Author + information
- aDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, California
- bDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. Michael S. Lee, UCLA Medical Center, David Geffen School of Medicine at UCLA, 100 UCLA Medical Plaza, Suite 630, Los Angeles California 90095-7392.
Atrial fibrillation is the most common cardiac arrhythmia, and ischemic stroke arguably represents the most significant sequelae of this rhythm disturbance. Current therapies for atrial fibrillation include targeting of risk factors, systemic medications, or invasive procedures such as catheter ablation; it must be remembered that these strategies only mitigate, but do not eliminate, the risk of stroke. Accordingly, atrial fibrillation remains a significant health care burden, and our therapies need improvement. In order to further improve outcomes, we must think “outside of the box,” or in some cases, outside of the heart, in order to broaden our therapeutic options.
In this issue of the Journal, Reddy et al. (1) present the CAPTURE (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients) trial, which is a first-in-human feasibility and safety study of a novel common carotid artery (CCA) filter device for stroke prevention in patients with atrial fibrillation. Their study is a nonrandomized trial of 25 patients across 3 centers who had atrial fibrillation with elevated stroke risk with a CHA2DS2-VASc score of ≥2, but who were deemed unable to take anticoagulation therapy. The investigators should be commended for undertaking an original investigation into a new therapy, particularly for patients in whom anticoagulation is not an option.
As the investigators point out, there is similarity between patients studied in the left atrial appendage closure (LAAC) trials and the patients selected for the CAPTURE trial. Current guidelines give a Class IIb recommendation for consideration of LAAC for patients with atrial fibrillation at elevated risk of embolic stroke with contraindications to anticoagulation therapy (2). Continued longer-term analysis of the 2 randomized clinical trials of the Watchman left atrial appendage occlusion device (the PROTECT AF [WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation] and PREVAIL [Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy] trials) demonstrate overall noninferiority of the Watchman device compared with warfarin anticoagulation with a significant reduction in hemorrhagic strokes as well as an improvement in survival (3). However, ischemic strokes were not reduced. In addition, although significantly improved compared with the initial experiences with the device, there are still well-described complications including pericardial effusion, vascular access bleeding and periprocedural stroke. It must be remembered that local site-specific therapy with LAAC does not prevent thromboemboli that originate outside of the LAA, which may occur ≤11% of the time in patients with nonvalvular atrial fibrillation or 56% of the time in those with valvular atrial fibrillation (4). An additional issue with the Watchman device is that in the United States (although not in Europe), instructions for use include 6 weeks of anticoagulation following implantation aimed at enhancing full endothelialization of the device.
Against this background, other strategies have been explored. An implantable deflector was developed in the past that was designed to deflect embolic material flowing through the CCA preferentially to the external carotid artery, thus decreasing the chance of large-vessel occlusion in the distribution of the internal carotid artery. This device is not currently being developed. In contrast to this approach, Reddy et al. (1) have introduced the concept of a “permanent” CCA helical filter, designed to capture emboli >1.4 mm in size. That specific size was selected on the basis of information that in patients with atrial fibrillation, the major anterior circulation strokes are caused by occlusions of the main branches of the carotid arteries (M1 and M2 and A1 and A2) (5–7) in the paper. The diameter of these branches is typically >1.5 mm. Accordingly, the investigators selected a filter size to capture emboli >1.4 mm thus preventing major strokes. The device implantation had a success rate of 92% with no observed major adverse events. There were 5 patients who developed local hematomas, which resolved with conservative management. Four patients had 6 thrombi that were visualized on ultrasound during the follow-up period. As this was a single-arm study with no comparator, no definitive statement can be made as to prevention of cerebrovascular events; however, the implication is that at least some of these visualized thrombi represent averted strokes. An extremely important limitation is the lack of any brain imaging with computed tomography or magnetic resonance imaging. Such imaging performed before implantation, and post-implantation and during follow-up will be essential.
Although this novel therapy generates enthusiasm, caution must be taken. Long-term data are required. Although in situ thrombosis was not definitively seen in their study, whether the device might be associated with the development of local thrombi that can then embolize is a concern. Additionally, the long-term vascular effects are unknown. The development of carotid stenosis, dissection, or pseudoaneurysm would significantly complicate the care of these patients who already have multiple comorbid conditions and are at high stroke risk. In addition, the device can address only large cardioembolic events in the anterior circulation, but the posterior circulation remains vulnerable. One of the most common causes of posterior circulation stroke is a cardioembolic etiology (8). Indeed, the investigators point out this limitation because one of their patients had 2 posterior circulation strokes during the follow-up period. This being the case, anticoagulation would likely still be recommended in patients who receive this CCA filter, if they can tolerate the medication. A final consideration is that only strokes in large vessels caused by emboli >1.4 mm will be potentially prevented. More distal strokes caused by smaller emboli will continue. Brain imaging in subsequent studies must be an essential component or endpoint to assess those.
The investigators have accomplished a rare feat in the treatment of atrial fibrillation, which is the development of a therapy with a new target in the pathophysiology of the disease. Many of our therapies for atrial fibrillation are aimed specifically at the heart (e.g., catheter ablation, left atrial appendage closure); it is exciting to see a new potential target for the prevention of its catastrophic sequelae. Future studies should be informative. The investigators have introduced the forthcoming CAPTURE 2 trial, which will investigate the use of the CCA filter in addition to oral anticoagulation. As the investigators point out, the risk of thromboembolism in patients who are adherent to oral anticoagulation is low (although certainly not zero); such a study would need to be large in order to detect a small incremental benefit. Thus, it will be imperative to establish the long-term safety of this method before expanding the therapeutic application of this novel device to include a lower-risk patient population.
↵∗ 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.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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