Author + information
- Received April 21, 2016
- Revision received June 27, 2016
- Accepted July 14, 2016
- Published online October 24, 2016.
- S1936879816311402-390c0c6b3303f7290da7267f3107c03fGennaro Giustino, MDa,
- S1936879816311402-954c0e442dda11ea9fe815a36852b4b3Roxana Mehran, MDa,
- S1936879816311402-68345a795bf62423f259775db3839e7cRoland Veltkamp, MDb,
- S1936879816311402-2c48752bf07f14ec90f35c84c9db62b0Michela Faggioni, MDa,
- S1936879816311402-5b7b375dab503053708852ae29b9fc39Usman Baber, MDa and
- S1936879816311402-1faeab01d76932a52311a433244b7451George D. Dangas, MD, PhDa,∗ ()
- aInterventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bDepartment of Stroke Medicine, Division of Brain Sciences, Imperial College, London, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. George D. Dangas, Mount Sinai Hospital, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
Objectives The aim of this study was to investigate the efficacy and safety of intraprocedural embolic protection (EP) during transcatheter aortic valve replacement (TAVR).
Background Randomized controlled trials (RCTs) investigating the efficacy of EP devices during TAVR were relatively underpowered.
Methods A systematic review and study-level meta-analysis was performed of randomized controlled trials that tested the efficacy and safety of EP during TAVR. Trials using any type of EP and TAVR vascular access were included. Primary imaging efficacy endpoints were total lesion volume and number of new ischemic lesions. Primary clinical efficacy endpoints were any deterioration in National Institutes of Health Stroke Scale and Montreal Cognitive Assessment scores at hospital discharge. Primary analyses were performed using the intention-to-treat approach.
Results Four randomized clinical trials (total n = 252) were included. Use of EP was associated with lower total lesion volume (standardized mean difference −0.65; 95% confidence interval [CI]: −1.06 to −0.25; p = 0.002) and smaller number of new ischemic lesions (standardized mean difference −1.27; 95% CI: −2.45 to −0.09; p = 0.03). EP was associated with a trend toward lower risk for deterioration in National Institutes of Health Stroke Scale score at discharge (risk ratio: 0.55; 95% CI: 0.27 to 1.09; p = 0.09) and higher Montreal Cognitive Assessment score (standardized mean difference 0.40; 95% CI: 0.04 to 0.76; p = 0.03). Risk for overt stroke and all-cause mortality were nonsignificantly lower in the EP group.
Conclusions Use of EP seems to be associated with reductions in imaging markers of cerebral infarction and early clinical neurological effectiveness in patients undergoing TAVR.
Transcatheter aortic valve replacement (TAVR) has emerged as a standard of care to treat degenerative aortic stenosis in patients deemed at high or prohibitive risk for surgical aortic valve replacement (SAVR) (1). Patients undergoing TAVR are often older, frail, and affected by multiple comorbidities, implying a significant risk for thromboembolic cerebrovascular events (1,2). Overt stroke is the most feared complication of TAVR, being associated with a strong effect on morbidity and mortality (3). Early studies suggested that TAVR is associated with an increased risk for stroke compared with medical treatment or SAVR (1,2). Additionally, several studies have demonstrated a very high incidence of new cerebral ischemic lesions on post-procedural diffusion-weighted magnetic resonance imaging (DW-MRI) and of high-intensity transient signals evaluated with transcranial Doppler (4). In current TAVR practice, the rate of overt stroke during or early after TAVR is relatively low (≤2%) (5); however, the frequency and burden of microembolization and cerebral ischemic injury may still have a substantial impact on mid- and long-term cognitive function (4). Therefore, for TAVR to expand to lower risk patients, measures to mitigate neurological risk are warranted. Additionally, several studies in surgical cohorts have demonstrated greater cognitive function impairment post-SAVR compared with patients undergoing coronary artery bypass graft surgery (6,7).
The application of embolic protection (EP) has been explored in several small observational and few randomized studies in TAVR, but its efficacy and safety remain unclear. Therefore, by pooling study-level data from randomized controlled trials (RCTs), in the present meta-analysis we sought to investigate imaging and clinical neurological outcomes associated with intraprocedural EP in patients with severe aortic stenosis undergoing TAVR.
We performed a systematic review and study-level meta-analysis of RCTs that tested the efficacy of EP devices during TAVR according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (8). RCTs investigating the efficacy of EP with any device and for any TAVR vascular access were included. All nonrandomized studies reporting outcomes with EP during TAVR were excluded. We opted to include only RCTs in order to reduce the selection and confounding bias of observational pilot studies. The 2 study groups were defined by randomized assignment to either intraprocedural EP or not. The pre-specified imaging neurological endpoints were total lesion volume (TLV), assessed with DW-MRI, and number of new ischemic lesions. The pre-specified primary clinical neurological endpoints were any clinical deterioration from baseline in National Institutes of Health Stroke Scale (NIHSS) and Montreal Cognitive Assessment (MoCA) scores at discharge. Secondary endpoints were percentage of patients with new cerebral ischemic lesions, mean number of new cerebral ischemic lesions, clinically overt stroke at follow-up, all-cause mortality at follow-up, fluoroscopic time, and acute kidney injury. Imaging endpoints were evaluated as well according to the type of valve implanted (balloon-expandable [BE] vs. self-expandable [SE]), where available. All endpoints were estimated at the maximum time of follow-up reported according to the intention-to-treat (ITT) principle.
MEDLINE, Scopus, the Cochrane Library, and TCTMD.org were searched for abstracts, papers, and conference reports published until December 31, 2015. There were no language restrictions. The following key words were used for the search: “TAVR embolic protection,” “TAVR embolic protection randomized controlled trial,” “TAVR stroke,” “TAVR Claret,” “TAVR Triguard,” and “TAVR Embol-X.” Two investigators (G.G. and M.F.) independently reviewed the studies and reported the results in a structured dataset. Disparities between investigators regarding the inclusion of each trial were resolved by consensus by a third independent investigator (G.D.D.). Pre-specified data elements were extracted from each trial and included in a structured dataset; these elements included type of EP device, baseline characteristics, TAVR access site, type of transcatheter heart valve device implanted, risk for bias, and outcome measures, including imaging endpoints (TLV, mean number of new ischemic lesions, number of patients with new ischemic lesions), clinical endpoints (any worsening in NIHSS or MoCA score, clinically overt stroke, all-cause mortality, acute kidney injury), and procedural variables (fluoroscopic time). Additionally, device success (defined as the correct deployment and retrieval of the device) was captured. Endpoints were collected according to both the ITT and the per treatment (PT) principles. Considering the potential effectiveness of EP devices on intraprocedural (acute) events, the primary analysis included all events reported as close as possible to the date of the index TAVR procedure in each RCT. Risk for bias in each trial for both the primary imaging (TLV) and clinical (risk for NIHSS score deterioration at discharge) endpoints was evaluated using the Cochrane tool, as described by Higgins et al. (9); the following elements potential source of bias were evaluated: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and selective reporting (reporting bias). For each element, a qualitative attribution of bias was given (low risk, intermediate risk, or high risk for bias) by 2 independent investigators (G.G. and M.F.). Disparities between investigators regarding the risk for bias were resolved by a third independent investigator (G.D.D.).
We estimated risk ratios (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) for all available categorical and continuous variables, respectively. Given the possible heterogeneity in outcomes ascertainment across trials, we opted to use the SMD because it is a more conservative summary statistic that expresses the size of the intervention effect in each study relative to the variability observed in that study. During data extraction, continuous variables reported as medians with low and high ends of the range were converted to means and SDs according to the method of Hozo et al. (10). If ranges were not directly reported, these were extracted by visual estimation of the plots. The primary analytic method was the more conservative random-effect model according to DerSimonian and Laird. The primary and secondary analytic approaches (for the imaging and neurological endpoints) were according the ITT and PT principles, respectively. Publication bias for the primary imaging and clinical endpoints was estimated via visual inspection of the funnel plot. Heterogeneity among trials for each outcome was estimated with chi-square tests and quantified with I2 statistics (with I2 >75% indicating substantial heterogeneity) (11). If a trial did not report 1 of the pre-specified primary and efficacy endpoints, it was excluded from that specific analysis. Analysis for the imaging neurological endpoints was stratified by type of valve (BE and SE TAVR devices), with subsequent formal interaction testing. Analyses were conducted using Cochrane’s Review Manager (RevMan) version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark).
The research flow diagram according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines is illustrated in Online Figure 1. Of more than 200 screened reports, 4 RCTs (n = 252) that met the inclusion criteria were found (Table 1).
The CLEAN-TAVI (Claret Embolic Protection and TAVI) trial (NCT01833052) was a double-blind RCT that assigned 100 patients to either EP (n = 50) with the Claret Montage dual filter or to no EP (n = 50). Patients were all treated with femoral access and SE devices. All patients underwent DW-MRI at baseline and on day 2, day 7, and day 30 (not available for data extraction) after TAVR. The reported DW-MRI field strength was 3 T. All patients underwent serial assessment with the NIHSS at 2, 7, and 30 days. DW-MRI endpoints at 7 days were included in this analysis. The dropout rate for DW-MRI assessment at 7 days was 13% (87 of 100). NIHSS results at 2 days were included. The dropout rate for NIHSS assessment was not reported. Device success was achieved in 96% of patients (48 of 50). The primary publication was not available at the time of the execution of this study.
The DEFLECT-III (A Prospective, Randomized Evaluation of the TriGuard™ HDH Embolic Deflection Device During TAVI) trial (NCT02070731) study (12) was a single-blind RCT in which 85 patients were randomized to either EP (n = 46) with the deflector TriGuard HDH or no EP (n = 39). Ninety-six percent of patients underwent TAVR through a transfemoral approach and 4% through a transapical approach. BE valves were implanted in 63% of patients and SE valves in 31%. DW-MRI was performed in all patients on day 4 ± 2 and day 30 ± 7 after TAVR. The DW-MRI field strength was not reported. All patients underwent serial neurological assessment with the NIHSS, MoCA, and computerized Cogstate Research Test. DW-MRI endpoints at 4 days were included. The dropout rate for DW-MRI assessment at 4 days was 30% (33 of 46 in the EP group and 26 of 39 in the no-EP group). NIHSS and MoCA assessment at discharge was included. The dropout rate for NIHSS and MoCA assessment at discharge was 6% (5 of 85). Device success was achieved in 88.9% of patients (40 of 45).
The TAo-EmbolX (Intraprocedural Intraaortic Embolic Protection With the EmbolX Device in Patients Undergoing Transaortic Transcatheter Aortic Valve Implantation) (NCT01735513) trial (13) randomized 30 patients to either EP (n = 14) with Embol-X or no EP (n = 16). All patients underwent TAVR through a transaortic approach, and all patients received BE valves. DW-MRI was performed at baseline (pre-TAVR) and within a week after TAVR. The reported DW-MRI field strength was 1.5-T. No specific serial neurological assessment was performed. The dropout rate for DW-MRI assessment was 0% (0 of 30). Device success was 100% (14 of 14).
The MISTRAL-C (MRI Investigation in TAVI With Claret) trial (NTR4236) study was a multicenter, double-blind randomized trial that randomly assigned 65 patients to TAVR with (n = 32) or without (n = 33) EP with the Sentinel Cerebral Protection System. All patients underwent DW-MRI at baseline (pre-TAVR) and 5 days after TAVR. The reported DW-MRI field strength was 3 T. All patients underwent serial neurocognitive assessment with NIHSS, MoCA, Mini Mental State Examination, and Center for Epidemiological Studies Depression Scale by trained neurologist blinded to allocation at baseline and 5 days after TAVR. Both DW-MRI and clinical neurological evaluation at 5 days were included. The dropout rates for DW-MRI and neurological clinical assessment were 43% (28 of 65) and 26% (17 of 63), respectively. Device success was achieved in 94% of patients (30 of 32).
Overall risk for bias was deemed low in all included RCTs (Online Table 1).
Neurological imaging endpoint
TLV was reported in all 4 RCTs, number of new ischemic lesions in 3 RCTs, and number of patients with new ischemic lesions in 3 RCTs. At ITT analysis, use of EP during TAVR was associated with lower TLV (SMD −0.65; 95% CI: −1.06 to −0.25; I2 = 50%; p = 0.002) (Figure 1A), smaller mean number of new ischemic lesions (SMD −1.28; 95% CI: −2.48 to −0.08; I2 = 90%; p = 0.004) (Figure 1B) and a trend toward a smaller number of patients with new ischemic lesions (72.4% vs. 82.5%; RR: 0.87; 95% CI: 0.73 to 1.04; I2 = 0%; p = 0.12) (Figure 1C). There was no evidence of publication bias for TLV and mean number of new ischemic lesions endpoints on visual inspection of the funnel plot (Online Figure 2). The direction of the effect estimates for the neurological imaging endpoint was consistent in the PT analysis (Online Figure 3). In particular, in PT analysis, use of EP was associated with lower TLV (SMD −0.84; 95% CI: −1.13 to −0.56; I2 = 0%; p < 0.0001) (Online Figure 3A), smaller mean number of new ischemic lesions (SMD −1.30; 95% CI: −2.48 to −0.12; I2 = 90%; p = 0.03) (Online Figure 3B), and a trend toward a smaller number of patients with new ischemic lesions (69.4% vs. 82.5%; RR: 0.83; 95% CI: 0.68 to 1.01; I2 = 0%; p = 0.06) (Online Figure 3C).
Single lesion volume was reported only in the DEFLECT-III and MISTRAL-C trials. Use of EP was associated with a trend toward lower volume by ITT analysis (SMD −0.69; 95% CI: −1.69 to 0.31; I2 = 80%; p = 0.17) (Online Figure 4A), which became highly significant by PT analysis because of a significant change in the effect estimate in the DEFLECT-III trial (SMD −1.05; 95% CI: −1.50 to −0.60; I2 = 0%; p < 0.0001).
TLV and the percentage of patients with new ischemic lesions according to valve type were reported in 2 RCTs. The effect of EP during TAVR was consistent between BE and SE devices, with a nonsignificant interaction test results for both TLV (pinteraction = 0.99) (Figure 2A) and risk for new ischemic lesions (pinteraction = 0.25) (Figure 2B), and absence of within-subgroup heterogeneity for both endpoints (I2 = 0% for TLV in the SE and BE subgroups, I2 = 0% for new ischemic lesions in the SE and BE subgroups).
Neurological clinical endpoint
NIHSS evaluation and MoCA score at discharge were reported in 3 and 2 RCTs, respectively. Patients who were randomized to intraprocedural EP had a trend toward lower risk for worsening in NIHSS score at discharge (8.3% vs. 16.8%; RR: 0.55; 95% CI: 0.27 to 1.09; I2 = 0%; p = 0.09) (Figure 3A). Patients randomized to EP had higher MoCA scores at discharge (SMD: 0.40; 95% CI: 0.04 to 0.76; I2 = 0%; p = 0.03) (Figure 3B). There was no evidence of publication bias for the risk for NIHSS score deterioration and MoCA score at discharge at visual inspection of the funnel plot (Online Figure 2). Neurological clinical endpoint estimates were consistent at the PT analysis (Online Figure 5). Clinically overt stroke was reported in 3 RCTs. EP was associated with a nonsignificant lower risk for stroke at 30-day follow-up (2.2% vs. 4.5%; RR: 0.56; 95% CI: 0.11 to 2.82; I2 = 0%; p = 0.49) (Figure 3C) in the ITT analysis.
Procedural outcomes and safety
Use of EP was associated with increased fluoroscopic time (SMD 0.28; 95% CI: −0.02 to 0.58; I2 = 0%; p = 0.06) (Online Figure 6A). There were no differences in acute kidney injury (2.1% vs. 5.6%; RR: 0.54; 95% CI: 0.05 to 6.11; I2 = 42%; p = 0.62) (Online Figure 6B). No evidence of other major intraprocedural complications became evident in the systematic review of all RCTs.
Finally, EP was associated with a nonsignificant lower risk for all-cause mortality at 30-day follow-up (1.4% vs. 5.1%; RR: 0.32; 95% CI: 0.08 to 1.34; I2 = 0%; p = 0.12) (Figure 4).
In the present meta-analysis we investigated the efficacy and safety of EP use during TAVR. The main findings of the present study are as follows: 1) EP is associated with significantly lower TLV and number of new ischemic lesions after TAVR as assessed with DW-MRI (results were consistent in PT analysis, with an accentuation of the magnitude of the benefit on all 3 neuroimaging endpoints); 2) EP resulted in higher MoCA scores and a trend toward lower risk for any worsening in NIHSS score at discharge (results were consistent in PT analysis); 3) EP was associated with a nonsignificant reduction in stroke and all-cause mortality; and 4) use of EP was safe, with no evidence of increased adverse events alongside a trend toward increased fluoroscopic time.
TAVR has become a standard of care for patients with severe aortic stenosis deemed at high or prohibitive risk for surgery (1). However, several concerns regarding its neurological safety rose early after its introduction into clinical practice (14,15). The incidence of clinically apparent neurological events after TAVR is variable because of clinical endpoint definitions, ascertainment bias, and underdiagnosis due to lack of standardized, routine imaging and neurocognitive assessment (16). Early after TAVR, cerebral embolization is strongly related to technical and procedural factors such as retrograde crossing of the degenerated stenotic aortic valve during diagnostic catheterization; catheter manipulation in an aortic arch with severe atherosclerosis; preparatory balloon aortic valvuloplasty prior to bioprosthesis implantation; eventual device malpositioning, dislodgment, or embolization; and need for valvular balloon post-dilation in case of significant residual paravalvular leak. Histopathologic studies revealed that emboli composition is heterogeneous, with thrombotic material and tissue-derived debris identified in 74% and 63% of patients with embolization, respectively (16). As ischemic brain injury related to TAVR spans a spectrum ranging from clinically overt strokes to seemingly silent ischemic lesions identified with brain imaging studies and neurocognitive assessment, its evaluation is challenging (4,15). Previous studies suggested that new cerebral parenchymal ischemic lesions are common, usually multiple, and distributed to both cerebral hemispheres (4). Clinically covert ischemic brain injury can result in both acute and chronic cognitive and functional impairment, which may have a substantial effect on morbidity and mortality (17). Hence, intraprocedural strategies to mitigate cerebral embolization risk and development of permanent neurological deficit are essential to expand TAVR’s indication to lower risk populations. Additionally, prior studies in surgical cohorts indicated a higher risk for neurocognitive deterioration in patients undergoing SAVR compared with age-matched patients undergoing coronary artery bypass graft surgery (7).
RCTs investigating the efficacy and safety of EP during TAVR have been small and relatively underpowered for imaging and neurocognitive endpoints. Additionally, TAVR studies with serial imaging follow-up are challenging because of technical and logistic limitations in this older and sick patient population, with dropout rates as high as 40% at 30 days (12). The present study-level meta-analysis with enhanced statistical power was intended to better define the role of EP during TAVR. EP was associated with significantly reduced TLV and number of ischemic lesions compared with no EP, alongside higher MoCA score and a trend toward lower risk for NIHSS score worsening at discharge. TLV is currently considered the most informative brain imaging measure, with excellent intrarater and interrater concordance for diffusion-weighted imaging and fluid-attenuated inversion recovery magnetic resonance imaging, and is among the strongest predictors of supratentorial stroke outcomes (18). The MoCA and NIHSS scores are validated metrics of neurocognitive function and neurologic dysfunction, respectively, with excellent interrater reliability and a strong predictor of long-term outcomes after cerebrovascular events (19). Additionally, we observed an accentuation of the benefits of EP on the neuroimaging endpoint in the PT analysis. Possibly, this is consistent with the fact that when device success is achieved, intraprocedural EP is indeed effective in preventing cerebral embolization.
The results of the present meta-analysis must be put into perspective with the recently published DW-MRI study from the BRAVO 2/3 (Effect of Bivalirudin on Aortic Valve Intervention Outcomes 2/3) trial, which tested the safety and efficacy of bivalirudin versus unfractionated heparin in patients undergoing TAVR (20). In this neuroimaging study (in which EP was used in only 2 patients [3.3%]), the mean number of new ischemic lesions was 2.1 ± 3.6 and 0.9 ± 1.1, the prevalence of patients with new ischemic lesions was 65.5% and 58.1%, and the mean TLV was 902 ± 2.933 mm3 and 1.050 ± 3.308 mm3 in the bivalirudin and unfractionated heparin groups, respectively. Compared with the present meta-analysis (mean number of new ischemic lesions 6.1, prevalence of patients with new ischemic lesions 77%, mean TLV 252.4 mm3), the smaller number of new ischemic lesions detected in the BRAVO 2/3 magnetic resonance imaging study may be due to a greater ascertainment in the core laboratories of EP studies or to the lower incidence of such events in contemporary practice at tertiary centers. These findings warrant the implementation of standardized definitions and consistent methods for neuroimaging and neurocognitive evaluation in cardiovascular devices trials.
The effect of EP on neurological imaging endpoints appeared to be uniform between SE and BE valve types, which differ significantly in terms of design and implantation technique. Although this analysis could have been underpowered to detect statistically significant interactions, our results are consistent with previous reports that failed to detect significant differences in stroke incidence and transcranial Doppler-detected embolizations (14,20).
There was no evidence of safety concerns with intraprocedural EP. EP use was associated with overall device success of 97% and longer fluoroscopic time. The small yet possibly clinically relevant EP failure rate must be interpreted carefully. Cardiac computed tomography has become a standard of care at many TAVR centers because it allows the characterization of the ascending aorta, aortic valve anatomy and calcifications, aortic root size, and height of the coronary ostia from the aortic annular plane (21). Additionally, cardiac computed tomographic angiography can be used to assess peripheral vascular access sites and coronary and great epicardial vessel anatomy (21). Therefore, computed tomographic angiography may play a pivotal role in screening patients suitable for EP and/or selecting the optimal type of EP device according to the underlying anatomy.
We failed to detect a significant reduction in clinically overt stroke and all-cause mortality. However, both endpoints were numerically lower in the EP group. The present total sample size may be insufficient to detect significant differences in overt stroke because of the rarity of this event. Larger RCTs designed to detect differences in hard clinical endpoints and long-term neurocognitive assessments are therefore warranted to provide conclusive evidence regarding the efficacy of EP during TAVR. For this purpose, several larger RCTs investigating outcomes with EP are currently ongoing (NCT02214277, NCT02536196). Because a substantial number of emboli during TAVR are of thrombotic origin, complementary antithrombotic strategies to EP are warranted. Recent studies demonstrated that both alternative anticoagulation agents (22) and anticoagulation regimens (23) are safe in terms of neurological complications and are possibly associated with a lower risk for bleeding compared with conventional antithrombotic strategies. Conversely, the role of antiplatelet agents in reducing the risk for intra- and periprocedural cerebrovascular events has been poorly investigated. The role of antiplatelet agents to prevent periprocedural thrombotic complications during TAVR may merit further investigation.
First, the present findings are subject to the inherent limitations of the included RCTs due to study design, follow-up, imaging and neurocognitive assessment dropout, and endpoint ascertainment; additionally, statistical heterogeneity was substantial for some neuroimaging endpoints, underscoring differences across trials. Second, some of the endpoints were not available in all of the included randomized trials, thereby introducing risk for bias, and the different timings and field strengths of magnetic resonance imaging ascertainment introduces heterogeneity in brain ischemic lesion imaging characterization; additionally, 2 of the 4 included RCTs were not published. Third, most of the valves implanted in the included RCTs were SE or BE first-generation TAVR devices; as new-generation TAVR devices seem to be associated with improved efficacy and safety compared with older generations (24), the magnitude of the benefit of EP may be attenuated with newer devices. Fourth, because of the relatively small sample size and low event rates, the present study was underpowered to detect differences in hard clinical endpoints such as stroke and all-cause mortality. Finally, because longer term (≥1-year) follow-up was not available, we could not investigate the effect of intraprocedural EP on long-term functional status.
Neuroprotection with EP devices during TAVR was associated with improved early imaging and clinical neurological outcomes. The neurological benefits of EP appear to be consistent among valve types. Although the differences in overt stroke were not significant, use of intraoperative EP was associated with a numeric stroke reduction, which may become significant in larger RCTs powered for hard endpoints. Given the substantial limitations of the included RCTs, the results of the present meta-analysis are only hypothesis generating, and further prospective, adequately powered RCTs are needed to establish the role of EP during TAVR.
WHAT IS KNOWN? Intraprocedural EP emerged as an attractive strategy to prevent intraprocedural stroke and mitigate the burden of subclinical cerebral embolization during TAVR. Previous RCTs evaluating EP devices were of small size and relatively underpowered to detect differences in neurological imaging and clinical endpoints.
WHAT IS NEW? In this meta-analysis of the available RCTs, use of EP seems to be associated with a significant reduction in imaging markers of cerebral infarction and improved early clinical neurological status.
WHAT IS NEXT? The safety and efficacy of routine EP during TAVR need to be established in prospective RCTs powered to detect differences in hard clinical endpoints.
For supplemental figures and a table, please see the online version of this article.
Dr. Dangas is unpaid consultant to Bayer Daiichi-Sankyo and Medtronic and his spouse has received consulting fees (minor level) for Janssen and AstraZeneca and has stock options (minor level) of Claret Medical. Dr. Mehran has received consulting fees from Janssen and AstraZeneca and stock options (<1%) of Claret Medical. Dr. Veltkamp has received research support and consulting and speaking honoraria from Bayer, Boehringer, Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, Medtronic, Morphosys, St. Jude Medical, Apoplex Medical Technologies, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- diffusion-weighted magnetic resonance imaging
- embolic protection
- Montreal Cognitive Assessment
- National Institutes of Health Stroke Scale
- per treatment
- randomized controlled trial
- risk ratio
- surgical aortic valve replacement
- standardized mean difference
- transcatheter aortic valve replacement
- total lesion volume
- Received April 21, 2016.
- Revision received June 27, 2016.
- Accepted July 14, 2016.
- American College of Cardiology Foundation
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