Pathology of valved venous homografts used as right ventricle-to-pulmonary artery conduits in congenital heart disease surgery

Carreon, Chrystalle Katte; Benini, A.; Baird, Christopher W.; Hoganson, David M.; Borisuk, Michele; Emani, Sitaram M.; Hofferberth, Sophie C.; Padera, Robert F.; Sanders, Stephen P.

doi:10.1016/j.jtcvs.2018.08.102

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…Surgical intervention for CHD is currently the only form of treatment, however the majority of these patients require multiple reinterventions throughout their life, with fibrosis, occlusion and calcification limiting the lifespan of implanted materials [15][16][17] . Animal models, predominantly murine and porcine recapitulate the surgical aspect of CHD, however, due to the abrupt change from healthy to pathogenic through intervention, they fail to recapitulate the developmental aetiology of CHD and the slow changes in pressure and cellular composition.…”

Section: Discussionmentioning

confidence: 99%

Altered inflammatory state and mitochondrial function identified by transcriptomics in paediatric congenital heart patients prior to surgical repair

Bartoli-Leonard,

Harris,

Saunders

et al. 2024

Preprint

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Background: Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. In contrast to adult heart disease, which disproportionately affects the left ventricle, complex CHD can be characterized by increased right ventricular (RV) pressure, leading to RV hypertrophy and eventually failure, with RV function known to be a major predictor in sustained cardiac health in these patients. Little understanding of the differences in the molecular landscape of RVs in disease compared to control is known and harnessing this understanding might present novel therapeutic strategies to improve surgical outcomes and reduce the need for reintervention. Methods: RV samples were collected from discarded myocardial tissue from paediatric patients under 16 years of age undergoing their first cardiac surgery at Bristol Royal Hospital for Children or obtained from control autopsy subjects. RNA sequencing and subsequent cellular deconvolution was conducted in CHD samples and integrated with publicly available control dataset. Cellular deconvolution, pathway network analysis and gene ontology were conducted and changes in expression of markers was confirmed via histological analysis. Results: Presence of CHD drove significant divergence of transcriptome with 511 differentially expressed genes (log fold change ≥ +/-2, padj ≤ 0.05), with 82% shared genes present in both sample groups. Known CHD linked genes; TBX5, JAG1, NOTCH2 and NOTCH1 were reduced in CHD RV compared to controls (padj = 2.24E-07, 1.38E-27, 7.76E-31 and 9.11E-7 respectively). Mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67E-132, 2.23E-107, respectively) were increased in CHD compared to control. Gene set enrichment identified mitochondrial dysfunctional pathways, predominately changes to the respiratory functions. Negative regulation of mitochondrial functions and metabolism was identified in functional network analysis. Key adaptive immune cell markers T helper cell markers CD4 and SELL were significantly downregulated (p < 0.0001, p=0.003, respectively). Cytotoxic T cell markers CD8a, LAGE3 and CD49a were significantly increased in CHD compared to control (p = 0.0006, p < 0.0001, p < 0.0118, respectively) as was proinflammatory marker Caspase1 (p=0.0055). Histological analysis confirmed an increase in cellular bodies with the CHD RV tissue and positive staining for both CD45 and CD8 in CHD RV tissue, which was absent in control. Deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (0.0223) no change in fibroblasts of B cells present. Network analysis identified positive regulation of the immune system and cytokine signalling clusters within the inflammation functional network as were lymphocyte activation and leukocyte differentiation. Conclusions: Utilizing RV tissue from paediatric patients undergoing CHD cardiac surgery this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T cell presence prior to reparative surgery.

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Section: Discussionmentioning

confidence: 99%

Altered inflammatory state and mitochondrial function identified by transcriptomics in paediatric congenital heart patients prior to surgical repair

Bartoli-Leonard,

Harris,

Saunders

et al. 2024

Preprint

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“…Theoretically, FVH has thinner walls and fewer donor cell components, which is beneficial to the infiltration and growth of host cells after implantation. Carreon et al found that 1 year after being implanted as a pulmonary conduit, the venous walls underwent remodeling with only minimal inflammation and calcification, and the venous valve leaflets were relatively spared from hyperplasia with preserved function ( 64 ). However, more studies are required to explore the fate of FVH in RVOT position.…”

Section: Clinical Outcomes Of Available Conduitsmentioning

confidence: 99%

Conduits for Right Ventricular Outflow Tract Reconstruction in Infants and Young Children

et al. 2021

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Purpose of Review: Right ventricular outflow tract (RVOT) reconstruction remains a challenge due to the lack of an ideal conduit. Data and experience are accumulating with each passing day. Therefore, it is necessary to review this topic from time to time. This is a 2021 update review focused on the history, evolution, and current situation of small-sized conduits (≤ 16 mm) for RVOT reconstruction in infants and young children.Recent Findings: Currently, the available small-sized (≤16 mm) conduits can meet most clinical needs. Homograft is still a reliable choice for infants and young children validated by a half-century clinical experience. As an alternative material, bovine jugular vein conduit (BJVC) has at least comparable durability with that of homograft. The performance of expanded polytetrafluoroethylene (ePTFE) is amazing in RVOT position according to limited published data. The past century has witnessed much progress in the materials for RVOT reconstruction. However, lack of growth potential is the dilemma for small-sized conduits. Tissue-engineering based on cell-free scaffolds is the most promising technology to obtain the ideal conduit.Summary: No conduit has proved to have lifelong durability in RVOT position. We are far from the ideal, but we are not in a state of emergency. In-depth clinical research as well as innovation in material science are needed to help improve the durability of the conduits used in infants and young children.

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“…Ofer et al ( 65 ) reported that homograft valved femoral veins have similar short- and medium-term performance to homograft aorta or pulmonary artery in reconstructing the right ventricular outflow tract and are an attractive alternative to the smaller conduits used in neonates and infants. Histopathological evaluation showed that the valve maintained most of its function, and venous wall remodeling included only mild inflammation and calcification ( 66 ). A summary of clinical trials of homograft valved conduits over the past decade is shown in Table 1 .…”

Section: Clinical Application Of Homograft Valved Conduitmentioning

confidence: 99%

Application of Homograft Valved Conduit in Cardiac Surgery

Huyan

Chang

Song

2021

Front. Cardiovasc. Med.

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Valved conduits often correct the blood flow of congenital heart disease by connecting the right ventricle to the pulmonary artery (RV-PA). The homograft valved conduit was invented in the 1960s, but its wide application is limited due to the lack of effective sterilization and preservation methods. Modern cryopreservation prolongs the preservation time of homograft valved conduit, which makes it become the most important treatment at present, and is widely used in Ross and other operations. However, homograft valved conduit has limited biocompatibility and durability and lacks any additional growth capacity. Therefore, decellularized valved conduit has been proposed as an effective improved method, which can reduce immune response and calcification, and has potential growth ability. In addition, as a possible substitute, commercial xenograft valved conduit has certain advantages in clinical application, and tissue engineering artificial valved conduit needs to be further studied.

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Pathology of valved venous homografts used as right ventricle-to-pulmonary artery conduits in congenital heart disease surgery

Cited by 11 publications

References 24 publications

Altered inflammatory state and mitochondrial function identified by transcriptomics in paediatric congenital heart patients prior to surgical repair

Altered inflammatory state and mitochondrial function identified by transcriptomics in paediatric congenital heart patients prior to surgical repair

Conduits for Right Ventricular Outflow Tract Reconstruction in Infants and Young Children

Application of Homograft Valved Conduit in Cardiac Surgery

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