689. Streptococcus suis Endocarditis: Echocardiographic Features and Clinical Outcomes

Background Streptococcus suis (S. suis) is a zoonotic pathogen that transmits to the human with direct contact of pig or raw pork ingestion. This infection has been described in Asia, especially Thailand, Vietnam, and China. S. suis could cause wide range of infection, including endocarditis. This study aimed to describe the clinical features, echocardiogram findings, and outcomes of S. suis endocarditis. Methods A single center, ten-year (January 2009 to December 2018), retrospective cohort was conducted among patients who were diagnosed with S.suis endocarditis in 1,200-bed hospital in Northern, Thailand. Results Forty-three patients of S.suis endocarditis were identified during the study period. Of those, 28 (65%) patients had positive blood culture and 15 (35%) was diagnosed by 16SRNA bacterial identification from heart valve tissue. Majority (81%) were male with median age of 35. There were 62 affected valves in 43 patients. Twenty patients (48%) had vegetation larger than 10 mm in diameter and 35 (81.4%) patients had moderately severe or severe valvular regurgitation. Valvular perforation was described in 23 patients (53%). Perivalvular complications were founded in 15 patients (35%). Systemic embolism occurred in 17 (40%) patients. Cardiac operation was undertaken in 35 (81%) patients. There were 2 in-hospital deaths (5%) and 6 patients (14%) had disabilities. Moderately severe/severe regurgitation, systemic embolism, and no cardiac operation were significantly associated with disability or death from univariate analysis. By logistic regression analysis, systemic embolism was the only risk factor for disability or death (OR = 12.6, 95% CI 1.3-123.5, p = 0.029). Presenting signs/symptoms, prediction score and laboratory data on admission Conclusion S. suis endocarditis had high rate of valvular damage with complications and resulting systemic embolism. Surgery is required in majority of the patients. Embolism was associated with disability or death. Disclosures All Authors: No reported disclosures

Cell colonization potential of thermoplastic silicone-based polyurethane nonwovens for novel heart valve prosthesis

Heart valve tissue engineering aims at creating living valves through colonization of scaffolds with patient’s own cells. Various cell sources have been explored focusing mainly on endothelialization of the scaffold surface. Endothelial like cells, such as endothelial progenitor cells (EPCs), which can be isolated from peripheral blood or bone marrow could be a suitable option. In this study we investigated cell colonization potential of ovine EPCs (OEPCs) on thermoplastic silicone-based polyurethane (TSPU) polymer scaffolds. TSPU nonwovens with and without vascular endothelial growth factor (VEGF) functionalization were used. SEM images showed that by day 3 the cells were growing as patches on the surface of both polymer groups. The cell patches continued growing and started covering more of the nonwoven surface. On day 7 the cells had almost covered the scaffold surface. The cells were more uniformly distributed as monolayer on the functionalized TSPU compared to the non-functionalized nonwovens. Live/Dead staining provided bright green fluorescence on the samples, indicating metabolically active alive cells. These static cell seeding experiments demonstrated that functionalized TPSU nonwovens support endothelialization. The feasibility of TPSU nonwovens as heart valve prosthesis scaffold could be further explored with animal studies in an ovine model.

Towards computer aided diagnosis of infective endocarditis in whole-slide images of heart valve tissue using FISH

Infective endocarditis (IE) is an infection of the endocardium, and the heart valves associated with high morbidity and mortality. Fluorescence in situ Hybridization (FISH) is a molecular imaging technique used for diagnosis of IE based on histological heart valve tissue sections. FISH allows detection and identification of microorganisms and gives information about their quantity and spatial distribution. This information is important to guide appropriate antibiotic treatment. However, as manual FISH image analysis is time- and costexpensive, an automated image analysis pipeline (consisting of tissue segmentation, bacteria detection, and spot detection modules) is proposed to assist locating potential regions with microorganisms. The proposed approach was evaluated in a study, where five observers manually assessed a set of 171 fields-of-view (FoVs) captured in 400-fold magnification from 10 randomly chosen WSI for the presence of microorganisms, morphologically detected by the nucleic acid stain DAPI. The task of the observers was to mark the presented image using a 2-class score (‘positive/questionable’ or ‘negative’). The human assessment was compared to the results suggested by the algorithm. The proposed algorithm locates and ranks potential regions with microorganisms in heart valve sections so that experts can validate them in higher power FoVs for the presence of bacteria and identify their species. The automated system for preselecting and recommending adequate FoVs is thus a starting point to support experts and save human resources. It is now ready to be further developed for the detection of bacteria by FISH.

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy

In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf porous polymeric scaffolds containing leaflets and conduit are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo. However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering.