Side-by-Side Comparison of LAA Occlusion Performance With the Amplatzer Cardiac Plug and Amplatzer Amulet

Abstract: Background. The Amplatzer Amulet, a second-generation device for left atrial appendage occlusion (LAAO), has been designed to facilitate the implantation process, improve the closure performance, and reduce the risk of complications. The objective of this study was to compare the outcomes of the Amplatzer Cardiac Plug (ACP) with the Amplatzer Amulet for LAAO, with a special focus on the incidence of residual leaks. Methods. This was a prospective, single-center review of consecutive patients undergoing percutaneous LAAO with either ACP or Amulet devices. The first transesophageal echocardiography (TEE) at follow-up (1-3 months) was utilized to assess the occurrence of residual leaks. Results. Between November 2009 and August 2013, a total of 59 patients underwent LAAO with either the ACP device (n = 31) or Amulet device (n = 28). The device was successfully implanted in 58 patients (98.3%). There was no procedural device embolization, stroke, or cardiac tamponade. Follow-up TEE was available in 86% (50 patients; 25 ACP devices and 25 Amulet devices). At follow-up, there was no procedural device embolization, and only 1 patient who received an Amulet device presented with device thrombosis at follow-up. Amulet use was associated with a significant reduction of any leak (minor, moderate, or major) compared with ACP use (48% ACP vs 8% Amulet; P=.01). Conclusion. In this initial series, the Amulet showed similar procedural and short-term clinical outcomes compared with the ACP. The Amulet was, however, associated with a significant reduction of residual leaks at follow-up. 

J INVASIVE CARDIOL 2016;28(1):34-38

Key words: left atrial appendage, stroke, Amulet, Amplatzer Cardiac Plug, atrial fibrillation

_______________________________________

The left atrial appendage (LAA) is the main reservoir for thrombus in non-valvular atrial fibrillation (NVAF).¹ Currently, LAA occlusion (LAAO) represents a valid alternative to oral anticoagulation in patients with an absolute or relative contraindication to these agents.^2,3 The PLAATO system (ev3, Inc) was the first dedicated device that was successfully used to close the LAA.⁴ Since then, several other devices have been tested. Among them, the Amplatzer Cardiac Plug (ACP; St. Jude Medical) and the Watchman device (Atritech) are the ones with a higher penetration worldwide. The LAA is a complex structure with a highly variable anatomy.⁵ The heterogeneous morphology of the LAA represents a relevant challenge for achieving optimal results with the available devices. Although the experience of operators is increasing, some device improvement is deemed necessary to deal with certain complex LAA anatomies. The second generation of the ACP device, the Amplatzer Amulet (St. Jude Medical) has been designed to facilitate the implantation process and reduce the occurrence of complications like device embolization, device thrombosis, and residual leaks.⁶ Since the Amulet has been recently released, the clinical follow-up is limited. Therefore, the main objective of the present study was to compare the short-term performance of the ACP and Amplatzer Amulet with a special focus on the incidence of residual leaks at follow-up. 

Methods

Patient population. Patients who underwent percutaneous LAA closure between November 2009 and June 2012 for the ACP and July 2012 and August 2013 for the Amulet at the Montreal Heart Institute were included in the study. The clinical, procedural, angiographic, and echocardiographic outcome variables of these patients were prospectively collected and analyzed. All patients were >18 years old, had NVAF (paroxysmal, persistent, or permanent) with a high risk for stroke (CHADS₂ score ≥2), and at least one contraindication for oral anticoagulation therapy. Exclusion criteria for LAA closure included LAA thrombus, mobile aortic atheroma, and symptomatic carotid artery disease. 

All patients provided written informed consent before the procedure. The Director of Professional Services at the Montreal Heart Institute approved the review of medical charts and documentation. This study was initiated by the investigators and was not financed by any company.

Amplatzer Cardiac Plug and Amplatzer Amulet descriptions. The ACP and Amulet are first-generation and second-generation devices for LAA occlusion, respectively. Both are self-expanding dedicated devices with a distal lobe and a proximal disc connected by an articulated waste. The distal lobe conforms to the inner LAA wall in a depth of approximately 10 to 15 mm, the articulated waist allows a proper orientation of the device into the LAA, and the proximal disc seals the LAA ostium.⁷ Both devices are retrievable and repositionable, and are implanted via 9-14 Fr sheath. The Amulet has several design novelties compared with the ACP: (1) device preloaded system; (2) larger available sizes (31 mm and 34 mm); (3) longer lobe length (7.5-10 mm); (4) longer connecting waist (5.5-8 mm); (5) larger disc diameters (lobe +6 to 7 mm); (6) increased number of stabilizing wires (6-10 pairs) on the lobe; (7) inverted attaching end-screw on the disc to reduce the risk of device thrombosis; and (8) new delivery cable with an inner 0.014˝ wire for tension release.^6,8 

Device implantation. All procedures were performed under general anesthesia by the same operator, with fluoroscopic and three-dimensional transesophageal echocardiography (3D-TEE) guidance (iE33 ultrasound system and X7-2t matrix array transducer; Philips Healthcare). After crossing the atrial septum with the delivery system, all patients received intravenous heparin to keep an activated clotting time of at least 250 seconds throughout the entire procedure. 

The size of the device was selected based on angiographic and TEE measurements. Several contrast injections of 8-10 mL in the 30° right anterior oblique projection with 20° cranial and caudal angulation were used for the angiographic assessment. For TEE, the LAA was assessed in the mid-esophageal and high-esophageal views from 0°-180° (particularly at 0°, 45°, 75°, 90°, and 120°). The mean LAA diameter at a depth between 10-15 mm from the ostium was used to choose the device size. The degree of device oversizing was based on the LAA anatomy and the operator’s experience, but was typically 2-6 mm larger than the mean LAA diameter.

Angiographic analysis. The implantation was considered successful if the lobe of the device was deployed inside the LAA and the operator was pleased with the position and stability of the device.

After device implantation, the shape of the distal lobe was evaluated by two independent reviewers and classified as “tire-like or optimal-deformation,” “strawberry-like or over-deformation,” or “square-like or under-deformation.”^9,10 Intraobserver and interobserver agreement was 100%.

Transesophageal analysis. The primary outcome of the study was the comparison of residual TEE leaks at follow-up between the two devices. Intraprocedural and follow-up TEE were analyzed by two experienced observers blinded to the clinical and procedural information and put in consensus in case of disagreement (AA and XF). Device leak was defined as the presence of a Doppler signal inside the LAA after deployment. The presence of peridevice flow was classified as: (1) severe (multiple jets or free flow); (2) major (>3 mm jet); (3) moderate (1-3 mm jet); (4) minor (<1 mm jet); and (5) absent (no jet).^4,11 Intraobserver agreement was 100% and interobserver variability presented a kappa value of 0.920 (95% confidence interval, 0.843-0.997). There were two disagreements between observers. In both cases, the leak was considered minor for one observer and moderate for the other. After consensus between both reviewers, both patients were classified as having a moderate leak. 

All TEEs underwent careful interrogation for device thrombosis. Device thrombosis was considered in the presence of any protruding thrombus other than a flat coverage of the device.

Clinical follow-up. Clinical follow-up was carried out by patient visit, medical report review, and phone contact. A questionnaire was used to collect information regarding the clinical status or the occurrence of cardiovascular events. 

Statistical analysis. The results are expressed as mean ± standard deviation (SD) for normally distributed data. Continuous variables that were not normally distributed are expressed as medians with interquartile ranges (IQR). Comparisons between groups were performed using the unpaired t-test or Mann-Whitney U-test for continuous variables, and Chi² or Fisher’s exact test for categorical variables. A one-way ANOVA test with a Bonferroni correction was used to define statistical difference between groups when appropriate. Interobserver and intraobserver variability for angiographic and TEE leak assessment was determined by kappa statistics. Results were considered statistically significant at a P-value <.05. Statistical analyses were carried out using SPSS package version 16.0 (IBM, Inc).

Results

Fifty-nine consecutive patients, 31 (53%) with ACP and 28 with Amulet (47%), underwent percutaneous LAA closure during the study period. Baseline and echocardiographic characteristics of the study population are shown in Table 1. 

Device implantation. The device was successfully implanted in 58/59 patients (98.3%). In 1 Amulet patient, the deployment was attempted but the device could not be implanted, as the LAA was bilobar and had a small and short (<10 mm) landing area. The size of the first device was changed in 5 ACP cases (16%) and 1 Amulet case (3.7%; P=.12), because the operator was not satisfied with the initial result. In the Amulet group, 3 patients had very large LAAs with a landing area diameter >31 mm that were successfully sealed with a 34 mm device. In addition, 2 patients in the ACP group and 4 patients in the Amulet group had a very challenging anatomy, with a chicken-wing morphology characterized by an early (<20 mm from the ostium) and severe bend (∼180°) that was occluded using the sandwich technique.¹² 

Overall, the device was oversized by 3.2 ± 1.9 mm and 3.9 ± 2.0 mm in relation to the mean angiographic and TEE diameters, respectively. The degree of oversizing was not different among devices with respect to mean angiographic diameters (3.9 ± 1.6 mm with ACP vs 2.5 ± 2.0 mm with Amulet; P=.47) and mean TEE diameters (4.2 ± 2.0 mm with ACP vs 3.6 ± 1.9 mm with Amulet; P=.80).

The 22 mm ACP was the most common size used for both devices (34%). Procedural times (139 ± 39 minutes for ACP vs 134 ± 34 minutes for Amulet; P=.86) and fluoroscopy times (20 ± 10 minutes for ACP vs 19 ± 9 minutes for Amulet; P=.77) did not present significant differences. The shape of the device was optimal in 21/31 (68%) of the ACPs (strawberry-like in 7 cases and square-like in 3 cases) and 25/28 (89%) of the Amulets (strawberry-like in 3 cases), without significant differences (P=.09). 

Angiographic contrast injection after device implantation was available in 57/59 patients (97%) and showed successful sealing in 97% and 100% of the ACP and Amulet patients, respectively.

In-hospital outcomes. None of the patients developed intraprocedural device embolization, stroke, or cardiac tamponade. One patient in the Amulet group (1.7%) had a transient (<1 minute) ST elevation during the procedure without further consequence. Transthoracic echocardiography and chest x-ray 24 hours post procedure ruled out the presence of any device embolization. Three patients in the ACP group presented with mild or moderate pericardial effusion before the procedure, but TTE did not reveal any significant change 24 hours after the procedure. 

Clinical follow-up. Clinical follow-up was available in all ACP patients and 20 Amulet patients (71%). Mean follow-up duration was 29.8 months (IQR, 22.1-40.7 months) and 2.6 months (IQR, 1.5-4.6 months) for the ACP and Amulet patients, respectively. Although 4/51 ACP patients (7.8%) died during follow-up, no cardiovascular deaths were reported. Two patients (3.9%) suffered a stroke at follow-up; both were in the ACP group. Interestingly, 1 of the patients with a stroke at follow-up had a major leak at the 3-month TEE. The other patient had no residual leak post implantation or device thrombosis, but no follow-up TEE was available because the patient refused it. No clinical events were reported in the Amulet group. 

Transesophageal echocardiographic follow-up. Follow-up TEE was available in 50 patients (86%; 25 ACPs and 25 Amulets). The mean time duration between the index procedure and control TEE was 2.7 months (IQR, 1.4-4.5 months): 3.1 months (IQR, 3.1-7.3 months) for ACP vs 1.4 months (IQR, 1.2-1.7 months) for Amulet (P<.001). None of the patients had device embolization and only 1 Amulet patient presented with device thrombosis at follow-up. In error, the patient did not receive clopidogrel for 1 week after the procedure. Importantly, the same patient had a larger thrombus over an atrial septal defect occluder that was implanted on the same day of his LAA occlusion. The device thrombus was treated with dalteparin for 7 months, leading to progressive resolution and no clinical events.

As shown in Table 2, Doppler interrogation revealed no significant differences in postimplantation TEE leaks. However, the use of Amulet was associated with a significant reduction of follow-up TEE leaks compared with the ACP (P=.01). Of note, the 2 ACP patients with major leaks after device deployment did not show significant leaks at follow-up, and the 4 patients with major leaks at follow-up (3 ACPs and 1 Amulet) did not show significant leaks after device deployment. The shape of the device and the degree of oversize were not associated with the presence of postimplantation or follow-up TEE leaks.

Discussion

The present article shows the absence of significant differences in procedural success and short-term complications between the Amulet and ACP devices. The use of the Amulet was, however, associated with a lower incidence of leaks at follow-up as compared with the ACP.

In our series, percutaneous LAA occlusion with either the ACP or the Amulet showed a high rate of success with a low incidence of major procedural or in-hospital complications (cardiac tamponade, device embolization, and procedural stroke). The ACP was implanted in all patients and successful closure was achieved in 97% of patients. Similarly, the Amulet could be deployed in all patients except 1 (96.5%), and all of them showed successful closure by contrast injection. In addition, the Amulet allowed the closure of very large LAAs¹³ and facilitated the occlusion of challenging anatomies like the chicken wing.¹² Schmid et al¹⁴ showed the superiority of ACP devices compared with non-dedicated occlusion devices for LAAO. More recently, and in agreement with our findings, the same group published a manuscript showing a high success rate with both ACP (98%) and Amulet (94%) with no significant differences in procedural outcomes among devices, although no specific analysis on the degree of follow-up TEE leaks was performed.¹⁵

Although we did not observe significant differences in postimplantation TEE leaks, the Amulet showed a lower incidence of residual leaks at follow-up. In PROTECT AF, the incidence of major leaks (>3 mm) with the Watchman device was 32.4% at 45 days.¹¹ A recent publication showed no major leaks (>3 mm) at 90 days in 17 patients treated with Amulet.¹⁶ In our series, the prevalence of major leaks (>3 mm) at follow-up was 12% with the ACP and 4% with the Amulet. However, when assessing any detectable residual leak (minor, moderate, or major), the differences between devices became more significant as they were detected in 48% of the ACPs and 8% of the Amulets. Although the increased experience of the operator with LAA occlusion in the Amulet series might explain a better expertise in terms of apposition and sizing, there are other technical features that might play a role in this finding: (1) the Amulet provides a larger dimension of the disc and lobe, which may translate into better sealing of the ostium and landing area, respectively; (2) two novel sizes are available (31 and 34 mm) allowing a proper oversizing in large LAAs; and (3) the increased number of anchors might provide higher stability to the system. In contrast with a previous publication from our group,⁷ in this larger series of patients, the degree of oversizing was not found to play a role in the occurrence of residual leaks at follow-up. With the increased experience of our group, device oversizing tended to be based more on the mean than the largest LAA diameters. Indeed, the largest LAA diameter was felt to be misleading in elliptical appendages with large differences between the long-axis and short-axis diameters. 

Another important finding of our study that is in agreement with a previous publication⁷ was the detection of follow-up leaks that were not present in the postimplantation TEE and vice versa. In fact, this phenomenon was already observed with the PLAATO system.⁴ Although the lack of detection of TEE leaks might be explained by the differences in TEE image acquisition between postimplantation and follow-up studies, the present finding highlights the need for accurate screening of residual TEE leaks after LAAO. 

In our series, only 2 patients presented with a stroke at follow-up. Although 1 of these patients had a residual leak, the small number of events and the different follow-up preclude any solid conclusion. In fact, the presence of follow-up leaks after percutaneous occlusion has not been associated with a higher rate of thromboembolic events in the PROTECT-AF study.¹¹ However, incomplete sealing of the LAA has been linked to a higher risk of cardioembolic events in patients undergoing LAA surgical closure.^17,18 For this reason, while waiting for future data with a larger number of patients, we believe that complete sealing after LAAO should be pursued in all procedures.

Study limitations. The main limitations of the current study are the retrospective nature of the study, the absence of randomization, and the relatively small sample size. Limited sample size and variable follow-up periods have affected clinical outcomes and impede comparisons between devices. However, this does not affect the main focus of the paper, which was the comparison of procedural and short-term outcomes as well as the assessment of residual leaks after LAAO at the first TEE follow-up. 

Conclusion

In this initial series of patients, the Amulet showed similar procedural and short-term clinical outcomes compared with the ACP. However, the Amulet was associated with a significant reduction of residual leaks at follow-up. Further data with a larger number of patients and longer follow-up will be necessary to confirm these results and will allow comparisons of the long-term clinical outcomes.

References

1.    Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755-759.

2.    Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369-2429.

3.    Tzikas A, Freixa X, Ibrahim R. Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: ready for the prime time? Exp Rev Cardiovasc Ther. 2013;11:1587-1589.

4.    Ostermayer SH, Reisman M, Kramer PH, et al. Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high-risk patients with non-rheumatic atrial fibrillation: results from the International Multi-center Feasibility Trials. J Am Coll Cardiol. 2005;46:9-14.

5.    Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol. 2012;60:531-538.

6.    Freixa X, Chan JL, Tzikas A, Garceau P, Basmadjian A, Ibrahim R. The Amplatzer Cardiac Plug 2 for left atrial appendage occlusion: novel features and first-in-man experience. EuroIntervention. 2013;8:1094-1098.

7.    Freixa X, Tzikas A, Sobrino A, Chan J, Basmadjian AJ, Ibrahim R. Left atrial appendage closure with the Amplatzer Cardiac Plug: impact of shape and device sizing on follow-up leaks. Int J Cardiol. 2013;168:1023-1027.

8.    Freixa X, Abualsaud A, Chan J, et al. Left atrial appendage occlusion: initial experience with the Amplatzer Amulet. Int J Cardiol. 2014;174:492-496.

9.    Park JW, Bethencourt A, Sievert H, et al. Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation: initial European experience. Catheter Cardiovasc Interv. 2011;77:700-706.

10.    Sobrino A, Tzikas A, Freixa X, et al. Intra-procedural imaging of the left atrial appendage: implications for closure with the Amplatzer cardiac plug. Arch Cardiol Mex. 2014;84:17-24. Epub 2014 Mar 16.

11.    Viles-Gonzalez JF, Kar S, Douglas P, et al. The clinical impact of incomplete left atrial appendage closure with the Watchman Device in patients with atrial fibrillation: a PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) substudy. J Am Coll Cardiol. 2012;59:923-929.

12.    Freixa X, Tzikas A, Basmadjian A, Garceau P, Ibrahim R. The chicken-wing morphology: an anatomical challenge for left atrial appendage occlusion. J Interv Cardiol. 2013;26:509-514.

13.    Freixa X, Kwai Chan JL, Tzikas A, Garceau P, Basmadjian A, Ibrahim R. Percutaneous closure of a very large left atrial appendage using the Amplatzer Amulet. Can J Cardiol. 2013;29:1329.e9-1329.e11. Epub 2013 Mar 29

14.    Schmida M, Gloekler S, Saguner AM, et al. Transcatheter left atrial appendage closure in patients with atrial fibrillation: comparison between non-dedicated and dedicated Amplatzer devices. Cardiovasc Med. 2013;16:123-130.

15.    Gloekler S, Shakir S, Doblies J, et al. Early results of first versus second generation Amplatzer occluders for left atrial appendage closure in patients with atrial fibrillation. Clin Res Cardiol. 2015;104:656-665. Epub 2015 Mar 4.

16.    Lam SC, Bertog S, Gafoor S, et al. Left atrial appendage closure using the Amulet device — an initial experience with the second generation Amplatzer cardiac plug. Catheter Cardiovasc Interv. 2015;85:297-303. Epub 2014 Sep 5.

17.    Katz ES, Tsiamtsiouris T, Applebaum RM, Schwartzbard A, Tunick PA, Kronzon I. Surgical left atrial appendage ligation is frequently incomplete: a transesophageal echocardiograhic study. J Am Coll Cardiol. 2000;36:468-471.

18.    Garcia-Fernandez MA, Perez-David E, Quiles J, et al. Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal echocardiographic study. J Am Coll Cardiol. 2003;42:1253-1258.

_____________________________________________

From the ¹Montreal Heart Institute, Montreal, Quebec, Canada; ²Hospital Clinic of Barcelona, Barcelona, Spain; and ³AHEPA University Hospital, Thessaloniki, Greece.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Freixa reports proctoring fees from St. Jude Medical. Dr Tzikas reports personal fees from St. Jude Medical. Dr Ibrahim reports consultant and proctoring fees from St. Jude Medical, Boston Scientific, and Gore.

Manuscript submitted March 30, 2015, provisional acceptance given May 18, 2015, final version accepted June 1, 2015.

Address for correspondence: Dr Réda Ibrahim, Montreal Heart Institute, Interventional Cardiology, 5000 Rue de Belanger, Montreal, Canada H1T 1C8. Email: reda.ibrahim@icm-mhi.org