Homograft Valve Research Articles

Subcoronary Technique for Orthotopic Implantation of Aortic Scaffold Reinforced with Polytetrafluoroethylene Strips in Sheep: A pilot Study

Over the time, numerous studies have been reported describing successful pulmonary valve replacement, either with xenografts or allografts, performed in sheep model. In contrast, comparable results have not been achieved yet for aortic valve replacement in orthotopic position, which involves a more difficult surgical technique, high hemodynamic demands for the implanted valve and poor survival of animals undergoing this kind of surgery. To our knowledge, in Romania, these were the first orthotopic allogeneic aortic root implantations using the subcoronary technique, carried out by our team. We established feasible perioperative, anesthetic and surgical protocols, which will be used in future studies to evaluate the in vivo functional performances of decellularized valves compared with autologous adipose derived stem cells seeded valves. Therefore, a unique research core was created, which is currently the only center of this kind in our country, by joining a multidisciplinary team consisting of biomedical engineers, cardiovascular surgeons, anesthesiologists, cardiologists, pathologists, microbiologists and veterinarians, who will continue the research activity in the field of tissue engineering and translate experimental results into clinical activity.

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.

Audit of homograft valve bank.

Even today, the search for the ideal cardiac valve continues. With advantages of having superior flow dynamics, avoidance of anticoagulation, and resistance to infection, homograft has been shown to have an edge over conventional prosthetic and bioprosthetic valves. But they suffer from disadvantages of limited availability and durability. Our center operates one of the oldest functioning valve banks in the country. We present our experience with homograft valve banking with antibiotic and cryopreserved homografts spread over a quarter century. For donor selection, procurement, sterilization, and preservation, the recommendations of the American Association of Tissue Banks are being followed in accordance with statutory provisions of the Transplantation of Human Organs Act, 1994. During 25-year period (1993-2017), 777 hearts were procured. Age of the donors ranged from 2 to 60years and hearts were procured within 24h of death. A total of 1646 homografts (774 pulmonary, 774 aortic, 60 mitral valves, 20 descending thoracic aortae, and 18 monocusps) were harvested. A total of 546 (32%) homografts were rejected for various reasons. Nine hundred sixty-seven (56.7%) homografts were used in different procedures. Of these, 478 were pulmonary homografts, 425 were aortic homografts, 39 mitral homografts, 18 monocusps, and 7 descending thoracic aorta homografts. One hundred fifty-four (16%) homografts were antibiotic preserved and the rest 813 (84%) were cryopreserved. It is possible to run a homograft valve bank with minimum costs. Though, cryopreservation is more expensive, it provides an opportunity to store the valves for an indefinite period and maintain an uninterrupted supply of homografts.

Early results of a modified biological valved conduit for the Bentall procedure.

Few bioprosthetic valved conduits for aortic root surgery are commercially available. Long-term Warfarin therapy (mechanical), potential root calcification (xeno- or homograft valves), and the need for additional ascending aorta grafts are concerns associated with currently used valved conduits. A simplified, self-assembled bioroot conduit comprising currently available materials that facilitates future intervention and exhibits advantages of a bioprosthesis was used. From November 2015 to January 2017, 17 consecutive patients underwent urgent or elective aortic root surgery. A bioroot conduit, constructed using 28 or 30 mm of sinus of Valsalva Gelweave tube graft and a 3 to 5 mm smaller bioprosthetic Trifecta valve sewn into the sinus of Valsalva base, was preconstructed in the operating room before sternotomy. The size of the valved conduit was based on the distal ascending aorta or proximal arch and not aortic annular dimension. The bioroot was sutured to the native aortic annulus at the level of the bottom skirt of the Valsalva graft without contacting the sewing cuff of the bioprosthetic valve. All patients survived the operation and were discharged home without long-term anticoagulation therapy. The mean age was 65 ± 12 years, and 13 patients were male. The cardiopulmonary bypass duration was 169 ± 84 minutes, and the cross-clamp (XC) duration was 110 ± 32 minutes. The operation was elective in 12 patients, urgent/emergent in five, and redo in three. A simplified self-assembled bioroot Bentall conduit is appropriate for aortic root reconstruction. Use of a patient-tailored valved conduit will not prolong the cardiac ischemic time and will facilitate future valve replacement.

Calcification and Thrombosis as Mediators of Bioprosthetic Valve Deterioration

Calcific aortic valve disease is the most common indication for surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) of diseased valves worldwide. 1 For years,...

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

Risk factors associated with contamination of allograft valves in a tissue bank.

The contamination of the transport solution used in cardiovascular allografts can occur from different sources. Risk factors associated with positive microbiological test of transport solution have not been reported previously. This study aimed to determine the risk factor for contamination of transport solution used in the heart valve allografts stored in a Brazilian tissue bank. This retrospective study was conducted on all donors of cardiovascular allografts stored in a tissue bank from December 2008 to December 2017. Microbiological cultures for aerobic and anaerobic bacteria, fungi/yeasts were carried out in TS. Clinical variables were included. From 1001 transport solution, 52% were contaminated. A total of 770 microorganisms were identified, and Staphylococcus spp. was identified in 248 isolates (32.2%). Skin bacteria from skin microbiota were the most commonly identified microorganisms (Staphylococcus spp., Cutibacterium spp., Corynebacterium spp., and Bacillus spp.), occurring in 49.6%. The presence of a diagnosis of healthcare-associated infection was not associated with skin contamination (odds ratio [OR] 0.62 [0.41-0.94]; p = 0.014). Conditions like fever, use of antibiotics, and leukocytosis were less likely associated with contamination of transport solution. A longer warm ischemic time was associated with higher frequency of contamination. In the multivariable analysis, warm ischemic time was independently associated with contamination, and antibiotic therapy was a factor that decreased the rate of contamination (p < 0.05). Contamination of transport solution is associated with modifiable risk factors, such as warm ischemic time. Measures to minimize contamination should be employed to avoid unnecessary tissue discharges.

Comparing the Long-Term Outcome of Right Ventricle to Pulmonary Artery Conduit Insertion Using the Medtronic Freestyle Porcine Valve Versus Pulmonary Allograft Valve in Adult Patients With Congenital Heart Disease

Aim: To compare and assess the long-term outcomes of pulmonary artery conduit insertion using the Medtronic Freestyle porcine valve (MFV) versus pulmonary allograft valve (PAV) in adult patients with congenital heart disease.

Improved long-term durability of allogeneic heart valves in the orthotopic sheep model.

Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.

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.

Homograft Versus Conventional Prosthesis for Surgical Management of Aortic Valve Infective Endocarditis: A Systematic Review and Meta-analysis.

Surgical management of aortic valve infective endocarditis (IE) with cryopreserved homograft has been associated with lower risk of recurrent IE, but there is equipoise with regard to the optimal prosthesis. This systematic review and meta-analysis were performed to compare outcomes between homograft and conventional prosthesis for aortic valve IE. We searched MEDLINE database to September 2017 for studies comparing homograft versus conventional prosthesis. The main outcomes were all-cause mortality, recurrent IE, and reoperation. There were 18 included comparative observational studies with 2232 patients (median follow up = 5 [interquartile range: 2-7] years, 30% prosthetic valve endocarditis); four studies were adjusted for baseline differences. There were no differences in perioperative mortality or stroke despite a greater proportion of staphylococcal endocarditis, abscess, and root replacements but less multivalve involvement in the homograft group. Long-term outcomes of all-cause mortality [incidence rate ratio (IRR) = 1.03, 95% confidence interval (CI) = 0.81-1.31, P = 0 .83, for unmatched, and IRR = 0.82, 95% CI = 0.36-1.84, P = 0.63, for matched studies], recurrent endocarditis (IRR = 1.01, 95% CI = 0.53-1.93, P = 0.96, for unmatched, and IRR = 1.04, 95% CI = 0.49-2.19, P = 0.92, for matched studies), and reoperation (IRR = 1.60, 95% CI = 0.80-3.21, P = 0.18, for unmatched, and IRR = 3.17, 95% CI = 0.52-19.44, P = 0.21, for matched studies) were not different comparing homograft versus conventional prosthesis. There was a significantly increased need for reoperation with homograft versus mechanical prosthetic valves, but this comparison was based on limited data. Homografts and conventional prostheses offer similar survival and freedom from recurrent endocarditis and reoperation for aortic valve IE. Homografts may be associated with greater risk of reoperation compared with mechanical valves.

Influence of Cryopreservation on Structural, Chemical, and Immunoenzymatic Properties of Aortic Valve Allografts

ObjectivesThe problems in preparing (including cryopreservation) and implanting aortic valve allografts (AVAs) is widely elaborated, but some issues need explanation. Material and MethodsTwenty AVAs cryopreserved in dimethylsulphoxide/RPMI solution under −160°C for 1–15 years and 3 controls stored at +4°C up to 2 weeks, from 19 male and 4 female donors, aged 20–51, ±30.8 years, were examined using light (LM), digital (DM), and scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy (EDS), and enzyme-linked immunosorbent assay immunoenzymatic tests (PECAM1, CD34). ResultsAll AVAs were macroscopically correct. LM revealed normal structure of leaflets but massive endothelial decellularization (±59 cells remained on the surface of 5 mm scraps). DM and SEM demonstrated generally normal collagen structures, but local alterations, probably influenced by freezing-thawing (gaps, separated plates) or being initial phase of native degeneration (grains). EDS detected a little elevated calcium amount in 1 specimen only. The mean PECAM1 and CD34 concentrations were at similar low level in all probes. ConclusionsFresh and cryopreservation technologies did not significantly influence the basic properties of AVA leaflets; however, massive endothelial decellularization was present in both groups. Therefore, no endocardial cell activity nor signs of inflammation were observed. These results were independent of donors' age and sex, processing technology, and time of storage of cryopreserved AVAs.

Vitrification of aortic valve homografts suppresses NLRP3 inflammasome activation and alleviates the inflammatory response after transplantation

Vitrification of aortic valve homografts suppresses NLRP3 inflammasome activation and alleviates the inflammatory response after transplantation

Bioburden in transport solutions of human cardiovascular tissues: a comparative evaluation of direct inoculation and membrane filter technique.

All cardiac allograft tissues are under potential contamination, requiring a validated terminal sterilization process or a minimal bioburden. The bioburden calculation is important to determine the bacterial burden and further decontamination and disinfection strategies for the valve processing. The aim of this study was to determine the bioburden from transport solution (TS) of heart valves obtained from non-heart-beating and heart-beating donors in different culture methods. The bioburden from TS was determined in 20 hearts donated for valve allograft tissue using membrane filter (MF) and direct inoculation. Tryptic soy agar and Sabouraud plates were incubated and colonies were counted. Ninety-five percent of samples from this study were obtained from heart-beating donors. The warm ischemic time period for heart was 1.06 ± 0.74h and the cold ischemic time period was 25.66 ± 11.16h. The mean TS volume was 232.68 ± 96.67mL (48.5-550mL). From 20 samples directly inoculated on TSA agar plates, 2 (10%) were positive. However, when MF was used, from 20 samples in TSA, 13 (65%) were positive with a mean count of 1.36 ± 4.04CFU/mL. In Sabouraud plates, the direct inoculation was positive in 5 samples (25%) with a mean count of 0.24 ± 0.56CFU/mL. The use of MF increased the positivity to 50% (10 samples from a total of 20) with a mean of 0.28 ± 0.68CFU/mL. The positivity was superior using MF in comparison with direct inoculation (p < 0.05). The bioburden of TS is low and MF is the technique of choice due to higher positivity.

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.

Aortic Root Surgery: A single center experience

Background Aortic root surgery varies widely in techniques and from institution to institution. Success requires precision and superb post-operative care. The purpose of this study was to evaluate the indications and outcomes of this procedure at a single small volume academic medical center. Methods The study was carried out with IRB approval, consisting of 99 patients undergoing aortic root surgery from January 2013 to June 2015. 45 underwent procedures for aneurysm, 11 for infective native valve endocarditis, 16 for prosthetic valve endocarditis, 21 for aortic root dissection, and 14 for other etiologies. The procedures were performed using homograft (10), composite (8), or biologic (81) valves. 28 of the operations included a second procedure, and 39 of the operations were redo procedures. Results Complications analyzed included operative death (8.9%), stroke (10%), surgical site infection (1.1%), and cardiac arrest (6.5%). Mortality rates were: aneurysm 2.2%, infective endocarditis 7.4%, dissection 19%, and other etiologies 7.1%. Conclusions In comparing our institution to others, we found that complications were on average within the range of published studies.

Safety and efficacy of Sapien 3 valve for percutaneous pulmonary valve implantation

Efficacy of Sapien XT valve has been reported for percutaneous pulmonary valve implantation (PPVI). Implantation is complex given the rigidity and the of the Novaflex ® delivery system. Sapien 3 valve is the latest evolution of Edwards valves with a more flexible Commander ® delivery system. We report our results of off-label use of Sapien 3 for PPVI. Between September 2016 and April 2017, 16 procedures were performed with the Sapien 3 and compared to 26 procedures performed with the Sapien XT between January 2015 and July 2016. Sapien 3 were implanted in 16 patients [26 years old (23–38)]. Conduit were native patched valves ( n = 6), bioprosthesis ( n = 4), tube ( n = 4), homograft ( n = 1) and Melody valve ( n = 1). All patients had pulmonary prestenting (Andrastent XXL, n = 12; eV3 LDmax, n = 4). Valve implantation was performed during a second procedure in 5 cases. Valve diameters were 23 ( n = 3), 26 ( n = 4) and 29 mm ( n = 9). Valves were successfully implanted in all cases. After procedure, one patient had minor pulmonary valve regurgitation. Peak-to-peak gradient across the valves was ≤ 15 mmHg in 14 cases. Two patients had minor valve mismatch. Nor valve dysfunction nor infective endocarditis was reported during follow-up. Procedure duration, fluoroscopy time, dose-length product and kerma were lower with Sapien 3 compared to Sapien XT procedures (0.002, 0.01, 0.006, and 0.007 respectively). Sapien 3 valve implantation in pulmonary position with the Commander delivery system is efficient and faster. However, the lack of valve covering onto the delivery system remains an issue.

Aortic Root Replacement with Decellularized Aortic Valve Allografts: 10 Years of Experience of a Pioneer Series

Aortic Root Replacement with Decellularized Aortic Valve Allografts: 10 Years of Experience of a Pioneer Series

Medtronic Freestyle Versus Pulmonary Allograft Valve in Surgical Pulmonary Valve Replacement for Adults Following Correction of Tetralogy of Fallot or Variants

Background: Late pulmonary valve replacement (PVR) after corrective surgery for Tetralogy of Fallot (TOF) has shown good short-term and long-term outcomes. To determine the preferred bioprosthetic valve to use for PVR in this setting, outcomes using the Medtronic Freestyle and pulmonary allograft valve were reviewed.