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Transcatheter left atrial appendage closure for stroke prevention in atrial fi brillation with Amplatzer cardiac plug: the Belgian Registry Joëlle Kefer, Paul Vermeersch, Werner Budts, Tom Depotter, Adel Aminian, Edouard Benit & Francis Stammen To cite this article: Joëlle Kefer, Paul Vermeersch, Werner Budts, Tom Depotter, Adel Aminian, Edouard Benit & Francis Stammen (2013) Transcatheter left atrial appendage closure for stroke prevention in atrial fi brillation with Amplatzer cardiac plug: the Belgian Registry, Acta Cardiologica, 68:6, 551-558, DOI: 10.1080/AC.68.6.8000001 To link to this article: https://doi.org/10.1080/AC.68.6.8000001
Published online: 23 May 2017.
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Acta Cardiol 2013; 68(6): 551-558
[ Original article ]
Transcatheter left atrial appendage closure for stroke prevention in atrial ﬁbrillation with Amplatzer cardiac plug: the Belgian Registry Joëlle KEFER1, MD, PhD; Paul VERMEERSCH2, MD; Werner BUDTS3, MD, PhD; Tom DEPOTTER4, MD; Adel AMINIAN5, MD; Edouard BENIT6, MD; Francis STAMMEN7, MD 1
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium; 2Middelheim ZNA, Antwerpen, Belgium; UZ Leuven, Leuven, Belgium; 4OLV Ziekenhuis Aalst, Belgium; 5CHU Charleroi, Charleroi, Belgium; 6Jessaziekenhuis, Hasselt, Belgium; 7 Heilig Hart Roeselare, Roeselare, Belgium. 3
Aims The aim of the present study was to evaluate the procedural feasibility, the safety and the 1-year outcome following left atrial appendage (LAA) closure using the Amplatzer cardiac plug (ACP) in Belgium.
Methods and results Data were prospectively collected among 90 consecutive patients, undergoing LAA closure with an ACP in 7 Belgian centres between June 2009 and September 2012. The patients (56 males, 74 ± 8 years) were at high risk for stroke (CHA2DS2-VASc = 4.4 ± 1.8) and bleeding (HAS-BLED = 3.3 ± 1.3). Technical success was obtained in all but one patient and procedural success was 95%. Procedural major adverse events (MAE) were 3 tamponades resulting in death in one case. Minor complications were 3 insigniﬁcant pericardial eﬀusions, 2 transient myocardial ischaemia due to air embolism and 1 femoral pseudoaneurysm. At 1-y follow-up, there were 4 deaths, 2 minor strokes, 1 tamponade and 1 myocardial infarction. Overall survival was 94% and freedom from MAE was 88%. In our population, the expected annual stroke risk according to the CHA2DS2-VASc score was 5.08%, while the observed stroke rate was 2.14%/year. Conclusions The Belgian registry shows that LAA closure using the ACP device is feasible and safe. At 1-y follow-up, the observed stroke rate was 2.14%/year, less than predicted by the CHA2DS2-VASc score. Longer follow-up is needed to evaluate the long-term safety and its eﬃcacy in reducing stroke. Keywords Left atrial appendage – stroke prevention – atrial ﬁbrillation – anticoagulant – bleeding.
INTRODUCTION Atrial fibrillation (AF) is the most common arrhythmia in adults, and is responsible for 15-20% of ischaemic strokes1,2. Stroke occurs at an annual rate of about 0.2%, is associated with high costs and is the third leading cause of death after heart disease and cancer3. Stroke may result in serious consequences, especially within
Address for correspondence: Joëlle Kefer, MD, PhD, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Interventional Cardiology, Avenue Hippocrate, 10-2881, 1200 Brussels, Belgium. E-mail: [email protected]
Received 3 July 2013; accepted for publication 18 July 2013.
the context of AF4,5 with a 1-year mortality up to 30% and a high rate of long-term disability. The efficacy of long-term anticoagulation in lowering the risk of cardioembolic stroke and death is well demonstrated6. However, patients at high risk for stroke could have a contraindication for chronic anticoagulation7, and are often outside the therapeutic window8. New anticoagulants have been developed with less pharmacological interactions and less stringent requirements for INR monitoring, but are still associated with a substantial risk for bleeding and intracranial haemorrhage9,10,11. The most important cardiac source of thromboemboli in nonvalvular AF is the left atrial appendage (LAA)12,13. Because LAA is a discrete anatomic structure14, it may be excluded from the systemic circulation by surgical excision15, in order to prevent cardioembolic AF-related stroke. Currently, surgical resection of the LAA is widely
J. Kefer et al.
performed as a concomitant procedure during openheart surgery16. Percutaneous catheter-based devices have been developed to close the LAA by a non-surgical mini-invasive approach : the PLAATO (ev3, Plymouth, MN, USA, no longer manufactured), the WATCHMAN (Boston Scientific, Natick, MA, USA) and the Amplatzer cardiac plug (ACP) (St. Jude Medical, St Paul, MN, USA) devices demonstrated the feasibility of the technique17,18, the non-inferiority versus warfarin for the prevention of stroke19 and the need for a learning curve, even when performed with meticulous care by skilled operators, to reduce the incidence of major adverse events (MAE) < 5% 20-24. Can this type of complex technology be safely introduced in a real world environment? What is its clinical impact on stroke reduction? The Belgian registry reports the initial experience in an all-comer population of patients with AF at high risk for stroke and contra-indication to anticoagulation, undergoing LAA closure with an ACP device in 7 Belgian centres.
Between June 2009 and September 2012, patients treated in Belgium by an ACP implantation for LAA occlusion were prospectively enrolled in the study. Eligible patients for the procedure had paroxysmal or permanent AF, were at high risk for cardioembolic stroke (defined by a CHA2DS2-VASc score ≥ 2) and not candidates for anticoagulant therapy at long term because of severe bleeding, unstable INR, poor compliance, history of fall, high risk for haemorrhage (defined by a HASBLED score ≥ 3), or recurrent embolism under anticoagulant medication. Exclusion criteria were: thrombus in the LAA, unsuitable anatomy (orifice diameter > 28.5 mm, depth < 10 mm) depicted by transoesophageal echocardiography (TEE), significant valvular disease, recent (within 3 months) myocardial infarction, previous closure of the interatrial septum with device implantation, unstable haemodynamics, patient not able to sign the informed consent form. Study protocol
A specific database was created for the study including characteristics of the patients, procedural, echocardiographic and follow-up data. Centres starting this procedure in Belgium were selected to participate in this multicentre registry. All the data were prospectively collected by the centres which reported their results in a specific spreadsheet, including their first patients followed by all the other consecutive cases. Cases not attempted due to LAA thrombus visualized by TEE at
the beginning of the procedure were not included in the study. After the procedure, patients received lifelong low-dose aspirin associated with clopidogrel 75 mg/day for 1 month and anticoagulants were stopped. Endocarditis prophylaxis was recommended. Before discharge, clinical examination, electrocardiography, transthoracic echocardiography and a biplane chest X-ray were performed. A clinical and transthoracic echocardiography follow-up was schedulded at 30 days and 1 year. A TEE was performed systematically at 6 months and repeated in case of an unexpected event during the follow-up, in order to evaluate the LAA seal and the absence of thrombus on the device. Patient survival and occurrence of clinical events during the follow-up were determined from reviews of medical records or direct patient and/or referring physician contact in December 2012. The protocol was approved by the Ethics Committee of the Université Catholique de Louvain (N° B403201111506) and all the patients signed an informed consent form. Procedure
The ACP implantation is performed under general anaesthesia using TEE and fluoroscopic guidance. A sheath is advanced from the femoral vein to the left atrium after transseptal puncture and heparin administration (to achieve an ACT at 250 seconds). Antibiotics are given. An LAA angiogram is performed on several projections, including at least a right anterior oblique cranial view, in order to determine the diameters of the orifice and the landing zone of the LAA. Measurements are also performed by 2- and/or 3-dimensional TEE allowing selection of the optimal size of the ACP device. The ACP is a self-expanding prosthesis constructed from nitinol mesh and polyester patch, that consists of a distal lobe and a proximal disc, connected by a central waist20,21,22. The lobe has stabilizing wires to assure retention in the LAA cavity and the disc seals the outer shape of the orifice (pacifier-principle). The device is available in eight diameters referring to the lobe, stepwise by 2 mm (between 16 and 30 mm). The disc is 4 or 6 mm larger than the lobe. The device selected for implantation is oversized (3-4 mm) with respect to the landing zone diameter. After device deployment, stability tests are performed before release: tire shape of the lobe, concavity of the disk, which should be separated from the lobe, orientation of the device perpendicular to the neck, depth of the lobe (2/3 of the lobe should be deeper than the circumflex artery visualized by TEE), and finally a “gentle-pull” manoeuvre is performed to ensure sufficient anchoring. If needed, the ACP device can be recaptured and redeployed or replaced by a different-size implant. A last contrast angiogram is performed to assess
The Belgian Amplatzer Cardiac Plug Registry
the definitive position of the ACP and the presence of a residual flow in the LAA (figure 1). After release, residual leak is graded by TEE as none, small (< 3 mm jet) or large (≥ 3 mm jet) by colour Doppler; pericardium, left pulmonary veins and mitral valve are systematically inspected in order to exclude pericardial effusion and interference of the prosthesis with the surrounding structures. Deﬁnitions
Technical success was defined as successful delivery and deployment of the ACP device in the LAA. Occlusion success was defined as a seal of the LAA without large residual leak assessed by TEE (< 3 mm jet colour Doppler). Procedural success was defined as a technical success with no MAE. MAE were death, stroke, tamponade, device embolization, systemic embolism, myocardial infarction, major bleeding requiring intervention or transfusion, other complication requiring surgery. Minor complications included insignificant pericardial effusions left untreated, transient myocardial ischaemia because of air embolism, embolization of the device in the venous system by detachment from the delivery system recaptured
Fig. 1 (A) LAA (ostium and landing zone) measurements by TEE. (B) cineangiogram of the LAA performed on a right anterior oblique cranial projection. (C) deployment of the ACP in the LAA cavity, still attached to the delivery cable. (D) angiogram by the delivery sheath after the ACP release.
percutaneously without surgery, or minor bleeding not requiring intervention or transfusion. Statistics
Continuous variables are presented as mean ± 1 standard deviation. Categorical variables are presented as counts and percentages. Estimates for freedom from the composite of death and MAE were obtained by the Kaplan-Meier estimation method. A P value < 0.05 was considered statistically significant. Analyses were performed using the XLSTAT software (version Pro 2009 for Windows, Addinsoft, France).
Characteristics of patients are listed in table 1. There were 90 patients (56 males) with a mean age of 74 ± 8 years (range 50 to 88 years), a mean CHA2DS2-VASc score of 4.4 ± 1.8 (range 2 to 9) and a mean HAS-BLED score of 3.3 ± 1.3 (range 1 to 8). Figure 2 provides the risk scores distribution within the study population. Thirty-seven
J. Kefer et al. Procedure Table 1 Patient characteristics n = 90 Age (y)
mean ± SD
74 ± 8
mean ± SD
4.4 ± 1.8
mean ± SD
3.3 ± 1.3
Congestive heart failure
Age > 75
Vascular disease (CAD-PAD)
Drugs or alcohol
Abnormal renal or liver function
Technical success was obtained in all but one patient (99%) in whom the LAA anatomy was not suitable for closure using the largest ACP device due to the size of the LAA orifice > 30 mm. The appendage was unilobar in 55 (61%) and multilobar in 35 (39%) cases. The mean diameter of the LAA orifice was measured at 21.6 ± 4.4 mm (range: 13-31 mm), the LAA landing zone at 21.3 ± 4.2 mm (range: 10-30 mm). The mean size of the implanted ACP device was 24.5 ± 3.8 mm; figure 3 shows the ACP sizes selected for implantation. In 59 cases, the device implantation was successful at the first attempt. A second attempt was needed in 16 patients and a third in 7 other cases. A successful implantation was obtained at the fourth, fifth, sixth, seventh and ninth attempt in 2, 1, 1, 1 and 2 patients, respectively. The implantation was managed using the first device selected in 93% of cases, while the device had to be changed in 6 cases. The mean fluoroscopy time was 22 ± 14 minutes and the contrast amount was 95 ± 47 ml. There were 38 associated procedures: 34 coronary angiograms, 3 AF ablations and 1 septum closure. Adverse events
There were 4 procedural/in-hospital MAE in 3 patients (4.4%): one tamponade due to a chicken wing shape LAA perforation by the delivery system, treated successfully by the device deployment followed by pericardiocentesis; another tamponade, observed several hours after a successful procedure, was treated succesfully by pericardiocentesis and a last one, due to the LAA perforation, was treated by surgery but resulted in death. The rate of minor complications was 6%: 3 insignificant pericardial effusions left untreated, 2 transient myocardial ischaemia due to air embolism and 1 femoral pseudoaneurysm. There were no strokes, no device embolizations. Procedural success in our population was 95%. The 1-year data were available in 75 patients; Fig. 2 Risk scores distribution in our population. Top: CHA2DS2-VASc score; bottom: HAS-BLED score.
percent of patients experienced a previous stroke and 53% had a history of bleeding. AF was paroxysmal in 44% and permanent in 56% of patients. The mean duration time of AF was 5.6 ± 4.6 years. The most prevalent reasons for being a candidate for LAA closure were: haemorrhage in 55 patients, recurrent embolism under anticoagulant therapy in 15 patients, followed by unstable INR, poor compliance or other contra-indication for anticoagulant therapy; 8 patients combined haemorrhage and recurrent embolism.
Fig. 3 Sizes of the ACP devices implanted in the study. ACP = Amplatzer cardiac plug.
The Belgian Amplatzer Cardiac Plug Registry
during this follow-up period, one additional tamponade was diagnosed 20 days after the procedure and successfully treated by pericardiocentesis, 2 patients experienced a minor ischaemic stroke: they both underwent a TEE showing a sealed LAA with no thrombus on the device. Four deaths were observed, unrelated to the device or the procedure. Causes of death were renal failure, cancer, myocardial infarction and aortic bioprosthetic endocarditis. In this last case, a TEE showed the absence of vegetation on the ACP device, not interfering with the bioprosthetic valve with a complete seal of the LAA. Overall survival was 99% and 94% at 30 days and 1 year, respectively; 30-day and 1-year freedom from MAE was 95% and 88%, respectively (figure 4). The observed stroke rate in our population was 2.14%/year, while the expected annual stroke risk according to the CHA2DS2-VASc score was 5.08%. Table 2 summarizes the complications observed in our population.
Fig. 4 Kaplan-Meier analysis shows the freedom from death and/ or major adverse event after ACP implantation. ACP: Amplatzer cardiac plug.
LAA seal was evaluated by TEE during the procedure immediately after ACP release among 51 patients: a residual leak was graded as none in 42 and small in 8 cases. A large residual leak was observed in only one case; therefore, occlusion of the LAA was achieved in 98% of the investigated cases (figure 5). A TEE follow-up was available 6 to 12 months after the procedure in 50 patients, showing the absence of thrombus on the device in all cases. Among the 8 patients having a small residual leak at the time of the procedure, 3 had a complete seal at follow-up, while 2 remained unchanged and 3 other patients had no TEE control. Unfortunately, the only patient experiencing a large residual leak after ACP implantation had no TEE follow-up.
Fig. 5 Residual leak immediately after Amplatzer cardiac plug release graded by transoesophageal echocardiography.
Table 2 Adverse events
Minor pericardial eﬀusion
J. Kefer et al. Medication
At discharge, after 89 successful procedures, 81 patients were on dual antiplatelet therapy, 3 on only one antiplatelet agent and 5 (5.6%) received anticoagulant therapy. On the 75 patients achieving the 1-y follow-up, 5 patients (6.8%) remained on anticoagulant therapy: one after a recurrent stroke, one after a pulmonary embolism and 3 others because of physician preference; two patients were on dual antiplatelet therapy and the remainder received only one antiplatelet agent (aspirin in 66 and clopidogrel in 2 patients).
DISCUSSION This study, reporting the initial experience obtained in 7 Belgian centres shows that: – LAA closure using the ACP device is feasible in an all-comer population by centres with a beginning experience; – ACP implantation is safe both during the procedure and up to 1 year; – the stroke rate observed is low and less than predicted by the CHA2DS2-VASc score. Feasibility
In our population, ACP was successfully implanted in all but one patient. The technical success was 99%, similar to the Spanish data (34 successful implantations in 35 consecutive patients) reported by Lopez-Minguez et al.23 and to the CAP registry24 (95% successful implantations, 437/460); these recent publications achieved a higher rate of successful procedure than the initial European experience with the ACP20 (technical success of 96%, 137 on 143 patients) or the first series published using the Watchman19 (88% successful implantations, 408/463). This suggests that the teams received appropriate teaching, with a good understanding of the procedure; they included patients with a suitable anatomy using a careful examination of the LAA by TEE, except for one patient who had a very large orifice > 30 mm, underestimated during the screening. Safety
There were 4.4% of MAE and one procedural death due to tamponade. These results are consistent with the CAP registry (3.7%), and slightly better than the initial ACP European registry or the PROTECT AF study19,20, reporting 7.3 and 7.7% of MAE, respectively. There were no procedural strokes, suggesting: (1) a good monitoring of the coagulation (ACT > 250 seconds) during the procedure, and, (2) the absence of air embolism in the brain
during the transseptal puncture or the delivery system manipulation. We did not observe any device embolization, and the size of the device was rarely changed (7%): this could be explained by accurate measurements of the LAA orifice and landing zone using 2- and 3-D TEE plus angiography. All the procedural MAE were tamponade (3.3%) with a rate similar to the series of Park et al. (4%) and of the PROTECT AF trial (5.2%). Only one of them was treated by surgery and was fatal; the two other tamponades were successfully treated by pericardiocentesis. This point suggests that the recommended strategy in case of tamponade due to LAA perforation would be delivery of the ACP in order to minimize the blood flow in the appendage body, and, subsequently, reduce the bleeding, followed by pericardiocentesis and protamin injection. During the 1-year follow-up, we did not observe any late dysfunction or migration of the device and no traumatic damage of the surrounding structures; this is consistent with the PLAATO echocardiographic followup data reported by Hanna et al.25. No thrombus was visualized on the device during the study period but only 50/90 patients underwent only one TEE examination at 6 months. Lopez-Minguez reported 14% of thrombus visualized on the ACP device during a close follow-up, which was done by TEE at 1, 3, 6 and 12 months: 4 on 5 thrombi occured within 3 months after implantation. In this series, only one patient experienced a neurologic event (transient ischaemic attack) related to the thrombus. In the PROTECT AF study, device-associated thrombus was observed in 4.2% of patients. It is possible that the rate of device-related thrombus in the Belgian registry was underreported, due to an incomplete TEE follow-up. In our study, overall survival was 94% and freedom from MAE was 88% at 1 year: the Belgian data are similar to those of the PLAATO registry published by Block et al.18 and the PROTECT AF follow-up trial reported by Reddy et al.26. Stroke rate
In our study, two minor ischaemic strokes were observed during the follow-up, the annual stroke rate was 2.14%. The annual stroke incidence after PLAATO implantation was 2.8% (18) and 2.3% after Watchman implantation19. The design of the ACP device (the lobe is deep in the LAA body and the disk seals the outer shape of the orifice) allows a high rate of effective occlusion of the LAA. In our series, 98% of the investigated patients had a successful occlusion, and 82% had no residual leak immediately after release of the prosthesis. In the PROTECT AF trial, 14% of patients had a residual peri-device flow > 5 mm after 45 days, and continued warfarin. In our study, only 5 patients remained on anticoagulant therapy; all the others received antiplatelet therapy. The predicted annual
The Belgian Amplatzer Cardiac Plug Registry
stroke risk in the Belgian registry using the CHA2DS2VASc score was 5.08%, more than two times higher than the observed stroke rate; our population was also at high risk for bleeding (72% had a HASBLED score ≥ 3 and 53% of patients had a previous haemorrhage). With a reduction of 58% of the stroke rate and the absence of bleeding events during 1 year after the procedure, a reduction of the healthcare costs could be expected in this population at high risk for stroke and bleeding, by using a strategy of LAA closure followed by discontinuation of anticoagulants. The future is really promising for LAA closure: mitigation of the procedural complications by operator’s experience, complete LAA seal achieved by technical improvements of the devices and the delivery systems will make the procedure more efficient, while under medical therapy, despite new anticoagulants, there will still be a progressive increase in bleeding complications over time.
CONCLUSION The Belgian registry shows that, in an all-comer population of patients with AF at high risk for stroke and contraindication to anticoagulation, LAA closure using the ACP device is feasible (technical success 99%), efficient (occlusion success 98%) and safe (procedural success 95%), up to 1 year (overall survival 94%, event-free survival 88%). At 1-year follow-up, the observed stroke rate was 2.14%/year, while the annual stroke risk predicted by the CHA2DS2-VASc score in our population was 5.08%. Longer follow-up is needed to evaluate the long-term safety and its efficacy in reducing stroke.
CONFLICT OF INTEREST: none declared.
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Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123: 417-24. 26. Hanna I, Kolm P, Martin R, Reisman M, Gray W, Block P. Left atrial structure and function after percutaneous left atrial appendage transcatheter occlusion (PLAATO): six-month echocardiographic follow-up. J Am Coll Cardiol 2004; 43: 1868-72. 27. Reddy V, Doshi S, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin J, Holmes D; PROTECT AF Investigators. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3 year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial. Circulation 2013; 127: 720-9.