Author + information
- Received September 13, 2012
- Revision received February 6, 2013
- Accepted February 14, 2013
- Published online July 9, 2013.
- Marina Urena, MD∗,
- Josep Rodés-Cabau, MD∗∗ (, )
- Xavier Freixa, MD†,
- Jacqueline Saw, MD‡,
- John G. Webb, MD§,
- Mélanie Freeman, MD§,
- Eric Horlick, MD⋮,
- Mark Osten, MD⋮,
- Albert Chan, MD¶,
- Jean-Francois Marquis, MD#,
- Jean Champagne, MD∗ and
- Réda Ibrahim, MD†∗ ()
- ∗Quebec Heart & Lung Institute, Quebec City, Quebec, Canada
- †Montreal Heart Institute, Montreal, Quebec, Canada
- ‡Vancouver General Hospital, Vancouver, British Columbia, Canada
- §St. Paul's Hospital, Vancouver, British Columbia, Canada
- ⋮Toronto General Hospital, Toronto, Ontario, Canada
- ¶Royal Columbian Hospital, Vancouver, British Columbia, Canada
- #Ottawa Heart Institute, Ottawa, Ontario, Canada
Objectives The aim of this study was to evaluate the results associated with left atrial appendage closure (LAAC) with the AMPLATZER Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, Minnesota) in patients with nonvalvular atrial fibrillation and absolute contraindications to anticoagulation therapy.
Background Few data exist on the late outcomes after LAAC in patients with absolute contraindications to warfarin.
Methods A total of 52 patients with nonvalvular atrial fibrillation underwent LAAC with the ACP device in 7 Canadian centers. Most patients received short-term (1 to 3 months) dual-antiplatelet therapy after the procedure and single-antiplatelet therapy thereafter. A transesophageal echocardiography was performed in 74% of patients at the 6-month follow-up. No patient was lost to follow-up (≥12 months in all patients).
Results The mean age and median (interquartile range) CHADS2 score were 74 ± 8 years and 3 (2 to 4), respectively. The procedure was successful in 98.1% of the patients, and the main complications were device embolization (1.9%) and pericardial effusion (1.9%), with no cases of periprocedural stroke. At a mean follow-up of 20 ± 5 months, the rates of death, stroke, systemic embolism, pericardial effusion, and major bleeding were 5.8%, 1.9%, 0%, 1.9%, and 1.9%, respectively. The presence of mild peridevice leak was observed in 16.2% of patients at the 6-month follow-up as evaluated by transesophageal echocardiography. There were no cases of device thrombosis.
Conclusions In patients with nonvalvular atrial fibrillation at high risk of cardioembolic events and absolute contraindications to anticoagulation, LAAC using the ACP device followed by dual-/single-antiplatelet therapy was associated with a low rate of embolic and bleeding events after a mean follow-up of 20 months. No cases of severe residual leak or device thrombosis were observed at the 6-month follow-up.
- AMPLATZER Cardiac Plug
- atrial fibrillation
- percutaneous closure of left atrial appendage
Anticoagulation is contraindicated in as many as 10% of the patients with atrial fibrillation due to major bleeding (1) and as many as 50% of patients discontinue anticoagulation therapy 3 years after initiation of treatment (2). The PROTECT-AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial (3) showed that percutaneous left atrial appendage closure (LAAC) with the WATCHMAN device (Boston Scientific, Natick, Massachusetts) was not inferior to warfarin treatment in patients with nonvalvular atrial fibrillation (NVAF) and no contraindications to anticoagulation. However, published results of LAAC in patients with contraindications to anticoagulation have mainly been limited to small series of patients using the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) device (ev3 Inc., Plymouth, Minnesota), which is no longer available (4–8).
The AMPLATZER Cardiac Plug (ACP) device (St. Jude Medical, Minneapolis, Minnesota) consists of a self-expandable device with a distal lobe and proximal disk connected by an articulating waist (Figs. 1 and 2⇓⇓). Two recent studies reported the feasibility of LAAC with the ACP device in patients with NVAF and contraindications to anticoagulation therapy (9,10), but no data exist on the outcomes of such patients beyond 1-year follow-up. The objective of this study was therefore to evaluate the results associated with LAAC using the ACP device at a follow-up of ≥1 year in patients with NVAF and contraindications to anticoagulation therapy.
The study included a total of 52 consecutive patients with NVAF, contraindications to anticoagulation therapy, and an estimated risk of annual stroke of ≥2%, as determined by a CHADS2 score ≥1 (11) or CHA2DS2-VASc score ≥2 (12) underwent LAAC with the ACP device at 7 Canadian centers.
Device and procedure
The ACP device characteristics and LAAC procedure were previously described in detail (13). Transthoracic echocardiography was performed 24 h after the procedure in all patients.
Procedural success was defined as successful implantation of the ACP device in the left atrial appendage (LAA) with no severe residual leak. Major adverse events (MAEs) at the index hospitalization and during the follow-up period were defined according to the Valve Academic Research Consortium criteria (14) and included cardiovascular death, device embolization, stroke, systemic embolism, myocardial infarction, cardiac tamponade, major bleeding, and the need for cardiovascular surgery.
Heparin (100 U/kg) was administered during the procedure in all cases, and the final dose was adjusted to achieve an activated clotting time >250 s. No anticoagulation therapy was administered after the procedure. Antiplatelet therapy consisting of aspirin (80 to 325 mg/24 h) plus clopidogrel (75 mg/24 h), or aspirin or clopidogrel alone was given according to the operators' discretion for 30 to 180 days after the procedure, after which single-antiplatelet therapy was given.
Follow-up was performed by clinical visits or phone contact at 1, 6, and 12 months and yearly thereafter. Transesophageal echocardiography (TEE) was performed in 37 patients (74% of the patients at risk) at the 6-month follow-up. The presence of device thrombosis and residual intra- or peridevice leak were evaluated. Residual leak was defined as mild if intra- or peridevice flow was observed with a jet width ≥1 and <3 mm and severe if ≥3 mm (15).
Continuous variables are expressed as mean ± SD or median (25th to 75th percentiles) depending on distribution of the data. Categorical variables were compared using a chi-square test or Fisher exact test, and numerical variables using the Student t test or Wilcoxon rank sum test. Comparisons between observed and expected rates of thromboembolic and bleeding events were assessed using binomial tests. Kaplan-Meier curves were used to analyze cumulative outcomes at 2-year follow-up. All analyses were conducted using the SAS statistical package version 9.2 (SAS Institute Inc., Cary, North Carolina).
Procedural results and in-hospital outcomes
The main procedural findings and acute results are shown in Table 3. The procedure was successful in all patients but 1 (98.1%). One patient had a device embolization a few minutes after implantation, most likely related to device undersizing. The device was successfully retrieved percutaneously with no complications.
During the hospitalization period, there were no deaths or strokes. One patient had a transient ischemic attack (TIA) 24 h after the procedure while on aspirin plus clopidogrel therapy. TEE showed the absence of intracardiac thrombi and complete LAA sealing.
The mean follow-up was 20 ± 5 months (≥12 months in all patients). The late clinical outcomes are shown in Table 4. A total of 3 patients (5.8%) died during the follow-up period, and no death was related to the device. One patient had a lacunar stroke 16 months after the procedure, with complete recovery and no sequelae. The patient was receiving clopidogrel at the time of the event. Another patient had a TIA at the 6-month follow-up while on aspirin plus clopidogrel therapy. TEE showed the absence of cardiac thrombi and complete LAA sealing. One patient had a cardiac tamponade requiring pericardiocentesis 1 month after the procedure without evidence of perforation by TEE and computed tomography. Another patient experienced major bleeding related to angiodysplasia. The main clinical characteristics of patients with MAEs during the follow-up period are shown in Table 5. The rates of cumulative observed versus expected MAEs are shown in Figure 3. The Kaplan-Meier survival curves are shown in Figure 4.
Immediately after the procedure, a mild intradevice and peridevice leak were observed in 1 (1.9%) and 6 (11.5%) patients, respectively, and all but 1 leak had disappeared on TEE performed at the 6-month follow-up. A total of 5 patients with no leak immediately after the procedure had a mild peridevice leak as determined by TEE at the 6-month follow-up resulting in a global incidence of peridevice leaks at follow-up of 16.2%. A lower left ventricular ejection fraction was associated with the occurrence of a new peridevice leak at the 6-month follow-up (p = 0.016) (Table 6). None of the patients with residual leaks had a cardioembolic event. There were no cases of device thrombosis or late device embolization.
LAAC with the ACP device: acute results
LAAC with the ACP device was associated with a high rate of procedural success (98.1%) and low rate of periprocedural complications (device embolization, 1.9%; TIA, 1.9%; pericardial effusion, 1.9%). These results compared with those of previous studies on LAAC in patients with contraindications to anticoagulation therapy are shown in Table 7.
This study showed that a strategy of LAAC followed by antiplatelet therapy was associated with a low rate of embolic events (stroke, 1.9%; systemic embolism, 0%) at a mean follow-up of 20 months, lower than the event rate expected on the basis of the characteristics of the study population (Fig. 3). Of note, avoiding a short-term period of anticoagulation after LAAC was not associated with any embolic event or device thrombosis, suggesting that the use of percutaneous LAAC may be a therapeutic alternative to avoid thromboembolic events in patients with absolute contraindications to anticoagulation therapy. Also, the use of single-antiplatelet therapy was associated with a lower-than-expected rate of bleeding, with only 1 serious hemorrhagic event occurring during the follow-up period (1.9%) (Fig. 3). However, 2 cases of asymptomatic ACP device thrombosis were previously reported at 3 and 6 months after LAAC in patients on single-antiplatelet treatment (16), highlighting the need for larger studies to further evaluate the incidence and clinical relevance of device thrombosis in such patients.
Data on LAAC in patients with contraindications to anticoagulation therapy have been limited to a few series of patients who had undergone LAAC with the PLAATO device (4–8), no longer available, the recently presented ASAP (ASA Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology) (17) and the limited experience with the LARIAT device (18). Consistent with the results of the present study, LAAC followed by antiplatelet therapy was associated with a low rate of cerebrovascular events at follow-up (Table 7).
Mild residual leaks after percutaneous LAAC have been reported in as many as 32% and 75% of the patients after WATCHMAN and PLAATO device implantation, respectively (15,19). The low rate of residual leak observed in this study (16.2%) may be related to the double-disk structure of the ACP device with a larger proximal disk that covers the LAA orifice from the left atrium side, contributing to a better sealing of the LAA. Of note, in as many as 5 patients (13.5%) with no leak immediately after the procedure, a new peridevice leak developed over time. This was previously reported using the WATCHMAN device (20) and might be related to incomplete device endothelialization or some degree of device undersizing without periprocedural residual leak due to LAA contraction immediately after the implantation. Also, the fact that a low left ventricular ejection fraction was associated with a peridevice leak suggests that changes in the left atrial dimensions over time might play a role in the occurrence of these late leaks. Importantly, the presence of mild residual leaks was not associated with any cardioembolic event, and this was consistent with the results of previous studies (15).
Although this is the study with the longest follow-up in patients undergoing LAAC with the ACP device to date, the sample size was limited. The rate of expected events was based on historical controls, which have not been validated in the present population. The possibility of a type I error cannot be ruled out. These results will therefore have to be confirmed by randomized, controlled trials. TEE examinations at follow-up were incomplete, not analyzed in an echocardiography core laboratory, and only performed once, which may have limited the possibility of thrombus device detection. Finally, although clinical data were prospectively collected at each center, no pre-specified case report form or event adjudication committee was used.
In patients with NVAF at high risk of cardioembolic events and with contraindications to anticoagulation therapy, percutaneous LAAC with the ACP device followed by dual-/single-antiplatelet therapy was associated with a low rate of cardioembolic and bleeding complications at a mean follow-up of 20 months. LAAC was successful in >98% of patients, with a small proportion having mild residual leak, and no cases of severe residual leak or device thrombosis were observed. However, these results do not provide sufficient evidence to state that LAAC without anticoagulation provides sufficient safety to recommend this approach until adequate data from clinical trials can be obtained. Also, larger studies with a longer follow-up and a more complete echocardiographic follow-up will have to confirm these results.
Drs. Rodés-Cabau, Webb, Horlick, Osten, and Ibrahim are consultants for St. Jude Medical. Dr. Saw is a proctor for St. Jude Medical. Dr. Ibrahim is a proctor for St. Jude Medical and Gore Medical; and has financial relationships (lectures and advisory boards) with Boston Scientific and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- AMPLATZER Cardiac Plug
- left atrial appendage
- left atrial appendage closure
- major adverse event(s)
- nonvalvular atrial fibrillation
- transesophageal echocardiography
- transient ischemic attack
- Received September 13, 2012.
- Revision received February 6, 2013.
- Accepted February 14, 2013.
- 2013 American College of Cardiology Foundation
- Ostermayer S.H.,
- Reisman M.,
- Kramer P.H.,
- et al.
- Block P.C.,
- Burstein S.,
- Casale P.N.,
- et al.
- Bayard Y.L.,
- Omran H.,
- Neuzil P.,
- et al.
- Gage B.F.,
- van Walraven C.,
- Pearce L.,
- et al.
- Lip G.Y.,
- Frison L.,
- Halperin J.L.,
- Lane D.A.
- Leon M.B.,
- Piazza N.,
- Nikolsky E.,
- et al.
- Viles-Gonzalez J.F.,
- Kar S.,
- Douglas P.,
- et al.
- Reddy V.Y.,
- Mobius-Winkler S.,
- Miller M.A.,
- et al.
- Bartus K.,
- Han F.T.,
- Bednarek J.,
- et al.