Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: ready for the prime time? Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Michigan University on 10/28/14 For personal use only.

Expert Rev. Cardiovasc. Ther. 11(12), 1587–1589 (2013)

Apostolos Tzikas Interbalkan European Medical Centre, Thessaloniki, Greece

Xavier Freixa Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain

Re´da Ibrahim Author for correspondence: Montreal Heart Institute, Universite´ de Montre´al, Montreal, Canada Tel.: +1 514 376 3330; ext. 3800 [email protected]

“Direct comparisons with standard oral anticoagulation treatment need adequately long follow-up in order to conclude weather the technique ‘earns back the money spent upfront’ in terms of efficacy and safety.” Atrial fibrillation (AF) is a very common arrhythmia and its prevalence increases exponentially after 65 years of age [1]. The most fearful complication of AF, thromboembolism, has stimulated vigorous research in the field of antithrombotic drug therapy. The introduction of novel anticoagulants may improve primary and/or secondary prevention compared with the previous standard therapy, warfarin [2–4]. However, all antithrombotic regimens share the same important limitation: increased risk for bleeding. The introduction of percutaneous left atrial appendage (LAA) occlusion for thromboembolic protection in patients with nonvalvular AF can potentially overcome such limitation. Results from the randomized clinical trials PROTECT AF and PREVAIL for the Watchman device and initial registry reports for the Ampatzer Cardiac Plug (ACP) have so far been promising [5,6,101]. Also, percutaneous ligation with the Lariat device has shown favorable initial results [7]. With percutaneous LAA occlusion technology being in its infancy, there are a number of important issues that have to be addressed, starting with the indications for LAA occlusion today. According to the latest update of the European Society of Cardiology guidelines for AF management, percutaneous LAA occlusion may be considered in patients with

increased risk for stroke and contraindication for long-term oral anticoagulation (OAC) therapy (IIb – level of evidence B) [8]. Nonetheless, in real-world clinical practice, physicians also treat patients with other indications, namely those with high bleeding risk (HASBLEED score ‡3), high risk of falling, poor medical compliance and patients who had a stroke while taking OAC drugs. Even pure patient preference for ‘optimal protection’ has occasionally been considered an indication for LAA occlusion. Decision-making is based more on individual patient characteristics than any official recommendation, which is only partly justified by the presence of several comorbidities. In our opinion, contraindication to OAC or documented embolic stroke while on OAC should be the main indications for LAA occlusion. Another question that pertains to the above is whether discontinuation of all antithrombotic drugs is acceptable after LAA occlusion and at which time point. According to the literature, in nonvalvular AF, 90% of thrombi are located in the LAA [9]; there is still an important 10% that could potentially present a significant risk. Moreover, in the initial weeks after the procedure, device endothelialization is incomplete, possibly leading to thrombus formation on the device. For the moment, antithrombotic

KEYWORDS: atrial fibrillation • future perspectives • imaging • left atrial appendage • stroke prevention



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Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Michigan University on 10/28/14 For personal use only.


Tzikas, Freixa & Ibrahim

treatment after LAA occlusion is decided on an individual patient basis. In the PROTECT AF study, patients received warfarin for 45 days and switched to antiplatelets (aspirin ± clopidogrel) if a significant peridevice leak was excluded by trans-esophageal echocardiography (TEE) [5]. Recently, the ASAP study showed that the 45 days transition period on warfarin could be avoided, and antiplatelet treatment is enough after LAA occlusion with the Watchman device [10]. On the other side, the recommendation of dual antiplatelet therapy for 1–3 months and then monotherapy following LAA occlusion with the ACP is rather arbitrary since it is not supported by net clinical data. A reasonable question that plagues physicians relates to the justification for discontinuing all antithrombotic regimens after LAA occlusion, especially in patients with very high HASBLED score or octogenarians. Decision-making can get even more complicated with the introduction of novel OACs, which have potential advantages compared with warfarin. Again, one can only advocate an ‘individual approach.’ Furthermore, it is important to examine whether residual peridevice flow should play a role in the decision-making process. The clinical relevance of ‘incomplete LAA occlusion’ and peridevice flow has been investigated in a subgroup analysis of the PROTECT AF study population [11]. No association between peridevice leaks and thromboembolism at follow-up were found. However, the study was underpowered to detect such an association with confidence due to the small event rate. On the other hand, literature coming from surgically excluded/excised LAA shows that incomplete closure is associated with increased incidence of thrombus in the remnant appendage [12]. Therefore, additional data are needed in order to confirm that peridevice leaks are benign. Until then, complete sealing of the LAA should be a priority and should be taken into account when we try to improve implantation techniques and new device designing. Notably, the ability of TEE to detect slow peridevice flow may be limited, so other imaging modalities like multi-slice computed tomography (MSCT) could also be considered and tested [102]. Detection of peridevice sluggish flow using the color Doppler signal in TEE may give false-negative (very slow flow that remains undetected) or false-positive results (overlap with the pulmonary vein flow). The ideal imaging modality for patient screening and for procedural planning has to be identified. Standard practice is using 2D-TEE, but MSCT or 3D-TEE may have potential advantages. The LAA is a highly variable anatomic structure, and any 2D technique has important limitations, especially in oval-shape configurations [13]. MSCT has been successfully used for patient planning in another recently developed technique, transcatheter aortic valve implantation, showing accuracy and high reproducibility of the measurements [14]. A 3D-TEE performed by an experienced operator can be quite valuable in understanding the complex LAA anatomy. Nevertheless, the accuracy of 3D-TEE measurements remains to be proved. Intracardiac echocardiography shares some of the limitations of 1588

TEE (i.e., relatively low spatial resolution compared with MSCT), and, though of higher cost, carries the advantage of avoiding general anesthesia and being suitable for patients with esophageal disease. The role and the timing of TEE at followup remain unclear; further studies are needed to investigate TEEs positive or negative predictive value for stroke after LAA occlusion. For any imaging modality being used, it is essential to define some anatomical landmarks that can be used for LAA analyses. The left superior pulmonary vein ridge and a short axis view of the left circumflex artery are usually used. Definition of the LAA ostium and ‘neck’ is very important when using an ACP, whereas for the Watchman device, it is important to measure the depth of the LAA and to assess the presence of >1 lobe and its dimensions. In any case, we believe there is a need for developing a ‘common language’ among operators and investigators (both in anatomic and endpoint definitions) that will facilitate knowledge transmission and allow easier comparison of published results. Technically speaking, a LAA occlusion procedure requires certain advanced skills, such as transseptal puncture experience, familiarity with implantable medical devices, as well as good understanding of LAA and surrounding structures’ anatomy. Currently, the vast majority of interventional cardiologists does not have such experience and is routinely performing coronary diagnostics and interventions. Electrophysiologists typically are more familiar with transseptal puncture, though they seldom use self-expanding devices and very large sheaths. Interventionalists specialized in structural and congenital procedures, though presently a minority in comparison to the abovementioned groups, probably combine most of the skills needed for LAA occlusion. On the other hand, the procedure has a quite steep learning curve even for operators with adequate background. Therefore, in order to increase patient safety, ‘adhesion’ of the LAA occlusion technology should be gradual and careful while well-designed training programs should be developed and introduced in clinical practice. Most of the complications related to LAA occlusion happen during or 1–2 days after the procedure. However, late adverse events may occur; therefore, we would recommend a regular follow-up strategy for at least 1 year after the procedure and yearly thereafter. Moreover, careful clinical data collection and exposure in peer-review medical journals are highly advocated for every center performing LAA occlusion procedures, in order to increase our understanding in this new technique. In conclusion, LAA occlusion is a promising, technically demanding and fairly complication-prone preventive procedure. Direct comparisons with standard OAC treatment need adequately long follow-up in order to conclude weather the technique ‘earns back the money spent upfront’ in terms of efficacy and safety. In the meantime, we would praise for careful patient selection, adequate training, clinical vigilance and research in order to ‘get ready for the prime time’. Expert Rev. Cardiovasc. Ther. 11(12), (2013)

Stroke prevention in patients with atrial fibrillation

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict



Papers of special note have been highlighted as: • of interest •• of considerable interest

Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Michigan University on 10/28/14 For personal use only.


Lloyd-Jones DM, Wang TJ, Leip EP et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110, 1042–1046 (2004).


Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361, 1139–1151 (2009).


Connolly SJ, Eikelboom J, Joyner C et al. Apixaban in patients with atrial fibrillation. N. Engl. J. Med. 364, 806–817 (2011).


Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365, 883–891 (2011).



with the subject matter or materials discussed in the manuscript with the exemption of being occasional proctors for St Jude Medical Inc. No writing assistance was utilized in the production of this manuscript.

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. 62, 108–118 (2013). Camm AJ, Lip GY, De Caterina R et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur. Heart J. 33, 2719–2747 (2012). Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann. Thorac. Surg. 61, 755–759 (1996).


Reddy VY, Mo¨bius-Winkler S, Miller MA et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: ASA Plavix feasibility study with Watchman left atrial appendage closure technology (ASAP study). J. Am. Coll. Cardiol. 61(25), 2551–2556 (2013).


Holmes DR, Reddy VY, Turi ZG et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 374, 534–542 (2009).


The single randomized study on LAA occlusion published so far.

A study on Watchman in patients with contraindication to warfarin.


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. 77, 700–706 (2011).


The largest ACP study published so far.

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. 59, 923–929 (2012). •

Important study on incomplete closure.


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. 52, 924–929 (2008).


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. doi:10.1016/j.ijcard.2012.10.031 (2012) (Epub ahead of print).


Tzikas A, Schultz CJ, Piazza N et al. Assessment of the aortic annulus by multislice computed tomography, contrast aortography, and trans-thoracic echocardiography in patients referred for transcatheter aortic valve implantation. Catheter Cardiovasc. Interv. 77, 868–875 (2011).

Websites 101

The Heart. www.theheart.org/article/1515107.do


Role of MSCT in LAAO. www.laaocclusion.org/lectures/ is_there_a_role_in_of_msct_prior_ to_the_laa_occlusion_procedure_ and_in_post_procedure_care


Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: ready for the prime time?

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