TY - JOUR
T1 - Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement
T2 - Insights From the SENTINEL Trial
AU - Lazar, Ronald M.
AU - Pavol, Marykathryn A.
AU - Bormann, Tobias
AU - Dwyer, Michael G.
AU - Kraemer, Carlye
AU - White, Roseann
AU - Zivadinov, Robert
AU - Wertheimer, Jeffrey C.
AU - Thöne-Otto, Angelika
AU - Ravdin, Lisa D.
AU - Naugle, Richard
AU - Mechanic-Hamilton, Dawn
AU - Garmoe, William S.
AU - Stringer, Anthony Y.
AU - Bender, Heidi A.
AU - Kapadia, Samir R.
AU - Kodali, Susheel
AU - Ghanem, Alexander
AU - Linke, Axel
AU - Mehran, Roxana
AU - Virmani, Renu
AU - Nazif, Tamim
AU - Parhizgar, Azin
AU - Leon, Martin B.
N1 - Funding Information:
The SENTINEL trial was funded by Claret Medical. Dr. Lazar is a consultant to and holds stock options in Claret Medical. Dr. Bormann has been a paid advisor to Claret Medical. Dr. Dwyer has received consultant fees from Claret Medical and EMD Serono; and has received research grant support from Novartis. Ms. Kraemer has received financial support from Claret Medical. Ms. White is a consultant to and former employee of Abbott Vascular. Dr. Zivadinov has received speaking and consultant fees from EMD Serono, Novartis, Claret Medical, Celgene, and Genzyme-Sanofi; has received research support from Biogen Idec, Teva Pharmacuticals, EMD Serono, Novartis, Claret Medical, IMS Health, and Genzyme-Sanofi; and serves on the editorial boards of Journal of Alzheimer's Disease, BMC Medicine, BMC Neurology, Veins and Lymphatics, and CNS Drugs. Dr. Wertheimer is a paid consultant to Medtronic, and the Parkinson’s Alliance. Dr. Thöne-Otto has received financial support from Keystone Heart. Dr. Stringer has received research funding from the U.S. Department of Veterans Affairs. Dr. Kodali is a consultant for Edwards Lifesciences; has served on scientific advisory boards of Thubrikar Aortic Valve and Dura Biotech; and holds equity in Thubrikar Aortic Valve. Dr. Linke has received grant support from Medtronic, Edwards Lifesciences, and Boston Scientific; and has been a consultant to Abbott Vascular. Dr. Mehran receives institutional research support from Eli Lilly/Daiichi Sankyo, Inc., Bristol-Myers Squibb, AstraZeneca, The Medicines Company, OrbusNeich, Bayer, Beth Israel Deaconess, Novartis Pharmaceuticals, Medtronic, and CSL Behring; is a consultant for Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, Boston Scientific, Shanghai BraccoSine Pharmaceutical, Cardiovascular Systems, Inc., and Medscape; is a consultant (paid to the institution) for Abbott Laboratories, CardioKinetix, and Spectranetics; serves on the scientific advisory board of Abbott Laboratories; serves on executive committees/data safety monitoring boards for Janssen Pharmaceuticals, Osprey Medical, and Watermark Research Partners; and holds equity or stock options in Claret Medical and Elixir Medical. Dr. Virmani is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W. L. Gore. Dr. Nazif is a consultant to Edwards Lifesciences. Dr. Parhizgar is president and CEO of and has equity in Claret Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2018 American College of Cardiology Foundation
PY - 2018/2/26
Y1 - 2018/2/26
N2 - Objectives: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. Background: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. Methods: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. Results: Among 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. Conclusions: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.
AB - Objectives: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. Background: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. Methods: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. Results: Among 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. Conclusions: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.
KW - MRI brain imaging
KW - TAVR
KW - aortic valve stenosis
KW - neurocognition
UR - http://www.scopus.com/inward/record.url?scp=85042453845&partnerID=8YFLogxK
U2 - 10.1016/j.jcin.2017.10.041
DO - 10.1016/j.jcin.2017.10.041
M3 - Article
C2 - 29397361
AN - SCOPUS:85042453845
VL - 11
SP - 384
EP - 392
JO - JACC: Cardiovascular Interventions
JF - JACC: Cardiovascular Interventions
SN - 1936-8798
IS - 4
ER -