Author + information
- Received April 8, 2019
- Revision received April 29, 2019
- Accepted April 30, 2019
- Published online August 12, 2019.
- Vivek Y. Reddy, MDa,b,∗ (, )@IcahnMountSinai,
- Petr Neuzil, MD, PhDa,
- Tom de Potter, MDc,
- Jan van der Heyden, MDd,
- Selma C. Tromp, MDe,
- Benno Rensing, MDd,
- Eva Jiresova, MDa,
- Libor Dujka, MDa and
- Veronika Lekesova, MDa
- aDepartment of Cardiology, Homolka Hospital, Prague, Czech Republic
- bDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York, New York
- cDepartment of Cardiology, OLV Ziekenhuis, Aalst, Belgium
- dDepartment of Cardiology, Sint-Antonius Ziekenhuis, Nieuwegein, the Netherlands
- eDepartment of Clinical Neurophysiology, Sint-Antonius Ziekenhuis, Nieuwegein, the Netherlands
- ↵∗Address for correspondence:
Dr. Vivek Y. Reddy, Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, P.O. Box 1030, New York, New York 10029.
Background Patients with high stroke risk and atrial fibrillation who are unsuitable to oral anticoagulants (OACs) require other stroke prevention strategies. A novel permanent coil filter directly placed into both common carotid arteries (CCAs) was designed to capture emboli >1.4 mm in diameter.
Objectives The multicenter, nonrandomized, first-in-human clinical CAPTURE (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients) trial sought to determine the feasibility and safety of bilateral CCA filter placement.
Methods Eligible patients had atrial fibrillation, CHA2DS2-VASc (Congestive heart failure, Hypertension, Age 75 years, Diabetes, Stroke/transient ischemic attack, Vascular disease, Age 65 to 74 years, Sex category) ≥2, OAC unsuitability, CCA size 4.8 to 9.8 mm, and no carotid stenosis >30%. Under ultrasound guidance, after direct transcutaneous carotid puncture with a 24-gauge needle, a motorized unit expels the filter to unfurl in the artery. Patients received aspirin/clopidogrel for 3 months, and aspirin thereafter. Primary endpoints were: 1) procedural success—bilateral, properly positioned CCA filters; and 2) 30-day incidence of major adverse events—death, stroke, major bleeding, filter migration, CCA thrombus, or stenosis. Carotid ultrasounds were conducted post-procedure, pre-discharge, at 1 week, and at 1, 3, 6, and 12 months.
Results At 3 centers, 25 patients were enrolled: age 71 ± 9 years, CHA2DS2-VASc = 4.4 ± 1.0, prior embolism in 48%. Procedure success was 92% (23 of 25 patients); 1 patient had unilateral deployment. There were no device/procedure-related major adverse events; minor puncture site hematomas/edema occurred in 5 of 25 (20%). After 6-month mean follow-up, asymptomatic thrombi were detected in 4 patients (1 bilateral, 4 unilateral), adjudicated as captured (n = 3), unclassified (n = 2), or in situ (n = 0). In all patients, the thrombi dissolved with subcutaneous heparin. In 1 patient, 2 device/procedure-unrelated minor strokes occurred.
Conclusions Permanent carotid filter placement for stroke prophylaxis is technically feasible and safe. (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients [CAPTURE]; NCT03571789)
- atrial fibrillation
- carotid filter
- common carotid artery
- embolic protection
- oral anticoagulation
- stroke prevention
Preventing stroke is arguably the most important clinical management goal in the treatment of atrial fibrillation (AF). In AF patients with CHA2DS2-VASc (Congestive heart failure, Hypertension, Age 75 years, Diabetes, Stroke/transient ischemic attack, Vascular disease, Age 65 to 74 years, Sex category) ≥2 not treated with oral anticoagulants (OAC), the average annual stroke risk weighted by the observed risk distribution is ∼5%/year (2% and 11%/year in CHA2DS2-VASc 2 and 9, respectively) (1,2). Warfarin and nonwarfarin oral anticoagulants (NOACs) reduce this risk by approximately 65% (3). However, in high-risk patients (CHA2DS2-VASc ≥4 or history of stroke), the annual stroke risk despite taking OACs remains excessive at 2% to 4% (4,5). Furthermore, AF-related stroke more often involves the anterior circulation, and it is typically more severe—17% versus 8% mortality in non-AF patients (6).
The pathogenesis of ischemic stroke in AF is most often an embolus emerging from the heart or large arteries and lodging into a cerebral artery. The size of the infarct and extent of brain damage are directly related to the size of the embolus. In AF patients, approximately 80% of strokes are total or partial anterior circulation strokes (major strokes) caused by occlusions of the main branches of the carotid arteries, M1-2 and A1-2 (6). The diameter of these branches is typically >1.5 mm (7–9). Since an embolus with a given size occludes an artery of similar or smaller size, preventing emboli >1.4 mm from reaching the cerebral anterior circulation may reduce the risk of major stroke.
Accordingly, a novel, permanent, bilateral pair of common carotid artery (CCA) filters was developed to capture such emboli >1.4 mm, thereby preventing major cerebral stroke. They are placed into the CCAs using 24-gauge needles that directly puncture the vessel. This technology is intended for high-risk AF patients who may or may not be receiving OAC. In preclinical in vitro and ovine studies: 1) the filter was reproducibly implantable; 2) it was nonthrombogenic, nonocclusive, and mechanically stable; 3) simulated emboli exceeding 1.4 mm were captured; 4) autologous thromboemboli did not disintegrate upon capture; and 5) captured thromboemboli either did not progress or completely regressed over a period of 21 days (Yodfat et al., unpublished data). Herein, we report the results from an ongoing first-in-human clinical trial of the feasibility and safety of the CCA filter, evaluated in AF patients unsuitable for OAC.
The CAPTURE (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients) (NCT03571789) clinical trial is a first-in-human, multicenter, nonrandomized feasibility study of the CCA filter. An independent data safety monitoring board oversaw the safety of the trial, and an independent clinical events committee adjudicated endpoint events (Online Appendix). The trial was funded by Javelin Medical Ltd., the developer of the CCA filter. The study was conducted by Javelin with independent monitoring by a contract clinical research organization (GENAE, Antwerp, Belgium). The trials were approved by each center’s local ethics committee and the corresponding national regulatory agencies.
Patients with persistent or permanent AF (later amended to any AF) unsuitable for OAC and CHA2DS2-VASc ≥4 (later amended to CHA2DS2-VASc ≥2) were included in the trial. Patients with CCA atherosclerosis or carotid stenosis >30% were excluded. The detailed inclusion and exclusion criteria provided in the protocol appear in the Online Appendix. Written informed consent was obtained from all patients.
Permanent carotid coil filter
The permanent carotid coil filter (Vine, Javelin Medical Ltd., Yokneam, Israel) is made from a super-elastic nitinol wire with a circular cross-section (diameter 240 μm). In the undeployed state, the filter assumes a substantially linear shape within the lumen of a 24-gauge insertion needle. Upon deployment, the filter unfolds into a helix that resides within the CCA lumen, connected to a linear stem that traverses the CCA wall and 2 anchors—internal and external (Figures 1 and 2). The helix includes 3 segments: supporting coils, filtering portion, and leading coils. The filtering portion has the outline of a cone with the apex facing upstream. The distance between consecutive coils is approximately 1.0 mm. The filter is inserted using the CCA coil Inserter (Figure 3) under ultrasound guidance: the 24-gauge insertion needle punctures the skin in the neck atop the CCA, and the filter is automatically deployed upon pressing the CCA Inserter operating button. The filter may be retrieved up to 4 h following implantation using a pulling wire that is connected to the stem and extends outside the patient’s skin. The filter is available in 11 sizes (0.5-mm increments) to accommodate CCA diameters between 5 and 10 mm.
Immediately prior to the procedure, patients received low-molecular-weight heparin IV (25 to 50 U/kg incrementally until reaching activated clotting time >200 s) and clopidogrel (loading dose 600 mg). Following CCA diameter measurement, a filter oversized with respect to the CCA by 0.2 to 0.7 mm was selected and was deployed under local anesthesia with ultrasound guidance (Figure 3, Online Video 1). If proper deployment was not achieved, the filter was pulled out using the pulling wire and immediately replaced. Pressure was then applied for several minutes to prevent bleeding from the skin puncture site. The procedure was then repeated for the contralateral CCA. Following bilateral deployment, proper position of implants was verified by x-ray, the pulling wires were cut, and the skin was lifted over the stubs of these wires to “hide” the ends under the skin. Pressure bandages were then applied, and the patient was released to recovery. The first 5 enrolled patients had staged implantation procedures 4 weeks apart, with the filter implanted in the right CCA during the first procedure and in the left CCA during the second procedure.
Post-procedure and follow-up
Following the procedure, patients were prescribed clopidogrel 75 mg daily for 3 months and aspirin (ASA), 81 to 100 mg daily for the duration of the study. Patients were hospitalized overnight following the procedure. They had bilateral ultrasound imaging at 0.5 to 4 h following the procedure. Ultrasound imaging and clinical and neurological follow-up were scheduled at 1 day, 1 week, and 1, 3, 6, and 12 months following the procedure.
The detailed list of endpoints of the CAPTURE study is presented in the Online Appendix. The primary safety endpoint, evaluated at 30 days, was device- or procedure-related major adverse events (MAE), defined as the composite of death, stroke, major bleeding, CCA stenosis >70%, filter migration, CCA thrombus, or any CCA complication requiring endovascular treatment or surgery to repair. The primary feasibility endpoint, also evaluated at 30 days, was procedure success, defined as the absence of device- or procedure-related MAEs, along with proper filter positioning in each CCA. Proper filter position is defined as: 1) having the supporting coil in contact with the CCA wall; 2) the absence of device migration, fracture, or coils outside of the CCA lumen; and 3) no entangled or overlapping coils inside of the CCA lumen. Secondary endpoints included the absence of device-related MAEs and properly positioned filter in each CCA, both evaluated at 3, 6, and 12 months, and successful filter deployment attempts. Thrombi on the filter adjudicated by the CEC as “definitely” or “probably” device-related were counted toward the endpoint, while those adjudicated as “unrelated” or “possibly” device-related were not.
CAPTURE is a feasibility study with no formal hypothesis testing, and therefore, no power analyses were performed. Subjects are followed on an intent-to-treat basis. Study results are presented using descriptive statistics. For continuous variables, the results include number, mean, and SD, where pertinent. Presented data for categorical variables include the number and percent of subjects in each category.
A total of 36 patients signed a consent form and underwent ultrasound screening: 8 patients (22%) were excluded due to prohibitive carotid arterial atherosclerosis (n = 4), stenosis in the internal, external, or common carotid artery (n = 2), excessive CCA lumen diameter variability (n = 1), and CCAs out of the requisite 4.8- to 9.8-mm range. Three additional patients withdrew consent. The remaining 25 patients constituted the study cohort, and were treated between March 2, 2018, and November 2, 2018. The mean age was 71.3 years, 16 (74%) were male, and the mean CHA2DS2-VASc score was 4.4 (Table 1). Nearly one-half of the patient cohort (48%) had a history of stroke, TIA, or thromboembolism, with 12% having a history of multiple strokes. Prior OAC use, either warfarin or a DOAC, occurred in 60% of the patients.
Of the 25-patient cohort, 23 (92%) received properly positioned filters bilaterally (Table 2, Figure 4). One patient received a properly positioned filter unilaterally due to a CCA atheromatous plaque in the contralateral CCA that was not recognized during the screening ultrasound. The final patient underwent an unsuccessful procedure attempt because of poor ultrasonic visibility.
In addition to the 47 successful deployments, there were 9 additional attempts that did not deploy correctly, were all (100%) successfully retracted using the pulling wire, and were immediately reimplanted successfully; thus, the overall rate of successful deployment was 47 of 56 (84%).
There were 0 (0%) MAEs during the procedure (Table 2)—including no cases (0%) of death, stroke, major bleeding, CCA stenosis, filter migration, CCA thrombus, or any CCA complication requiring endovascular treatment or surgery to repair. Five patients (20%) had hematoma with or without concomitant edema immediately following the procedure. These patients were just managed conservatively, as all resolved over time without treatment.
All 25 patients were fully evaluable for the primary endpoints at ≥30 days post-procedure. The primary safety endpoint of absence of device or procedure-related MAEs (death, stroke, major bleeding, CCA stenosis >70%, CCA thrombus, or any CCA complication requiring endovascular treatment or surgery to repair), evaluated at 30 days, was achieved in all 25 (100%) patients (Table 3). The primary feasibility endpoint of procedural success (2 properly positioned filters and absence of device/procedure-related MAEs at 30 days) was achieved in 23 (92%) patients. One patient missed the primary feasibility endpoint due to receiving only 1 implant, and the other patient missed the endpoint due to receiving no implants.
Of the 24 patients receiving at least 1 implant, the median follow-up was 6 months (range 3 to 12 months; interquartile range: 3 to 6 months). All patients (100%) who completed each of these follow-up visits met the secondary safety endpoint of absence of device-related MAEs (Table 4). The secondary performance endpoint of having 2 properly positioned implants was achieved in 23 of 24 (96%), 11 of 12 (92%), and 3 of 4 (75%) of the patients who completed the 3-, 6-, and 12-month follow-up visits, respectively. The patient with unilateral filter placement is the only one who did not meet these secondary performance endpoints. The patient without both filters was excluded from the study after completing the 1-month follow-up. Finally, of the 47 implants that were properly positioned at the end of the procedure, 47 (100%) remained properly positioned at all subsequent follow-ups.
Other outcome assessments
In addition to the primary and secondary safety endpoints, additional outcome assessments were made (Table 5). Three patients died of causes unrelated to the procedure or the device (pneumonia, brain cancer, and heart failure decompensation). One patient had 2 consecutive minor strokes adjudicated by the clinical events committee as device-unrelated. In both instances, cardiovascular magnetic resonance revealed involvement in both posterior and anterior circulation territories. This is most consistent with a shower of emboli originating proximal to the devices. The device did not stop the anterior circulation thrombi, likely because they were <1.4 mm in size. Consistent with the small size of these emboli, and minor nature of the strokes, the patient’s symptoms have resolved completely.
One patient experienced a device-unrelated major bleed (intracranial, subdural, and intracerebral hemorrhage) and traumatic brain injury from a fall at 8 months; this patient largely recovered, with only slight residual aphasia. This patient also had an incidental finding of thrombus on the filter, without symptoms of stroke. Due to the coincident nature of this fall and thrombus, the fall was classified by the CEC as “possibly device-related,” although no causal relationship between the 2 was demonstrated. No patient (0%) had carotid stenosis or occlusion.
There were 6 occurrences of thrombi on the CCA filter (1 bilateral, 4 unilateral) that were identified by ultrasound imaging in 4 patients during the study (Figure 5). All thrombi were reported by the sites as most probably captured, and not in situ thrombi; the CEC adjudicated 3 thrombi as captured, and undetermined in 2. The thrombi varied in thickness between 0.15 and 2.0 mm, and in length between about 2.0 and 10 mm. One patient had bilateral thrombi at 1 month and an additional unilateral thrombus at 2.5 months. Two patients had unilateral thrombi at 1 month, and 1 patient had a unilateral thrombus at 9 months. All thrombi were without concomitant symptoms of stroke. Five of the thrombi resolved with subcutaneous (SQ) low-molecular-weight heparin (8,000 to 10,000 U/12 h) within 0.5 to 5 months. The last thrombus is more recent, and it is almost completely resolved with SQ heparin. No thrombus caused an interruption to blood flow by color Doppler ultrasound.
The present study suggests that deployment of a permanent coil filter in the human CCA is feasible and safe (Central Illustration). The filter captured 6 thromboemboli in 4 patients, none of whom developed stroke symptoms. Furthermore, 5 of the 6 thrombi have resolved with SQ heparin, and the last is almost completely resolved. The per-patient procedural success rate was 92% (23 of 25 patients), and the rate of successful filter deployment was 84% (47 of 56 patients). The 30-day device-related MAE rate was 0%. Minor AEs—puncture site hematoma/edema—occurred in 20% (5 of 25 patients). During an average follow-up of 6 months, there was no evidence of in situ thrombus formation or CCA stenosis.
Implantation failures (9 of 56) were related to implant/CCA sizing mismatch and poor visibility of the CCA and needle in cases of very deep (>4 cm below skin) CCAs. In all cases of implantation failure, the implant was retracted immediately—an important capability that had been part of the design of the device. In 7 cases, another properly-sized filter was then successfully placed; however, in 1 patient, no CCA filter was placed after 2 consecutive failed implantations and successful retractions.
The observed low procedural risk is consistent with evidence that inadvertent carotid artery puncture during jugular cannulation is innocent, despite its relatively common occurrence (∼3% of cannulations) (10). It is also consistent with data showing that CCA punctures with smaller than 18-gauge needles are innocent (11). The risk of inadvertent plaque rupture during carotid puncture was mitigated by excluding atheromatous CCA segments by pre-procedure ultrasound screening. Puncture site skin hematoma was related to soft tissue needle trauma—no peri-CCA hematoma was observed in these cases at ultrasound imaging. In 3 of these cases, there was concomitant neck edema (confirmed by computed tomographic scanning), which most probably resulted from local reaction of soft tissue to blood oozing. All cases of hematoma/edema resolved over time without treatment. These minor adverse events could probably be minimized by more meticulous application of local pressure at the puncture site for several minutes following implantation.
Preclinical studies revealed no neointimal growth on the implant, including the supporting and leading coils that are in contact with the carotid arterial wall (Yodfat et al., unpublished data). This observation is likely related to the relatively low radial force exerted by the implant on the arterial wall (5% to 10% oversized relative to CCA systolic diameter) compared with arterial stents (12). For example, a standard 8-mm stent spanning the carotid bifurcation from a 6-mm common carotid artery to a 4-mm internal carotid artery results in ∼30% and 100% oversizing, respectively. The CCA filter is fixed in place by a stem traversing the arterial wall and equipped with extraluminal and intraluminal anchors. This serves to reduce or even eliminate migration irrespective of the relatively low friction between the implant and the arterial wall.
Thrombi observed on the filter were reported as captured embolic material, not in situ formation. This observation is consistent with the low rate (<1%) of thrombus formation on “free floating” stent and graft struts crossing coronary, renal, and carotid ostia (13–16). In this study, AF patients were treated with dual antiplatelet therapy for 3 months (ASA + clopidogrel) followed by ASA alone; accordingly, the risk of device-related thrombus formation is likely low in both AF patients who are unsuitable for OAC and AF patients with planned (i.e., surgery) or unplanned interruptions of OAC.
The appearance of the thrombi in all cases was elongated and mobile, resembling the string-like appearance of captured thrombi in ovine studies in 5 of 6 cases (Yodfat et al., unpublished data). Thrombus that formed spontaneously during preclinical ovine studies appears very different—these are larger and more regularly shaped echogenic masses (Figure 5). In addition, in situ thrombi observed in these ovine studies invariably appeared within 1 h of implantation, whereas all thrombi observed on filters in the present study appeared between 1 week and 9 months.
All 4 patients with thrombi observed on their filters had a history of stroke, and 2 of them had a history of recurrent stroke. This is consistent with the reasonable hypothesis that they might be more likely to elaborate frequent emboli compared with AF patients without a history of stroke. The rate at which patients were identified with thrombus on the CCA filters in the present study is ∼30% per patient-year (4 patients per 12.5 patient-years), which is approximately 5 to 6 times the expected stroke rate in the study population (1,2,17,18). This is consistent with the 2 important observations. First, embolic showers are frequent in AF patients, as evident from random transcranial Doppler monitoring of the middle cerebral artery: 26% of AF patients during 2 consecutive 1-h monitoring periods (19). Most of these emboli are harmless, but some cause symptomatic stroke or multiple asymptomatic brain infarcts: silent strokes are observed in 45% of AF patients with no history of stroke (20). Second, stroke studies of intraprocedural carotid filter placement suggest that the number of particles coursing through the carotids during the procedure and exceeding 1 mm in size is an order of magnitude greater than the rate of clinical stroke. In carotid artery stenting, emboli of size >1 and >2 mm were observed in 50% and 40% of protection filters, respectively; however, the clinical stroke rate at 30 days was only 2.9%—major at 0.5% and minor at 2.4% (21,22). During transaortic valve implantation, emboli of size >1 and >2 mm were observed in 100% and 20% of temporary carotid filters, respectively, while the stroke rate at 30 days in the control (no filter) arm was only 9.1% (23).
Of the 6 thrombi observed in the present study, 4 originated between 1-week and 1-month post-procedure. All 4 patients with thrombi on the filter had discontinued OACs within 30 days of the implantation procedure. Stroke risk in the 30 days after rivaroxaban temporary (>3 days) or permanent (>30 days) discontinuation is 6% and 26%/year, respectively (24). It is therefore likely that patients who stop OAC produce thromboemboli more frequently right after OAC discontinuation than at “steady state.”
In the present study, all 4 patients with thrombi on filter were treated with SQ heparin until complete thrombus resolution. But the observed absence of stroke in these patients was predicated by the relatively intensive ultrasound surveillance strategy, with subsequent SQ heparin; it is unknown if the natural fibrinolytic process would have likewise been sufficient to ensure thrombus resolution. On the other hand, we should note that evidence to support heparin treatment is also lacking: with IVC filters, at 6 months, 60% of captured emboli regress and 30% do not progress, irrespective of heparin administration (25). It is possible that regression of captured thromboemboli within the arterial circulation would occur regardless of heparin treatment.
There is overlap between the CAPTURE patients and left atrial appendage closure candidates. Left atrial appendage closure devices avoid some limitations of the CCA filter, but they do not prevent nonappendage origin emboli potentially addressable by the filter. Moreover, the filter implantation procedure is less invasive, is faster (minutes), is performed by 1 operator without general anesthesia, does not require transesophageal echocardiography, and will likely become an outpatient procedure in the future. This minimalistic nature of the procedure, combined with the simple workflow, have prompted the design of a randomized trial studying the role of the CCA filter in addition to optimal OAC in high-risk patients (see the following section).
Although this is only a 3-center study of a relatively small number of patients, the feasibility and safety observed in this study provides the basis for larger safety and multicenter randomized clinical trials to definitively establish the safety and efficacy of this therapy. Accordingly, CAPTURE 2 (NCT03892824) is an observational safety trial including patients at high risk for stroke (CHA2DS2-VASc ≥4 and a history of ischemic stroke) receiving OAC/DOAC and bilateral filter implantation. A randomized efficacy trial is also planned to compare OAC/DOAC therapy with OAC/DOAC therapy plus bilateral carotid filter placement with a primary efficacy endpoint of ischemic stroke in filter-protected carotid territories. One advantage of this strategy: because all patients with carotid filters will also receive concomitant OAC, there is less need for periodic ultrasound surveillance to identify captured thromboemboli.
We studied relatively few patients, with few operators. Indeed, this nonrandomized first-in-human trial is best interpreted as a proof-of-concept study requiring further randomized trials to adequately establish the therapy’s place in clinical practice. Although the evidence strongly suggests that the 6 thrombi identified during follow-up were captured thromboemboli, and not in situ thrombus development, this is difficult to definitively prove. One patient had 2 consecutive minor posterior circulation strokes involving multiple territories including posterior circulation territories. This underscores a limitation of the technology—it provides no protection against posterior circulation embolic strokes. Also, it does not protect against submillimetric emboli slipping through the filtering portion. Although such particles are likely to be subclinical or only cause minor strokes, the overall risk-benefit ratio must be established in randomized trials. Finally, we did not collect the reasons for OAC unsuitability in this study.
In this first-in-human study, permanent carotid coil implantation was feasible and safe. The capture of thromboemboli was also demonstrated.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Permanent coil filters placed in the carotid arteries bilaterally can capture thromboembolic material >1.4 mm in diameter without causing stroke.
TRANSLATIONAL OUTLOOK: Larger randomized trials are warranted to evaluate the safety and efficacy of this stroke prevention strategy in patients with atrial fibrillation.
This trial was supported by the manufacturer of the carotid coil filter, Javelin Medical Ltd. Drs. Neuzil, Jiresova, and Dujka are supported by a scientific grant from the Czech Ministry of Health (DRO NNH 00023884 IG 180504). Dr. Reddy has served as a consultant for and has stock in Javelin Medical; has served as a consultant to Abbott, Acutus Medical, Affera, Apama Medical, Aquaheart, Autonomix, Axon, Backbeat, BioSig, Biotronik, Cardiofocus, Cardionomic, CardioNXT/AFTx, Circa Scientific, Corvia Medical, East End Medical, EBR, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Impulse Dynamics, Keystone Heart, LuxCath, Medlumics, Medtronic, Middlepeak, Nuvera, Philips, Stimda, Thermedical, Valcare, and VytronUS; and has equity in Acutus Medical, Affera, Apama Medical, Aquaheart, Autonomix, Backbeat, BioSig, Circa Scientific, Corvia Medical, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Keystone Heart, LuxCath, Manual Surgical Sciences, Medlumics, Middlepeak, Newpace, Nuvera, Surecor, Valcare, Vizara, and VytronUS. Drs. Neuzil, de Potter, van der Heyden, Tromp, and Rensing have received grant support from Javelin Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Abbreviations and Acronyms
- atrial fibrillation
- common carotid artery
- major adverse event
- nonwarfarin oral anticoagulation
- oral anticoagulation
- Received April 8, 2019.
- Revision received April 29, 2019.
- Accepted April 30, 2019.
- 2019 The Authors
- Friberg L.,
- Skeppholm M.,
- Terént A.
- Vanassche T.,
- Lauw M.N.,
- Eikelboom J.W.,
- et al.
- Yoshimura S.,
- Koga M.,
- Sato S.K.,
- et al.
- Saxena R.,
- Lewis S.,
- Berge E.,
- Sandercock P.A.,
- Koudstaal P.J.
- Rai A.T.,
- Hogg J.P.,
- Cline B.,
- Hobbs G.
- Gundlund A.,
- Xian Y.,
- Peterson E.D.,
- et al.
- Cullinane M.,
- Wainwright R.,
- Brown A.,
- Monaghan M.,
- Markus H.S.
- Angelini A.,
- Reimers B.,
- Della Barbera M.,
- et al.
- Kapadia S.R.,
- Kodali S.,
- Makkar R.,
- et al.
- Patel M.R.,
- Hellkamp A.S.,
- Lokhnygina Y.,
- et al.