Author + information
- Received February 13, 2018
- Revision received May 9, 2018
- Accepted June 22, 2018
- Published online November 14, 2018.
- Stephanie L. Sellers, PhDa,b,
- Christopher T. Turner, PhDc,
- Janarthanan Sathananthan, MBChB, MPHd,
- Timothy R.G. Cartlidge, MDe,
- Frances Sina,b,
- Rihab Bouchareb, PhDf,
- John Mooney, MD, PhDa,
- Bjarne L. Nørgaard, MD, PhDg,
- Jeroen J. Bax, MD, PhDh,
- Pascal N. Bernatchez, MDb,
- Marc R. Dweck, MBChB, PhDe,
- David J. Granville, PhDb,c,
- David E. Newby, MD, PhDe,
- Sandra Lauck, PhDd,
- John G. Webb, MDd,
- Geoffrey W. Payne, PhDi,
- Philippe Pibarot, PhD, DVMf,
- Philipp Blanke, MDa,
- Michael A. Seidman, MD, PhDb,c and
- Jonathon A. Leipsic, MDa,b,d,∗ ()
- aDepartment of Radiology, St. Paul’s Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- bCentre for Heart Lung Innovation, St. Paul’s Hospital and University of British Columbia, Vancouver, British Columbia, Canada
- cDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- dCentre for Heart Valve Innovation, St. Paul’s Hospital, Vancouver, British Columbia, Canada
- eBritish Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom
- fPulmonary and Cardiology Research University Institute, Laval University, Quebec City, Quebec, Canada
- gDepartment of Cardiology, Aarhus University Hospital Skejby, Aarhus, Denmark
- hDepartment of Cardiology, Leiden University Medical Centre, Leiden, South Holland, the Netherlands
- iUniversity of Northern British Columbia, Prince George, British Columbia, Canada
- ↵∗Address for correspondence:
Dr. Jonathon Leipsic, Department of Radiology, St. Paul’s Hospital, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.
Objectives This study investigated processes causing leaflet thickening and structural valve degeneration (SVD).
Background Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes.
Methods Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms.
Results THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis.
Conclusions There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD.
Supported by Edwards Lifesciences and unrestricted grants from the Silber and Belzberg Family Foundations. Dr. Leipsic is supported by the Canadian Research Chair in Advanced CardioPulmonary Imaging; and consults for Edwards Lifesciences, HeartFlow, and Circle CVI; and holds stock options in HeartFlow and Circle CVI. Dr. Pibarot is supported by the Canadian Research Chair in Valvular Heart Disease; and provides uncompensated core laboratory services for Edwards Lifesciences and Medtronic. Dr. Newby is supported by British Heart Foundation (BHF) grants CH/09/002, RE/13/3/30183, and RM/13/2/30158; and is a recipient of Wellcome Trust Senior Investigator Award WT103782AIA. Dr. Dweck is supported by BHF grant FS/14/78/31020; and is a recipient of Sir Jules Thorn Award for Biomedical Research 2015. Dr. Blanke is a consultant for Edwards Lifesciences, Tendyne, WL Gore, and Circle Cardiovascular Imaging. Drs. Blanke and Leipsic provide uncompensated computed tomography services for Edwards Lifesciences, Medtronic, Neovasc, Aegis, and Tendyne Holdings. Dr. Webb consults for Edwards Lifesciences and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 13, 2018.
- Revision received May 9, 2018.
- Accepted June 22, 2018.
- 2018 American College of Cardiology Foundation
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