ORIGINAL ARTICLE
Epicardial Surgical Ligation of the Left Atrial Appendage Is Safe, Reproducible, and Effective by Transesophageal Echocardiographic Follow-up Alex Zapolanski, MD,* Christopher K. Johnson, BS,* Omid Dardashti, MD,* Ryan M. O’Keefe,* Nancy Rioux, RN,* Giovanni Ferrari, PhD,*Þ Richard E. Shaw, PhD,* Mariano E. Brizzio, MD,* and Juan B. Grau, MD*Þ
Objective: The left atrial appendage (LAA) is the source of 90% of thrombi in patients with atrial fibrillation. Our double LAA ligation (LLAA) technique was shown to be 96% successful in a small study. However, the outcomes of these patients have yet to be compared with a set of nonligated patients. Methods: From 2005 to 2012, a total of 808 patients received LAA using our double ligation technique using both a polydioxanone (PDS) II endosnare and a running 4-0 Prolene pledgeted suture. The 30-day outcomes of these patients were compared with that of nonligated patients. Fifty-six of the ligated patients had a postoperative transesophageal echocardiography (TEE). An echocardiographer reviewed the follow-up TEEs for LAA remnant and/or residual flow into the LAA using color Doppler imaging. The patients with LAA flow and/or remnant depth of 1 cm or greater were deemed to have an unsuccessful exclusion. Results: The ligated group had a trend of less postoperative atrial fibrillation (19.4% vs 22.9%, P = 0.07) and an overall significantly lower in-hospital mortality (0.7% vs 3.0%, P G 0.001) and lower 30-day mortality (0.7% vs 3.4%, P G 0.0001). The LAA was successfully excluded in 53 (94.7%) of the 56 patients with TEE. Conclusions: Double LAA ligation correlates with lower rates of in-hospital and 30-day mortality. This advantage comes without an increase in perioperative complications. This technique can easily be performed off or on pump, is very reproducible, and comes at a very low
cost compared with LAA occlusion devices. Stroke has a multifactorial etiology; successful LLAA removes one potential source of thrombi perioperatively and in the long-term. Key Words: Left atrial appendage, Epicardial surgical technique, Transesophageal echocardiography, Atrial fibrillation. (Innovations 2013;8:371Y375)
O
Address correspondence and reprint requests to Juan B. Grau, MD, The Valley Heart and Vascular Institute, 223 North Van Dien Ave, Ridgewood, NJ USA. E-mail: [email protected]. Copyright * 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery ISSN: 1556-9845/13/0805-0371
ne in every four people older than 40 years are at risk to develop atrial fibrillation (AF), making it the most common arrhythmia in the United States.1 The most serious complication arising from AF is a fivefold increased risk for stroke.2 This risk is further intensified when combined with other factors such as age, valvular disease, and hypertension.2 Strokes are the third leading cause of death in America, with 10% of transient ischemic attacks (TIAs) and 50% of cerebrovascular accidents (CVAs) occurring as a result of AF.2,3 Although anticoagulation medications substantially reduce the risk for stroke, there are significant issues to consider regarding their use. The greatest concerns with anticoagulant therapy are the increased risk for bleeding and potential drug interactions.4 In 2003 and 2004, anticoagulants were linked to more deaths than any other therapeutic drug.3 With its narrow therapeutic range and need for continuous laboratory monitoring, it is estimated that only one fourth of AF patients are receiving optimal anticoagulation therapy.5 In recent years, new anticoagulants have been introduced in the armamentarium to prevent strokes in AF patients. The safety, efficacy, and therapeutic margin on the real-world use of these agents (dabigatran, rivaroxaban, and apixaban) have to be better elucidated in the coming years. With 90% of thrombi in patients with nonrheumatic AF originating in the left atrial appendage (LAA), the LAA has been referred to as ‘‘the most lethal human attachment.’’6,7 In light of this, some surgeons have proposed closing the LAA as a method to eliminate a major risk for stroke.3 There are numerous techniques to achieve LAA closure, but they generally fall into two categories: excision (in which the LAA is amputated) or exclusion (in which the LAA orifice is obliterated). Previous studies have shown complete amputation of the LAA to have a better success rate than suture exclusion (73% vs 23%).8
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Video clip is available online.
Accepted for publication September 18, 2013. From *The Valley Columbia Heart Center, Columbia University College of Physicians and Surgeons, Ridgewood, NJ USA; and †The University of Pennsylvania School of Medicine, Glenolden, PA USA. A video clip is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.innovjournal.com). Please use Firefox when accessing this file. Disclosure: The authors declare no conflicts of interest.
Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Zapolanski et al
However, it has been proposed that the removal of the LAA could affect the body’s ability to regulate volume because the LAA produces 30% of the body’s atrial natriuretic peptide.9 This potential hazard is avoided by ligating the LAA.10 The literature indicates that the average success rate of successful LAA elimination is 55% to 66%.11 We have developed a very safe technique for epicardial ligation of the LAA during cardiac surgery using only a polydioxanone (PDS) II endoloop (Ethicon, Somerville, NJ USA) and sutures (Ethicon, Somerville, NJ USA). However, the efficacy of this ‘‘double ligation’’ technique had only been established in a small number of patients using transthoracic echocardiography as the validating tool to evaluate efficacy.12 In this study, we evaluate the effectiveness of our safe double ligation technique, representing the third largest study of LAA ligation and the first large-scale study since 2008.8 To test the efficacy of this method, we also included a subgroup analysis of 56 ligated patients who had a postoperative transesophageal echocardiographic (TEE) follow-up.
METHODS From 2005 to 2011, a total of 3195 patients underwent cardiac surgery at our institution (Fig. 1). Of these, 808 patients received our previously published technique of double ligation. This procedure uses both a PDS II endoloop (Ethicon, Somerville, NJ USA) and a running 4-0 polypropylene pledgeted suture (Ethicon, Somerville, NJ USA) to exclude the LAA.12 A total of 1196 patients underwent either LAA excision or ligation with another technique and were excluded from this analysis.
TABLE 1. Patient Demographics Nonligated n Female Age G64 65Y74 975 Body mass index G25 25Y29 930 Previous myocardial infarction Peripheral vascular disease Cardiovascular disease Valve disease Previous stroke Ejection fraction G35% Left main disease No. diseased vessels 1 vessel 2 vessels 3 vessels Emergent surgery Chronic heart failure Previous atrial fibrillation Diabetes Hypertension Smoker Dyslipidemia Renal failure Surgery type Isolated CABG Isolated valve CABG + valve CABG + valve + other Other
Ligated
350
969 36.1%
212
808 26.2%
345 253 371
35.6% 26.1% 38.3%
267 261 280
33.0% 32.3% 34.7%
248 376 345 250 101 105 121 48 91 157
25.6% 38.8% 35.6% 25.8% 10.4% 10.8% 12.5% 5.0% 9.4% 16.2%
186 337 285 350 89 102 90 41 116 289
23.0% 41.7% 35.3% 43.3% 11.0% 12.65% 11.06% 5.1% 14.4% 35.8%
441 118 410 61 274 104 274 781 406 548 58
45.5% 12.2% 42.3% 6.3% 28.3% 10.7% 28.3% 80.6% 41.9% 56.6% 6.0%
135 124 549 62 235 161 282 678 414 446 60
16.7% 15.3% 67.9% 7.7% 29.1% 19.9% 34.9% 83.9% 51.2% 55.2% 7.4%
364 216 163 39 187
37.6% 22.3% 168% 4.0% 19.3%
510 44 109 40 105
63.1% 5.4% 13.5% 5.04% 13.0%
P 0.00 0.03
0.39
0.00 0.69 0.24 0.51 0.91 0.00 0.00 0.00
0.25 0.47 0.00 0.00 0.07 0.00 0.57 0.23 0.27 0.00
CABG indicates coronary artery bypass graft.
FIGURE 1. Schematic of patient selection. LAA indicates left atrial appendage; TEE, transesophageal echocardiogram.
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A comparison of the double ligation patients and the nonligated patients (n = 969) can be found in Table 1. Reoperative patients were excluded from this study (n = 222). The double ligation is achieved in three steps (Fig. 2).12 The first is to isolate the LAA and place a PDS II endoloop around the base, making sure to position the knot on the lateral aspect of the appendage. This way, the surgeon is able to engage and retain the endoloop on the medial aspect of the LAA. Next, the endoloop is tightened while making sure that the suture is tied without sliding it out of position. The suture is kept as low as possible, maximizing the amount of LAA excluded. It should be emphasized that caution in tightening the suture is imperative because excessive force could potentially injure the tissue. The endoloop has two purposes: first, to define the level of ligation, and second, to reduce the pressure within the LAA during the second stage of the technique. Next, a 4-0 polypropylene purse-string suture supported with multiple Teflon pledgets is placed slightly distal to the endoloop. This suture achieves complete exclusion of the appendage.
Copyright * 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery
Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Efficacy and Safety of LAA Double Ligation
tissue but also, when these come together after tying, provide the surgeon initial tactile confirmation that the LAA has been completely ligated. Lastly, the LAA is opened to ensure complete ligation from the left atrium. We expect that by evacuating the appendage, the remaining atrial tissue will scar down. After evacuation, two large hemoclips are placed at the tip for safety. Further corroboration of complete ligation is achieved by immediate postoperative TEE assessment. A short video of the LLAA, Supplemental Digital Content 1, is available online at http://links.lww.com/INNOV/A35. A follow-up TEE was done in 56 of the double ligation patients. Transesophageal echocardiography was performed by independent cardiologists for the following indications: precardioversion for arrhythmia (n = 32), to check valvular and cardiac function (n = 11), to explore for emboli/thrombi (n = 8), or to detect vegetation (n = 1). Other reasons include documenting an intracardiac shunt (n = 1) and ruling out tamponade (n = 1) and endocarditis (n = 2) (Table 2). The studies were performed on the Philips ie33 ultrasound machine (Koninklijke Philips Electronics N.V., Andover, MA USA). Evaluation of TEEs was performed by a single independent qualified echocardiographer. Studies used evaluated the LAA in multiple views, with color Doppler across the LAA to assess any residual flow into the appendage. Transesophageal echocardiography has long been used to investigate the blood flow of and detect thrombi in the LAA.13 The LAA was considered successfully ligated if its obliteration was observed on two-dimensional imaging, with no remnant stump greater than 1 cm remaining, and as long as absence of color flow by Doppler was also documented.
RESULTS Overall, the ligated group had a higher rate of comorbidities. Despite this, the ligated group had a trend of less postoperative AF (19.4% vs 22.9%, P = 0.07) and an overall significantly lower in-hospital mortality (0.7% vs 3.0%, P G 0.001) and lower 30-day mortality (0.7% vs 3.4%, P G 0.0001) (Table 3). Of the 808 patients in the ligated group, 496 (61.4%) had off-pump surgery performed. There TABLE 2. Transesophageal Echocardiogram Follow-up Data FIGURE 2. The double ligation technique. A, Step 1: Isolate the LAA and place a PDS II endoloop around the base, making sure to position the knot on the lateral aspect of the appendage. The snare should be kept as low as possible to maximize the amount of LAA excluded. Next, tighten the endoloop with caution because excessive force could potentially injure the tissue. B, Step 2: Place a 4-0 polypropylene purse-string suture supported with multiple Teflon pledgets slightly distal to the endoloop. This completes the exclusion of the LAA. This can be achieved without bleeding because the endoloop lessens the pressure in the LAA. C, Step 3: Lastly, ensure total exclusion by opening the LAA. The remaining atrial tissue is expected to scar down. Two large hemoclips are placed at the tip for safety. Complete LLAA is confirmed by postoperative TEE. LAA indicates left atrial appendage; LLAA, double left atrial appendage ligation; TEE, transesophageal echocardiogram.
Placement of the suture at this point can be accomplished without bleeding because the endoloop reduces the pressure in the LAA even when it is not completely occlusive. The four pledgets not only reinforce the closure and protect the atrial
Results n Patient age Male Days between surgery and TEE CVA or TIA Reason for TEE Detect embolism/thrombus/clot Detect vegetation Evaluate valve/ventricular function Precardioversion or ablation Other LLAA success LAA flow Remnants Remnant depth
56 70.52 T 11.83 43 (76.79%) 293.64 T 435.47 2 (3.57%) 8 (14.29%) 1 (1.79%) 11 (19.64%) 32 (57.14%) 4 (7.14%) 53 (94.64%) 3 (5.36%) 4 (7.14%) 0.53 T 0.15
CVA indicates cerebrovascular accident; LAA, left atrial appendage; LLAA, double left atrial appendage ligation; TEE, transesophageal echocardiogram; TIA, transient ischemic attack.
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TABLE 3. Overall Postsurgical Outcomes Nonligated Reoperation for bleeding Myocardial infarction Permanent stroke Transient stroke Atrial fibrillation In-hospital mortality 30-day mortality
38 3 14 2 222 20 24
3.9% 0.3% 1.4% 0.21% 22.9% 2.1% 2.5%
Ligated 23 5 6 1 157 6 6
2.8% 0.6% 0.7% 0.12% 19.4% 0.7% 0.7%
P 0.22 0.33 0.16 0.65 0.07 0.02 0.01
was a significantly higher incidence of reoperation for bleeding in the patients receiving the ligation on pump (5.1% vs 1.4%, P = 0.00). None of the re-explorations for bleeding involved the LAA as the source. Otherwise, there were no differences in surgical outcome based on performing the double ligation technique on or off pump. There were 56 patients who underwent LAA ligation and had a TEE postoperatively (Table 2). The mean T SD age of this subgroup was 70 T 11 years. A total of 76.8% of these patients were men. Fifty-three (94.7%) of 56 closures were successful (Fig. 3), with three patients with persistent flow in the LAA. Although four patients showed remnant LAA, none of them had a remnant that exceeded a depth of 0.6 cm. Two (3.6%) of the 56 TEE patients had a CVA; however, neither of them had a remnant or Doppler flow into the LAA by TEE criteria.
DISCUSSION The efficacy of LAA elimination has long been debated. This study represents the largest study since 2008 and includes contemporary patients. The safety of the technique is demonstrated by a low incidence of complications and significantly reduced rates of in-hospital and 30-day mortality, despite the fact that the ligated patients were sicker preoperatively. The subanalysis of the patients with follow-up TEE results revealed that double LAA ligation (LLAA) was successful in 94.7% of attempts. This figure is comparable with our previously established 96% (27/28) success rate of double ligation seen
when using intraoperative TEE and postoperative transthoracic echocardiography using Definity (Bristol-Myers Squibb Medical Imaging, North Billerica, MA USA) contrast.12 The success of the double ligation technique is likely due to the fact that the endoloop precisely defines the base of the LAA, allowing for a very aggressive exclusion of most of the LAA tissue. This is reinforced by running the 4-0 Prolene suture above the loop. Final success is confirmed by opening the appendage, even during off-pump cases. Complete ligation of the LAA using this combined technique has a much greater success rate than other surgical techniques. The reported success of LAA excision and suture exclusion is 73% and 23%, respectively.8 Prior studies have shown surgeon experience to be a significant factor in procedure success. Successful occlusion rates double after a surgeon has performed four cases.10 Our previous analysis demonstrated that the double ligation technique does not add significant time to the operation, taking only an additional 5 T 3 minutes to perform.12 In addition, the results displayed in Table 4 indicate that the double ligation technique can be performed safely off pump, with comparable results with those patients receiving the procedure on pump. The success rate of LAA closure found in our TEE subgroup suggests that most of the larger cohort had successful LAA exclusion. The overall incidence of CVA or TIA in the 1777 patients was found to be 1.3% (n = 23), approximately half of the national average.14 The frequency of CVA in the ligated group was half of that seen in the nonligated group, although this did not reach statistical significance in this series (0.7% vs 1.4%, P = 0.16). The ligated LAA could have contributed to this lower rate of permanent and transient stroke; however, it is important to stress that the causes of stroke are multifactorial and are well beyond the scope of this study. The frequency of stroke in the follow-up TEE subgroup is three times less than that reported in similar studies (3.6% vs 13%).8 Unsuccessful LAA occlusion could potentially have disastrous consequences. Thrombi have been shown to develop in 41% of partially closed LAA.8 This is believed to be the result of stagnant blood trapped in a partially closed appendage. However, the link between partial LAA ligation and increased risk for stroke has not been confirmed. Nevertheless, this theoretical risk combined with the prevalence of stroke in patients with ligated LAA suggests that patients who qualify should continue anticoagulation medication to provide the maximum protection from a CVA or TIA. There are several devices designed to percutaneously occlude the LAA. The most commonly used is the WATCHMAN TABLE 4. Outcomes in Ligated Patients by Pump Status
FIGURE 3. Representative TEE of a successful LLAA. Transesophageal view at 65 degrees confirming successful ligation of the left atrial appendage, with absence of color flow into prior appendage site. LLAA indicates double left atrial appendage ligation; TEE, transesophageal echocardiogram.
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No. patients Reoperation for bleeding Myocardial infarction Permanent stroke Transient stroke Atrial fibrillation In-hospital mortality 30-day mortality
Off pump
On pump
496
312
7 2 2 1 88 4 4
1.4% 0.4% 0.4% 0.2% 17.7% 0.8% 0.8%
16 3 4 0 69 2 2
5.1% 1.0% 1.3% 0.0% 22.1% 0.6% 0.7%
P 0.00 0.32 0.16 0.43 0.13 0.79 0.79
Copyright * 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery
Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Efficacy and Safety of LAA Double Ligation
LAA occlusion device, which has been shown to have a successful implantation rate of 82%.4 In addition, the LARIAT device uses a catheter-based approach to successfully ligate the LAA in 96% of patients.15 Several devices are still in the early testing phase but have promising results.4,11 A 3-month follow-up of AtriClip, recently approved by the Food and Drug Administration, showed the device to successfully occlude the LAA in 67 (95.7%) of 70 patients.16 These three devices all have similar success rates to double ligation; however, these devices cost between $2000 (AtriClip) and $6600 (WATCHMAN) for a single device versus the cost of double ligation of $117.
cost, and low complication rate seen in this series suggest that the double ligation technique is a reliable, effective, and safe method of LLA ligation. Although stroke has a multifactorial etiology, successful LLAA removes one potential source of thrombi perioperatively and in the long-term.
Limitations This study has a few potential limitations. There may be a selection bias stemming from the fact that this was a retrospective study looking at patients with a TEE after LAA ligation. Because these patients required a TEE, these patients may be sicker than the rest of the population, as demonstrated by the higher incidence of stroke in the TEE group versus the entire ligated group (3.6% vs 0.82%). Multiple surgeons performed the surgeries, and this nonrandomized study does not account for the variability between surgeon skill, experience, and technique. This study aimed to show the safety and the success rate of the double ligation technique; therefore, the causes of CVA were not investigated. This study was conducted at a medium-sized, nonacademic hospital that serves a large, affluent population with the resources and the knowledge to maintain healthier lifestyles. These characteristics may infer an overall different experience than what may occur at a large academic or small community hospital.
CONCLUSIONS Safe and reliable surgical ligation of the LAA can be achieved using the double ligation technique on and off pump. A subset analysis of patients with TEE follow-up demonstrated a 94.7% success rate, which is higher than any previously reported surgical method and is comparable with the highest percutaneous techniques. The double ligation technique also carries with it the added benefit of being relatively inexpensive compared with other modalities of LAA occlusion. Double ligation was associated with lower incidences of stroke, bleeding complications, and myocardial infarctions as well as a trend for lower rates of AF than in nonligated patients 30 days after surgery. Interestingly, there were significantly lower rates of in-hospital and 30-day mortality in the patients receiving double ligation than those who did not. The high success rate, low
REFERENCES 1. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042Y1046. 2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983Y988. 3. Contractor T, Khasnis A. Left atrial appendage closure in atrial fibrillation: a world without anticoagulation? Cardiol Res Pract. 2011;2011:752808. 4. Bartus K, Bednarek J, Myc J, et al. Feasibility of closed-chest ligation of the left atrial appendage in humans. Heart Rhythm. 2011;8:188Y193. 5. Leitha¨user B, Park JW. Cardioembolic stroke in atrial fibrillation-rationale for preventive closure of the left atrial appendage. Korean Circ J. 2009; 39:443Y458. 6. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755Y759. 7. Johnson WD, Ganjoo AK, Stone CD, Srivyas RC, Howard M. The left atrial appendage: our most lethal human attachment! Surgical implications. Eur J Cardiothorac Surg. 2000;17:718Y722. 8. Kanderian AS, Gillinov AM, Pettersson GB, Blackstone E, Klein AL. Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography. J Am Coll Cardiol. 2008;52:924Y929. 9. Al-Saady NM, Obel OA, Camm AJ. Left atrial appendage: structure, function, and role in thromboembolism. Heart. 1999;82:547Y554. 10. Healey JS, Crystal E, Lamy A, et al. Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. Am Heart J. 2005;150:288Y293. 11. Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306Y311. 12. Zapolanski A, Brizzio ME, Sperling JS, Bronstein EH, Shaw RE. Safe and complete exclusion of the left atrial appendage: a simple epicardial approach. Innovations. 2008;3:161Y163. 13. Nakajima H, Seo Y, Ishizu T, et al. Analysis of the left atrial appendage by three-dimensional transesophageal echocardiography. Am J Cardiol. 2010;106:885Y892. 14. Lloyd-Jones D, Adams RJ, Brown TM, et al., for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statisticsV2010 update: a report from the American Heart Association. Circulation. 2010;121:e46Ye215. 15. Bartus K, Han FT, Bednarek J, et al. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol. 2013;62:108Y118. 16. Ailawadi G, Gerdisch MW, Harvey RL, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J Thorac Cardiovasc Surg. 2011;142:1002Y1009, 1009.
CLINICAL PERSPECTIVE This is an interesting retrospective case series of 108 patients who underwent ligation of their left atrial appendage using a simple technique developed by the authors. In the 56 patients who underwent postoperative transesophageal echocardiography, the left atrial appendage was successfully occluded in 53 (95%) of patients. The authors noted a lower in-hospital and 30-day mortality in the ligated group, but this was likely due to selection basis and would need to be confirmed by a prospective trial. This study suggests that the double ligation technique is able to successfully exclude the left atrial appendage. Further prospective studies are needed to determine whether this technique would be associated with any differences in late stroke or mortality. The low cost of this technique is attractive.
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Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Epicardial Surgical Ligation of the Left Atrial Appendage Is Safe, Reproducible, and Effective by Transesophageal Echocardiographic Follow-up Alex Zapolanski, MD,* Christopher K. Johnson, BS,* Omid Dardashti, MD,* Ryan M. O’Keefe,* Nancy Rioux, RN,* Giovanni Ferrari, PhD,*Þ Richard E. Shaw, PhD,* Mariano E. Brizzio, MD,* and Juan B. Grau, MD*Þ
Objective: The left atrial appendage (LAA) is the source of 90% of thrombi in patients with atrial fibrillation. Our double LAA ligation (LLAA) technique was shown to be 96% successful in a small study. However, the outcomes of these patients have yet to be compared with a set of nonligated patients. Methods: From 2005 to 2012, a total of 808 patients received LAA using our double ligation technique using both a polydioxanone (PDS) II endosnare and a running 4-0 Prolene pledgeted suture. The 30-day outcomes of these patients were compared with that of nonligated patients. Fifty-six of the ligated patients had a postoperative transesophageal echocardiography (TEE). An echocardiographer reviewed the follow-up TEEs for LAA remnant and/or residual flow into the LAA using color Doppler imaging. The patients with LAA flow and/or remnant depth of 1 cm or greater were deemed to have an unsuccessful exclusion. Results: The ligated group had a trend of less postoperative atrial fibrillation (19.4% vs 22.9%, P = 0.07) and an overall significantly lower in-hospital mortality (0.7% vs 3.0%, P G 0.001) and lower 30-day mortality (0.7% vs 3.4%, P G 0.0001). The LAA was successfully excluded in 53 (94.7%) of the 56 patients with TEE. Conclusions: Double LAA ligation correlates with lower rates of in-hospital and 30-day mortality. This advantage comes without an increase in perioperative complications. This technique can easily be performed off or on pump, is very reproducible, and comes at a very low
cost compared with LAA occlusion devices. Stroke has a multifactorial etiology; successful LLAA removes one potential source of thrombi perioperatively and in the long-term. Key Words: Left atrial appendage, Epicardial surgical technique, Transesophageal echocardiography, Atrial fibrillation. (Innovations 2013;8:371Y375)
O
Address correspondence and reprint requests to Juan B. Grau, MD, The Valley Heart and Vascular Institute, 223 North Van Dien Ave, Ridgewood, NJ USA. E-mail: [email protected]. Copyright * 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery ISSN: 1556-9845/13/0805-0371
ne in every four people older than 40 years are at risk to develop atrial fibrillation (AF), making it the most common arrhythmia in the United States.1 The most serious complication arising from AF is a fivefold increased risk for stroke.2 This risk is further intensified when combined with other factors such as age, valvular disease, and hypertension.2 Strokes are the third leading cause of death in America, with 10% of transient ischemic attacks (TIAs) and 50% of cerebrovascular accidents (CVAs) occurring as a result of AF.2,3 Although anticoagulation medications substantially reduce the risk for stroke, there are significant issues to consider regarding their use. The greatest concerns with anticoagulant therapy are the increased risk for bleeding and potential drug interactions.4 In 2003 and 2004, anticoagulants were linked to more deaths than any other therapeutic drug.3 With its narrow therapeutic range and need for continuous laboratory monitoring, it is estimated that only one fourth of AF patients are receiving optimal anticoagulation therapy.5 In recent years, new anticoagulants have been introduced in the armamentarium to prevent strokes in AF patients. The safety, efficacy, and therapeutic margin on the real-world use of these agents (dabigatran, rivaroxaban, and apixaban) have to be better elucidated in the coming years. With 90% of thrombi in patients with nonrheumatic AF originating in the left atrial appendage (LAA), the LAA has been referred to as ‘‘the most lethal human attachment.’’6,7 In light of this, some surgeons have proposed closing the LAA as a method to eliminate a major risk for stroke.3 There are numerous techniques to achieve LAA closure, but they generally fall into two categories: excision (in which the LAA is amputated) or exclusion (in which the LAA orifice is obliterated). Previous studies have shown complete amputation of the LAA to have a better success rate than suture exclusion (73% vs 23%).8
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Video clip is available online.
Accepted for publication September 18, 2013. From *The Valley Columbia Heart Center, Columbia University College of Physicians and Surgeons, Ridgewood, NJ USA; and †The University of Pennsylvania School of Medicine, Glenolden, PA USA. A video clip is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.innovjournal.com). Please use Firefox when accessing this file. Disclosure: The authors declare no conflicts of interest.
Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Zapolanski et al
However, it has been proposed that the removal of the LAA could affect the body’s ability to regulate volume because the LAA produces 30% of the body’s atrial natriuretic peptide.9 This potential hazard is avoided by ligating the LAA.10 The literature indicates that the average success rate of successful LAA elimination is 55% to 66%.11 We have developed a very safe technique for epicardial ligation of the LAA during cardiac surgery using only a polydioxanone (PDS) II endoloop (Ethicon, Somerville, NJ USA) and sutures (Ethicon, Somerville, NJ USA). However, the efficacy of this ‘‘double ligation’’ technique had only been established in a small number of patients using transthoracic echocardiography as the validating tool to evaluate efficacy.12 In this study, we evaluate the effectiveness of our safe double ligation technique, representing the third largest study of LAA ligation and the first large-scale study since 2008.8 To test the efficacy of this method, we also included a subgroup analysis of 56 ligated patients who had a postoperative transesophageal echocardiographic (TEE) follow-up.
METHODS From 2005 to 2011, a total of 3195 patients underwent cardiac surgery at our institution (Fig. 1). Of these, 808 patients received our previously published technique of double ligation. This procedure uses both a PDS II endoloop (Ethicon, Somerville, NJ USA) and a running 4-0 polypropylene pledgeted suture (Ethicon, Somerville, NJ USA) to exclude the LAA.12 A total of 1196 patients underwent either LAA excision or ligation with another technique and were excluded from this analysis.
TABLE 1. Patient Demographics Nonligated n Female Age G64 65Y74 975 Body mass index G25 25Y29 930 Previous myocardial infarction Peripheral vascular disease Cardiovascular disease Valve disease Previous stroke Ejection fraction G35% Left main disease No. diseased vessels 1 vessel 2 vessels 3 vessels Emergent surgery Chronic heart failure Previous atrial fibrillation Diabetes Hypertension Smoker Dyslipidemia Renal failure Surgery type Isolated CABG Isolated valve CABG + valve CABG + valve + other Other
Ligated
350
969 36.1%
212
808 26.2%
345 253 371
35.6% 26.1% 38.3%
267 261 280
33.0% 32.3% 34.7%
248 376 345 250 101 105 121 48 91 157
25.6% 38.8% 35.6% 25.8% 10.4% 10.8% 12.5% 5.0% 9.4% 16.2%
186 337 285 350 89 102 90 41 116 289
23.0% 41.7% 35.3% 43.3% 11.0% 12.65% 11.06% 5.1% 14.4% 35.8%
441 118 410 61 274 104 274 781 406 548 58
45.5% 12.2% 42.3% 6.3% 28.3% 10.7% 28.3% 80.6% 41.9% 56.6% 6.0%
135 124 549 62 235 161 282 678 414 446 60
16.7% 15.3% 67.9% 7.7% 29.1% 19.9% 34.9% 83.9% 51.2% 55.2% 7.4%
364 216 163 39 187
37.6% 22.3% 168% 4.0% 19.3%
510 44 109 40 105
63.1% 5.4% 13.5% 5.04% 13.0%
P 0.00 0.03
0.39
0.00 0.69 0.24 0.51 0.91 0.00 0.00 0.00
0.25 0.47 0.00 0.00 0.07 0.00 0.57 0.23 0.27 0.00
CABG indicates coronary artery bypass graft.
FIGURE 1. Schematic of patient selection. LAA indicates left atrial appendage; TEE, transesophageal echocardiogram.
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A comparison of the double ligation patients and the nonligated patients (n = 969) can be found in Table 1. Reoperative patients were excluded from this study (n = 222). The double ligation is achieved in three steps (Fig. 2).12 The first is to isolate the LAA and place a PDS II endoloop around the base, making sure to position the knot on the lateral aspect of the appendage. This way, the surgeon is able to engage and retain the endoloop on the medial aspect of the LAA. Next, the endoloop is tightened while making sure that the suture is tied without sliding it out of position. The suture is kept as low as possible, maximizing the amount of LAA excluded. It should be emphasized that caution in tightening the suture is imperative because excessive force could potentially injure the tissue. The endoloop has two purposes: first, to define the level of ligation, and second, to reduce the pressure within the LAA during the second stage of the technique. Next, a 4-0 polypropylene purse-string suture supported with multiple Teflon pledgets is placed slightly distal to the endoloop. This suture achieves complete exclusion of the appendage.
Copyright * 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery
Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Efficacy and Safety of LAA Double Ligation
tissue but also, when these come together after tying, provide the surgeon initial tactile confirmation that the LAA has been completely ligated. Lastly, the LAA is opened to ensure complete ligation from the left atrium. We expect that by evacuating the appendage, the remaining atrial tissue will scar down. After evacuation, two large hemoclips are placed at the tip for safety. Further corroboration of complete ligation is achieved by immediate postoperative TEE assessment. A short video of the LLAA, Supplemental Digital Content 1, is available online at http://links.lww.com/INNOV/A35. A follow-up TEE was done in 56 of the double ligation patients. Transesophageal echocardiography was performed by independent cardiologists for the following indications: precardioversion for arrhythmia (n = 32), to check valvular and cardiac function (n = 11), to explore for emboli/thrombi (n = 8), or to detect vegetation (n = 1). Other reasons include documenting an intracardiac shunt (n = 1) and ruling out tamponade (n = 1) and endocarditis (n = 2) (Table 2). The studies were performed on the Philips ie33 ultrasound machine (Koninklijke Philips Electronics N.V., Andover, MA USA). Evaluation of TEEs was performed by a single independent qualified echocardiographer. Studies used evaluated the LAA in multiple views, with color Doppler across the LAA to assess any residual flow into the appendage. Transesophageal echocardiography has long been used to investigate the blood flow of and detect thrombi in the LAA.13 The LAA was considered successfully ligated if its obliteration was observed on two-dimensional imaging, with no remnant stump greater than 1 cm remaining, and as long as absence of color flow by Doppler was also documented.
RESULTS Overall, the ligated group had a higher rate of comorbidities. Despite this, the ligated group had a trend of less postoperative AF (19.4% vs 22.9%, P = 0.07) and an overall significantly lower in-hospital mortality (0.7% vs 3.0%, P G 0.001) and lower 30-day mortality (0.7% vs 3.4%, P G 0.0001) (Table 3). Of the 808 patients in the ligated group, 496 (61.4%) had off-pump surgery performed. There TABLE 2. Transesophageal Echocardiogram Follow-up Data FIGURE 2. The double ligation technique. A, Step 1: Isolate the LAA and place a PDS II endoloop around the base, making sure to position the knot on the lateral aspect of the appendage. The snare should be kept as low as possible to maximize the amount of LAA excluded. Next, tighten the endoloop with caution because excessive force could potentially injure the tissue. B, Step 2: Place a 4-0 polypropylene purse-string suture supported with multiple Teflon pledgets slightly distal to the endoloop. This completes the exclusion of the LAA. This can be achieved without bleeding because the endoloop lessens the pressure in the LAA. C, Step 3: Lastly, ensure total exclusion by opening the LAA. The remaining atrial tissue is expected to scar down. Two large hemoclips are placed at the tip for safety. Complete LLAA is confirmed by postoperative TEE. LAA indicates left atrial appendage; LLAA, double left atrial appendage ligation; TEE, transesophageal echocardiogram.
Placement of the suture at this point can be accomplished without bleeding because the endoloop reduces the pressure in the LAA even when it is not completely occlusive. The four pledgets not only reinforce the closure and protect the atrial
Results n Patient age Male Days between surgery and TEE CVA or TIA Reason for TEE Detect embolism/thrombus/clot Detect vegetation Evaluate valve/ventricular function Precardioversion or ablation Other LLAA success LAA flow Remnants Remnant depth
56 70.52 T 11.83 43 (76.79%) 293.64 T 435.47 2 (3.57%) 8 (14.29%) 1 (1.79%) 11 (19.64%) 32 (57.14%) 4 (7.14%) 53 (94.64%) 3 (5.36%) 4 (7.14%) 0.53 T 0.15
CVA indicates cerebrovascular accident; LAA, left atrial appendage; LLAA, double left atrial appendage ligation; TEE, transesophageal echocardiogram; TIA, transient ischemic attack.
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Innovations & Volume 8, Number 5, September/October 2013
Zapolanski et al
TABLE 3. Overall Postsurgical Outcomes Nonligated Reoperation for bleeding Myocardial infarction Permanent stroke Transient stroke Atrial fibrillation In-hospital mortality 30-day mortality
38 3 14 2 222 20 24
3.9% 0.3% 1.4% 0.21% 22.9% 2.1% 2.5%
Ligated 23 5 6 1 157 6 6
2.8% 0.6% 0.7% 0.12% 19.4% 0.7% 0.7%
P 0.22 0.33 0.16 0.65 0.07 0.02 0.01
was a significantly higher incidence of reoperation for bleeding in the patients receiving the ligation on pump (5.1% vs 1.4%, P = 0.00). None of the re-explorations for bleeding involved the LAA as the source. Otherwise, there were no differences in surgical outcome based on performing the double ligation technique on or off pump. There were 56 patients who underwent LAA ligation and had a TEE postoperatively (Table 2). The mean T SD age of this subgroup was 70 T 11 years. A total of 76.8% of these patients were men. Fifty-three (94.7%) of 56 closures were successful (Fig. 3), with three patients with persistent flow in the LAA. Although four patients showed remnant LAA, none of them had a remnant that exceeded a depth of 0.6 cm. Two (3.6%) of the 56 TEE patients had a CVA; however, neither of them had a remnant or Doppler flow into the LAA by TEE criteria.
DISCUSSION The efficacy of LAA elimination has long been debated. This study represents the largest study since 2008 and includes contemporary patients. The safety of the technique is demonstrated by a low incidence of complications and significantly reduced rates of in-hospital and 30-day mortality, despite the fact that the ligated patients were sicker preoperatively. The subanalysis of the patients with follow-up TEE results revealed that double LAA ligation (LLAA) was successful in 94.7% of attempts. This figure is comparable with our previously established 96% (27/28) success rate of double ligation seen
when using intraoperative TEE and postoperative transthoracic echocardiography using Definity (Bristol-Myers Squibb Medical Imaging, North Billerica, MA USA) contrast.12 The success of the double ligation technique is likely due to the fact that the endoloop precisely defines the base of the LAA, allowing for a very aggressive exclusion of most of the LAA tissue. This is reinforced by running the 4-0 Prolene suture above the loop. Final success is confirmed by opening the appendage, even during off-pump cases. Complete ligation of the LAA using this combined technique has a much greater success rate than other surgical techniques. The reported success of LAA excision and suture exclusion is 73% and 23%, respectively.8 Prior studies have shown surgeon experience to be a significant factor in procedure success. Successful occlusion rates double after a surgeon has performed four cases.10 Our previous analysis demonstrated that the double ligation technique does not add significant time to the operation, taking only an additional 5 T 3 minutes to perform.12 In addition, the results displayed in Table 4 indicate that the double ligation technique can be performed safely off pump, with comparable results with those patients receiving the procedure on pump. The success rate of LAA closure found in our TEE subgroup suggests that most of the larger cohort had successful LAA exclusion. The overall incidence of CVA or TIA in the 1777 patients was found to be 1.3% (n = 23), approximately half of the national average.14 The frequency of CVA in the ligated group was half of that seen in the nonligated group, although this did not reach statistical significance in this series (0.7% vs 1.4%, P = 0.16). The ligated LAA could have contributed to this lower rate of permanent and transient stroke; however, it is important to stress that the causes of stroke are multifactorial and are well beyond the scope of this study. The frequency of stroke in the follow-up TEE subgroup is three times less than that reported in similar studies (3.6% vs 13%).8 Unsuccessful LAA occlusion could potentially have disastrous consequences. Thrombi have been shown to develop in 41% of partially closed LAA.8 This is believed to be the result of stagnant blood trapped in a partially closed appendage. However, the link between partial LAA ligation and increased risk for stroke has not been confirmed. Nevertheless, this theoretical risk combined with the prevalence of stroke in patients with ligated LAA suggests that patients who qualify should continue anticoagulation medication to provide the maximum protection from a CVA or TIA. There are several devices designed to percutaneously occlude the LAA. The most commonly used is the WATCHMAN TABLE 4. Outcomes in Ligated Patients by Pump Status
FIGURE 3. Representative TEE of a successful LLAA. Transesophageal view at 65 degrees confirming successful ligation of the left atrial appendage, with absence of color flow into prior appendage site. LLAA indicates double left atrial appendage ligation; TEE, transesophageal echocardiogram.
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No. patients Reoperation for bleeding Myocardial infarction Permanent stroke Transient stroke Atrial fibrillation In-hospital mortality 30-day mortality
Off pump
On pump
496
312
7 2 2 1 88 4 4
1.4% 0.4% 0.4% 0.2% 17.7% 0.8% 0.8%
16 3 4 0 69 2 2
5.1% 1.0% 1.3% 0.0% 22.1% 0.6% 0.7%
P 0.00 0.32 0.16 0.43 0.13 0.79 0.79
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Copyright © 2013 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 8, Number 5, September/October 2013
Efficacy and Safety of LAA Double Ligation
LAA occlusion device, which has been shown to have a successful implantation rate of 82%.4 In addition, the LARIAT device uses a catheter-based approach to successfully ligate the LAA in 96% of patients.15 Several devices are still in the early testing phase but have promising results.4,11 A 3-month follow-up of AtriClip, recently approved by the Food and Drug Administration, showed the device to successfully occlude the LAA in 67 (95.7%) of 70 patients.16 These three devices all have similar success rates to double ligation; however, these devices cost between $2000 (AtriClip) and $6600 (WATCHMAN) for a single device versus the cost of double ligation of $117.
cost, and low complication rate seen in this series suggest that the double ligation technique is a reliable, effective, and safe method of LLA ligation. Although stroke has a multifactorial etiology, successful LLAA removes one potential source of thrombi perioperatively and in the long-term.
Limitations This study has a few potential limitations. There may be a selection bias stemming from the fact that this was a retrospective study looking at patients with a TEE after LAA ligation. Because these patients required a TEE, these patients may be sicker than the rest of the population, as demonstrated by the higher incidence of stroke in the TEE group versus the entire ligated group (3.6% vs 0.82%). Multiple surgeons performed the surgeries, and this nonrandomized study does not account for the variability between surgeon skill, experience, and technique. This study aimed to show the safety and the success rate of the double ligation technique; therefore, the causes of CVA were not investigated. This study was conducted at a medium-sized, nonacademic hospital that serves a large, affluent population with the resources and the knowledge to maintain healthier lifestyles. These characteristics may infer an overall different experience than what may occur at a large academic or small community hospital.
CONCLUSIONS Safe and reliable surgical ligation of the LAA can be achieved using the double ligation technique on and off pump. A subset analysis of patients with TEE follow-up demonstrated a 94.7% success rate, which is higher than any previously reported surgical method and is comparable with the highest percutaneous techniques. The double ligation technique also carries with it the added benefit of being relatively inexpensive compared with other modalities of LAA occlusion. Double ligation was associated with lower incidences of stroke, bleeding complications, and myocardial infarctions as well as a trend for lower rates of AF than in nonligated patients 30 days after surgery. Interestingly, there were significantly lower rates of in-hospital and 30-day mortality in the patients receiving double ligation than those who did not. The high success rate, low
REFERENCES 1. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042Y1046. 2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983Y988. 3. Contractor T, Khasnis A. Left atrial appendage closure in atrial fibrillation: a world without anticoagulation? Cardiol Res Pract. 2011;2011:752808. 4. Bartus K, Bednarek J, Myc J, et al. Feasibility of closed-chest ligation of the left atrial appendage in humans. Heart Rhythm. 2011;8:188Y193. 5. Leitha¨user B, Park JW. Cardioembolic stroke in atrial fibrillation-rationale for preventive closure of the left atrial appendage. Korean Circ J. 2009; 39:443Y458. 6. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755Y759. 7. Johnson WD, Ganjoo AK, Stone CD, Srivyas RC, Howard M. The left atrial appendage: our most lethal human attachment! Surgical implications. Eur J Cardiothorac Surg. 2000;17:718Y722. 8. Kanderian AS, Gillinov AM, Pettersson GB, Blackstone E, Klein AL. Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography. J Am Coll Cardiol. 2008;52:924Y929. 9. Al-Saady NM, Obel OA, Camm AJ. Left atrial appendage: structure, function, and role in thromboembolism. Heart. 1999;82:547Y554. 10. Healey JS, Crystal E, Lamy A, et al. Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. Am Heart J. 2005;150:288Y293. 11. Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306Y311. 12. Zapolanski A, Brizzio ME, Sperling JS, Bronstein EH, Shaw RE. Safe and complete exclusion of the left atrial appendage: a simple epicardial approach. Innovations. 2008;3:161Y163. 13. Nakajima H, Seo Y, Ishizu T, et al. Analysis of the left atrial appendage by three-dimensional transesophageal echocardiography. Am J Cardiol. 2010;106:885Y892. 14. Lloyd-Jones D, Adams RJ, Brown TM, et al., for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statisticsV2010 update: a report from the American Heart Association. Circulation. 2010;121:e46Ye215. 15. Bartus K, Han FT, Bednarek J, et al. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol. 2013;62:108Y118. 16. Ailawadi G, Gerdisch MW, Harvey RL, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J Thorac Cardiovasc Surg. 2011;142:1002Y1009, 1009.
CLINICAL PERSPECTIVE This is an interesting retrospective case series of 108 patients who underwent ligation of their left atrial appendage using a simple technique developed by the authors. In the 56 patients who underwent postoperative transesophageal echocardiography, the left atrial appendage was successfully occluded in 53 (95%) of patients. The authors noted a lower in-hospital and 30-day mortality in the ligated group, but this was likely due to selection basis and would need to be confirmed by a prospective trial. This study suggests that the double ligation technique is able to successfully exclude the left atrial appendage. Further prospective studies are needed to determine whether this technique would be associated with any differences in late stroke or mortality. The low cost of this technique is attractive.
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