Aortic Valve Homograft Research Articles

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p < 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient > 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p < 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality

Aortic valved homograft degeneration: surgical or transcatheter approach for repeat aortic valve replacement?

Aortic valved allografts (homografts) have been used alternatively to mechanical or biological valve prostheses in expectation of better durability; however, homograft valves do degenerate, and redo procedures have proven challenging due to heavy wall calcification. The aim of the study was to compare the outcome of open surgical (SAVR) and transcatheter aortic valve replacement (TAVR) in degenerated homografts. Between 1993 and 2022, 81 patients underwent repeat aortic valve procedures having previously received an aortic homograft. The redo had become necessary due to regurgitation in 85% and stenosis in 15%. Sixty-five percent underwent open surgery, 35% TAVR. Isolated SAVR was possible in 79%, and root procedures were necessary in 21%. TAVR was performed in 79% via transfemoral and 21% via transapical access. Median prosthetic valve size was 23 (22.3-23.2) mm in the SAVR and 26 (25.2-26.9) in the TAVR group. Thirty-day mortality was 0% in the TAVR and 7% in the SAVR group (P = n.s.). TAVR showed a significantly better outcome concerning prolonged ventilation (0 vs 21%, P = 0.013) as well as ICU (1 vs 2 days; P < 0.001) and in-hospital stay (10.5 vs 13 days; P = 0.028). Five-year survival was statistically comparable between groups, and no severe leakage was observed. SAVR following structural homograft degeneration shows acceptable results, but the perioperative risk remains substantial and poorly predictable. TAVR presents a reasonable and more easily accessible alternative and is associated with good short- and mid-term results. In the absence of relevant contraindications, TAVR is presently the preferred treatment option for these patients at our center.

Comparative Analysis of Morphological and Morphometric Features of Human, Pig, Calf, and Sheep Aortic Valves: A Cross-sectional Study

Introduction: The aortic valve plays a critical role in maintaining unidirectional blood flow from the left ventricle into the aorta, ensuring efficient circulation throughout the body. Comprising three cusps-the left coronary, right coronary, and non-coronary cusps-the intricate anatomy of the aortic valve is essential for its proper function. The scarcity of aortic valve homografts for transplantation has led to increased interest in studying readily available sources for suitable and durable xenografts. Aim: To compare the morphological and morphometric characteristics of the aortic valves in humans with those in pigs, calves, and sheep. Materials and Methods: The present cross-sectional study was conducted over a three-week period in July 2022. Aortic valves were collected from humans, pigs, calves, and sheep. Five human hearts were obtained from the Anatomy Department of Adichunchanagiri Institute of Medical Sciences, BG Nagar. Additionally, five hearts each from calves, pigs, and sheep were obtained from a nearby abattoir. The hearts were then fixed in a 10% formaldehyde solution for approximately 18 hours. All fat and muscle surrounding the aorta were removed, and the aorta with intact valves was dissected. An incision was made between the left coronary and non-coronary aortic cusps to measure the individual cusps. Morphological and morphometric measurements, including annulus diameter, cusp height, commissural distances, and length of the lunula, were taken using a vernier calliper. The obtained values were statistically compared using paired t-test. Results: The mean values of various measurements of human aortic valves were found to be similar to those of pig aortic valves. Both humans and pigs have three aortic cusps, namely the left, right, and non-coronary cusps. The mean diameter of the aortic annulus in humans was 2.18 cm, while in pigs it was 2.28 cm. The height of the left and right cusps in both human and pig aortic valves was approximately 1.6 cm, whereas the height of the non-coronary cusp was 1.64 cm in humans and 1.38 cm in pigs. The external inter-commissural distance of the left cusp was 2.48 cm, and that of the right cusp was 2.58 cm in both humans and pigs. The external inter-commissural distance of the non-coronary cusp was 2.4 cm in humans and 2.36 cm in pigs. The length of the lunula and internal inter-commissural length of the aortic cusps in humans were relatively similar to those in pigs. However, when compared to measurements in cows and sheep, significant variations were observed. Conclusion: The study findings provide valuable insights into the potential suitability of pig aortic valves for xenograft transplantation and their implications for cardiac surgical procedures.

Aortic Valve Reinterventions after Ozaki: Clinical Case Series from Four Centers

Introduction. One of surgical methods for treatment of aortic valve (AV) pathology is Aortic Valve Neocuspidalization Ozaki procedure (AVNeo). Thus, according to the latest systematic review, freedom from reoperation within one, three, five years after AVNeo was 98%, 97% and 96%. Available references provide few descriptions of reoperations after AVNeo. Aim. To analyze the immediate results of AV reinterventions after AVNeo. Materials and methods. In the medium term, reinterventions after AVNeo were necessary for 11 patients (4.3%). The age of patients ranged from 26 to 69 years. 11 patients who underwent surgery included 6 males and 5 females. Four patients had class III-IV CHF, according to NYHA classification. Three patients had previously been operated on for infective endocarditis (IE), and five patients had bicuspid aortic valve. The duration of follow-up, from AVNeo surgery to reinterventions, ranged from 3 to 43 months. Results and discussion. All patients underwent an isolated AV intervention. The main causes of dysfunction were IE (six patients) and leaflet rupture in the commissural area (five patients). Seven patients underwent aortic valve replacement with mechanical valves, one patient — with aortic homograft valve, one patient — with tissue valve and two patients underwent valve repair. In the early postoperative period, one patient had bleeding with the development of cardiac tamponade and one patient had a haemorrhagic stroke. No patients had ARF, perioperative myocardial damage, sternal infection or permanent pacemaker implantation. Two patients died during the hospital period. Conclusions. AV reinterventions are associated with a high incidence of complications and deaths. Therefore, prevention of IE and commissure enhancement should reduce the frequency of repeated interventions, which is to be confirmed by prospective studies in large cohorts of patients.

Ross Operation in Pediatric Population: Impact of the Surgical Timing and the Native Pulmonary Diameter on the Outcome.

Aortic valve replacement early in life may be inevitable. Ross operation, until present day, remains the favorite surgical option in pediatrics with irreparable aortic valve disease. Nonetheless, the necessity for re-operation was always its principal limitation due to aortic valve failure or homograft degeneration. We present our 25years of experience in the pediatric population. From August 1994 until June 2018, 157 children below 18years underwent the Ross operation. This retrospective review aims at assessing the long-term outcomes, as well as the risk factors for re-operation after Ross procedure. Median age was 10.9years, of which seven patients were infants, 79 children, and 71 adolescents. The median follow-up time was 14years. Hospital mortality was 0.6%. Freedom from autograft re-operation for children was 96.7% and 94.1% at 10 and 20years, respectively; whereas for adolescents, it was 92.6% and 74.9% at 10 and 20years. For children, freedom from homograft re-operation was 92.5%, 83.5%, and 56.2% at 10, 15, and 20years; while for adolescents, it was 96.8%, 91.8%, and 86.7% at 10, 15, and 20years. Homograft size (p = 0.008) and childhood (p = 0.05) were risk factors for homograft re-operation. Pulmonary valve diameter > 24mm (p = 0.044) and adolescence (p = 0.032) were risk factors for autograft re-operation. Our experience demonstrated excellent early and late survival. While children have preferential outcomes concerning autograft re-operation, those who received a smaller homograft had a higher right-sided re-intervention incidence than adolescents. Pulmonary diameter > 24mm at surgery was an indicator of future autograft failure.

Report on outcomes of valve-in-valve transcatheter aortic valve implantation and redo surgical aortic valve replacement in the Netherlands.

ObjectiveWe sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) or reoperative surgical aortic valve replacement (redo-SAVR) in the Netherlands.MethodsPatients who had undergone ViV-TAVI or redo-SAVR for a degenerated biological aortic valve prosthesis in the Netherlands between January 2014 and December 2018 were eligible for this retrospective study. Patients with a prior homograft, active endocarditis or mechanical aortic valve prosthesis were excluded. Patients were matched using the propensity score. The primary endpoint was a composite of 30-day all-cause mortality and in-hospital postoperative stroke. Secondary endpoints were all-cause mortality at different time points, in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year. Baseline characteristics and outcome data were collected from the Netherlands Heart Registration.ResultsFrom 16 cardiac centres, 653 patients were included in the study (374 ViV-TAVI and 279 redo-SAVR). European System for Cardiac Operative Risk Evaluation I (EuroSCORE I) was higher in ViV-TAVI patients (19.4, interquartile range (IQR) 13.3–27.9 vs 13.8, IQR 8.3–21.9, p < 0.01). After propensity score matching, 165 patients were matched with acceptable covariate balance. In the matched cohorts, the primary endpoint was not significantly different for ViV-TAVI and redo-SAVR patients (odds ratio 1.30, 95% confidence interval 0.57–3.02). Procedural, 30-day and 1‑year all-cause mortality rates, incidence of in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year were also similar between cohorts.ConclusionPatients with degenerated aortic bioprostheses treated with ViV-TAVI or redo-SAVR have similar mortality and morbidity.Supplementary InformationThe online version of this article (10.1007/s12471-021-01608-0) contains supplementary material, which is available to authorized users.

The Ross procedure is the optimal solution for young adults with unrepairable aortic valve disease.

While aortic valve repair remains the ideal intervention to restore normal valvular function, the optimal aortic valve substitute for patients with a non-repairable aortic valve remains an ongoing subject for debate. In particular, younger patients with a non-repairable valve represent a unique challenge because of their active lifestyle and long life expectancy, which carries a higher cumulative risk of prosthesis-related complications. The Ross procedure, unlike prosthetic or homograft aortic valve replacement (AVR), provides an expected survival equivalent to that of the age and gender-matched general population. Contemporary data has shown that the Ross procedure can be performed safely in centers with expertise, and is associated with improved valvular durability, hemodynamics and quality of life.

Aortic allograft infection risk

ObjectiveIntrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. MethodsFrom January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. ResultsDuring follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. ConclusionsThe low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.

Inverted aortic bioprosthetic for mitral valve replacement with Ross procedure: case report

BackgroundA 34-year-old gentleman presented with Staphylococcus salivarius infective endocarditis 13 years after aortic homograft and mitral valve repair for degenerative bicuspid aortic valve associated with rheumatic heart disease. The homograft had calcified, and the mitral repair had deteriorated with severe regurgitation. Multidisciplinary team decision to restore best quality of life was for re-do Ross procedure with bi-leaflet preserving mitral valve replacement with an inverted RESILIA aortic valve as the patient was fundamentally against lifelong anti-coagulation.Case presentationThe aortic homograft was excised, and coronary arteries dissected out followed by harvesting of the pulmonary autograft. The mitral valve was accessed via a trans-septal approach. On examination, there was a restricted and thickened posterior mitral valve leaflet. An inverted 27-mm INSPIRIS RESILIA aortic bio-prosthesis was placed with mitral cusps preserved. The pulmonary autograft was implanted in an intra-annular position, and a 26-mm pulmonary homograft was used to replace the pulmonary valve. Echocardiogram at 4 weeks revealed preserved LV function and well-functioning prosthetic, autograft and homograft.ConclusionAn inverted RESILIA valve, with its anti-structural valve deterioration properties, can be used in the mitral position with preservation of the mitral cusps to avoid anti-coagulation with the hope of reducing need for re-operation in line with patient wishes.

Aortic valve repair in children without use of a patch

BackgroundWe aimed to assess the long-term outcomes of children in whom the aortic valve could be repaired without the use of patch material. We hypothesized that if the aortic valve is of sufficiently good quality to perform repair without patches, a durable repair could be achieved. MethodsAll children (n = 102) who underwent aortic valve repair without the use of a patch between 1980 and 2016 were reviewed. ResultsThe median patient age at operation was 2 years (interquartile range, 1 month to 9.6 years). There were 25 neonates and 17 infants. There was no operative mortality. Mean overall survival at 10 years was 97.7% ± 0.01% (95% confidence interval, [CI] 91.0%-99.4%). Forty-three patients (42.2%) required 56 aortic valve reoperations, including 24 redo aortic valve repairs, 22 Ross procedures, 8 mechanical aortic valve replacements, and 2 homograft aortic valve replacements. Mean freedom from aortic valve reoperation at 10 years was 57.4% ± 0.06% (95% CI, 44.9%-68.1%), and freedom from aortic valve replacement at 10 years was 74.5% ± 0.05% (95% CI, 63.0%-82.9%) at 10 years. Freedom from aortic valve reoperation at 10 years was 33.1% ± 0.1% (95% CI, 14.5%-53.2%) in neonates and 68.9% ± 0.06% (95% CI, 54.5%-79.6%) in older children (P < .01). ConclusionsIn approximately one-third of children undergoing aortic valve repair, the repair could be achieved without patches. In these children, aortic valve repair was achieved without operative mortality. Infants and older children have low reoperation rates, whereas reoperation rates in neonates are higher. Initial repair allows valve replacement to be delayed to later in childhood, when a more durable result may be achieved.

Sharing of decision-making for infective endocarditis surgery: a narrative review of clinical and ethical implications.

Infective endocarditis (IE) is nowadays one of the most challenging disease in cardiac surgery because of its multifaceted clinical and anatomical presentation. Despite the many clinical and surgical advances achieved in the past 60 years, there is a lack of evidence regarding the ideal strategy. The present review aims to investigate and highlight two main novel concepts for the decision-making of the best substitute. Firstly, the concept of an “endocarditis team”: a coordinated multidisciplinary effort in the diagnostic work-up, especially in conditions of high risk of embolization or clinical deterioration. A good “endocarditis team” has the role to overcome such problem, in order to ensure a prompt and balanced strategy. Secondly, which ethical considerations are required to drive the choice of valvular substitute. The choice of best valve substitute is a relevant issue of debate, not only with operative but also prognostic and accordingly ethical aftermaths. Many different solutions have been developed to substitute the infected valve. Among these: mechanical prosthesis (MP), biological stented prosthesis (BP), sutureless bioprosthesis and cryopreserved homografts (CHs). Patients need to be informed in detail about the technical issues pertaining the use of these valve substitute. We will discuss the evidences regarding the risk of recurrent infections or future potentially severe calcification of aortic homograft valve and wall (in other words, the failure of the homograft) and the difficulties in managing the reoperation.

Long-term outcomes of valve-in-valve transcatheter aortic valve implantation for degenerate homograft aortic valve replacement.

Long-term outcomes of valve-in-valve transcatheter aortic valve implantation for degenerate homograft aortic valve replacement.

Performance and Durability of Cryopreserved Allograft Aortic Valve Replacements

The value of allografts for aortic root replacement is controversial, with recent concern about limited durability. Currently, we prefer allografts for invasive infective endocarditis. Purposes of this study were to assess allograft performance and durability in our cumulative experience with aortic allografts. From January 1987 to January 2017, 2042 adults received 2110 aortic allograft root replacements at our institution: 986 (47%) for infective endocarditis (669 [68%] for prosthetic valve endocarditis) and 1124 (53%) for other indications. Mean recipient age was 54 ± 15 years, and mean allograft donor age was 35 ± 13 years. Follow-up was 85% complete and comprised 17,253 patient-years of data. Longitudinal allograft performance was extracted from 6339 available echocardiographic studies. Durability was assessed by explant for allograft structural failure. Allograft mean gradient at hospital discharge was 6 mm Hg and 9, 13, and 15 mm Hg at 5, 10, and 15 years post-implant, respectively. Severe aortic regurgitation was 0% at hospital discharge, but 14%, 25%, and 35% at 5, 10, and 15 years, respectively. A total of 405 allografts were explanted for structural failure, actuarially 2%, 14%, 34%, and 51% at 5, 10, 15, and 20 years, respectively. Risk factors for structural failure were younger recipient age, larger body surface area, hypertension, and thoracic aorta disease; donor factors were older age and larger allograft size. Implant for infective endocarditis was not associated with accelerated structural failure. This study affirms allografts' long-term acceptable hemodynamic performance and durability. Concern about structural failure should not limit allograft use. Recipient hypertension, allograft size, and donor age are modifiable risk factors.

Transcatheter aortic valve replacement using the ACURATE NEOTM valve to treat pure aortic regurgitation in a degenerated aortic homograft valve.

Transcatheter aortic valve replacement using the ACURATE NEOTM valve to treat pure aortic regurgitation in a degenerated aortic homograft valve.

Surgical Options for Aortic Root Replacement in Destructive Endocarditis.

ObjectiveTo analyze patients’ preoperative characteristics, surgical data, postoperative courses, and short- and long-term outcomes after implantation of different full-root prostheses for destructive aortic valve endocarditis.MethodsBetween 1999 and 2018, 80 patients underwent aortic root replacement due to infective endocarditis in our institution. We analyzed the abovementioned data with standard statistical methods.ResultsThe Freestyle stentless porcine prostheses were implanted in 53 (66.25%) patients, biological valve conduits in 13 (16.25%), aortic root homografts in nine (11.25%), and mechanical valve conduits in five (6.25%). There were no significant preoperative differences between the groups. The incidence of postoperative complications and intensive care unit length of stay did not differ significantly between the groups. The 30-day mortality rate was low among Freestyle patients (n=8, 15.1%) and high in the mechanical conduit cohort (n=3, 60%), though with borderline statistical significance (P=0.055). The best mean survival rates were observed after homograft (13.7 years) and stentless prosthesis (8.1 years) implantation, followed by biological (2.8 years) and mechanical (1.4 years) conduits (P=0.014). The incidence of reoperations was low in the mechanical conduit group (0) and stentless bioroot group (n=1, 1.9%), but two (15.4%) patients with biological conduits and three (33.3%) patients with homografts required reoperations in the investigated follow-up period (P=0.005).ConclusionIn patients with the destructive form of aortic valve endocarditis, homografts and stentless porcine xenografts offer better survival rates than stented valve conduits; however, the reoperation rate among patients who received homograft valves is high.

Aortic or Pulmonary Valved Homograft Right Ventricle to Pulmonary Artery Conduit in the Norwood Procedure.

Several modifications of the Norwood procedure utilizing valved right ventricle to pulmonary artery conduits have recently been reported. Our group has been using aortic or pulmonary valved homografts combined with PTFE tube grafts for now 16 years. In this report, we review our technique in detail and describe any changes that have occurred over the years. We provide detailed illustrations of our preferred surgical technique, report outcome data, and compare it to the other conduit options available. Between 2006 and 2015, 130 stage I Norwood procedures were performed at our institution, 100 of them using valved conduits. Our technique is described and illustrated in detail. Early mortality was 15%. Postoperative percutaneous intervention on the conduit was required in 29% of cases. While a randomized trial comparing different valved conduits is lacking, we believe a composite conduit made from homograft aortic or pulmonary valves and PTFE tube grafts is an excellent choice in stage I Norwood procedure.

A CASE OF VALVE-IN-VALVE TRANSCATHETER VALVE REPLACEMENT IN BACTERIAL ENDOCARDITIS

Aortic valve (AV) homograft is the preferred treatment for aortic prosthetic valve bacterial endocarditis (PVBE). However, many patients present with rapid deterioration due to heart failure (HF) and are poor surgical candidates. Valve-in-Valve (ViV) TAVR is a widely used treatment for failing

Structural changes arising from different thawing protocols on cryopreserved human allograft's aortic valve leaflets.

The aim of our experimental work was to assess the impact and morphological changes that arise during different thawing protocols on human aortic valve (AV) leaflets resected from cryopreserved aortic root allografts (CARAs). Two thawing protocols were tested: 1. CARAs were thawed at a room temperature (23°C); 2. CARAs were placed directly into a water bath at a temperature of 37°C. After all the samples were thawed, non-coronary AV leaflets were sampled from each specimen and fixed in a 4% formaldehyde solution before they were sent for morphological analysis. All the samples were washed in distilled water for 5 min and dehydrated in a graded ethanol series (70%, 85%, 95%, and 100%) for 5 min at each level. The tissue samples were then immersed in 100% hexamethyldisilazane (HMDS) for 10 min, and then air-dried in an exhaust hood at room temperature. Processed samples were mounted on stainless steel stubs and coated with gold. Histological analysis was performed with the use of an electron microscope on a scanning mode operating at 25 kV - BS 301. Thawing protocol 1 (room temperature at 23°C): 6 (100%) samples showed loss of the endothelial covering of the basal membrane with no damage to the basal lamina. Thawing protocol 2 (water bath at 37°C): 5 (83%) samples showed loss of the endothelial covering of the basal membrane with no damage to the basal lamina. One (17%) sample showed loss of the endothelial covering the basal membrane with significant damage to the basal membrane. Based on our experimental work, we can clearly conclude that cryopreserved AV leaflet allografts show identical structural changes at different rates of thawing.

The Ross procedure versus prosthetic and homograft aortic valve replacement: a systematic review and meta-analysis.

Young adults undergoing aortic valve replacement (AVR) have decreased life expectancy compared to matched controls. The Ross procedure aims to improve valve lifespan while avoiding anticoagulation. We prepared a systematic review and meta-analysis to assess the Ross procedure compared to conventional AVR. We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies evaluating the Ross procedure versus any conventional AVR in adult patients. We performed screening, full-text assessment, risk of bias evaluation and data collection independently and in duplicate. We evaluated the risk of bias with the ROBINS-I and Cochrane tools and quality of evidence with the GRADE framework. We pooled data using the random- and fixed-effects models. Thirteen observational studies and 2 randomized controlled trials (RCTs) were identified (n = 5346). No observational study was rated as having low risk of bias. The Ross procedure was associated with decreased late mortality in observational and RCT data [mean length of follow-up 2.6 years, relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84, I2 = 58%, very low quality]. The RCT estimate of effect was similar (mean length of follow-up 8.8 years, RR 0.33, 95% CI 0.11-0.96, I2 = 66%, very low quality). No difference was observed in mortality <30 days after surgery. All-site reintervention was similar between groups in cohorts and significantly reduced by the Ross procedure in RCTs (RR 1.41, 95% CI 0.89-2.24, I2 = 55%, very low quality and RR 0.41, 95% CI 0.22-0.78, I2 = 68%, high quality, respectively). Observational data, with residual confounding, and RCT data suggest a late survival benefit with the Ross procedure with no increased risk of reintervention when compared to conventional AVR. Considering the quality of available evidence and limited follow-up, additional high-quality randomized studies are required to strengthen these findings. CRD42016052512.

Retraction: The cryoprotectant trehalose could inhibit ERS-induced apoptosis by activating autophagy in cryoprotected rat valves.

Valvular diseases are common health problems that are strongly related to high morbidity and mortality; aortic valve allograft transplantation may be a promising way to improve survival and relieve symptoms. However, ideal tissue viability has not been observed with common valve cryopreservation methods, which could lead to apoptosis and necrosis in cryopreserved tissue. It has been observed that trehalose plays a positive role by acting to maintain cell structures and protect cells from stress responses. In this study, we studied the effects of trehalose in protecting rat valve tissue from the cooling process. We found improved higher cell function in rat valves treated with trehalose during cryopreservation than in those treated with dimethyl sulphoxide (DMSO). To further explore the mechanisms, we found that trehalose could down-regulate the expression of cleaved caspase-3, an important molecule involved in cell apoptosis. In addition, treatment with trehalose also decreased Glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), the key proteins in the endoplasmic reticulum stress (ERS) process. Intriguingly, we observed that trehalose promotes cryoprotected rat valve cell autophagy via an mTOR-independent but p38 MAPK-dependent signaling pathway. Additionally, miR-221 and miR-32 have been implicated in such cell activities. In summary, our study offers a new and meaningful cryopreservation approach for valve allograft storage.