Failure of decellularized porcine small intestinal submucosa as a heart valved conduit

Jan Willem van Rijswijk; Hanna Talacua; Khadija Mulder; Gerardus P J van Hout; Carlijn V C Bouten; Paul F Gründeman; Jolanda Kluin

doi:10.1016/j.jtcvs.2019.09.164

Failure of decellularized porcine small intestinal submucosa as a heart valved conduit

J Thorac Cardiovasc Surg. 2020 Oct;160(4):e201-e215. doi: 10.1016/j.jtcvs.2019.09.164. Epub 2020 Jan 10.

Authors

Jan Willem van Rijswijk¹, Hanna Talacua², Khadija Mulder³, Gerardus P J van Hout⁴, Carlijn V C Bouten⁵, Paul F Gründeman⁴, Jolanda Kluin⁶

Affiliations

¹ Department of Cardiothoracic Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
² Department of Cardiothoracic Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
³ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
⁴ Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
⁶ Department of Cardiothoracic Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: j.kluin@amsterdamumc.nl.

PMID: 32151387
DOI: 10.1016/j.jtcvs.2019.09.164

Abstract

Objective: Decellularized extracellular matrix made from porcine small intestinal submucosa, commercially available as CorMatrix (CorMatrix Cardiovascular, Inc, Roswell, Ga) is used off-label to reconstruct heart valves. Recently, surgeons experienced failures and words of caution were raised. The aim of this study was to evaluate decellularized porcine small intestinal submucosa as right-sided heart valved conduit in a xenogeneic animal model.

Methods: A pulmonary valve replacement was performed with custom-made valved conduits in 10 lambs and 10 sheep (1 month [3 lambs and 3 sheep], 3 months [3 lambs and 3 sheep], 6 months [4 lambs and 4 sheep]). Valve function was assessed after implantation and before the animal was put to death. Explanted conduits were inspected macroscopically and analyzed using immunohistochemistry and scanning electron microscopy. They also underwent mechanical testing and testing for biochemical composition.

Results: All valved conduits were successfully implanted. Five sheep and 2 lambs died due to congestive heart failure within 2 months after surgery. In the animals that died, the valve leaflets were thickened with signs of inflammation (endocarditis in 4). Five sheep and 8 lambs (1 month: 6 out of 6 animals, 3 months: 4 out of 6 animals, 6 months: 3 out of 8 animals) survived planned follow-up. At the time they were put to death, 5 lambs had significant pulmonary stenosis and 1 sheep showed severe regurgitation. A well-functioning valve was seen in 4 sheep and 3 lambs for up to 3 months. These leaflets showed limited signs of remodeling.

Conclusions: Fifty percent of sheep and 20% of lambs died due to valve failure before the planned follow-up period was complete. A well-functioning valve was seen in 35% of animals, albeit with limited signs of tissue remodeling at ≤3 months after implantation. Further analysis is needed to understand the disturbing dichotomous outcome before clinical application can be advised.

Keywords: animal model; decellularized small intestinal submucosa; heart valve surgery; pulmonary valve replacement; xenograft.

MeSH terms

Animals
Bioprosthesis / adverse effects*
Disease Models, Animal
Echocardiography
Female
Heart Valve Diseases / diagnosis
Heart Valve Diseases / surgery*
Heart Valve Prosthesis / adverse effects*
Heart Valve Prosthesis Implantation / adverse effects*
Intestinal Mucosa / transplantation*
Microscopy, Electron, Scanning
Prosthesis Design
Prosthesis Failure
Pulmonary Valve / surgery*
Pulmonary Valve / ultrastructure
Sheep
Swine
Tissue Engineering