Decellularized Versus Standard Cryopreserved Homografts for Pulmonary Valve Replacement in the Ross Procedure

Decellularized Versus Standard Cryopreserved Homografts for Pulmonary Valve Replacement in the Ross Procedure | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Decellularized Versus Standard Cryopreserved Homografts for Pulmonary Valve Replacement in the Ross Procedure Muneaki Matsubara, Isabella Scheichl, Thibault Schaeffer, Jonas Palm, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9081025/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background The optimal right ventricular outflow tract (RVOT) conduit in the Ross procedure remains controversial. This study addresses outcomes of decellularized (DH) and cryopreserved homograft (CH) for RVOT reconstruction. Methods Patients aged 8 years or older who underwent the Ross procedure using DH or CH were reviewed. Conduit durability and pulmonary valve function were compared between both groups. Results A total of 59 patients were included (26 DH-patients and 33 CH-patients). The median age at Ross procedure (DH: 18 (IQR: 13–30) vs. CH: 15 (IQR: 12–22) years, p = 0.133) and the homograft diameters (DH: 24 (22–26) vs. CH: 23 (22–24) mm, p = 0.163) were similar between the groups. When comparing postoperative events within the first 5 years between the groups, none of the DH-patients experienced infective endocarditis, homograft explantation, or catheter intervention. Whereas, in the CH group, 2 patients developed infective endocarditis, 2 underwent explantation, and one underwent Melody implantation. Following up with serial echocardiography for up to 5 years, none of the DH-patients developed significant pulmonary stenosis (PS > 40 mmHg), and one patient developed significant pulmonary regurgitation (PR: moderate or worse). In contrast, 2 patients in the CH group demonstrated significant PS, and 5 patients showed significant PR. Freedom from graft dysfunction, defined by endocarditis, explantation, Melody implantation, significant PS, and significant PR, tended to be better in DH than CH (90.9% vs. 79.0% at 5 years, p = 0.155). Conclusions Our results demonstrated better short-term valve performance with DH than with CH following the RVOT reconstruction during the Ross procedure. decellularized homograft Ross procedure right ventricular outflow tract Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The Ross procedure is a favorable option for aortic valve replacement in pediatric and young adult patients, given the autograft´s growth potential, long-term durability, favorable hemodynamics, and avoidance of anticoagulation [ 1 – 3 ]. In this operation, the diseased aortic valve is replaced by the patient’s own pulmonary valve. Subsequently, the right ventricle outflow tract (RVOT) from which the pulmonary valve was retrieved must be substituted [ 4 – 8 ]. The established choice of RVOT graft is the standard cryopreserved homograft (CH) [ 5 ]. However, CHs are associated with various problems such as homograft dysfunction due to degeneration and immune response, endocarditis, and graft calcification [ 6 – 8 ]. These processes lead to increased rates of pulmonary stenosis (PS) and pulmonary regurgitation (PR), ultimately necessitating reoperation and reintervention. To address these limitations, decellularized homografts (DH) have been introduced in Brazil, Canada, the USA, and Germany, to reduce immunogenicity and potentially improve valve performance and durability, using various decellularization protocols [ 9 – 15 ]. DHs are produced by decellularizing the donor heart valve, leaving only the extracellular matrix, which can be repopulated by the patients’ own cells after implantation [ 15 ]. In previous studies, DHs have demonstrated favourable outcomes compared to CH or the bovine jugular vein (BJV) conduits, including excellent hemodynamic performance and superior valve function [ 16 , 17 ]. Since 2019, our institution has been utilizing DH developed in Hannover, Germany. We primarily implanted DH for various types of RVOT reconstructions in children and young adults, particularly in conjunction with the RVOT reconstruction at the Ross procedure. To compare the durability and valve function of DH and CH, RVOT reconstruction by the Ross procedure seems to be better than those with other complex congenital heart disease, such as Tetralogy of Fallot or pulmonary atresia due to the consistent orthotopic implantation during the Ross procedure compared to the diverse heterotopic implantation during the repair of heart defects with no or small pulmonary valves [ 4 ]. Thus, this study aims to address our institutional results by comparing short-term outcomes of DH and standard CH for RVOT reconstruction in the Ross procedure, with a specific focus on the incidence of endocarditis, the proportion of surgical explantation/Melody implantation, and detailed pulmonary valve function. Materials and Methods Data availability statement The data that support the findings of this study are available upon reasonable request. Ethical statement The Institutional Review Board of the Technical University of Munich approved the study (approved number 2025-232-S-NP on May 05, 2025) and waived the need for informed consent from the patients who were retrospectively analyzed in the study. Patients and data collection We conducted a retrospective, single-center study reviewing all patients who underwent the Ross procedure between June 2001 and December 2024. Patients aged 8 years or older who underwent RVOT reconstruction using DH or CH were included in this study. Medical records, including patient characteristics, pre- and postoperative variables, as well as echocardiographic assessments, were obtained from internal archives and referred clinics. Serial echocardiographic follow-up data were assessed for pulmonary valve stenosis and regurgitation at variable intervals: 3, 6, 9 months, one year, and every 6 months thereafter. The different proportions of endocarditis, surgical explantation, and Melody implantation for graft dysfunction were compared between the grafts over time. Significant PS was defined as a peak gradient >40 mmHg, and significant PR was defined as moderate or worse. Finally, homograft dysfunction was defined as endocarditis, surgical explantation, Melody implantation, significant homograft stenosis, or regurgitation. Freedom from homograft dysfunction was estimated using Kaplan-Meier analysis. Homograft donation and processing of DH Homografts were donated in accordance with current European Directives via four different tissue banks. Donors were mostly adults. Due to the limited availability of small-sized homografts, both aortic and pulmonary homografts were used to find size-matched DH for the pediatric population. Decellularization was performed at Corlife, a biotech spin-off company of Hannover Medical School, using detergent treatment on the homografts [18]. All decellularization and washing steps were performed under continuous shaking at room temperature. To control for DH sterility, the last washing solution and a tissue sample of each DH were incubated for over 14 days. DH were stored at 4° Celsius up to 120 days (Espoir PV) and 180 days (Arise AV), respectively. German regulatory approval was issued by the Paul Ehrlich Institute [18]. Operative Techniques The surgical techniques of the Ross procedure were described in our previous study [19]. Shortly, the procedure was performed through a median sternotomy with standard cardiopulmonary bypass and mild systemic hypothermia with the use of cold crystalloid cardioplegia for myocardial protection. The implantation of the autograft was performed by a full-root replacement technique. Implantation of the homografts in the RVOT was performed as usual . This part of the surgery was performed totally or partially without cardioplegic arrest. Echocardiography Echocardiograms from post-Ross procedures as part of this study were reviewed to assess pulmonary valve function according to guidelines [20]. PS was evaluated by the peak pressure gradient over the pulmonary valve . PR was graded as none, trivial, mild, moderate, and severe, based on the jet width and length. Statistical analysis Categorical variables are presented as absolute numbers and percentages, using a chi-square test for analysis. Continuous variables are shown as medians with interquartile ranges (IQR), compared using an independent sample t-test for normally distributed data, and the Mann-Whitney U test for non-normally distributed data. Longitudinal analysis of pulmonary valve function was performed using linear mixed-effects models to account for the correlation of repeated measurements within patients. For both peak gradient and grade of PR, models were constructed with graft type (DH vs CH), time since surgery (years), and their interaction term as fixed effects, with a random intercept for each patient. The Kaplan-Meier method was used to calculate survival and freedom from graft dysfunction after the Ross procedure, with comparisons being made between DH and CH using the log-rank test. Data were analyzed with SPSS version 28.0 and R version 4.0, with scatter plot analysis and graphs generated in R version 4.2. Results Patients characteristics A total of 59 patients were included (26 patients with DH and 33 with CH). The patients' characteristics are shown in Table 1. Most patients had a primary diagnosis of combined aortic stenosis and insufficiency in both DH and CH groups (69 vs. 73%, p=0.768). A bicuspid aortic valve was observed in 28 patients (12 in DH and 16 in CH, p=0.859). Previous interventional aortic valvuloplasty had been performed in 9 patients (7 in DH and 2 in CH, p=0.027), and previous aortic valve surgery had been performed in 15 patients (5 in DH and 10 in CH, p=0.332). Perioperative outcomes Perioperative outcomes are shown in Table 2. The median age at the Ross procedure was 19 (IQR: 13-30) years in the DH group and 15 (IQR: 12-23) years in the CH group (p=0.150). The median diameter of the homograft was 24 (22-26) mm in the DH group and 23 (22-24) mm in the CH group (p=0.163). Pulmonary homograft was less frequent in the DH group than in the CH group (65% vs. 88%, p=0.038). The median cardiopulmonary bypass (CPB) time was similar between the groups (182 vs. 159 minutes, p=0.052), but the median aortic cross-clamp time was longer in the DH group than in the CH group (146 vs. 123 minutes, p=0.002). Postoperatively, the median ICU stay (2 vs. 3 days, p=0.951) and hospital stay (9 vs. 12 days, p=0.396) were similar between both groups. There was one pacemaker implantation in the CH group. There was no hospital mortality. One DH-patient had severe ventricular dysfunction postoperatively, not related to the homograft implantation, and was bridged to successful heart transplantation by means of ECMO and left ventricular assist device support. Follow-up data (homograft durability after the Ross procedure) The median follow-up time was 3.0 (ICR: 2.0-3.8, max 5.4) years in the DH group, and 15.4 (3.5-18.6) years in the CH group. There was no late death. When the postoperative events within 5 years were compared between the groups, no patient in the DH group experienced infective endocarditis, homograft explantation, or catheter intervention. Whereas, in the CH group, 2 patients developed infective endocarditis 0.1 and 0.4 years postoperatively, 2 patients explanted homografts 0.1 and 0.5 years postoperatively, and one patient underwent Melody implantation 4.8 years postoperatively. Graft durability, defined by endocarditis, graft explantation, Melody implantation, was similar between the DH group and the CH group (100% vs. 93.9% at 3 years, p=0.202, Figure 1). Longitudinal analysis of pulmonary valve function after the Ross procedure At a maximum of 5 years of follow-up with serial echocardiography, no patient in the DH group developed significant PS, and one patient developed significant PR at 3.2 years postoperatively. In contrast, 2 patients in the CH group demonstrated significant PS 1.6 and 4.7 years postoperatively, and 5 patients showed significant PR 0.4, 0.5, 1.2, 3.5, and 4.7 years postoperatively. A linear mixed-effects model was used to analyze temporal changes in peak gradient, accounting for repeated measurements within patients (Figure 2). The model revealed a significant increase in the peak gradient over time (p<0.001). The estimated rate of gradient progression was +4.22 mmHg/year (95% confidence interval (CI): 2.88-5.57) in the CH group, compared to +2.23 mmHg/year in the DH group. Although the interaction between graft type and time did not reach conventional statistical significance (β=-1.99, 95% CI: -4.21 to 0.23, p=0.078), there was a trend suggesting slower progression of PS in the DH group. When the postoperative period was divided into two groups (before 3 years postoperatively and 3 years or more), there was no difference in the peak pressure gradient before 3 years between the DH and CH groups (p=0.379, Figure 3). However, there was a significant difference in the DH and in the CH group between 3 and 5 years postoperatively (p=0.008). Mixed-effects analysis of PR grade demonstrated a significant main effect of graft type (β=-0.36, p=0.048), indicating that DH was associated with lower regurgitation grades compared to CH throughout the follow-up period (Figure 4). There was also a significant time effect (β=0.18/year, p<0.001), indicating progressive worsening of regurgitation over time in the overall cohort. Freedom from homograft dysfunction Freedom from homograft dysfunction, defined by endocarditis, explantation, Melody implantation, significant PS, or significant PR, tended to be better in the DH group than the CH group, but the p-value did not reach significance (90.9% vs. 79.0% at 5 years, p=0.155, Figure 5). Discussion Summary of the Results Our data from patients who received the DH during the Ross procedure showed better graft performance than CH in the short term. At a maximal 5 year follow-up after the Ross procedure, there was no incidence of homograft endocarditis, homograft explantation, or Melody implantation in the DH patients. Serial echocardiographic data demonstrated that no patient in the DH group had developed significant PS. RVOT reconstruction in the setting of the Ross procedure Since the first description by Donald Ross, the Ross procedure continues to be a viable form of aortic valve replacement with favorable hemodynamics and long-term viability [1-3]. For a long time, CHs have been the gold standard for the repair of the RVOT during the Ross procedure, but their use has been associated with increased risk of reoperation and immunological responses [4-8]. Other conduits, such as the BJV conduit, were also used for RVOT reconstruction at the Ross procedure, but their outcomes were not better than CHs [17]. Conversely, the DHs have been proposed to achieve more favorable hemodynamics [16, 17]. While previous isolated observational studies and multi-center studies have reported the clinical outcomes of DH and CH use in the Ross procedure, the results were different from center to center, and the controversy over the optimal strategy still exists [9-12]. In general, the reports using decellularized cryopreserved homografts demonstrated outcomes comparable to the CH [11-13], and the reports using fresh decellularized homografts showed a better outcomes compared to the CH [14-17]. The advantage of fresh decellularized homografts over cryopreserved homografts Decellularized heart valves based on human tissue were introduced to the clinic about 15 years ago and are one of the most advanced approaches successfully introduced to the clinic to date [15]. The concept is based on the extraction of cellular components from the extracellular matrix of donated cadaveric valves with and without subsequent cryopreservation. Cryopreserved decellularized pulmonary homografts, when used for pulmonary valve replacement, have shown better or comparable long-term performance than standard cryopreserved homografts [12-14]. Decellularized fresh homografts, which omit an additional cryopreservation step, have also demonstrated superior results when compared to standard homografts [15-17]. Studies from the Hannover group developed a decellularized protocol for fresh-harvested homografts and demonstrated that DH are superior compared to standard CH, in a recent prospective multicentre study [16, 17]. They demonstrated that actuarial 8-year freedom from allograft dysfunction and freedom from allograft reintervention were comparable. However, longitudinal echocardiographic analyses showed a significantly lower progression rate of peak RVOT gradients in the DH group during the first 3 years after the operation. These DH are commercially available in Germany, and our center has been using them since 2019. The short-term outcomes of our study are in line with the results of the multicenter study [16, 17]. There is strong evidence that the elimination of immunogenic cells from the valvular matrix using different decellularization protocols significantly decreases immunologic responses in valve recipients [21, 22]. Sarikouch et al. showed that once implanted, these decellularized scaffolds undergo extensive remodeling in vivo by repopulation with autologous cells [23]. Cryopreserved homografts have been the principal conduits used for decades for RVOT reconstruction [4-8]. These valves proved to be resistant to infection and provided excellent initial physiological hemodynamic properties. However, in the majority of reports, all patients exhibit some conduit valve regurgitation and, in addition, the homografts calcify. Accelerated graft degeneration has been observed especially in children and young adults as a result of high immunologic competence in these patients [7]. Therefore, we believe that there are theoretical and practical advantage of fresh decellularized homografts over cryopreserved homografts. The existing studies showed superior hemodynamic performance of fresh decellularized homografts compared with cryopreserved homografts [24, 25]. Disadvantages of DH The greatest disadvantage of DH is its availability. The DH should be fresh, decellularized after procurement, and should be kept at 4 degrees. Therefore, the availability is limited in their size and preservation period. After the decellularization process, the DH should be kept at 4 degrees and should be implanted within 2-4 months. Actually, we maintain a patient waiting list, and nominate the size-matched DH. Some of the patients could not receive a DH because of the lack of a DH with a suitable size. The second limitation is the cost. In fact, DH costs four times as much as CH, which is again due to the small number of units processed. Furthermore, early degeneration of DH has been observed in a small subset of patients, raising questions of residual immunogenicity, and we assume that early cellular immune response following implantation of DH might occur in these patients [27, 28]. In this study, one DH-patient developed significant PR. It might be the case, and further investigation is mandatory. Future prospective We believe that fresh DH is actually the best option for the RVOT reconstruction in the Ross operation. The DH availability, especially for small patients, is the first concern. Reducing the cost is the second issue to be solved. For the direct implantation of decellularized aortic homograft for aortic valve replacement, we are careful to closely monitor clinical outcomes in this setting. Study limitations This study was limited by its retrospective, non-randomized, single-center design. Changes in surgical and medical management during the study period likely influenced outcomes. Improvement of the quality and accuracy of echocardiography during the study period might have impacted our results. Conclusions The initial results of our study were encouraging in patients who underwent the Ross operation with DH for RVOT reconstruction. The DH group was free of endocarditis and explantation, and the valve function seems to be better than in the CH group within 5 years of follow-up. A longer follow-up study is necessary to assess the durability and functional outcomes of the DH. Abbreviations BJV: bovine jugular vein CH: cryopreserved homograft CI: confidence interval DH: decellularized homograft IQR: interquartile ranges PS: pulmonary stenosis PR: pulmonary regurgitation RVOT: right ventricular outflow tract Declarations Conflict of interest statement The authors declare no potential conflicts of interest concerning the research, authorship, or publication of this article. Acknowledgement We thank Mr. Daniel Lucic for his contribution to the collection of follow-up data. References Ross DN, Radley-Smith R, Somerville J (1969) Pulmonary autograft replacement for severe aortic valve disease. Br Heart J 31(6):797–798 Al-Halees Z, Pieters F, Qadoura F et al (2002) The Ross procedure is the procedure of choice for congenital aortic valve disease. J Thorac Cardiovasc Surg 123(3):437–442 Weixler VHM, Howell AJ, Samman B et al (2025) Thirty years of experience with full-root Ross procedure in the pediatric population-Timing matters! JTCVS Open 28:415–427 Selamet Tierney ES, Gersony WM, Altmann K et al (2005) Pulmonary position cryopreserved homografts: durability in pediatric Ross and non-Ross patients. J Thorac Cardiovasc Surg 130(2):282–286 Brown JW, Ruzmetov M, Rodefeld MD et al (2008) Right ventricular outflow tract reconstruction in Ross patients: does the homograft fare better? Ann Thorac Surg 86(5):1607–1612 Böhm JO, Hemmer W, Rein JG et al (2009) A single-institution experience with the Ross operation over 11 years. Ann Thorac Surg 87(2):514–520 Kalfa D, Feier H, Loundou A et al (2011) Cryopreserved homograft in the Ross procedure: outcomes and prognostic factors. J Heart Valve Dis 20(5):571–581 El Sherif N, Dearani JA, Connolly HM et al (2023) Complexity and Outcome of Reoperations After the Ross Procedure in the Current Era. Ann Thorac Surg 115(3):633–639 da Costa FDA, Etnel JRG, Charitos EI et al (2018) Decellularized Versus Standard Pulmonary Allografts in the Ross Procedure: Propensity-Matched Analysis. Ann Thorac Surg 105(4):1205–1213 Réa ABBADC, da Costa FDA, Adam EL et al (2025) Improving outcomes of right ventricular outflow tract reconstruction during the Ross operation: Homograft decellularization and surgical technique. JTCVS Open 25:25–38 Chauvette V, Bouhout I, Tarabzoni M et al (2022) Pulmonary homograft dysfunction after the Ross procedure using decellularized homografts: a multicenter study. 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J Am Soc Echocardiogr 23:465–495 Coti I, Wenda S, Andreeva A et al (2020) Donor-specific HLA antibodies after fresh decellularized vs cryopreserved native allograft implantation. HLA 96(5):580–588 Neumann A, Sarikouch S, Breymann T et al (2014) Early systemic cellular immune response in children and young adults receiving decellularized fresh allografts for pulmonary valve replacement. Tissue Eng Part A 20(5–6):1003–1011 Sarikouch S, Theodoridis K, Hilfiker A et al (2019) Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves. Ann Thorac Surg 108(2):581–589 Oripov F, Ramm R, Falk C et al (2022) Serial assessment of early antibody binding to decellularized valved allografts. Front Cardiovasc Med 9:895943 Ebken J, Mester N, Smart I et al (2021) Residual immune response towards decellularized homografts may be highly individual. Eur J Cardiothorac Surg 59(4):773–782 Tables Table 1 Table 1. Patient characteristics Total DH CH p-value Number of patients 59 26 (44.1) 33 (55.9) Male sex 34 (57.6) 14 (53.8) 20 (60.6) 0.602 Main Dignosis Aortic stenosis (AS) 6 (10.2) 3 (11.5) 3 (9.1) 0.757 Aortic insufficiency (AI) 7 (11.9) 1 (3.8) 6 (18.2) 0.091 AS & AI 42 (71.2) 18 (69.2) 24 (72.7) 0.768 Aortic valve morphology Tricuspid 30 (50.8) 13 (50.0) 17 (51.5) 0.908 Bicaspid 28 (47.5) 12 (46.2) 16 (58.5) 0.859 Monocuspid 1 (1.7) 1 (3.8) 0 (0.0) 0.256 Associated anomalies Ao. asc. enlargement 14 (23.7) 8 (30.8) 6 (18.2) 0.259 Mitral valve vitium 6 (10.2) 3 (11.5) 3 (9.1) 0.757 ASD 2 (3.4) 2 (7.7) 0 (0.0) 0.105 VSD 3 (5.1) 1 (3.8) 2 (6.1) 0.701 Shone complex 1 (1.7) 0 (0.0) 1 (3.0) 0.371 Previous interventions Balloon valvuloplasty 9 (15.3) 7 (26.9) 2 (6.1) 0.027 Aortic valve repair 15 (25.4) 10 (30.3) 5 (19.2) 0.332 Table 2 Table 2. Perioperative variables Total DH CH p-value Number of patients 59 26 (44.1) 33 (55.9) Operative variables Age at operation 16 (13–26) 19 (13–30) 15 (12–23) 0.150 Weight at operation 55 (41–67) 59 (41–72) 52 (41–65) 0.408 CPB 169 (147–200) 182 (150–213) 159 (146–182) 0.052 AXC 136 (119–155) 146 (124–166) 123 (109–145) 0.002 Diameter of homograft 23 (22–25) 24 (22–26) 23 (22–24) 0.163 Pulmonary homograft 46 (78.0) 17 (65.4) 29 (87.9) 0.038 Concomitant procedure LVOT myectomy 5 (8.5) 3 (11.5) 2 (6.1) 0.453 Ao.asc. replacement 18 (30.5) 10 (38.5) 8 (24.2) 0.239 ASD closure 2 (3.4) 2 (7.7) 0 (0.0) 0.105 VSD closure 3 (5.1) 1 (3.8) 2 (6.1) 0.701 Mitral valve procedure 2 (3.4) 1 (3.8) 1 (3.0) 0.863 Postoperative variables ICU stay 3 (2–4) 2 (2–4) 3 (2–5) 0.951 HSP stay 10 (9–15) 9 (8–11) 12 (10–16) 0.396 CPR 1 (1.7) 0 (0.0) 1 (3.0) 0.371 ECMO 1 (1.7) 1 (3.8) 0 (0.0) 0.256 Pacemaker 1 (1.7) 0 (0.0) 1 (3.0) 0.371 Hospital mortality 0 (0.0) 0 (0.0) 0 (0.0) . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 31 Mar, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviews received at journal 18 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers invited by journal 16 Mar, 2026 Editor assigned by journal 11 Mar, 2026 Submission checks completed at journal 10 Mar, 2026 First submitted to journal 10 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9081025","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":603632244,"identity":"12137849-e665-4818-aae3-8b01147f9885","order_by":0,"name":"Muneaki Matsubara","email":"","orcid":"","institution":"TUM University Hospital, German Heart Center","correspondingAuthor":false,"prefix":"","firstName":"Muneaki","middleName":"","lastName":"Matsubara","suffix":""},{"id":603632245,"identity":"6bc19300-bd05-407e-a9bf-3632277facc3","order_by":1,"name":"Isabella Scheichl","email":"","orcid":"","institution":"TUM University Hospital, German 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Center","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Ewert","suffix":""},{"id":603632252,"identity":"8f5a8c4c-f425-4cc0-8bcb-5e1b0f465b59","order_by":8,"name":"Jürgen Hörer","email":"","orcid":"","institution":"TUM University Hospital, German Heart Center","correspondingAuthor":false,"prefix":"","firstName":"Jürgen","middleName":"","lastName":"Hörer","suffix":""},{"id":603632253,"identity":"06e4beaa-27dc-40b5-aefe-d9bbf4822878","order_by":9,"name":"Masamichi Ono","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAnklEQVRIiWNgGAWjYHACxge8DUBKAoh5iNTCbECyFjYJ0rTwSzcfq3i7YxuD7uzeAwxvKojQIjnnWNrNuWduM5jdOZfAOOcMEVoMbuSY3eZtA2q5kWPAzNtGpJZihJZ/RGphRmhpIEKL5Iy0ZMm5bbd5QFoOzjlGhBZ+ieSDH9623ZYDajF88KaGCC0wAI6RAyRoGAWjYBSMglGADwAALuE2R4X9mhcAAAAASUVORK5CYII=","orcid":"","institution":"TUM University Hospital, German Heart Center","correspondingAuthor":true,"prefix":"","firstName":"Masamichi","middleName":"","lastName":"Ono","suffix":""}],"badges":[],"createdAt":"2026-03-10 08:10:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9081025/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9081025/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104385545,"identity":"cb7090f3-cdae-4947-a355-f9c349e0f666","added_by":"auto","created_at":"2026-03-11 08:41:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":507946,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimate for freedom from conduit endocarditis, explantation, or intervention after the Ross procedure in patients with DH and CH.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/853b16997b9114d923c31024.png"},{"id":104385565,"identity":"5727c9ad-f171-4de1-8180-a5b83e47793f","added_by":"auto","created_at":"2026-03-11 08:41:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1054251,"visible":true,"origin":"","legend":"\u003cp\u003ePeak pressure gradient over time following RVOT reconstruction with decellularized homograft (DH, blue) and cryopreserved homograft (CH, red). Solid lines represent fitted values from a linear mixed-effects model with patient as a random effect. The dashed line indicates the threshold for significant stenosis (\u0026gt;40 mmHg).\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/7681a3d2ed8fa5061e900aa1.png"},{"id":104385486,"identity":"dcc9e838-a398-4a37-ba13-fef45749b844","added_by":"auto","created_at":"2026-03-11 08:40:40","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":71641,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whiskers dot plots showing serial peak gradient over pulmonary valves in DH and CH. The upper and lower whiskers mark the minimum and maximum values, the upper and lower borders of the box represent the upper and lower quartiles, and the middle horizontal line represents the median.\u003c/p\u003e","description":"","filename":"image3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/b828512ae9550b72043b787e.jpg"},{"id":104385489,"identity":"42f9d075-baee-49d9-9990-df324d9cca42","added_by":"auto","created_at":"2026-03-11 08:40:40","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1054200,"visible":true,"origin":"","legend":"\u003cp\u003ePulmonary regurgitation grade over time following RVOT reconstruction with DH (blue) and CH (red). Points are jittered for visualization. Mixed-effects analysis showed significantly lower regurgitation grades in DH compared to CH (p=0.048). The dashed line indicates the threshold for significant regurgitation (≥moderate).\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/dd6ca9df8671ad62e1a488ac.png"},{"id":104385564,"identity":"623c4256-b49b-4cbd-b6a0-ffc13aa86032","added_by":"auto","created_at":"2026-03-11 08:41:06","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":554559,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimate for freedom from conduit dysfunction after the Ross procedure in patients with DH and CH.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/f1d2cc77bb02b8258ac5b45e.png"},{"id":104385732,"identity":"77d138f3-2ebc-416f-8378-417ecff6007e","added_by":"auto","created_at":"2026-03-11 08:41:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3816741,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9081025/v1/97e06bcd-b6de-45e1-b4f1-1cc5c62d53e5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Decellularized Versus Standard Cryopreserved Homografts for Pulmonary Valve Replacement in the Ross Procedure","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe Ross procedure is a favorable option for aortic valve replacement in pediatric and young adult patients, given the autograft\u0026acute;s growth potential, long-term durability, favorable hemodynamics, and avoidance of anticoagulation [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In this operation, the diseased aortic valve is replaced by the patient\u0026rsquo;s own pulmonary valve. Subsequently, the right ventricle outflow tract (RVOT) from which the pulmonary valve was retrieved must be substituted [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The established choice of RVOT graft is the standard cryopreserved homograft (CH) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, CHs are associated with various problems such as homograft dysfunction due to degeneration and immune response, endocarditis, and graft calcification [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These processes lead to increased rates of pulmonary stenosis (PS) and pulmonary regurgitation (PR), ultimately necessitating reoperation and reintervention.\u003c/p\u003e \u003cp\u003eTo address these limitations, decellularized homografts (DH) have been introduced in Brazil, Canada, the USA, and Germany, to reduce immunogenicity and potentially improve valve performance and durability, using various decellularization protocols [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. DHs are produced by decellularizing the donor heart valve, leaving only the extracellular matrix, which can be repopulated by the patients\u0026rsquo; own cells after implantation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In previous studies, DHs have demonstrated favourable outcomes compared to CH or the bovine jugular vein (BJV) conduits, including excellent hemodynamic performance and superior valve function [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Since 2019, our institution has been utilizing DH developed in Hannover, Germany. We primarily implanted DH for various types of RVOT reconstructions in children and young adults, particularly in conjunction with the RVOT reconstruction at the Ross procedure. To compare the durability and valve function of DH and CH, RVOT reconstruction by the Ross procedure seems to be better than those with other complex congenital heart disease, such as Tetralogy of Fallot or pulmonary atresia due to the consistent orthotopic implantation during the Ross procedure compared to the diverse heterotopic implantation during the repair of heart defects with no or small pulmonary valves [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThus, this study aims to address our institutional results by comparing short-term outcomes of DH and standard CH for RVOT reconstruction in the Ross procedure, with a specific focus on the incidence of endocarditis, the proportion of surgical explantation/Melody implantation, and detailed pulmonary valve function.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Institutional Review Board of the Technical University of Munich approved the study (approved number 2025-232-S-NP on May 05, 2025) and waived the need for informed consent from the patients who were retrospectively analyzed in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and data collection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective, single-center study reviewing all patients who underwent the Ross procedure between June 2001 and December 2024. Patients aged 8 years or older who underwent RVOT reconstruction using DH or CH were included in this study. Medical records, including patient characteristics, pre- and postoperative variables, as well as echocardiographic assessments, were obtained from internal archives and referred clinics. Serial echocardiographic follow-up data were assessed for pulmonary valve stenosis and regurgitation at variable intervals: 3, 6, 9 months, one year, and every 6 months thereafter. The different proportions of endocarditis, surgical explantation, and Melody implantation for graft dysfunction were compared between the grafts over time. Significant PS was defined as a peak gradient \u0026gt;40 mmHg, and significant PR was defined as moderate or worse. Finally, homograft dysfunction was defined as endocarditis, surgical explantation, Melody implantation, significant homograft stenosis, or regurgitation. Freedom from homograft dysfunction was estimated using Kaplan-Meier analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHomograft donation and processing of DH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHomografts were donated in accordance with current European Directives via four different tissue banks. Donors were mostly adults. Due to the limited availability of small-sized homografts, both aortic and pulmonary homografts were used to find size-matched DH for the pediatric population.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDecellularization was performed at Corlife, a biotech spin-off company of Hannover Medical School, using detergent treatment on the homografts [18]. All decellularization and washing steps were performed under continuous shaking at room temperature. To control for DH sterility, the last washing solution and a tissue sample of each DH were incubated for over 14 days. DH were stored at 4° Celsius up to 120 days (Espoir PV) and 180 days (Arise AV), respectively. German regulatory approval was issued by the Paul Ehrlich Institute [18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOperative Techniques\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe surgical techniques of the Ross procedure were described in our previous study [19]. Shortly, the procedure was performed through a median sternotomy with standard cardiopulmonary bypass and mild systemic hypothermia with the use of cold crystalloid cardioplegia for myocardial protection. The implantation of the autograft was performed by a full-root replacement technique. Implantation of the homografts in the RVOT was performed as usual . This part of the surgery was performed totally or partially without cardioplegic arrest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEchocardiography\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEchocardiograms from post-Ross procedures as part of this study were reviewed to assess pulmonary valve function according to guidelines [20]. PS was evaluated by the peak pressure gradient over the pulmonary valve . PR was graded as none, trivial, mild, moderate, and severe, based on the jet width and length.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCategorical variables are presented as absolute numbers and percentages, using a chi-square test for analysis. Continuous variables are shown as medians with interquartile ranges (IQR), compared using an independent sample t-test for normally distributed data, and the Mann-Whitney U test for non-normally distributed data. Longitudinal analysis of pulmonary valve function was performed using linear mixed-effects models to account for the correlation of repeated measurements within patients. For both peak gradient and grade of PR, models were constructed with graft type (DH vs CH), \u0026nbsp;time since surgery (years), and their interaction term as fixed effects, \u0026nbsp;with a random intercept for each patient. The Kaplan-Meier method was used to calculate survival and freedom from graft dysfunction after the Ross procedure, with comparisons being made between DH and CH using the log-rank test. Data were analyzed with SPSS version 28.0 and R version 4.0, with scatter plot analysis and graphs generated in R version 4.2.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 59 patients were included (26 patients with DH and 33 with CH). The patients' characteristics are shown in Table 1. Most patients had a primary diagnosis of combined aortic stenosis and insufficiency in both DH and CH groups (69 vs. 73%, p=0.768). A bicuspid aortic valve was observed in 28 patients (12 in DH and 16 in CH, p=0.859). Previous interventional aortic valvuloplasty had been performed in 9 patients (7 in DH and 2 in CH, p=0.027), and previous aortic valve surgery had been performed in 15 patients (5 in DH and 10 in CH, p=0.332).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePerioperative outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePerioperative outcomes are shown in Table 2. The median age at the Ross procedure was 19 (IQR: 13-30) years in the DH group and 15 (IQR: 12-23) years in the CH group (p=0.150). The median diameter of the homograft was 24 (22-26) mm in the DH group and 23 (22-24) mm in the CH group (p=0.163). Pulmonary homograft was less frequent in the DH group than in the CH group (65% vs. 88%, p=0.038). The median cardiopulmonary bypass (CPB) time was similar between the groups (182 vs. 159 minutes, p=0.052), but the median aortic cross-clamp time was longer in the DH group than in the CH group (146 vs. 123 minutes, p=0.002). Postoperatively, the median ICU stay (2 vs. 3 days, p=0.951) and hospital stay (9 vs. 12 days, p=0.396) were similar between both groups. There was one pacemaker implantation in the CH group. There was no hospital mortality. One DH-patient had severe ventricular dysfunction postoperatively, not related to the homograft implantation, and was bridged to successful heart transplantation by means of ECMO and left ventricular assist device support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up data (homograft durability after the Ross procedure)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up time was 3.0 (ICR: 2.0-3.8, max 5.4) years in the DH group, and 15.4 (3.5-18.6) years in the CH group. There was no late death. When the postoperative events within 5 years were compared between the groups, no patient in the DH group experienced infective endocarditis, homograft explantation, or catheter intervention. Whereas, in the CH group, 2 patients developed infective endocarditis 0.1 and 0.4 years postoperatively, 2 patients explanted homografts 0.1 and 0.5 years postoperatively, and one patient underwent Melody implantation 4.8 years postoperatively. Graft durability, defined by endocarditis, graft explantation, Melody implantation, was similar between the DH group and the CH group (100% vs. 93.9% at 3 years, p=0.202, Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLongitudinal analysis of pulmonary valve function after the Ross procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt a maximum of 5 years of follow-up with serial echocardiography, no patient in the DH group developed significant PS, and one patient developed significant PR at 3.2 years postoperatively. In contrast, 2 patients in the CH group demonstrated significant PS 1.6 and 4.7 years postoperatively, and 5 patients showed significant PR 0.4, 0.5, 1.2, 3.5, and 4.7 years postoperatively.\u003c/p\u003e\n\u003cp\u003eA linear mixed-effects model was used to analyze temporal changes in peak gradient, accounting for repeated measurements within patients (Figure 2). The model revealed a significant increase in the peak gradient over time (p\u0026lt;0.001). The estimated rate of gradient progression was +4.22 mmHg/year (95% confidence interval (CI): 2.88-5.57) in the CH group, compared to +2.23 mmHg/year in the DH group. Although the interaction between graft type and time did not reach conventional statistical significance (β=-1.99, 95% CI: -4.21 to 0.23, p=0.078), there was a trend suggesting slower progression of PS in the DH group. When the postoperative period was divided into two groups (before 3 years postoperatively and 3 years or more), there was no difference in the peak pressure gradient before 3 years between the DH and CH groups (p=0.379, Figure 3). However, there was a significant difference in the DH and in the CH group between 3 and 5 years postoperatively (p=0.008).\u003c/p\u003e\n\u003cp\u003eMixed-effects analysis of PR grade demonstrated a significant main effect of graft type (β=-0.36, p=0.048), indicating that DH was associated with lower regurgitation grades compared to CH throughout the follow-up period (Figure 4). There was also a significant time effect (β=0.18/year, p\u0026lt;0.001), indicating progressive worsening of regurgitation over time in the overall cohort.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFreedom from homograft dysfunction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFreedom from homograft dysfunction, defined by endocarditis, explantation, Melody implantation, significant PS, or significant PR, tended to be better in the DH group than the CH group, but the p-value did not reach significance (90.9% vs. 79.0% at 5 years, p=0.155, Figure 5).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eSummary of the Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur data from patients who received the DH during the Ross procedure showed better graft performance than CH in the short term. At a maximal 5 year follow-up after the Ross procedure, there was no incidence of homograft endocarditis, homograft explantation, or Melody implantation in the DH patients. Serial echocardiographic data demonstrated that no patient in the DH group had developed significant PS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRVOT reconstruction in the setting of the Ross procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince the first description by Donald Ross, the Ross procedure continues to be a viable form of aortic valve replacement with favorable hemodynamics and long-term viability [1-3]. For a long time, CHs have been the gold standard for the repair of the RVOT during the Ross procedure, but their use has been associated with increased risk of reoperation and immunological responses [4-8]. Other conduits, such as the BJV conduit, were also used for RVOT reconstruction at the Ross procedure, but their outcomes were not better than CHs [17]. Conversely, the DHs have been proposed to achieve more favorable hemodynamics [16, 17]. While previous isolated observational studies and multi-center studies have reported the clinical outcomes of DH and CH use in the Ross procedure, the results were different from center to center, and the controversy over the optimal strategy still exists [9-12]. In general, the reports using decellularized cryopreserved homografts demonstrated outcomes comparable to the CH [11-13], and the reports using fresh decellularized homografts showed a better outcomes compared to the CH [14-17].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe advantage of fresh decellularized homografts over cryopreserved homografts\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDecellularized heart valves based on human tissue were introduced to the clinic about 15 years ago and are one of the most advanced approaches successfully introduced to the clinic to date [15]. The concept is based on the extraction of cellular components from the extracellular matrix of donated cadaveric valves with and without subsequent cryopreservation. Cryopreserved decellularized pulmonary homografts, when used for pulmonary valve replacement, have shown better or comparable long-term performance than standard cryopreserved homografts [12-14]. Decellularized fresh homografts, which omit an additional cryopreservation step, have also demonstrated superior results when compared to standard homografts [15-17].\u003c/p\u003e\n\u003cp\u003eStudies from the Hannover group developed a decellularized protocol for fresh-harvested homografts and demonstrated that DH are superior compared to standard CH, in a recent prospective multicentre study [16, 17]. They demonstrated that actuarial 8-year freedom from allograft dysfunction and freedom from allograft reintervention were comparable. However, longitudinal echocardiographic analyses showed a significantly lower progression rate of peak RVOT gradients in the DH group during the first 3 years after the operation. These DH are commercially available in Germany, and our center has been using them since 2019. The short-term outcomes of our study are in line with the results of the multicenter study [16, 17].\u003c/p\u003e\n\u003cp\u003eThere is strong evidence that the elimination of immunogenic cells from the valvular matrix using different decellularization protocols significantly decreases immunologic responses in valve recipients [21, 22]. Sarikouch et al. showed that once implanted, these decellularized scaffolds undergo extensive remodeling in vivo by repopulation with autologous cells [23].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCryopreserved homografts have been the principal conduits used for decades for RVOT reconstruction [4-8]. These valves proved to be resistant to infection and provided excellent initial physiological hemodynamic properties. However, in the majority of reports, all patients exhibit some conduit valve regurgitation and, in addition, the homografts calcify. Accelerated graft degeneration has been observed especially in children and young adults as a result of high immunologic competence in these patients [7]. Therefore, we believe that there are theoretical and practical advantage of fresh decellularized homografts over cryopreserved homografts. The existing studies showed superior hemodynamic performance of fresh decellularized homografts compared with cryopreserved homografts [24, 25].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisadvantages of DH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe greatest disadvantage of DH is its availability. The DH should be fresh, decellularized after procurement, and should be kept at 4 degrees. Therefore, the availability is limited in their size and preservation period. After the decellularization process, the DH should be kept at 4 degrees and should be implanted within 2-4 months. Actually, we maintain a patient waiting list, and nominate the size-matched DH. Some of the patients could not receive a DH because of the lack of a DH with a suitable size. The second limitation is the cost. In fact, DH costs four times as much as CH, which is again due to the small number of units processed. Furthermore, early degeneration of DH has been observed in a small subset of patients, raising questions of residual immunogenicity, and we assume that early cellular immune response following implantation of DH might occur in these patients [27, 28]. In this study, one DH-patient developed significant PR. It might be the case, and further investigation is mandatory.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFuture prospective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe believe that fresh DH is actually the best option for the RVOT reconstruction in the Ross operation. The DH availability, especially for small patients, is the first concern. Reducing the cost is the second issue to be solved. For the direct implantation of decellularized aortic homograft for aortic valve replacement, we are careful to closely monitor clinical outcomes in this setting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was limited by its retrospective, non-randomized, single-center design. Changes in surgical and medical management during the study period likely influenced outcomes. Improvement of the quality and accuracy of echocardiography during the study period might have impacted our results.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe initial results of our study were encouraging in patients who underwent the Ross operation with DH for RVOT reconstruction. The DH group was free of endocarditis and explantation, and the valve function seems to be better than in the CH group within 5 years of follow-up. A longer follow-up study is necessary to assess the durability and functional outcomes of the DH.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBJV: bovine jugular vein\u003c/p\u003e\n\u003cp\u003eCH: cryopreserved homograft\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u003c/p\u003e\n\u003cp\u003eDH: decellularized homograft\u003c/p\u003e\n\u003cp\u003eIQR: interquartile ranges\u003c/p\u003e\n\u003cp\u003ePS: pulmonary stenosis\u003c/p\u003e\n\u003cp\u003ePR: pulmonary regurgitation\u003c/p\u003e\n\u003cp\u003eRVOT: right ventricular outflow tract\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no potential conflicts of interest concerning the research, authorship, or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Mr. Daniel Lucic for his contribution to the collection of follow-up data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRoss DN, Radley-Smith R, Somerville J (1969) Pulmonary autograft replacement for severe aortic valve disease. 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Ann Thorac Surg 105(4):1205\u0026ndash;1213\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026eacute;a ABBADC, da Costa FDA, Adam EL et al (2025) Improving outcomes of right ventricular outflow tract reconstruction during the Ross operation: Homograft decellularization and surgical technique. JTCVS Open 25:25\u0026ndash;38\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChauvette V, Bouhout I, Tarabzoni M et al (2022) Pulmonary homograft dysfunction after the Ross procedure using decellularized homografts: a multicenter study. J Thorac Cardiovasc Surg 163(4):1296\u0026ndash;1305\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEtnel JRG, Suss PH, Schnorr GM et al (2018) Fresh decellularized versus standard cryopreserved pulmonary allografts for right ventricular outflow tract reconstruction during the Ross procedure: a propensity-matched study. 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Circulation 124:S115\u0026ndash;S123\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBobylev D, Horke A, Boethig D et al (2022) 5-year results from the prospective European multi-centre study on decellularized homografts for pulmonary valve replacement ESPOIR Trial and ESPOIR Registry data. Eur J Cardiothorac Surg 62(5):ezac219\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoethig D, Horke A, Hazekamp M et al (2019) A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data. Eur J Cardiothorac Surg 56(3):503\u0026ndash;509\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ehttps://\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003c/span\u003e\u003cspan address=\"http://www.pei.de/EN/medicinal-products/tissue-preparations/heart-valves/heart-valves-list.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, downloaded 2026-01-08\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026ouml;rer J, Hanke T, Stierle U et al (2009) Homograft performance in children after the Ross operation. Ann Thorac Surg 88(2):609\u0026ndash;615\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopez L, Colan SD, Frommelt PC et al (2010) Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. 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Eur J Cardiothorac Surg 59(4):773\u0026ndash;782\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":" \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTable\u0026nbsp;1. Patient characteristics\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eDH\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCH\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003ep-value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of patients\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e59\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e26 (44.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e33 (55.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMale sex\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e34 (57.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e14 (53.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e20 (60.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.602\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMain Dignosis\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAortic stenosis (AS)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (10.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (11.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (9.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.757\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAortic insufficiency (AI)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (11.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (18.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.091\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAS \u0026amp; AI\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e42 (71.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e18 (69.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e24 (72.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.768\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAortic valve morphology\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTricuspid\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e30 (50.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e13 (50.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (51.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.908\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBicaspid\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e28 (47.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (46.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e16 (58.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.859\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMonocuspid\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (1.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.256\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociated anomalies\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAo. asc. enlargement\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e14 (23.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (30.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (18.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.259\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMitral valve vitium\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (10.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (11.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (9.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.757\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eASD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (3.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (7.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.105\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVSD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (5.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (6.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.701\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eShone complex\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (1.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.371\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePrevious interventions\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBalloon valvuloplasty\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (15.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (26.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (6.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.027\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAortic valve repair\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (25.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (30.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (19.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.332\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTable\u0026nbsp;2. Perioperative variables\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eDH\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCH\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003ep-value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of patients\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e59\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e26 (44.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e33 (55.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eOperative variables\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAge at operation\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e16 (13\u0026ndash;26)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e19 (13\u0026ndash;30)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (12\u0026ndash;23)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.150\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWeight at operation\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e55 (41\u0026ndash;67)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e59 (41\u0026ndash;72)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e52 (41\u0026ndash;65)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.408\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCPB\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e169 (147\u0026ndash;200)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e182 (150\u0026ndash;213)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e159 (146\u0026ndash;182)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.052\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAXC\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e136 (119\u0026ndash;155)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e146 (124\u0026ndash;166)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e123 (109\u0026ndash;145)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.002\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDiameter of homograft\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e23 (22\u0026ndash;25)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e24 (22\u0026ndash;26)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e23 (22\u0026ndash;24)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.163\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePulmonary homograft\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e46 (78.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (65.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e29 (87.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.038\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eConcomitant procedure\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLVOT myectomy\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (8.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (11.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (6.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.453\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAo.asc. replacement\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e18 (30.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (38.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (24.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.239\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eASD closure\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (3.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (7.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.105\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVSD closure\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (5.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (6.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.701\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMitral valve procedure\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (3.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (3.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.863\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv 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Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"decellularized homograft, Ross procedure, right ventricular outflow tract","lastPublishedDoi":"10.21203/rs.3.rs-9081025/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9081025/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe optimal right ventricular outflow tract (RVOT) conduit in the Ross procedure remains controversial. This study addresses outcomes of decellularized (DH) and cryopreserved homograft (CH) for RVOT reconstruction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients aged 8 years or older who underwent the Ross procedure using DH or CH were reviewed. Conduit durability and pulmonary valve function were compared between both groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 59 patients were included (26 DH-patients and 33 CH-patients). The median age at Ross procedure (DH: 18 (IQR: 13–30) vs. CH: 15 (IQR: 12–22) years, p = 0.133) and the homograft diameters (DH: 24 (22–26) vs. CH: 23 (22–24) mm, p = 0.163) were similar between the groups. When comparing postoperative events within the first 5 years between the groups, none of the DH-patients experienced infective endocarditis, homograft explantation, or catheter intervention. Whereas, in the CH group, 2 patients developed infective endocarditis, 2 underwent explantation, and one underwent Melody implantation. Following up with serial echocardiography for up to 5 years, none of the DH-patients developed significant pulmonary stenosis (PS \u0026gt; 40 mmHg), and one patient developed significant pulmonary regurgitation (PR: moderate or worse). In contrast, 2 patients in the CH group demonstrated significant PS, and 5 patients showed significant PR. Freedom from graft dysfunction, defined by endocarditis, explantation, Melody implantation, significant PS, and significant PR, tended to be better in DH than CH (90.9% vs. 79.0% at 5 years, p = 0.155).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur results demonstrated better short-term valve performance with DH than with CH following the RVOT reconstruction during the Ross procedure.\u003c/p\u003e","manuscriptTitle":"Decellularized Versus Standard Cryopreserved Homografts for Pulmonary Valve Replacement in the Ross Procedure","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-11 08:38:32","doi":"10.21203/rs.3.rs-9081025/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-31T16:58:58+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"67293300227684598043187522577283392822","date":"2026-03-21T20:40:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-18T16:18:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"63871521297110540607329525800522570688","date":"2026-03-18T10:22:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312227749677157185317371002964475996299","date":"2026-03-16T19:41:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-16T19:38:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-11T13:39:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T03:41:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2026-03-10T07:55:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5834661c-4143-433b-993e-6259b33b70dc","owner":[],"postedDate":"March 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T20:09:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-11 08:38:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9081025","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9081025","identity":"rs-9081025","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}