Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial

Abstract

Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR).

Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR.

Design, setting, and participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016.

Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR.

Main outcomes and measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition.

Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004).

Conclusions and relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.

Trial registration: clinicaltrials.gov Identifier: NCT02389894.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Mack reported having prior uncompensated research relationships with Edwards LifeSciences and Abbott Vascular; and serving on an executive board for Medtronic (uncompensated). Dr Browndyke reported receiving personal fees from Claret Medical Inc. Dr Bowdish reported receiving personal fees from Edwards Lifesciences. Dr Messé reported receiving personal fees from Claret Medical Inc; and receiving personal fees from the Yale Cardiovascular Research Group for serving on a clinical event committtee. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients Through the Cerebral Embolic Protection Device Trial

aThese are the top 3 reasons for not meeting inclusion criteria. There were 1140 patients who were excluded for other reasons. bThe first 12 patients randomized to the control group served as controls for the intra-aortic filtration group only and the other 120 patients served as controls for both the suction-based extraction group and the intra-aortic filtration group.

Figure 2.. Distribution of Volume of Infarcted Brain Tissue by Randomization Group Observed on the Day 7 Diffusion-Weighted MRI Scan

Panels A and B depict the cumulative distribution of observed infarct volume up to the 90th percentile for each treatment group compared with the control group. The y-axis gives the percentage of patients with an observed total infarct volume less than or equal to that of the corresponding infarct volume on the x-axis. IQR indicates interquartile range; MRI, magnetic resonance imaging.

Figure 3.. Prevalence of Delirium Over Time

Delirium was measured by Confusion Assessment Method assessment at baseline and at days 1, 3, and 7. The probability of delirium over time was modeled using generalized estimating equations. The interaction term between days from surgery and randomization group was statistically significant (P < .05), indicating that the incidence of delirium over time was significantly different between the treatment groups and the control group.