Author + information
- †Second Cardiology Department, University of Athens, Attikon University Hospital, Athens, Greece
- ‡Department of Electrophysiology, Heart Center, University of Leipzig, Leipzig, Germany
- ↵∗Reprint requests and correspondence:
Dr. Gerhard Hindricks, University of Leipzig, Heart Center, Department of Electrophysiology, Strümpellstrasse 39, 04289 Leipzig, Germany.
Novel approaches to reduce stroke risk with oral anticoagulant medications or interventions are of the utmost importance to improve the quality of care for patients with atrial fibrillation (AF). Oral anticoagulation with vitamin K antagonists and, more recently, with novel oral anticoagulants (NOACs) has led to a remarkable reduction of stroke risk; however, some of the benefits with NOACs are counterbalanced by increased bleeding risks. The idea of developing interventions that reduce stroke risk but avoid long-term oral anticoagulation and thereby avoid increasing the bleeding risk appears very reasonable and attractive; however, such procedures should be both relatively safe and effective during long-term follow-up. The target for these interventions is the left atrial appendage (LAA), which is the major source for thromboembolism in patients with AF. Initial attempts to reduce stroke risks in patients with AF were made by cardiac surgeons performing excision, suture closure, or stapling of the LAA. These procedures have been performed for many decades in thousands of patients undergoing cardiac surgery for other conditions and, to a lesser extent, as standalone surgical procedures. Surprisingly, there are no data available indicating benefits for patients undergoing these procedures. Indeed, the only randomized study on surgical LAA exclusion, published years ago, did not show reduced stroke events in the treatment group (1). Percutaneous implantable devices for LAA occlusion were introduced more than a decade ago (2). Multiple uncontrolled, nonrandomized reports on the feasibility and safety aspects of percutaneous LAA occlusion techniques have been published, inducing some enthusiasm in favor of LAA occlusion (3). However, until now, only 1 randomized, multicenter controlled trial comparing LAA occlusion with warfarin therapy has been published in a peer-reviewed journal (4). The trial showed noninferiority of LAA occlusion compared with warfarin for the composite endpoint of stroke, systemic embolism, and cardiovascular death (4). Of note, the trial was underpowered to evaluate the major endpoint of interest, stroke. Follow-up data from the trial published recently also showed noninferiority for the composite endpoint but more primary safety events in the LAA occlusion group than in the warfarin group (5). A prospective nonrandomized study analyzed the outcome of AF patients and stroke risk factors with contraindications to oral anticoagulation when treated with an LAA occlusion device (6). The stroke rates observed were lower when compared to the expected stroke rates based on CHADS2 scores (a scoring system with points awarded for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism [doubled]); however, the residual stroke rate in the device group during a relatively short follow-up (14 ± 8 months) was still 2.3% per year. Taken together, it is evident that: 1) no data exist proving benefits for surgical LAA exclusion; 2) device-based LAA occlusion is feasible; 3) reduces stroke rates in selected patients with AF; and 4) has a significant complication rate. Moreover, no study has ever compared the effects of device-based LAA occlusion with NOACs. This certainly needs to be done to further clarify the future role of interventional LAA occlusion.
In this issue of the Journal, Price et al. (7) report the results of a novel method for occlusion of the LAA in patients with AF who are at increased risk for stroke but are considered unsuitable for long-term oral anticoagulation. The method is based on an invasive suture ligation of the LAA with the Lariat device (SentreHeart, Redwood City, California) by a combined transseptal and subxiphoid pericardial approach and could present an alternative to the established technique of LAA occlusion by use of a device as permanent implant and to minimally invasive surgical closure (8).
Experience with the Lariat device is still limited (9,10). The investigators report retrospective data from 8 U.S. sites in 154 patients undergoing an attempt at LAA ligation with the Lariat device. The patients had a high risk for stroke as documented by a median CHADS2 score of 3 and a median CHA2DS2-VASC score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, sex category) of 4; the median HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) was 3.
The results were modest. Device success, defined as suture deployment and a leak of <5 mm in the post-procedure transesophageal echocardiography examination, was achieved in 94%, but there was a high complication rate. Major complications, defined as death, myocardial infarction, stroke, Bleeding Academic Research Consortium bleeding ≥type 3, or cardiac surgery, were observed in 9.7% of the patients. Most frequent complications were major bleedings (9.1%), which in a significant proportion required blood transfusion, and significant pericardial effusion (10.4%). Of note, laceration or perforation of the LAA was seen in 4 patients.
Clinical follow-up data were available in the majority of patients. During a median follow-up of 112 days, the composite of out-of-hospital death, myocardial infarction, or stroke occurred in 3% of patients and late pericardial effusion in 2%. Among these late complications, there were 3 deaths, 2 of which were due to embolic events (lethal stroke and infarcted bowel), and 2 strokes (one nonlethal). Imaging follow-up data were less frequently available (in fewer than one-half of the patients). Importantly, a left atrial thrombus was depicted during follow-up, either with transesophageal echocardiography or with computed tomography, in 4 patients. Moreover, late leaks appeared to occur in a considerable proportion of patients (6% >5 mm leak, 14% <5 mm leak). Although the clinical significance of these leaks remains unknown, they may be associated with thrombus formation and subsequent clinical events or may require additional percutaneous closure.
Information provided by this study is valuable, because it is a systematic and honest depiction of outcomes after a novel treatment method for which only limited information is available. The current paper draws a considerably different picture than previously published single-center studies, which reported significantly lower complication rates (9,10). The studies included somewhat older patients with more comorbidities, but the exact reasons for these discrepancies remain unclear. As the authors correctly admit, their study has several limitations, including the retrospective design, but there are also some other points that limit the interpretation of the data. For instance, patients who did not undergo a planned ligation procedure because of LAA thrombus or because they were not considered candidates based on the computed tomography findings were not included. Because the authors do not give the respective numbers, we cannot know whether this concerned a substantial portion of patients who were screened. Similarly, imaging follow-up was performed in fewer than one-half of the patients. Therefore, we do not have a complete overview of the medium-term results of the procedure.
Patient selection is a major consideration with this type of procedure. Obviously, given the very good results of anticoagulation therapy with regard to stroke prevention in AF patients and the rising variety of available drugs with the addition of NOACs, the target population consists of patients who are not suitable for long-term anticoagulation. Indeed, in a recent European survey, 86% of the centers reported as indication for LAA occlusion the presence of an absolute contraindication to long-term anticoagulation (11). But how do we define lack of suitability for long-term anticoagulation therapy? Although this apparently remains an arbitrary decision by the treating cardiologist, it is somewhat surprising that 60% of the patients included in the present trial were taking oral anticoagulants before the procedure, and even more surprising, that 23% maintained anticoagulation therapy after the procedure. The most plausible explanation for this is a relatively lenient patient selection. However, the study results do not appear to justify the application of such a lenient selection on a wide scale given the high complication rate and the occasional medium-term failure of the method for thrombus prevention.
Intracranial bleeding is one of the most feared complications with anticoagulation therapy, and a patient with intracranial bleeding will certainly be considered a candidate for an LAA closure by means of invasive techniques, if stroke risk is high. NOACs have been consistently associated with a significant reduction of intracranial hemorrhage of approximately 50% compared with warfarin (12), but there are currently no data that would support the use of these agents in patients with previous intracranial bleeding.
The high complication rate in the present series is apparently related to the complexity of the procedure, which requires both a pericardial and a transseptal access. As with most invasive techniques, improved procedural outcomes are anticipated with increasing operators’ experience. Given the limited experience with the Lariat device, reflected in the low median number of included patients per site (n = 19), which notably comprised the entire Lariat experience at each site, this may be an important factor resulting in a significant reduction of complications in the future. However, at present, this is speculation.
Even if a patient is considered to be a candidate for LAA occlusion, why should this new technique be administered instead of the established occlusion with a permanent device or by means of minimally invasive surgery?
Given the considerable incidence of complications, the relatively high incidence of incomplete LAA occlusion, and the lack of long-term efficacy data, we agree with the suggestion of the authors that this method should be reserved only for very well-selected patients with substantial thromboembolic and bleeding risk. At present, the Lariat technique for LAA occlusion is certainly not ready for prime time. Further randomized controlled trials are definitely needed to assess the benefit-to-risk profile of the procedure.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Hindricks serves on advisory boards for St. Jude Medical, Biosense Webster, Biotronik, and Boston Scientific; and he has received grants from St. Jude Medicalhttp://dx.doi.org/10.13039/100006279, Biotronik, and Boston Scientific. Drs. Dagres and Rolf have reported that they have no relationships relative to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Nakai T.,
- Lesh M.D.,
- Gerstenfeld E.P.,
- Virmani R.,
- Jones R.,
- Lee R.J.
- Holmes D.R.,
- Lakkireddy D.R.,
- Whitlock R.P.,
- Waksman R.,
- Mack M.J.
- Reddy V.Y.,
- Doshi S.K.,
- Sievert H.,
- et al.
- Reddy V.Y.,
- Möbius-Winkler S.,
- Miller M.A.,
- et al.
- Price M.J.,
- Gibson D.N.,
- Yakubov S.J.,
- et al.
- Bartus K.,
- Han F.T.,
- Bednarek J.,
- et al.
- Stone D.,
- Byrne T.,
- Pershad A.
- Lip G.Y.,
- Dagres N.,
- Proclemer A.,
- et al.,
- conducted by the Scientific Initiative Committee, European Heart Rhythm Association