Mitral valve replacement for rheumatic heart disease in Southern Africa

Background: Threshold countries like South Africa provide cardiac surgery to a largely indigent population with rheumatic heart disease. Although repairs are a preferred treatment modality many rheumatic mitral valves can only be replaced. In view of significantly improved primary health care and broad access of the indigent population to communication technology we revisited the efficacy of mitral valve replacement (MVR) at the interface of the developing and developed world. Methods: A cohort of 280 patients (mean age 40.7±13.7y/range 12-80y/median 41y; 76.4% female) with rheumatic heart disease (21% MR; 11% MS; 68% mixed) undergoing mitral valve replacement (MVR) (88.2% mechanical versus 11.8% tissue valves) was analyzed

Long term outcome and EuroSCORE II validation in native valve surgery for active infective endocarditis in a South African cohort

Objectives: To evaluate the major risk factors for adverse short and long term outcomes in patients with active native valve infective endocarditis needing cardiac surgery and to validate the EuroSCORE II in our cohort of patients.Methods: We retrospectively studied 149 patients who underwent native valve surgery for infective endocarditis in June 2000 - May 2011 at our referral centre. Ninety-six patients met the inclusion criteria for the study: 29 aortic valve replacements (AVR), 27 mitral valve replacements (MVR), 28 aortic/mitral (double) valve replacements (DVR) and 12 mitral valve repairs (MV Repair).Results: Mechanical valves were implanted in 68 patients (70.8%), bioprosthetic valves in 16 (16.7%) and mitral annuloplasty rings in 12 (12.5%). The Cox proportional hazard model showed that the most important risk factors for early 30-day mortality were: critical preoperative state, emergency surgery, EuroSCORE II >12%, low cardiac output state (LCOS), HIV positive status, preoperative embolic episodes, vegetation size >1cm and postoperative ventilation >24 hours. The EuroSCORE II underestimated early mortality for the entire cohort. The discriminatory ability was evaluated with the receiver operating characteristic (ROC) curve with an area under the curve of 0.796. The discriminatory ability in the subgroup analysis showed that the AUROC curve was poorer for MVR (0.696), 0.837 for DVR and better for AVR group (0.92).Conclusions: The EuroSCORE II underestimated mortality in the highest risk groups and overestimated mortality in the lowest risk groups. The discriminatory ability and model fit were evaluated to be good and a EuroSCORE II >12% predicted a signifi cantly higher early and medium term mortality

Amine functionalization of cholecyst-derived extracellular matrix with generation 1 PAMAM dendrimer

This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Biomacromolecules, copyright © American Chemical Society after peer review. To access the final edited and published work, see http://pubs.acs.org/doi/pdf/10.1021/bm701055k.A method to functionalize cholecyst-derived extracellular matrix (CEM) with free amine groups was established in an attempt to improve its potential for tethering of bioactive molecules. CEM was incorporated with Generation-1 polyamidoamine (G1 PAMAM) dendrimer by using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide and N-hydroxysuccinimide cross-linking system. The nature of incorporation of PAMAM dendrimer was evaluated using shrink temperature measurements, Fourier transform infrared (FTIR) assessment, ninhydrin assay, and swellability. The effects of PAMAM incorporation on mechanical and degradation properties of CEM were evaluated using a uniaxial mechanical test and collagenase degradation assay, respectively. Ninhydrin assay and FTIR assessment confirmed the presence of increasing free amine groups with increasing quantity of PAMAM in dendrimer-incorporated CEM (DENCEM) scaffolds. The amount of dendrimer used was found to be critical in controlling scaffold degradation, shrink temperature, and free amine content. Cell culture studies showed that fibroblasts seeded on DENCEM maintained their metabolic activity and ability to proliferate in vitro. In addition, fluorescence cell staining and scanning electron microscopy analysis of cell-seeded DENCEM showed preservation of normal fibroblast morphology and phenotype

Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prosthese