How to counteract the lack of donor tissue in cardiac surgery? Initial experiences with a newly established homograft procurement program

Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support

A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data\u2020

OBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures.RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 +/- 14.4 years, DPH diameter 24.4 +/- 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 +/- 0.6 years, the primary efficacy end points mean peak gradient (16.1 +/- 12.1 mmHg) and regurgitation (mean 0.25 +/- 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 +/- 10.4 years, diameter 24.1 +/- 4.2 mm, follow-up 5.1 +/- 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 +/- 2.1%, CH 84.4 +/- 3.2%, P = 0.029 and BJV 82.7 +/- 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 +/- 6.6%, CH 39.9 +/- 4.4%, n.s., BJV 47.5 +/- 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH.Thoracic Surger

Paediatric aortic valve replacement using decellularized allografts

OBJECTIVES: Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and mechanical AVR imposes constant anticoagulation with the inherent risks.METHODS: The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres.RESULTS: A total of 106 children (77 boys) were operated (mean age 10.1 +/- 4.8 years, DAH diameter 20.5 +/- 3.8 mm). A total of 60 (57%) had undergone previous surgical interventions: 34 with 1, 15 with 2 and 11 with >3. There was one early death in a 12-year-old girl, who underwent her fourth aortic valve operation, due to intracerebral haemorrhage on extracorporeal membrane oxygenation after coronary reimplantation problems following 3-sinus reconstruction 1 year earlier. One 2-year-old patient died due to sepsis 2 months postoperatively with no evidence for endocarditis. In addition, a single pacemaker implantation was necessary and a 2.5-year-old girl underwent successful HTx due to chronic myocardial failure despite an intact DAH. After a mean follow-up of 3.30 +/- 2.45 years, primary efficacy end points mean peak gradient (18.1 +/- 20.9 mmHg) and regurgitation (mean 0.61 +/- 0.63, grade 0-3) were very good. Freedom from death/explantation/endocarditis/bleeding/stroke at 5 years was 97.8 +/- 1.6/85.0 +/- 7.4/100/100/100% respectively. Calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.9 years), lower than in Ross patients (9.4 years) and in the same range as mechanical AVR (12.8 years).CONCLUSIONS: Even though the overall number of paediatric DAH patients and the follow-up time span are still limited, our data suggest that DAHs may present a promising additional option for paediatric AVR.Thoracic Surger

Paediatric aortic valve replacement using decellularized allografts: a multicentre update following 143 implantations and five-year mean follow-up

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced in 2008 as a further option for paediatric aortic valve replacement (AVR). METHODS: Prospective, multicentre follow-up of all paediatric patients receiving DAH for AVR in 8 European centres. RESULTS: A total of 143 DAH were implanted between February 2008 and February 2023 in 137 children (106 male, 74%) with a median age of 10.8 years (interquartile range 6.6–14.6). Eighty-four (59%) had undergone previous cardiac operations and 24 (17%) had undergone previous AVR. The median implanted DAH diameter was 21 mm (interquartile range 19–23). The median operation duration was 348 min (227–439) with a median cardiopulmonary bypass time of 212 min (171–257) and a median cross-clamp time of 135 min (113– 164). After a median follow-up of 5.3 years (3.3–7.2, max. 15.2 years), the primary efficacy end-points peak gradient (median 14 mmHg, 9–28) and regurgitation (median 0.5, interquartile range 0–1, grade 0–3) showed good results but an increase over time. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 5 years were 97.8 ± 1.2/88.7 ± 3.3/99.1 ± 0.9/100 and 99.2 ± 0.8%, respectively. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 10 years were 96.3 ± 1.9/67.1 ± 8.0/93.6 ± 3.9/ 98.6 ± 1.4 and 86.9 ± 11.6%, respectively. In total, 21 DAH were explanted. Seven were replaced by a mechanical AVR, 1 Ross operation was performed and a re-do DAH was implanted in 13 patients with no redo mortality. The calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.4 years), and in the same range as for Ross patients (9.2 years) and mechanical AVR (13.0 years). CONCLUSIONS: This large-scale prospective analysis demonstrates excellent mid-term survival using DAH with adverse event rates comparable to paediatric Ross procedures.Thoracic Surger

Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks

Jose Ignacio Rodríguez Martínez,1,2,* Cristina Castells-Sala,1,2,* Ana Rita Baptista Piteira,1,2 Giulia Montagner,3 Diletta Trojan,3 Pablo Martinez-Legazpi,4,5 Alejandra Acosta Ocampo,5,6 Maria Eugenia Fernández-Santos,5,6 Javier Bermejo,5– 7 Ramadan Jashari,8 Maria Luisa Pérez,1,9 Elba Agustí,1,9 Jaime Tabera,1,2 Anna Vilarrodona1,9 1Barcelona Tissue Bank, Banc de Sang i Teixits (BST), Barcelona, Spain; 2Biomedical Research Institute (IIB-Sant Pau; SGR1113), Barcelona, Spain; 3Fondazione Banca dei Tessuti del Veneto, Treviso, Italy; 4Department of Mathematical Physics and Fluids, Universidad Nacional de Educación a Distancia, UNED, Madrid, Spain; 5Centre for Biomedical Research in Cardiovascular Disease Network (CIBER-CV) and Red de Investigación Cooperativa Orientada a Resultados En Salud (RICORS) TERAV, from the Instituto de Salud Carlos III, Madrid, Spain; 6Department of Cardiology, Hospital General Universitario Gregorio Marañón, Gregorio Marañón Health Research Institute (Iisgm), Madrid, Spain; 7Facultad de Medicina, Universidad Complutense, Madrid, Spain; 8European Homograft Bank (EHB) Cliniques Universitaires, Saint-Luc, Bruxelles; 9Vall Hebron Institute of Research (VHIR), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Cristina Castells-Sala, Barcelona Tissue Bank (BTB), Banc de Sang i Teixits (BST, GenCAT), Passeig Taulat 116, Barcelona, E-08005, Spain, Tel +34 935573500, Email [email protected]: Cryopreserved homografts for valve replacement surgeries face a major problem regarding their durability after implantation and decellularized pulmonary heart valves have raised as potential new generation substitute for these surgeries. The present study aims to document the work performed for the safe implementation in public tissue banks of a new decellularization method for human pulmonary heart valves, based on previous risk evaluation.Methods: After assessing new preparation method associated risks, using EuroGTP-II methodologies, an extensive array of in vitro studies were defined to validate the new technique, mitigate the risks and provide quality and safety data.Results: Initial evaluation of risks using EuroGTP II tool, showed Final Risk Score of 23 (high risk), and four studies were devised to mitigate identified risks: (i) tissue structure integrity; (ii) cell content; (iii) microbiological safety; and (iv) cytotoxicity evaluation in final tissue preparation. Protein quantification, mechanical properties, and histological evaluation indicated no tissue damage, reducing implant failure probability, while cellular content removal demonstrated a 99% DNA removal and microbiological control ensured contamination absence. Moreover, in vitro results showed no cytotoxicity. Risk re-evaluation indicated a risk reduction to moderate risk (Final Risk Score = 10), suggesting that further evidence for safe clinical use would be needed at pre-clinical in vivo evaluation to mitigate remaining risks.Conclusions: The studies performed and reviewed bibliography were able to significantly reduce the original level of risk associated with the clinical application of this homograft’s preparation. However, additional in vivo studies and tissue stability tests are still necessary to address the remaining risks associated with reagents’ effect on extracellular matrix and storage conditions, which could influence implant failure, before the clinical evaluation procedures can be implemented to determine the efficacy and safety of the new decellularized heart valves. Keywords: Pulmonary valve, decellularization, extracellular matrix, risk assessment, EuroGTP I

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients.METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement.RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9–55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6mm (standard deviation 2.4). The median operation duration was 312min (IQR 234–417), the median cardiopulmonary bypass time was 154min (IQR 118–212) and the median cross-clamp time 121min (IQR 93–150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5h postoperation. There were 3 late deaths, 1 death due to endocarditis 4months postoperatively and 2 unrelated deaths after 5 and 7years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9years [IQR 5.1–6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0mmHg (IQR 7.8–17.6) and regurgitation of median 0.5 (IQR 0–0.5) of grade 0–3 were excellent. At 5years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively.CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.Thoracic Surger