring anatomy of LAA (Fig. 1). Informed consent with a clear understanding of the “off-the-label” compassionate use and possible open thoracic surgery was explained to all patients. Patients presented in a nonsedated post absorptive state to the hybrid operating room. General anesthesia with ventilator support and intra-operative transesophageal echocardiography (TEE) guidance was used in all patients. 2.3 Hardware components The LARIAT® device consist of five components: (1) a 20mm compliant, low profile, highly echogenic balloon catheter (EndoCATH®); (2) 0.025- and 0.035-in. opposite-pole magnet-tipped guide wires (FindrWIRZ); (3) a 12-F suture delivery device that delivers a 40-mm diameter, pre-tied suture loop contained on a closure snare composed of size 0 Teflon-coated braided polyester suture; (4) suture-release actuator; and (5) specially designed suture cutter. 2.4 Procedure details Pericardial access was obtained under fluoroscopic guidance using a pericardial needle with angled bevel (17-gauge Tuohy
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Fig. 1 Cardiac CT angiogram with 3D reconstruction images showing the complex and varied LAA morphologies of patients 1 (a), 2 (b), 3 (c), 4 (d), 5 (e), 6 (f), 7 (g), 8 (h), and 9 (i)
epidural needle from Hakko Corporation, Naganoken, Japan) as previously described [22]. Epicardial access was directed anteriorly with its trajectory directed toward the tip of the largest or the primary lobe of LAA as seen on cardiac CT images. A 0.035-in. guide wire with a floppy tip was advanced into the pericardial space, and the access was sequentially dilated to 14 F with the track directed toward the LAA. The SentreHEART pericardial sheath with a soft tip was then advanced over the guide wire into the pericardial space toward the tip of the primary lobe of LAA. Transseptal access was obtained using a standard TEE-guided technique for placement of the 8.5-F SL1 guide catheter into the left atrium. Heparin bolus (80 units/kg) and then continuous drip was administered to maintain activated clotting times (ACT) at 300–350 s. Left atrial appendogram was performed in orthogonal views at baseline and with balloon inflation at the LAA ostium to clearly delineate the ostium and the morphology of LAA with all its lobes. A 0.025-in. endocardial FindrWIRE, back-loaded over an EndoCATH® balloon catheter, was positioned at the tip of the left atrial appendage or the primary lobe and confirmed on anteroposterior and lateral views. Once in position, the
FindrWIRE was secured by closure of the rotating hemostasis valve. Another 0.035-in. FindrWIRE back-loaded with the LARIAT® catheter was advanced in the pericardial space. With gentle sweeping motion while advancing the epicardial wire toward the tip of the endocardial wire, the magnets on the tips of each FindrWIRE attract to each other and unite. This endo-epi magnetized union forms a continuous arc stabilizing the thin-walled LAA before the LARIAT® snare can be advanced over it to grasp the LAA ostium. Under the guidance of TEE and fluoroscopy, the LARIAT® snare was advanced over the LAA. At this point, the technique was carefully modified to include the entire LAA with all its lobes/ diverticulii making sure there was no remnant/dead space. 2.5 Modifications of the standard technique for complex LAA anatomies After first capturing of the longest or the largest lobe (primary lobe) where the endocardial FindrWIRE was first parked, the LARIAT® snare was careful maneuvered to capture the secondary lobes while making sure that it does not slip out from the primary lobe. Using slow and careful clockwise/
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counterclockwise motion of the LARIAT® catheter along with opening/closing position of snare, all secondary lobes/ complete LAA were captured (supplemental videos 4 and 5). Gentle forward tension on the endocardial FindrWIRE to longitudinally stretch the LAA along with gentle suction through the EndoCATH® catheter was applied with the LARIAT® partially closed near the LAA ostium as an attempt to reduce the LAA volume, width, and circumference. Capture of the entire LAA with LARIAT device was confirmed with color Doppler TEE showing capture and no flow across the LAA ostium. Reopening and repositioning of the LARIAT® device was repeated if necessary to ensure complete capture of the LAA before its final deployment. The balloon EndoCATH® was then fully deflated and pulled back to the LA along with the endocardial FindrWIRE. The suture was tightened around the ostium of LAA by retracting the suture-release actuator of the tensioning device. Final cinching of the suture was performed at an interval of 5 min to ensure complete closure. Left atrial angiogram was then performed to demonstrate flush LAA ligation confirmed by TEE color Doppler showing no flow. After deploying the suture, the LARIAT® was carefully disengaged from the LAA without using any extra force. The epicardial and transseptal catheters were then removed under fluoroscopic guidance after cutting the suture using the suture cutter. A schematic step-by-step flowchart on the use of LARIAT® device for large LAAs is shown in Fig. 2. 2.6 Transseptal puncture before pericardial access In 6 of the 9 cases, transseptal puncture followed by 5000 units of Heparin and left atrial appendography was performed first before obtaining pericardial access to allow optimal positioning and orientation of the pericardial puncture needle with LA appendogram as the guide (supplemental video 3). This was an important modification to the standard procedure. In the remaining three of nine patients, the initial pericardial access was guided by reviewing the 3D CT angiography before the transseptal access. 2.7 Minimally invasive thoracic surgery A standby minimally invasive lateral thoracotomy surgery was planned in advance in all patients in case of difficulties with epicardial deployment of the LARIAT® device and/or as an emergency rescue for potential percutaneous periprocedural complications. 2.8 Post procedure care Intrapericardial soft drain was left in place and all patients were transferred to CCU for close monitoring. A chest X-ray and transthoracic echocardiogram on post procedure day 1
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were performed in all patients. The indwelling drain was removed in the absence of any significant or expanding pericardial effusion on the next day. All patients received nonsteroidal anti-inflammatory drugs and/or colchicine to reduce pericardial frictional pain.
3 Results The clinical characteristic of patients is provided in Table 1. The average age was 68.1±8.2 years, four females, CHADS2 score of 2.5±1.1, CHA2DS2-VASc score of 3.4±0.8, and HAS-BLED score of 3.1±0.8. The major contraindications for OAC included life-threatening gastrointestinal (GI) bleeding (six out of nine patients), retinal bleeding (one patient), and ataxia with recurrent falls (one patient). One patient had LAA thrombus despite therapeutic INR and was deemed to have failure of OAC therapy. After initiating dual anticoagulation therapy using OAC and NOAC, the clot disappeared after 3 months on TEE. However, understanding the high risk for major bleeds, the patient refused to continue medical therapy and opted for LAA ligation. The mean LAA width was 48±49 mm (range 45–58 mm) in the axis perpendicular to the longitudinal axis of the LAA with additional anatomic variations. The LARIAT® delivery device was able to completely capture the LAA at the ostium and deliver the suture at the LAA ostium in all patients. Seven patients (78%) were safely treated percutaneously and only two patients required minimally invasive thoracotomy (one due to inability to release the epicardial snare from C-shaped LAA and other due to preexisting adhesions precluding pericardial entry) (Table 2). There were no complications with transseptal and epicardial accesses. Endo-epi connection of the FindrWIRZ was successfully achieved in all patients. However, in one of the three patients in whom epicardial access was obtained prior to transseptal access, a second pericardial access was required to optimally align the epicardial and endocardial FindrWIREs. A single LARIAT® device was able to capture the entire LAA in a piecemeal fashion with careful maneuvers as described for capturing multiple lobes/diverticulii. The mean length of stay with the compassionate use study population was 6±2.5 days in contrast to 5.29±5.86 days (p= 0.72) in patients with standard indications performed during the same time frame. This included the length of stay to optimize medications and for management of other comorbidities in all patients. There were no major periprocedural complications. Two patients developed moderate pericardial effusion that required extended pericardial drainage for 48 h without the need for further intervention or transfusion. The total aspirate was less than 500 ml in both cases.
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Fig. 2 Schematic step-by-step flow-chart on the pragmatic use of the LARIAT® device for complex LA anatomies
Patient 5 with preexisting pericardial adhesions had no history of prior cardiac surgery. However, he had two previous percutaneous pulmonary vein isolation procedures, and post procedure pericarditis was speculated to be the etiology for pericardial adhesions. After obtaining pericardial access, there was difficulty in passing the guide wire through the adhesions. A mini lateral thoracotomy with 5-cm incision was thus
performed to obtain free pericardial access and allow completion of the procedure using the standard percutaneous technique for LAA ligation. Patient 2 had difficulty in removing the LARIAT from the LAA after deploying the suture, compelling an urgent minimally invasive lateral thoracotomy to release the LARIAT from the LAA. This led to the thought process of applying
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Table 1
Pt1 Pt2 Pt3 Pt4 Pt5 Pt6 Pt7 Pt8 Pt9
Clinical characteristics of the study population Gender
Age
Contraindication for anticoagulation
CHADS2 score
CHA2DS2-VASc score
HAS-BLED score
M M M F F M F F M
67 79 73 60 82 61 65 67 59
GI bleed GI bleed GI bleed Retinal hemorrhage Ataxia, falls GI bleed GI bleed GI bleed LA thrombus with therapeutic INR
2 3 1 2 2 5 2 2 3
3 4 4 2 3 3 4 5 3
2 4 4 3 4 2 3 3 3
suction through the EndoCATH® catheter with the LARIAT partially closed to reduce the LAA volume and width before disengaging. The LAA was successfully excluded using the LARIAT device in all patients without the use of any additional surgical devices.
the same day of the procedure and never reinitiated in any patient till last follow-up. There was no stroke or transient ischemic attack on last follow-up with one patient lost to follow-up 2 months after the procedure.
3.1 Follow-up 4 Discussion The mean follow-up period was 19.3±8.2 months. All patients were scheduled to follow-up at 3 weeks, 3 months, and then every 6 months; TEE was done at 3 months per protocol, except in one patient where it was done at 2 months after the procedure. There was no suture leak, persistent flow, and residual or new pericardial effusion in any patient. All patients had pericardial pain for a few days after the procedure, which was well controlled by NSAIDS and or colchicine. There was no clinical or echocardiographic evidence of delayed pericardial inflammation or effusion noted in any patient during follow-up. All forms of anticoagulation was discontinued on Table 2
Procedural characteristics of the study population
LAA anatomy
Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 Pt 9
Our main finding is that LAA ligation may be safely and effectively performed even in patients that are currently excluded due to anatomical limitations by pragmatic modifications to the use of first-generation LARIAT® device. Our data indicate that the preclusion rate using 3D CT angiography for the use of LARIAT® device is rather high (nearly 27% in our cohort). Our observation also suggests that percutaneous LAA ligation in these patients may be best attempted with appropriate surgical backup. To our knowledge, this is the first study to report the incidence of patient preclusion due to
Problems encountered during
Large width >40 mm in all TSPa
Pericardial accessa Capturea and snare Cinchinga Releasea
Bilobed Cactus like Cauliflower like Long C shaped Long C shaped Chicken wing like Cauliflower like Long goose neck like Bilobed
None, 2 accessesb None None None Yes (adhesions) None None None None
None None None None None None None None None
None None None None None None None None None
None None None None None None None None None
None Yes None None None None None None None
Success Complications
OTS
Yes Yes Yes Yes Yes Yes Yes Yes Yes
n/a Yes n/a n/a Yes n/a n/a n/a n/a
None Could not release snare None None None None None None None
TSP transseptal puncture, OTS open thoracic surgery a b
Steps in LAA ligation including transseptal puncture, pericardial access, complete capture and snaring of the LAA, cinching, and release of LARIAT®
Double pericardial access performed as initial access was either too laterally or too medially placed. Approximately 10–15 ml of contrast was injected into the pericardial space before the second access was performed to facilitate the visualization of the pericardial space
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unfavorable LAA anatomy using the first-generation device. This is also the first to report initial experience on safety and efficacy of compassionate use of LARIAT® device for epicardial LAA ligation in a largest ever reported cohort of patients with complex LAA anatomies. Non-pharmacological approaches to reduce the risk of stroke in AF have evolved significantly over time, from surgical interventions to percutaneous procedures to occlude/ exclude the LAA [8–17, 29]. Overall surgical closure has longer procedure times with excess tissue manipulation and variable success rates. The first percutaneous left atrial appendage occlusion using the PLAATO occluder (Appriva Medical, Inc. from Sunnyvale, CA) and subsequently the WATCHMAN device (Aritech Inc, Plymouth, Minnesota) demonstrated safety, feasibility, and noninferiority to OAC. Follow-up data from the PROTECT AF study using LAA occlusion devices not only confirmed that “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin but also revealed a lower rate (3.2%) of both ischemic and hemorrhagic stroke in the device arm than in the control arm (4.5%) [14]. Additionally, the 5year results of the use of the percutaneous LAA occlusion device revealed an annual stroke/transient ischemic attack rate of 3.8%, which is less than the annual stroke rate of 6.6% predicted by the CHADS2 scoring system [15–21]. Recently, the results of LAA ligation using the LARIAT® device have generated much interest [22–28, 30]. The LARIAT® device causes flush ligation of the LAA ostium, leaving minimal chances for a remnant dead space or persistent flow. To date, direct comparison between LAA occlusion and ligation is lacking although absence of a foreign or thrombogenic intracardiac material with the LARIAT® device may be highly favorable to those with absolute contraindications to OAC. However, the use of LARIAT® device may be limited by the complexity of the LAA and its neighboring anatomy, and patients with history of cardiac surgery and pericarditis may be unsuitable due to the presence of pericardial adhesions preventing percutaneous epicardial access [26, 27]. Candidate selection for LAA ligation with LARIAT® device usually involves screening with 3D contrast cardiac CT angiography. The current preclusion criteria include [1] maximum LAA width more than 40 mm, [2] LAA apex directed behind the pulmonary trunk, [3] large bilobed LAA or multilobed LAA, or [4] posteriorly rotated heart. With the accumulation of experience over time, we have learned that pragmatic modifications of the standard procedure could improve the success rate, even in patients with such challenging anatomies. These include [1] obtaining transseptal access before epicardial access. This modification is safe and advantageous as such since LA appendogram after transseptal access serves as an important real-time road map using the same imaging modality (fluoroscopy) to direct the epicardial needle and align the trajectory of epicardial dilator/catheter, and [2] gentle
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twisting of the epicardial LARIAT® apparatus may facilitate capturing of multilobed LAA which is best started at the lobe that is inferiorly located and [3] suction through the EndoCATH® with the LARIAT partially closed near the LAA ostium with gentle forward tension on the endocardial FindrWIRE may help to reduce the volume and width of a large LAA and allow for successful and complete LAA capture. In our study, only two patients required complementary surgical intervention to complete the LAA ligation. Thoracoscopic stand-alone appendectomy may have been an option in this population [31]. The study population was primarily eligible only for surgical ligation due to unfavorable anatomy; however, since patients opted for a trial of percutaneous closure, in effect 78% (7 of 9 patients) of patients were successfully closed percutaneously without the need for surgery. We believe that every patient should be given a choice of options with its individual risk to benefit ratios depending on institutional expertise. Given the results of the current study, the risk to benefit ratio seems to tilt more toward benefit for a planned approach of percutaneous ligation with a clear understanding of the compassionate nature and the possibility of switching to surgical ligation. However, such attempts to percutaneously ligate large, complex LAA should only be performed with close surgical backup in the hybrid OR on patients who opt for and clearly understand the compassionate nature of the procedure. All patients should consent for open LAA ligation. A wellplanned collaboration between the operating cardiologists and cardiac surgeons after reviewing the detailed anatomy by 3D CT scan in all patients is important. This on-site surgical standby approach may also be useful in patients with unexpected pericardial adhesions. The results of this study do not alter the standard indications of LARIAT® ligation due to the retrospective nonrandomized nature of our study with small number of patients. Such compassionate procedure should be only performed in experienced centers at this time, and future studies with significantly larger sample sizes are needed. Eligible patients should be given all possible options and prepared for open ligation with the knowledge of a likelihood of surgery. Modification of the LARIAT® device with enlargement of the LARIAT® snare diameter to 55 mm as a secondgeneration device may help to percutaneously ligate complex LAA with ease. Novel noninvasive markers to diagnose preprocedure pericardial adhesions could help immensely in planning ahead and identifying potential need for surgery. 4.1 Limitations The major limitation of our study relates to its retrospective nature with small number of cases. Although only two patients required surgical intervention, there were only nine patients in
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the series. Another major limitation is that only a limited number of patients who consented for the procedure were studied, and thus outcome data from a prospective multicenter study may be helpful. Recent reports on persistent leaks and reopening of the device also warrant long-term follow-up of LAA suture-based ligation [32, 33].
5 Conclusions Current strict exclusion criteria for percutaneous LAA ligation result in a high preclusion rate for the procedure. LAA ligation however may be performed safely and effectively with careful modifications to the standard technique in patients with anatomically complex and large LAA who are prepared for open ligation in centers with experience. However, such cases should be well planned with close surgical backup. Data from further multicentric studies are needed before recommending LARIAT® ligation in patients with complex anatomy. Acknowledgments The authors would like to thank Dr. Sandeep Patel, MD, and Dr. Benjamin Y. Cheong, MD, for their contribution in cardiac 3D CT reconstruction images. Funding There was no industry funding obtained for this study. Conflict of interest There is no conflict of interest either real or perceived of any author in the publication of this manuscript. Disclosure None
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