The majority of patients requiring heart valve replacement in low- to middle-income countries (LMICs) need it for rheumatic heart disease (RHD). While the young age of such patients largely prescribes replacement with mechanical prostheses, reliable anticoagulation management is often unattainable under the prevailing socioeconomic circumstances. Cases of patients with clotted valves presenting for emergency surgery as a consequence of poor adherence to anticoagulation control are frequent.
View Article and Find Full Text PDFBackground And Objectives: The Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service.
View Article and Find Full Text PDFRNA interference is a promising therapeutical approach presently hindered by delivery concerns such as rapid RNA degradation and targeting of individual tissues. Injectable hydrogels are one potentially simple and direct route towards overcoming these barriers. Here we report on the utility of a combination of a mildly modified form of the clinically utilised fibrin hydrogel with Invivofectamine 3.
View Article and Find Full Text PDFBackground: Congenital heart disease (CHD) is a leading non-infectious cause of pediatric morbidity and mortality worldwide. Although the etiology of CHD is poorly understood, genetic factors including copy number variants (CNVs) contribute to the risk of CHD in individuals of European ancestry. The presence of rare CNVs in African CHD populations is unknown.
View Article and Find Full Text PDFLeaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification.
View Article and Find Full Text PDFObjectives: Large data sets have been published on short- and long-term outcomes following bidirectional Glenn surgery (BDG), or partial cavopulmonary connection, in high-income countries. Data from low-income and middle-income countries are few and often limited to the immediate postoperative period. The primary outcome was any in-hospital postoperative complication, assessed according to predefined criteria, in children who underwent BDG surgery at Red Cross War Memorial Children's Hospital.
View Article and Find Full Text PDFDespite early realization of the need to control inherent immunogenicity of bioprosthetic replacement heart valves and thereby mitigate the ensuing host response and its associated pathology, including dystrophic calcification, the problem remains unresolved to this day. Concerns over mechanical stiffness associated with prerequisite high cross-link density to effect abrogation of this response, together with the insinuated role of leaching glutaraldehyde monomer in subsequent dystrophic mineralization, have understandably introduced compromises. These have become so entrenched as a benchmark standard that residual immunogenicity of the extracellular matrix has seemingly been relegated to a very subordinate role.
View Article and Find Full Text PDFThe PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or "cohort-prevalences" of CHD-subtypes with international findings.
View Article and Find Full Text PDFFront Cardiovasc Med
September 2021
The use of bioprostheses for heart valve therapy has gradually evolved over several decades and both surgical and transcatheter devices are now highly successful. The rapid expansion of the transcatheter concept has clearly placed a significant onus on the need for improved production methods, particularly the pre-treatment of bovine pericardium. Two of the difficulties associated with the biocompatibility of bioprosthetic valves are the possibilities of immune responses and calcification, which have led to either catastrophic failure or slow dystrophic changes.
View Article and Find Full Text PDFDue to the abundance of lipoproteins in blood, it is challenging to characterize the biological functions and components of blood-derived extracellular vesicles. The aim of this study was to develop a multiple-step purification protocol to separate serum exosomes from serum proteins and lipoproteins and assess their regenerative potential. Exosomes were isolated by concentrating them in human serum using ultracentrifugation (UC), followed sequentially by density gradient (DG) UC and size exclusion chromatography (SEC).
View Article and Find Full Text PDFObjectives: While decellularization has previously significantly improved the durability of bioprosthetic tissue, remnant immunogenicity may yet necessitate masking through crosslinking. To alleviate the fears of reintroducing the risk of calcific degeneration, we investigated the application of rationally designed crosslinking chemistry, capable of abrogating mineralization in isolation, in decellularized tissue.
Methods: Bovine and porcine pericardium were decellularized using the standard Triton X/sodium deoxycholate/DNAse/RNAse methodology and thereafter combined incrementally with components of a four-stage high-density dialdehyde-based fixation regimen.
Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the aorta (CoA) is one of the commoner CHD conditions, affecting around 1/1800 live births. CoA is considered a CHD of critical severity. Unfortunately, the prognosis for a child born in a low and lower-middle income country (LLMICs) with CoA is far worse than in a high-income country.
View Article and Find Full Text PDFAims: Cardiac surgery in middle-income countries differs significantly from that in high-income countries regarding prevailing heart valve pathologies and access to cardiac surgery. Typically, rheumatic aortic regurgitation in the absence of calcification by far outweighs stenosis. As such, entirely different transcatheter aortic valve implantation (TAVI) concepts are required for these regions.
View Article and Find Full Text PDFObjective: Although the results of aortic valve replacement are well documented for industrialized countries, the outcome in patients with rheumatic aortic valve disease in low- to middle-income countries is less well explored. The aim of this study was to determine the long-term survival and clinical outcomes after isolated aortic valve replacement in patients with rheumatic heart disease in a Sub-Saharan country where follow-up of indigent patients is often challenging.
Methods: A retrospective review of 969 aortic valve replacements performed between 2003 and 2013 was conducted at Cape Town's Groote Schuur Hospital.
J Long Term Eff Med Implants
July 2019
In an attempt to avoid the destructive process of bioprosthetic heart-valve calcification associated with the use of glutaraldehyde, valves are today prepared using low concentrations of the crosslinking reagent. In this review, we summarize our findings and those of others that confirm that the immunogenicity of such tissue is not sufficiently masked and that a defined humoral response is indeed mounted against a repertoire of antigens unrelated to those associated with vascularized and noncross-linked xenograft organs. We demonstrate the need for increased cross-linking of tissue to satisfactorily mitigate that response; furthermore, we examine the impact of increased cross-link density on the macrophage as antigen presenting cell with respect to its involvement in both tissue erosion and pannus overgrowth.
View Article and Find Full Text PDFPump delivery of human interferon alpha-2B (IFNα2b) has the potential for inducing immunogenic drug aggregates. We therefore evaluated the immunogenicity of mechanically induced IFNα2b aggregates to assess this risk. Transgenic human-IFNα2b (TG) and wild-type (WT) FVB/N mice (n = 8 and n = 9/group, respectively) were administered mechanically agitated drug [45 Hz for 6 h (LLA) or 24 h (HLA)], chemically modified drug [low pH (pH 4.
View Article and Find Full Text PDFEur J Cardiothorac Surg
July 2013
Objectives: Different flow patterns and shear forces were shown to cause significantly more luminal narrowing and neointimal tissue proliferation in coronary than in infrainguinal vein grafts. As constrictive external mesh support of vein grafts led to the complete suppression of intimal hyperplasia (IH) in infrainguinal grafts, we investigated whether mesh constriction is equally effective in the coronary position.
Methods: Eighteen senescent Chacma baboons (28.
Background And Aim Of The Study: In developing countries rheumatic heart disease is the predominant indication for cardiac surgery. As the disease tends to progress, reoperation rates for mitral valve repairs are high. Against this background, the predictors of failure were assessed and the overall performance of repairs compared with replacements in a 10-year cohort of rheumatic single mitral valve procedures.
View Article and Find Full Text PDFBackground: Flow patterns and shear forces in native coronary arteries are more protective against neointimal hyperplasia than those in femoral arteries. Yet, the caliber mismatch with their target arteries makes coronary artery bypass grafts more likely to encounter intimal hyperplasia than their infrainguinal counterparts due to the resultant slow flow velocity and decreased wall stress. To allow a site-specific, flow-related comparison of remodeling behavior, saphenous vein bypass grafts were simultaneously implanted in femoral and coronary positions.
View Article and Find Full Text PDFEur J Cardiothorac Surg
February 2012
Objective: We examined whether the socio-economic circumstances of a developing country justify pulmonary artery banding (PAB) for the deferral of perceived high-risk patients requiring biventricular repair.
Methods: A retrospective cohort analysis was done on 143 consecutive patients with ventricular anatomy suitable for a biventricular repair, who had a pulmonary artery band applied between 1 January 2002 and 31 December 2007 as they were considered too high a risk to undergo corrective surgery. The goal in all patients was to lower their risk of definitive surgery by improving their clinical condition.
External mesh constriction of vein grafts was shown to mitigate intimal hyperplasia by lowering circumferential wall stress and increasing fluid shear stress. As under-constriction leaves vein segments unsupported and thus prone to neointimal proliferation while over-constriction may cause wall folding optimal mesh sizing holds a key to clinical success. Diameter fluctuations and the occurrence of wall folding as a consequence of external constriction with knitted Nitinol meshes were assessed in saphenous vein grafts from 100 consecutive coronary artery bypass (CABG) patients.
View Article and Find Full Text PDFThis study was concerned with the cluster analysis of saphenous vein graft data to determine a minimum number of diameters, and their values, for the constrictive smoothing of diameter irregularities of a cohort of veins. Mathematical algorithms were developed for data selection, transformation and clustering. Constrictive diameter values were identified with interactive pattern evaluation and subsequently facilitated in decision-tree algorithms for the data clustering.
View Article and Find Full Text PDFDespite indications that GA (glutaraldehyde)-crosslinked tissues remain prone to long-term degradation and calcification, it is still the reagent of choice in the fixation of bioprosthetic heart valves. We have shown previously that increased GA concentrations and diamine extension of cross-links with lysine incorporation lead to mitigated in vivo calcification, mainly of porcine aortic-wall tissue. The present study was performed to assess the correlation between the cross-link density of all three commonly used tissue types [PW (porcine aortic wall), PL (porcine aortic leaflet) and BP (bovine pericardium)] and tissue calcification in the subcutaneous rat model after GA treatment with or without lysine.
View Article and Find Full Text PDFObjective: Constrictive external Nitinol meshes have been shown to suppress neointimal tissue formation and preserve endothelial integrity in vein grafts. As this mitigating effect increased with the degree of constriction, we investigated whether extreme constriction was possible without leading to detrimental luminal encroachment.
Methods: A senescent non-human primate model (Chacma baboons/bilateral femoral interposition grafts) mimicking the clinical size-mismatch between vein grafts and run-off arteries was used.
Objective: Constrictive external mesh support of vein grafts was shown to mitigate intimal hyperplasia in animal experiments. To determine the degree of constriction required for the elimination of dimensional irregularities in clinically used vein grafts, a detailed anatomic study of human saphenous veins was conducted.
Methods: In 200 consecutive patients having coronary artery bypass grafting, harvested saphenous veins (length 34.