International Journal of Cardiology xxx (2014) xxx–xxx
IJCA-17846; No of Pages 5
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International Journal of Cardiology
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Left atrial appendage occlusion: Initial experience with the Amplatzer™ Amulet™☆
Xavier Freixa a,b, Ali Abualsaud a, Jason Chan a, Mohamed Nosair a, Apostolos Tzikas a,c, Patrick Garceau a,Arsène Basmadjian a, Réda Ibrahim a,⁎a Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canadab Department of Cardiology, Thorax Unit, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spainc Interbalkan European Medical Center, Thessaloniki, Greece
☆ Conflict of interests: Dr. Freixa, Tzikas and Ibrahim aSt. Jude Medical.⁎ Corresponding author at: Montreal Heart Institute, 5
Background: The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicateddevice for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitatethe implantation process, improve the sealing performance and further reduce the risk of complications. Theobjective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAAocclusion.Methods: This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. Theindication for LAA closure was a formal contraindication for oral anticoagulation or previous history of strokedue to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography(TEE) guidance. Transthoracic echocardiographywas performed 24h after the procedure in order to rule out pro-cedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1–3 months.Results: Between July-2012 and June-2013, 25 patients with a mean CHA2DS2-VASC of 4.3 ± 1.7 underwent LAA
occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without anyprocedural stroke, pericardial effusion or device embolization. None of the patients presented any clinicalevent at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks N3 mmand no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinicalexpression.Conclusion: In this initial series of patients, the Amulet showed a remarkable acute and short-term performancein terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence ofcomplications.
Despite the relatively recent introduction of the technique, percuta-neous left atrial appendage (LAA) occlusion is growing rapidly in refer-ence centers all over the world. In fact, percutaneous LAA occlusion iscurrently considered a valid alternative in patients with non-valvularatrial fibrillation (NVAF) and a formal contraindication for oralanticoagulation but it might also be considered in those at high-risk ofbleeding or drug cessation (IIB indication) [1].
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atrial appendage occlusion: I4
The LAA is very heterogeneous in size and morphology [2]. One ofthemain challenges of the technique is related to the proper appositionof the device, which is not variable in shape, in a highly variable struc-ture like the LAA [2]. The Amplatzer™ Cardiac Plug (ACP) (AGA-St-Jude, Minneapolis, MN, USA) and the Watchman™ (Atritech-BostonScientific, Natick, MA, USA) are currently the most widely used devicesfor LAA occlusion. Although different in design, both devices haveshown very promising data [3–6]. Despite the encouraging results, theneed of device evolution is deemed necessary in order to facilitate theimplantation process and reduce the occurrence of short and long-term complications. The Amplatzer™ Amulet™ (Amulet), an evolutionof the ACP, keeps the main shape of the ACP consisting of a distal lobeand a proximal disc but features other novelties designed not only toease the implantation process but also tominimize the risk of complica-tions [7]. Our group implanted the first-in-man Amulet for LAA occlu-sion in July 2012 [7]. The present paper describes the first worldwide
nitial experience with the Amplatzer™ Amulet™, Int J Cardiol (2014),
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experience with the Amulet in a series of patients who underwent LAAocclusion.
2. Methods
Between July 2012 and June 2013 all consecutive patients who underwent percutane-ous LAA closure with the Amulet at the Montreal Heart Institute, University of Montreal,Montreal, Quebec, Canadawere prospectively included in the study. All clinical, procedur-al, echocardiographic and outcome variables were prospectively collected. Patients weremore than 18 years old, had AF (paroxysmal, persistent or permanent) with a high riskfor stroke (CHADS2 score ≥ 2), and at least one contraindication for oral anticoagulationtherapy. Exclusion criteria for LAA closure included: LAA thrombus, mobile aortic athero-ma or symptomatic carotid artery disease.
All patients provided written informed consent before the procedure. The Director ofProfessional Services at the Montreal Heart Institute approved the review of medicalcharts and documentation. This initiativewas initiated by the investigators andwas not fi-nanced by any company. In addition, the authors of this manuscript have certified thatthey comply with the Principles of Ethical Publishing in the International Journal ofCardiology.
2.1. The Amplatzer™ Amulet™
The Amulet, like the ACP, is a self-expanding device for LAA occlusion with a distallobe and a proximal disc connected by an articulated waste. The distal lobe conforms tothe inner LAAwall in a depth between 10 and 15mm, the articulatedwaist allows a properorientation of the device into the LAA, and the proximal disc seals the LAA ostium. TheAmulet is also retrievable and repositionable and is implanted from the femoral vein(12–14 French delivery sheath size) using a transeptal approach.
Despite the similarity in design compared to the ACP, the Amulet has several novel-ties: 1) device pre-loaded system, 2) increased number of stabilizing wires (6 to 10pairs) on the lobe (Fig. 1), 3) inverted attaching end-screw on the disc to reduce the riskof device thrombosis (Fig. 2), 4) new delivery cable with an inner 0.014″wire for tensionrelease, 5) larger available sizes (31 mm and 34 mm), 6) longer lobe length (7.5 to10 mm), 7) longer connecting waist (5.5 to 8 mm) and 8) larger disc diameters (lobe +6 to 7 mm). A more comprehensive description of the Amulet dimensions and othernovel features have been reported elsewhere [7].
2.2. Device implantation
The procedure was performed under general anesthesia with simultaneous fluoro-scopic and TEE guidance (iE33 ultrasound system and X7-2t matrix array transducer,Philips Healthcare, Andover, MA, USA). The same operator performed all procedures.
The size of the device was selected based on angiographic and TEE measurements.Several contrast injections of 8 to 10ml in the RAO 30° Cranial 20°with a 5 FrenchmarkedPigtail (Merit Medical, UT, USA) were used for the angiographic assessment. For TEE, theLAA was assessed in the mid-esophageal and high-esophageal views from 0° to 180°.The largest, smallest, and the mean LAA diameter in a depth between 10 and 15 mmfrom the ostium measured in mid diastole on either angiography or TEE were used tochoose the size of the device. The degree of device over-sizing was based on the anatomyof the LAA and the experience of the operator but was typically 2 to 6 mm larger than theaverage LAA diameter and usually no less than the largest LAA diameter. In fact, the deviceselection criteria was similar to the one used with the ACP.
The degree of sealing was assessed behind the disc of the device by contrast injectionthrough the delivery system after implantation. We chose to evaluate the leak behind the
Fig. 1. Comparison between the ACP and the Amulet highlighting the difference in the numberwires (white arrows) compared to the ACP (left panel).
Please cite this article as: Freixa X, et al, Left atrial appendage occlusion: Ihttp://dx.doi.org/10.1016/j.ijcard.2014.03.154
disc and not the lobe as complete LAA sealing is the main goal of the device. Successfuldeployment was defined in case of final mild leak (one-third filling of the LAA behindthe device), trace leak (barely detectable filling) or absent leak (no detectable filling) [8].
2.3. In hospital and short-term follow-up
A transthoracic echocardiography (TTE) and a chest X-ray were performed the dayafter the procedure to rule out the presence of pericardial effusion or device embolizationbefore discharge. Patientswere treatedwith dual anti-platelet therapy (aspirin 80 mg/dayand clopidogrel 75 mg/day) for a minimum of three months followed by aspirinindefinitely.
Clinical follow-up was performed by a programmed clinical visit (1 to 3 months afterthe index procedure) supplemented bymedical-record review of any subsequent hospitaladmissions or additional visit. Patients underwent TEE prior to the clinical visit in order toassess the presence of device leaks and rule out complications such as pericardial effusion,device thrombosis or device embolization.
2.4. Statistical analysis
The results are expressed asmean± standard deviation (SD) for normally distributeddata. Continuous variables that were not normally distributed are expressed as medianswith interquartile ranges (IQR). Statistical analyses were done with the SPSS packagev16.0 (Chicago, IL, USA).
3. Results
During the study period, 25 patients underwent percutaneous LAAocclusion with the Amulet. Indications for the procedure were the in-ability to receive anticoagulation treatment in spite of a clear clinical in-dication in 22 patients (88%) and a prior history of cardioembolic eventsdue to INR lability in 3 (12%). The main reason for contraindicating oralanticoagulationwas gastrointestinal bleeding in 10 (45.5%), intracranialbleeding in 6 (27%), non-gastrointestinal bleeding in 5 (23%) andmulti-ple falls in 1 (4.5%). Baseline characteristics of the study population areshown in Table 1.
3.1. Procedural information
The Amulet was successfully implanted in 24 patients (96%). In onepatient, the smallest device (16 mm) was attempted but not implantedas the LAA was bi-lobar and presented a small and short (b10 mm)landing area. Echocardiographic and procedural data are shown inTable 2.
The selection of the Amulet sizewas based on imaging (angiographyand TEE). Overall, the device was oversized by 1.1 ± 1.9 mm and 2.2 ±2.1mm in relation to the largest angiographic and TEE diameter, respec-tively. A higher degree of oversizingwas observed compared to themeanangiographic (2.3 ± 2.0 mm) and TEE diameters (3.6 ± 2.0 mm). Threepatients presented very large LAAs with a landing diameter N31 mm
of stabilizing wires. Note: The Amulet (right panel) contains a higher number of stabilizing
nitial experience with the Amplatzer™ Amulet™, Int J Cardiol (2014),
Fig. 2. Comparison between the ACP and the Amulet highlighting the inversion of the disc end-screw. Note: Lateral (A) and oblique (C) view of the ACP showing the protruding end-screwof the disc. Lateral (B) and oblique (D) view of the Amulet highlighting the inverted end-screw of the disc.
Table 2Echocardiographic and procedural characteristics.
n = 24
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that were successfully sealed with a 34 mm device. In addition, four pa-tients presented a very challenging anatomy with a chicken-wing LAAcharacterized by an early (b20 mm from the ostium) and severe bend(~180°) that was occluded by implanting the lobe of the device insidethe wing of the appendage (sandwich technique).
There was no intra-procedural device embolization, stroke or peri-cardial effusion. One patient (4%) presented a transient ST elevation(1 min) during the procedure without further consequence. Trans-thoracic echocardiography 24 h post-procedure also ruled out thepresence of pericardial effusion or device embolization. The meanhospital stay after the procedure was 1.08 ± 0.27 days.
Table 1Baseline characteristics.
n = 25
Age (years) 74.7 ± 7.7Male gender n (%) 16 (64)Hypertension n (%) 22 (88)Diabetes mellitus n (%) 11 (44)Prior stroke n (%) 8 (32)Chronic atrial fibrillation n (%) 16 (64)Left ventricle ejection fraction b50% n (%) 4 [16]Baseline creatinine (mmol/L) 115.3 ± 39.0CHA2DS2-VASC score 4.1 ± 1.7HASBLED 4.6 ± 1.1
Please cite this article as: Freixa X, et al, Left atrial appendage occlusion: Ihttp://dx.doi.org/10.1016/j.ijcard.2014.03.154
3.2. Clinical and echocardiographic follow-up
Clinical follow-up at 2–3 months was available in 21 patients(87.5%). None of them presented any stroke, peripheral embolism,bleeding episode or hospital readmission.
LAA largest angiographic diameters (mm) 23.3 ± 3.8LAA largest TEE diameters (mm) 22.3 ± 4.7LAA mean angiographic diameters (mm) 21.9 ± 3.7LAA mean TEE diameters (mm) 20.4 ± 4.5Device oversizing (compared to the largest diameter)– Angiography and device (mm) 1.1 ± 1.9– TEE and device (mm) 2.2 ± 2.2Device oversizing (compared to the mean diameter)– Angiography and device (mm) 2.3 ± 2.0– TEE and device (mm) 3.6 ± 2.0Amulet dimensions: n (%)– 20 4 (16.6%)– 22 8 (33.3%)– 25 7 (29.2%)– 28 2 (8.3%)– 34 3 (12.5%)Fluoroscopy time (min) 19.8 ± 8.7Combined procedures:– Atrial septal defect closure n (%) 3 (12.5%)
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Follow-up TEE was also available in 21 patients (87.5%). The meantime duration between the procedure and the control TEE was1.46 months (IQR 1.2–2.3 months). All patients presented effectiveLAA sealing as none of them showed any residual leak N3 mm by TEE.Transesophageal echocardiography did not reveal any case of pericardi-al effusion or device embolization. One patient presented device throm-bosis two months after the procedure. By mistake, the patient did notreceive clopidogrel from the pharmacy during the first week after theprocedure. Noteworthy, the same patient had a larger thrombus overan atrial septal defect (ASD) occluder that was implanted on the sameday of his LAA occlusion. A chronic thrombocytopenia with a plateletcount between 50,000 and 100,000 × 109/L was the only hematologiccondition that was found. Since then, the thrombus has been treatedwith dalteparin for 7 months with progressive regression. The patientis still taking dalteparin and no clinical events were associated withthe thrombosis of the device.
4. Discussion
This initial clinical experience with the Amplatzer™ Amulet™ hasshown a remarkable feasibility and safety of the device for percutaneousLAA occlusion.
In our series, the Amulet showed a high successful implantation rate(96%). Although this was only an initial experience with the device, theprocedural success was similar to previous registries with the ACP [4,6,9–11] and Watchman [3,5] despite the presence of very challenginganatomies with three large LAAs (12.5%) and four complex chicken-wing LAAs (16.7%). In fact, the presence of N30 mm LAA is a contraindi-cation for the ACP and Watchman but not for the Amulet as two largersizes are available (31 and 34 mm) [12]. Another challenging situationis the presence of a complex chicken-wing with an early and severebend. In the absence of a clear landing area, the lobe of the devicemust “sit” inside the wing of the LAA. In this setting and given the in-creased number of stabilizing wires, the longer waist length and thelarger disc of the device, we felt that the Amulet providedmore implan-tation forgiveness compared to the ACP andWatchman [13]. The devicecould not be implanted in only one patient (4%) with a small LAA and ashort landing zone. No other percutaneous LAA occlusion systemswereattempted as the LAA was considered too small and short. In this sense,it is important to point out that the length of the lobe is 1 mm (for 16 to22 mm devices) to 3.5 mm (for 25 to 34 mm devices) longer than thefirst generation device (ACP) and therefore it needs a slightly largervolume and longer landing zone (10 to 15 mm). This feature should al-ways be considered when measuring the LAA but is especially relevantin patients with short and tapered appendages.
In contrast with previous registries, no procedural complicationswere observed and none of the patients had pericardial effusion or de-vice embolization. Although certain registries with the ACP have alsoshown a very low complication rate [14] and the experience of ourgroup with LAA occlusion might also explain this finding, the novelfeatures of the devicewere felt to play a relevant role in reducing the oc-currence of complications. The preloadedpackage speeded-up theprep-aration process and may have reduced the risk of air introduction intothe delivery system. In addition, the increased number of stabilizingwires, the longer waist and the larger disc provided more stability andforgiveness to the system, reducing the manipulation inside the LAAand therefore the potential risk of pericardial effusion. Although thenovel inner 0.014″ cable was used in all cases, it was found helpful inonly 2 (8.3%) in which the delivery catheter was not coaxial to theaxis of the LAA. In those cases, some changes in the position of the de-vice, particularly of the disc near the left upper pulmonary vein ridge,were observed after releasing the tension from the delivery cable. Al-though our group did not experience any complication related withthe novel delivery system, the inner 0.014″ wire has been a matter ofcontroversy for some operators as it was found to add complexity tothe device preparation, increase the risk of unintentional unscrew and
Please cite this article as: Freixa X, et al, Left atrial appendage occlusion: Ihttp://dx.doi.org/10.1016/j.ijcard.2014.03.154
reduce the recapturing strength. For those reasons, the delivery systemof the Amulet device is being redesigned in order to achieve a betterbalance between accuracy, simplicity, safety and strength. In thissense, the ACP delivery system might be a good alternative as it hasshown a relevant performance over the last years.
One of the most important findings of our study was the absence ofrelevant residual leaks (N3mm) at TEE follow-up. The absence of resid-ual leaks with the Amulet might be a result of a better sizing processwith the increased experience of the team but also of a better deviceperformance due to the improved anchoring, the larger dimensions ofthe lobe and the improved capacity to fully cover the LAA ostium withthe larger disc [15].
The degree of device oversizing is a pivotal factor for the proceduralsuccess. Following the manufacturer recommendations, the degree ofoversizing with the Amulet should range between 3 and 6 mm in rela-tion to the angiographic or TEE diameters at the landing zone. In our se-ries we use the mean angiographic and TEE diameter as the mainparameter to guide the selection of the device. Since the LAA is oval in80% of patients [16], the largest LAA diameter was felt to be misleadingin certain occasions as it may result in excessive oversizing and thusapposition difficulties in elliptical appendages with large differencesbetween the long and the short-axis diameters. In contrast, the meandiameter was found to be a more useful parameter for balancing thedifferences between axis. In addition, for more circular appendages,the mean diameters were also useful as the small differences betweenthe short and long-axis resulted in very similar values between themean and the largest diameter. The ideal imaging modality for patientscreening and procedural guiding remains to be identified. Although2D-TEE has demonstrated good results, other imaging techniquesnamely 3D-TEE [17] or multi-slice computed tomography (MSCT)might provide better spatial resolution and subsequently better deviceselection.
The short-term follow-up revealed no clinical events or readmissionsin any patient. The incidence of stroke with the ACP ranged between 0and 1.6% per year depending on the series [4,6,9–11]. Control TEE showedno device embolization and only one case of device thrombosis. Interest-ingly, this patient presented a concomitant thrombus in the LAA and ASDdevices that were implanted on the same day. Of note, the risk of devicethrombosiswas increased since the patient did not receive dual antiplate-let therapy after the procedure. In any case, the Amulet has beendesignedto prevent the occurrence of device thrombosis by inverting the attachingend-screw (Fig. 2). The incidence of device thrombosis with the ACPvaried from 0 to 14% [4,6,9–11]. Importantly, most of the ACP thrombosisoccurred at the level of the attaching end-screw pin as this was a promi-nent structure with a late endothelialization [11]. For this reason, therecessed pin of the Amulet is expected to reduce the incidence of devicethrombosis by creating a flat surface that might promote a more rapidendothelialization.
5. Limitations
The results of the present study must be interpreted with caution,as this was a single center and operator observational study with arelatively small number of patients, incomplete TEE follow-up andno comparison with other available devices. The aim of the presentpaper was to describe our initial experience with the Amulet aswell as to provide data that operators might find useful when usingthis device.
In conclusion, the present study describes our initial experiencewiththe newAmplatzer™ Amulet™ device for LAA occlusion. Clinical resultsdemonstrated feasibility with a high rate of procedural success and alow incidence of complications. Further data with a larger number ofpatients and longer follow-upwill be necessary to confirm these results,evaluate the occurrence of device thrombosis and compare the closureperformance with other available devices.
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