Successful Reconstruction of the Right Ventricular Outflow Tract by Implantation of Thymus Stem Cell Engineered Graft in Growing Swine.
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ABSTRACT:
SUBMITTER: Albertario A
PROVIDER: S-EPMC6609916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA's blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft's growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.
| S-EPMC8459923 | biostudies-literature
Project description:Peripheral artery disease (PAD) is a complex, often underdiagnosed illness with rising prevalence in western world countries. During the past decade there has been a rapid advance especially in the field of endovascular treatment of PAD. Here we present for the first time a case reporting on the placement of coronary stent graft in a peripheral vessel for the management of a peripheral side branch perforation. Interventional angiologists or radiologists may consider such an option for complication management after injury of smaller vessels during peripheral percutaneous interventions. Further specialization and novel options of complication management as described in our case may shift the treatment from surgical to even more endovascular treatment procedures in the future.
| S-EPMC4561936 | biostudies-literature
Project description:Cardiac metastasis from renal cell carcinoma (RCC) without inferior vena cava (IVC) involvements is extremely rare with few reported cases. Sarcomatoid RCC with rhabdoid feature is a rare pathologic type of RCC having aggressive behavior due to great metastatic potential. Here, we report a case of rapidly growing cardiac metastasis of RCC which brought on right ventricular outflow tract (RVOT) obstruction without IVC and right atrial involvement in a 61-year-old woman. Cardiac arrest occurred during radical nephrectomy and echocardiography revealed mass nearly obstructing the RVOT which was not recognized by preoperative echocardiography 1 month ago. Postoperative immunohistochemical evaluation of renal mass revealed sarcomatoid RCC with rhabdoid feature.
| S-EPMC5234337 | biostudies-literature
Project description:Current pediatric heart valve replacement options are suboptimal because they are incapable of somatic growth. Thus, children typically have multiple surgeries to replace outgrown valves. In this study, we present the in vivo function and growth potential of our tissue-engineered pediatric tubular valve. The valves were fabricated by sewing two decellularized engineered tissue tubes together in a prescribed pattern using degradable sutures and subsequently implanted into the main pulmonary artery of growing lambs. Valve function was monitored using periodic ultrasounds after implantation throughout the duration of the study. The valves functioned well up to 8 weeks, 4 weeks beyond the suture strength half-life, after which their insufficiency index worsened. Histology from the explanted valves revealed extensive host cell invasion within the engineered root and commencing from the leaflet surfaces. These cells expressed multiple phenotypes, including endothelial, and deposited elastin and collagen IV. Although the tubes fused together along the degradable suture line as designed, the leaflets shortened compared to their original height. This shortening is hypothesized to result from inadequate fusion at the commissures prior to suture degradation. With appropriate commissure reinforcement, this novel heart valve may provide the somatic growth potential desired for a pediatric valve replacement.
| S-EPMC5064828 | biostudies-literature
Project description: Not available
| S-EPMC8311498 | biostudies-literature
Project description:AimsOutflow graft obstruction is a poorly described complication following left ventricular assist device (LVAD) surgery. We sought to define the incidence of LVAD outflow graft obstruction and assess clinical outcomes with a percutaneous treatment strategy.Methods and resultsFrom January 2012 to October 2020, 322 patients with LVAD were managed at our institution. Patients with LVAD outflow graft obstruction were identified by cardiac computed tomography with angiography and invasive haemodynamic assessment and were subsequently treated with percutaneous intervention. Poisson regression was used to analyse time-dependent differences in the incidence of LVAD outflow graft obstruction. Kaplan-Meier analysis was used to estimate survival. Twenty patients (6.2%) developed haemodynamically significant LVAD outflow graft obstruction at a rate of 0.03 events per patient-year. Outflow graft obstruction presented a median of 33 (26-49) months after surgery. Patients presented with low estimated LVAD pump flow (95%), heart failure (90%), or both (85%), and 59% developed cardiogenic shock prior to intervention. The most common aetiology identified by cardiac computed tomography with angiography was external compression of the outflow graft (78%). On presentation, the median peak gradient in the outflow graft was 78 (64-100) mmHg. Outflow graft stenting was 100% successful with no in-hospital mortality, and it reduced the peak outflow graft gradient to 10 (2-17) mmHg (P < 0.001). Outflow graft stenting was durable with two patients (10%) requiring a repeat procedure over a median follow-up of 13 (7-20) months and did not impact survival.ConclusionsLeft ventricular assist device outflow graft obstruction is a relatively common and underappreciated cause of recurrent heart failure and LVAD dysfunction. Outflow graft stenting can be achieved with low morbidity and provides a long-term solution to this complication.
| S-EPMC8120379 | biostudies-literature
Project description:As the number of implanted left ventricular assist devices (LVADs) used increases, the frequency of chronic complications encountered also increases. The pause of blood flow in the outflow graft is a rare, but fatal, complication. The aim of this article was to present the case of a patient in whom HeartWare outflow graft occlusion was removed by balloon angioplasty and to examine the treatment modalities of HeartWare outflow graft occlusions that have been percutaneously performed to date. The literature was searched for percutaneous interventions on outflow grafts of the left ventricular assist devices. The results of six patients who underwent interventions on outflow grafts were analyzed. Three of six patients with HeartWare outflow graft stenosis were treated with covered stents, while the remaining three were treated with bare metal stents. All procedures were applied successfully. Percutaneous interventions can be performed with appropriate equipment in patients with HeartWare outflow graft stenosis or total occlusion.
| S-EPMC6280264 | biostudies-literature
Project description:Objectives: Conduits for reconstructing right ventricular outflow tract (RVOT) in children with congenital heart disease have evolved for better durability over the past decades, but conduits failure remains common. We designed decellularized and photooxidatively crosslinked bovine jugular vein conduit (DP-BJVC) and now aim to evaluate the midterm results of DP-BJVC for RVOT reconstruction. Methods: Ninety patients (median age: 4.2 years) undergoing RVOT reconstruction using DP-BJVC were prospectively followed for median of 4.7 years (range: 0.2-16.1 years). Kaplan-Meier analysis was used to examine the survival, freedom from conduit explantation and catheter-based reintervention. Risk factors were analyzed with Cox regression analysis. Results: Follow-up was completed in 92% of patients. There were five (5.6%) early deaths. The 10-year survival rate was 85.2%, with palliative procedure at DP-BJVC implantation as the risk factor. The 10-year freedom from conduit explantation and reintervention were 84.4 and 67.3% respectively, with previous cardiac operation as the only risk factor for explantation. Complications during the follow-up included conduit stenosis (peak gradient ≥50 mmHg) in 12 (12.9%), severe regurgitation in 2 (2.4%), and infective endocarditis in 2 (2.4%). The annual increase in gradient was highest in the first year (P = 0.003), but not appreciably afterwards. The echo-measured annulus diameter trends to increase by an average of 0.37 mm per year. Calcification appeared mild in the failed conduits. Conclusions: DP-BJVC provides satisfactory durability and functionality for RVOT reconstruction for children, with low morbidity of stenosis and endocarditis, as well as increase in diameter mildly with age in midterm follow-ups.
| S-EPMC8416030 | biostudies-literature
Project description:Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans.
| S-EPMC5538661 | biostudies-literature
Project description:Background:Pulmonary valve replacement is required for patients with right ventricular outflow tract (RVOT) dysfunction. Surgical and percutaneous pulmonary valve replacement are the treatment options. Percutaneous pulmonary valve implantation (PPVI) provides a less-invasive therapy for patients. The aim of this study was to evaluate the effectiveness and safety of PPVI and the optimal time for implantation. Methods:We searched PubMed, EMBASE, Clinical Trial, and Google Scholar databases covering the period until May 2018. The primary effectiveness endpoint was the mean RVOT gradient; the secondary endpoints were the pulmonary regurgitation fraction, left and right ventricular end-diastolic and systolic volume indexes, and left ventricular ejection fraction. The safety endpoints were the complication rates. Results:A total of 20 studies with 1246 participants enrolled were conducted. The RVOT gradient decreased significantly [weighted mean difference (WMD) = -19.63 mmHg; 95% confidence interval (CI): -21.15, -18.11; p < 0.001]. The right ventricular end-diastolic volume index (RVEDVi) was improved (WMD = -17.59 ml/m²; 95% CI: -20.93, -14.24; p < 0.001), but patients with a preoperative RVEDVi >140 ml/m² did not reach the normal size. Pulmonary regurgitation fraction (PRF) was notably decreased (WMD = -26.27%, 95% CI: -34.29, -18.25; p < 0.001). The procedure success rate was 99% (95% CI: 98-99), with a stent fracture rate of 5% (95% CI: 4-6), the pooled infective endocarditis rate was 2% (95% CI: 1-4), and the incidence of reintervention was 5% (95% CI: 4-6). Conclusions:In patients with RVOT dysfunction, PPVI can relieve right ventricular remodeling, improving hemodynamic and clinical outcomes.
| S-EPMC6572891 | biostudies-other