Author + information
- Received July 13, 2017
- Revision received October 26, 2017
- Accepted October 30, 2017
- Published online February 19, 2018.
- Ronald M. Lazar, PhDa,∗ (, )
- Marykathryn A. Pavol, PhDb,
- Tobias Bormann, PhDc,
- Michael G. Dwyer, PhDd,
- Carlye Kraemer, MSe,
- Roseann White, MAf,
- Robert Zivadinov, MD, PhDd,
- Jeffrey C. Wertheimer, PhDg,
- Angelika Thöne-Otto, PhDh,
- Lisa D. Ravdin, PhDi,
- Richard Naugle, PhDj,
- Dawn Mechanic-Hamilton, PhDk,
- William S. Garmoe, PhDl,
- Anthony Y. Stringer, PhDm,
- Heidi A. Bender, PhDn,
- Samir R. Kapadia, MDo,
- Susheel Kodali, MDp,
- Alexander Ghanem, MDq,
- Axel Linke, MDr,
- Roxana Mehran, MDs,
- Renu Virmani, MDt,
- Tamim Nazif, MDp,
- Azin Parhizgar, PhDu and
- Martin B. Leon, MDp
- aDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama
- bDepartment of Neurology, Columbia University Medical Center, New York, New York
- cDepartment of Neurology, Medical Center–University of Freiburg, Freiburg, Germany
- dBuffalo Neuroimaging Analysis Center, SUNY/Buffalo, Buffalo, New York
- eNorth American Science Associates, Minneapolis, Minnesota
- fDuke Clinical Research Institute, Durham, North Carolina
- gDepartment of Physical Medicine and Rehabilitation, Cedars-Sinai Medical Center, Los Angeles, California
- hClinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
- iDepartment of Neurology, Weill Medical College of Cornell University, New York, New York
- jNeurological Institute, Cleveland Clinic, Cleveland, Ohio
- kDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania
- lPsychology Department, MedStar Health, Washington, DC
- mDepartment of Rehabilitation Medicine, Emory University, Atlanta, Georgia
- nDepartment of Neurology, Mount Sinai School of Medicine, New York, New York
- oDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
- pDepartment of Medicine, Columbia University Medical Center, New York, New York
- qDepartment of Cardiology, Asklepios St Georg, Hamburg, Germany
- rHerzzentrum Leipzig–Universitätsklinik, Leipzig, Germany
- sDepartment of Medicine, Mount Sinai School of Medicine, New York, New York
- tCV Path Institute, Gaithersburg, Maryland
- uClaret Medical, Santa Rosa, California
- ↵∗Address for correspondence:
Dr. Ronald M. Lazar, Department of Neurology, SC650K, University of Alabama at Birmingham, Birmingham, Alabama 35294.
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.
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.
- Received July 13, 2017.
- Revision received October 26, 2017.
- Accepted October 30, 2017.
- 2018 American College of Cardiology Foundation