Stephanie L Sellers1, Christopher T Turner2, Janarthanan Sathananthan3, Timothy R G Cartlidge4, Frances Sin1, Rihab Bouchareb5, John Mooney6, Bjarne L Nørgaard7, Jeroen J Bax8, Pascal N Bernatchez9, Marc R Dweck4, David J Granville10, David E Newby4, Sandra Lauck3, John G Webb3, Geoffrey W Payne11, Philippe Pibarot5, Philipp Blanke6, Michael A Seidman10, Jonathon A Leipsic12. 1. Department of Radiology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 3. Centre for Heart Valve Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada. 4. British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom. 5. Pulmonary and Cardiology Research University Institute, Laval University, Quebec City, Quebec, Canada. 6. Department of Radiology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 7. Department of Cardiology, Aarhus University Hospital Skejby, Aarhus, Denmark. 8. Department of Cardiology, Leiden University Medical Centre, Leiden, South Holland, the Netherlands. 9. Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 10. Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 11. University of Northern British Columbia, Prince George, British Columbia, Canada. 12. Department of Radiology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Centre for Heart Valve Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada. Electronic address: jleipsic@providencehealth.bc.ca.
Abstract
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.
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.
Authors: Jacek Kwiecinski; Evangelos Tzolos; Timothy R G Cartlidge; Stephanie L Sellers; Daniel S Berman; Marc R Dweck; Alexander Fletcher; Mhairi K Doris; Rong Bing; Jason M Tarkin; Michael A Seidman; Gaurav S Gulsin; Nicholas L Cruden; Anna K Barton; Neal G Uren; Michelle C Williams; Edwin J R van Beek; Jonathon Leipsic; Damini Dey; Raj R Makkar; Piotr J Slomka; James H F Rudd; David E Newby Journal: Circulation Date: 2021-08-29 Impact factor: 39.918
Authors: Matteo Marro; Alexander P Kossar; Yingfei Xue; Antonio Frasca; Robert J Levy; Giovanni Ferrari Journal: J Am Heart Assoc Date: 2021-01-26 Impact factor: 5.501
Authors: Arnold C T Ng; David R Holmes; Michael J Mack; Victoria Delgado; Raj Makkar; Philipp Blanke; Jonathon A Leipsic; Martin B Leon; Jeroen J Bax Journal: Eur Heart J Date: 2020-09-01 Impact factor: 35.855