Samir Sarikouch1, Karolina Theodoridis2, Andres Hilfiker2, Dietmar Boethig3, Günther Laufer4, Martin Andreas4, Serghei Cebotari5, Igor Tudorache5, Dmitry Bobylev5, Lavinia Neubert6, Kristin Teiken6, Jan Lukas Robertus7, Danny Jonigk6, Philipp Beerbaum8, Axel Haverich5, Alexander Horke5. 1. Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany. Electronic address: sarikouch.samir@mh-hannover.de. 2. Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany. 3. Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany; Department for Pediatric Cardiology and Intensive Care, Hannover Medical School, Hannover, Germany. 4. Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria. 5. Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany. 6. Institute of Pathology, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hannover, Germany. 7. Department of Histopathology, Royal Brompton and Harefield Hospital, London, United Kingdom. 8. Department for Pediatric Cardiology and Intensive Care, Hannover Medical School, Hannover, Germany.
Abstract
BACKGROUND: Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans. METHODS: Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%. RESULTS: We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted κ of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% ± 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% ± 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization. CONCLUSIONS: Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients.
BACKGROUND: Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans. METHODS: Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%. RESULTS: We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted κ of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% ± 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% ± 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization. CONCLUSIONS: Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients.
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