[Skip to Content]
[Skip to Content Landing]

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

Educational Objective To learn the effectiveness of cerebral embolic protection devices in reducing ischemic central nervous system injury in patients undergoing surgical aortic valve replacement.
1 Credit CME
Key Points

Question  Can cerebral embolic protection devices reduce the incidence of stroke after surgical aortic valve replacement?

Findings  In this randomized clinical trial that included 383 patients, there was no significant difference in freedom from central nervous system infarction between suction-based extraction and a standard aortic cannula (32.0% vs 33.3%, respectively) or between intra-aortic filtration and a standard aortic cannula (25.6% vs 32.4%, respectively).

Meaning  The incidence of central nervous system infarction after surgical aortic valve replacement was not altered by either of the 2 cerebral embolic protection devices.

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

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ from JAMA Network is your new home for CME and MOC from a source you trust. Earn AMA PRA Category 1 CME Credit™ from relevant articles, audio, and Clinical Challenge image quizzes, explore interactives and videos, and – depending on your specialty or state – have your MOC points automatically transferred to the relevant board. Learn more about CME

Article Information

Corresponding Author: Annetine C. Gelijns, PhD, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1077, New York, NY 10029 (annetine.gelijns@mssm.edu).

Accepted for Publication: July 6, 2017.

Author Contributions: Ms Overbey and Dr Parides had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Mack and Acker are both first authors.

Concept and design: Mack, Acker, Gelijns, Parides, Browndyke, Moskowitz, Ailawadi, Thourani, Moquete, Iribarne, Perrault, Bowdish, Davatzikos, Winkle, Miller, Taddei-Peters, Rose, Weisel, Furie, Bagiella, Moy, O’Gara.

Acquisition, analysis, or interpretation of data: Mack, Acker, Gelijns, Overbey, Parides, Browndyke, Groh, Moskowitz, Jeffries, Ailawadi, Moquete, Iribarne, Voisine, Perrault, Bilello, Davatzikos, Mangusan, Smith, Michler, O'Sullivan, Taddei-Peters, Rose, Weisel, Bagiella, O'Gara, Messé.

Drafting of the manuscript: Mack, Acker, Gelijns, Overbey, Browndyke, Moskowitz, Moquete, Iribarne, Bowdish, O'Sullivan, Bagiella, O'Gara.

Critical revision of the manuscript for important intellectual content: Mack, Acker, Gelijns, Overbey, Parides, Browndyke, Groh, Jeffries, Ailawadi, Thourani, Moquete, Iribarne, Voisine, Perrault, Bowdish, Bilello, Davatzikos, Mangusan, Winkle, Smith, Michler, Miller, Taddei-Peters, Rose, Weisel, Furie, Bagiella, Moy, O'Gara, Messé.

Statistical analysis: Overbey, Parides, Browndyke, Jeffries, Iribarne, Perrault, Smith, Rose, Bagiella.

Obtained funding: Gelijns, Parides, Ailawadi, Bowdish, Michler, Miller, Rose, Weisel, Moy.

Administrative, technical, or material support: Acker, Browndyke, Iribarne, Voisine, Bowdish, Bilello, Michler, Miller, O'Sullivan, Taddei-Peters, Rose, Weisel.

Supervision: Mack, Acker, Gelijns, Parides, Groh, Moskowitz, Ailawadi, Thourani, Moquete, Perrault, Winkle, Michler, O'Sullivan, Weisel, O'Gara, Messé.

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.

Funding/Support: The trial was supported by cooperative agreement U01 HL088942 funded by the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, and the Canadian Institutes for Health Research. Additional support was provided by grant R01 AG014971 from the National Institutes of Health (Dr Davatzikos). Training in use of the Embol-X (Edwards Lifesciences) and CardioGard (CardioGard) devices was provided by the companies but they did not provide financial support for the study.

Role of the Funder/Sponsor: The representatives from the National Institutes of Health were involved in study design, management, and review of the manuscript. Edwards Lifesciences and CardioGard had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript or the decision to submit for publication.

Group Information: The members of the Cardiothoracic Surgical Trials Network (CTSN) are Dennis Buxton, Nancy L. Geller, Catherine Burke, Albert Lee, and Tyrone Smith (National Heart, Lung, and Blood Institute); Ilana Kogan Gombos (Canadian Institutes of Health Research); Kinjal Shah, Stephanie Pan, Alishba Aslam, Helena Chang, Melissa Chase, Kayla Dellefratte, Seth Goldfarb, Lopa Gupta, Katherine Kirkwood, Edlira Dobrev, Ron Levitan, Andrea Ratner, Milerva Santos, Nancy Sledz-Joyce, and Xia Ye (International Center for Health Outcomes and Innovation Research at Icahn School of Medicine at Mount Sinai; data coordinating center); Amanda Fenlon, Katherine Harrington, Kelly Hutcheson, Melissa Johnson, Jessica Jones, Megan Kolb, Sarah Lam, Lucy Miranda, Jackie Ward, Renessa Whitman, Brittany Zingler, William Ryan, Robert L. Smith, Pedro Nosnik, and Justin Whisenant (Baylor Research Institute); Edward G. Soltesz, Stephanie Mick, Irene Katzan, Brian Strippy, Shoi Smith, Michelle Garcia, and Mary Alice Bowman (Cleveland Clinic Foundation); Michael Argenziano (primary investigator), Michael Borger, Hiroo Takayama, Lyn Goldsmith, Nadia Sookraj, Talaya McCright-Gill, and Sowmya Sreekanth (Columbia University); Jock N. McCullough (primary investigator), Joseph P. DeSimone, Anthony W. DiScipio, Henry Stokes, Amanda St Ivany, Gaylin Petty, and Jim Hart (Dartmouth-Hitchcock Medical Center); John H. Alexander, Carmelo A. Milano, Donald D. Glower, Stacey Welsh, Sarah Casalinova, Victoria Johnson, Derek Smith, and Greg Tipton (Duke University); Robert Guyton, Omar Lattouf, Michael Halkos, Kim Baio, Tamara Prince, Natascha Cook, and Alexis A. Neill (Emory University); François Dagenais, Robert Laforce Jr, Kim O’Connor, Gladys Dussault, Manon Caouette, Hugo Tremblay, Nathalie Gagne, and Patricia Landry (Hôpital Laval); John G. Short, Reid D. Taylor, Tracy Nanney, Holly Aubart, Kristin Cross, Leslie McPeters, Christina Riggsbee, and Lucy Rixey (Mission Hospital); Joseph J. DeRose Jr, Daniel J. Goldstein, Ricardo A. Bello, William Jakobleff, Kathryn Kirchoff, Richard Zampolin, Rebecca Meli, Juan Garcia, Jon Goldenberg, and Lauren Kealy (Montefiore-Einstein Heart Center); Denis Bouchard, Michel Carrier, Jean François Tanguay, Pierre Pagé, Céline Odier, Filippo Codemartiri, Jonathan Lacharité, and Sophie Robichaud (Montreal Heart Institute); Keith A. Horvath (primary investigator), Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Greg Kumkumian, Mark Milner, and Zurab Nadareishvili (National Institutes of Health Heart Center at Suburban Hospital); Bryan A. Whitson (primary investigator), Juan Crestellano, Xuan Nguyen, Mohit Datta, Asia McDavid, and Denise Fadorsen (Ohio State University Medical Center); Maral Ouzounian (primary investigator), Terry Yau, Cheryl Jaigobin, Narinder Paul, Walter Kucharczyk, Nishit Fumakia, and Shakira Christie (Toronto General Hospital); John C. Mullen (primary investigator), Asvina Bissonauth, and Alexandra Hripko (University of Alberta Hospital); Bradley Taylor (primary investigator), James Gammie, John Cole, Robert Morales, Kristen Mackowick, Stephanie Deasey, and Julia Collins (University of Maryland); Jesse Raiten, Cen Zhang, Mary Lou Mayer, Caitlin McDonald, Holley Fok, Breanna Maffei, Stephen Cresse, and Christine Gepty (University of Pennsylvania); Vaughn A. Starnes, David Shavalle, Christi Heck, Amy Hackmann, Craig Baker, Fernando Fleischman, Mark Cunningham, Meng Law, Edward Lozano, Michelle Hernandez, and Sylvia Ramos (University of Southern California); Irving L. Kron, Karen Johnston, Ravi K. Ghanta, Leora Yarboro, Joe Carrera, Nicole Chiota-McCollum, Sandra Burks, Mike Cosner, China Green, Samantha Loya, Helen Kim, Jennifer Phillips, and Rachel Simon (University of Virginia).

Additional Contributions: We thank David A. Bull (chair), Patrice Desvigne-Nickens (executive secretary), Dennis O. Dixon, Rebecca Gottesman, Mark Haigney, Richard Holubkov, Constantino Iadecola, Alice Jacobs, Eric M. Meslin, John M. Murkin, and John A. Spertus (protocol review committee); Frank Sellke (chair), Cheryl L. McDonald (executive secretary), John Canty, Neal Dickert, Dennis O. Dixon, John S. Ikonomidis, Kyung Mann Kim, David O. Williams, Clyde W. Yancy, Seemant Chaturvedi, and Marc Chimowitz (data and safety monitoring board); James C. Fang and Wayne Richenbacher (medical monitors); Vivek Rao (chair), Rachel Miller, Jennifer Cook, David D’Alessandro, Frederick Han, Sean Pinney, and Mary N. Walsh (overall event adjudication committee); David Greer (chair), Koto Ishida, and Christian Stapf (events adjudication committee neurology subcommittee); Judy Hung, Xin Zeng, David Hung, and Sudarat Satitthummanid (echo core laboratory at Massachusetts General Hospital); Guray Erus, Lauren Karpf, and Lisa Desiderio (MRI core laboratory at the University of Pennsylvania); Joseph P. Mathew, Michael L. James, Yanne Toulgoat-Dubois, and Rachele Brassard (neurocognitive core laboratory at Duke University Medical Center); and Renu Virmanu, Maria E. Romero, and Ryan Braumann (histopathology core laboratory at CVPath Institute).

Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the US Department of Health and Human Services.

References
1.
Duke Clinical Research Institute. Adult cardiac surgery database: executive summary 10 years. http://www.sts.org/sites/default/files/documents/2016Harvest2_ExecutiveSummary_new.pdf. Accessed July 10, 2017.
2.
Grover  FL, Vemulapalli  S, Carroll  JD,  et al.  2016 Annual report of the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.  Ann Thorac Surg. 2017;103(3):1021-1035.PubMedGoogle ScholarCrossref
3.
Floyd  TF, Shah  PN, Price  CC,  et al.  Clinically silent cerebral ischemic events after cardiac surgery.  Ann Thorac Surg. 2006;81(6):2160-2166.PubMedGoogle ScholarCrossref
4.
Alassar  A, Soppa  G, Edsell  M,  et al.  Incidence and mechanisms of cerebral ischemia after transcatheter aortic valve implantation compared with surgical aortic valve replacement.  Ann Thorac Surg. 2015;99(3):802-808.PubMedGoogle ScholarCrossref
5.
Messé  SR, Acker  MA, Kasner  SE,  et al.  Stroke after aortic valve surgery.  Circulation. 2014;129(22):2253-2261.PubMedGoogle ScholarCrossref
6.
Puskas  JD, Winston  AD, Wright  CE,  et al.  Stroke after coronary artery operation.  Ann Thorac Surg. 2000;69(4):1053-1056.PubMedGoogle ScholarCrossref
7.
Salazar  JD, Wityk  RJ, Grega  MA,  et al.  Stroke after cardiac surgery: short- and long-term outcomes.  Ann Thorac Surg. 2001;72(4):1195-1201.PubMedGoogle ScholarCrossref
8.
Banbury  MK, Kouchoukos  NT, Allen  KB,  et al.  Emboli capture using the Embol-X intraaortic filter in cardiac surgery.  Ann Thorac Surg. 2003;76(2):508-515.PubMedGoogle ScholarCrossref
9.
Bolotin  G, Huber  CH, Shani  L,  et al.  Novel emboli protection system during cardiac surgery.  Ann Thorac Surg. 2014;98(5):1627-1633.PubMedGoogle ScholarCrossref
10.
Sacco  RL, Kasner  SE, Broderick  JP,  et al.  An updated definition of stroke for the 21st century.  Stroke. 2013;44(7):2064-2089.PubMedGoogle ScholarCrossref
11.
DeMets  DL, Lan  KKG.  Interim analysis: the alpha spending function approach.  Stat Med. 1994;13(13-14):1341-1352.PubMedGoogle ScholarCrossref
12.
O’Brien  PC, Fleming  TR.  A multiple testing procedure for clinical trials.  Biometrics. 1979;35(3):549-556.PubMedGoogle ScholarCrossref
13.
Glas  KE, Swaminathan  M, Reeves  ST,  et al.  Guidelines for the performance of a comprehensive intraoperative epiaortic ultrasonographic examination.  J Am Soc Echocardiogr. 2007;20(11):1227-1235.PubMedGoogle ScholarCrossref
14.
Stolz  E, Gerriets  T, Kluge  A,  et al.  Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement.  Stroke. 2004;35(4):888-892.PubMedGoogle ScholarCrossref
15.
Cook  DJ, Huston  J  III, Trenerry  MR,  et al.  Postcardiac surgical cognitive impairment in the aged using diffusion-weighted magnetic resonance imaging.  Ann Thorac Surg. 2007;83(4):1389-1395.PubMedGoogle ScholarCrossref
16.
Barber  PA, Hach  S, Tippett  LJ,  et al.  Cerebral ischemic lesions on diffusion-weighted imaging are associated with neurocognitive decline after cardiac surgery.  Stroke. 2008;39(5):1427-1433.PubMedGoogle ScholarCrossref
17.
Patel  N, Horsfield  MA, Banahan  C,  et al.  Impact of perioperative infarcts after cardiac surgery.  Stroke. 2015;46(3):680-686.PubMedGoogle ScholarCrossref
18.
Knipp  SC, Matatko  N, Schlamann  M,  et al.  Small ischemic brain lesions after cardiac valve replacement detected by diffusion-weighted magnetic resonance imaging.  Eur J Cardiothorac Surg. 2005;28(1):88-96.PubMedGoogle ScholarCrossref
19.
Uddin  A, Fairbairn  TA, Djoukhader  IK,  et al.  Consequence of cerebral embolism after transcatheter aortic valve implantation compared with contemporary surgical aortic valve replacement.  Circ Cardiovasc Interv. 2015;8(3):e001913.PubMedGoogle ScholarCrossref
20.
Vermeer  SE, Hollander  M, van Dijk  EJ,  et al.  Silent brain infarcts and white matter lesions increase stroke risk in the general population.  Stroke. 2003;34(5):1126-1129.PubMedGoogle ScholarCrossref
21.
Patel  N, Minhas  JS, Chung  EM.  Risk factors associated with cognitive decline after cardiac surgery: a systematic review.  Cardiovasc Psychiatry Neurol. 2015;2015:370612.PubMedGoogle ScholarCrossref
22.
Patel  N, Minhas  JS, Chung  EM.  The presence of new MRI lesions and cognitive decline after cardiac surgery.  J Card Surg. 2015;30(11):808-812.PubMedGoogle ScholarCrossref
23.
Meller  SM, Baumbach  A, Brickman  AM, Lansky  AJ.  Clinical implications for diffusion-weighted MRI brain lesions associated with transcatheter aortic valve replacement.  Catheter Cardiovasc Interv. 2014;83(3):502-508.PubMedGoogle ScholarCrossref
24.
König  IR, Ziegler  A, Bluhmki  E,  et al.  Predicting long-term outcome after acute ischemic stroke.  Stroke. 2008;39(6):1821-1826.PubMedGoogle ScholarCrossref
25.
Shahian  DM, O’Brien  SM, Filardo  G,  et al.  The Society of Thoracic Surgeons 2008 cardiac surgery risk models.  Ann Thorac Surg. 2009;88(1)(suppl):S43-S62.PubMedGoogle ScholarCrossref
26.
O’Brien  SM, Shahian  DM, Filardo  G,  et al.  The Society of Thoracic Surgeons 2008 cardiac surgery risk models.  Ann Thorac Surg. 2009;88(1)(suppl):S23-S42.PubMedGoogle ScholarCrossref
27.
Inouye  SK, Westendorp  RG, Saczynski  JS.  Delirium in elderly people.  Lancet. 2014;383(9920):911-922.PubMedGoogle ScholarCrossref
28.
Franco  K, Litaker  D, Locala  J, Bronson  D.  The cost of delirium in the surgical patient.  Psychosomatics. 2001;42(1):68-73.PubMedGoogle ScholarCrossref
29.
Saczynski  JS, Marcantonio  ER, Quach  L,  et al.  Cognitive trajectories after postoperative delirium.  N Engl J Med. 2012;367(1):30-39.PubMedGoogle ScholarCrossref
30.
Gottesman  RF, Grega  MA, Bailey  MM,  et al.  Delirium after coronary artery bypass graft surgery and late mortality.  Ann Neurol. 2010;67(3):338-344.PubMedGoogle Scholar
31.
Doganci  S, Gunaydin  S, Kocak  OM,  et al.  Impact of the intensity of microemboli on neurocognitive outcome following cardiopulmonary bypass.  Perfusion. 2013;28(3):256-262.PubMedGoogle ScholarCrossref
32.
Kapadia  SR, Kodali  S, Makkar  R,  et al.  Protection against cerebral embolism during transcatheter aortic valve replacement.  J Am Coll Cardiol. 2017;69(4):367-377.PubMedGoogle ScholarCrossref
33.
Lansky  AJ, Messé  SR, Brickman  AM,  et al.  Proposed standardized neurological endpoints for cardiovascular clinical trials.  J Am Coll Cardiol. 2017;69(6):679-691.PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Topics
State Requirements