Cardiothoracic Surgery

Permanent URI for this community

http://hdl.handle.net/11660/55

Browse

Browsing Cardiothoracic Surgery by Issue Date

Filter results by year or month
Now showing 1 - 6 of 6
  • Thumbnail Image
    ItemOpen Access
    Hydrodynamic and coagulation characteristics of a re-engineered mechanical heart valve in an ovine model
    (University of the Free State, 2017-01) Jordaan, Christiaan Johannes; Smit, F. E.; Dohmen, P. M.; Botes, L.
    Introduction A valve with haemodynamic properties mimicking a natural heart valve and having the durability that will exceed the life expectancy of the recipient patient without requiring lifelong anti-coagulation, would be considered by most as the Holy Grail of prosthetic heart valve design. Although mechanical heart valves have a superior durability compared to biological valves, the thrombogenicity of mechanical heart valves necessitates lifelong anti-coagulation therapy, balancing bleeding risk with thrombosis and emboli. The explantation of two UCT valves that had remained in pristine condition decades after implantation and the reviewing of historical data after implantation in children without anti-coagulation in the 1960s, led to the idea of re-engineering a poppet valve to possibly be used without anti-coagulation. This idea was revisited during the development of the Glycar Valve. Objective During the planning phase of this study three main objectives were considered: 1. To understand the principles of heart valve functioning with the resulting influence on thrombosis; to apply these principles while designing a mechanical heart valve that will be easy and affordable to produce and that can safely be used without anti-coagulation. This included an in-depth literature review of heart valve design, fluid-structure interaction within the valve as well as valvular thrombosis. 2. To use computational fluid dynamics followed by pulse duplication testing in the in vitro evaluation of a prototype mechanical heart valve (the Glycar valve) and to compare the findings to the commercially available Carbomedics bi-leaflet valve. 3. To study the Glycar valve in vivo in the ovine model, evaluating overall function and specifically, to assess the thrombogenicity of the valve without the use of anti-coagulant or anti-platelet therapy, in comparison to the Carbomedics bi-leaflet valve. Methods An extensive review of mechanical valve design, coagulation and available mechanical valve research and development methodology was performed . Thereafter several modifications were made to the original UCT valve in order to create the Glycar valve. The flow across the valve during systole was streamlined, reducing areas of flow acceleration across the valve and the poppet surface, reducing the viscous shear rate. The diastolic flow profile was changed and areas of stagnation were eliminated around the valve leaflets. Regurgitation jets were eliminated, which negated the problems associated with the ‘washing jets’ seen in bi-leaflet valves. A two-part CFD analysis (dynamic and non-dynamic) was performed on the Glycar valve to understand the flow patterns generated within the Glycar valve and across the valve components. Pulse duplication analysis was performed on the Glycar valve and the valvular performance during five simulated physiological conditions were compared to four different commercially available heart valves in the aortic position. In the in vivo study the bio-interaction of the Glycar valve was tested in the ovine model in the absence of anti-coagulation in comparison with a bi-leaflet valve. Two groups of five Glycar valves and one Carbomedics bi-leaflet valve were implanted in the pulmonary valve position in juvenile sheep. Group 1 was followed for six months and Group 2 for twelve months after implantation. Results The Glycar valve was centred on a CAD design, which was based on flow-dynamic principles. CFD confirmed acceptable flow-patterns - both during systole and diastole - with a greater than expected EOA (1.39 cm2) and a low transvalvular gradient (1.5 mmHg). Systolic flow patterns showed a low incidence of flow separation and recirculation, minimal areas of stasis and turbulence, reduced vortex formation and a surface shear stress that does not exceed the platelet activation threshold. The Glycar valve had comparative hydrodynamic properties and characteristics compared to the Carbomedics bi-leaflet valve in a simulated pulsatile environment. Pulse duplication comparison of the Glycar valve to commercially available mechanical and biological valves demonstrated similar pressure drops, Qrms, energy losses and EOA’s. However, at higher cardiac outputs (>8 L/min) the poppet valve developed significant regurgitation. The current Glycar valve design in the pulmonary position in the ovine model proved to be reliable and thrombo-resistant in the absence of anti-coagulation in the short term as well as in the long term follow-up. None of the valves, control valves included, showed any macroscopic or microscopic thrombi. Biochemistry and hematology did not demonstrate hemolysis, activation of coagulation or platelet activity. Histology showed no thrombi on the sewing cuff, housing, poppet or struts. None of the sheep had embolic events and no pulmonary embolic events or sequelae could be identified. Cardiac echocardiography confirmed normal prosthetic function in all valves except those with infective endocarditis. Conclusion The Glycar valve proved to be a suitable alternative to the traditional mechanical bi-leaflet valve design. The improvements made to the Glycar valve showed acceptable results in both the CFD analysis and pulse duplication testing, exceeding the minimum standards required by ISO 5840:2015 certification. In the ovine model the Glycar valve demonstrated acceptable haemodynamics and no trombo-embolic events were recorded in the absence of anti-coagulation or anti-platelet drugs. Future recommendations  This prosthesis should be tested in a more aggressive coagulation model at systemic pressures or in the more thrombogenic tricuspid valve position.  Improvement in the poppet design is required to address the regurgitation experienced at flows exceeding 8 L/min.  Fatique testing of the final valve design.
  • Thumbnail Image
    ItemOpen Access
    The impact of extended harvesting times on tissue integrity of cryopreserved ovine pulmonary homograts
    (University of the Free State, 2017-02) Bester, Dreyer; Smit, F. E.; Botes, L.; Dohmen, P. M.
    English: The use of aorta valve homografts in cardiac surgery was pioneered by Donald Ross and Barratt-Boyes (Ross, 1962; Barratt-Boyes, 1964) and today, pulmonary valve homografts remain the valved conduit of choice for reconstruction of the right ventricle outflow tract (RVOT) required in the treatment of common congenital cardiac conditions. Initially, homografts were harvested from cadavers generally within seventy-two hours after death, in a non-sterile environment, and then freshly preserved in a sterile antibiotic medium at 4°C. These homografts were then used within six to eight weeks after procurement (Botes et al., 2012). Cryopreservation was popularised by Marc O’Brien (O’Brien et al., 1987), which saw the introduction of the development of homograft banks. It was claimed that these valves retained a degree of viability, which enhances long term durability after implantation. Freshly unprocessed valves that were harvested under sterile conditions from beating heart donors or within hours after death, were implanted (unprocessed) shortly afterwards (Yacoub et al., 1995). These studies resulted in the demise of cadaver programmes and programmes cryopreserving homografts harvested from beating heart donors, or less than six hours to a maximum of twenty-four hours post mortem became the norm. On the other hand, it became clear that immune response to viable tissue, especially viable endothelium, resulted in earlier rejection of homografts, especially in children (Yankah et al., 1995). Furthermore, long term results of fresh antibiotic sterilised valves stored at 4°C compared to early cryopreservation of viable valves failed to confirm or support earlier expectations and were similar in several studies, notably in that of O’Brien et al, in 2001. In, a number of explant studies it was also concluded that homografts become nonviable and essentially acellular within months of implantation and are essentially nonviable scaffolds (Mitchell et al, 1998, Koolbergen et al, 2002). The primary role of immunological processes on homograft survival was therefore questioned. The damaging effect on homograft tissue during the cryopreservation process was also described (Schenke-Layland et al., 2006). Thus, during the last fifty years of homograft banking, cryopreservation remained the technique of choice with various studies suggesting that early post mortem harvesting has a beneficial effect on homograft survival after implantation. This could however not be demonstrated in several long term studies. The deleterious effect of truly viable valves and associated immune processes on homograft survival were also described. In addition, several studies showed that explanted valves were essentially acellular and thus nonviable. In reality, the time from post mortem cardiectomy or homograft bank receipt before processing and cryopreservation commonly extend to fourty-eight hours as reported in the Directory of European Cardiovascular Tissue Banks and Tissue Bank Addresses World Wide (2013). This implies that the inevitable cold ischaemic time before cryopreservation is extended to three to four days in a significant percentage of cases anyway. This, and the complexity of issues of homograft viability as well as inconclusive long term advantages of homograft viability in published series, beg the question whether cadaver programmes should not be re-evaluated. The Bloemfontein homograft bank is an almost exclusively cadaver donor based programme, with average post mortem harvest times exceeding twenty-four hours (mean thirty hours). Unpublished clinical results evaluating outcomes of pulmonary homografts implanted in the RVOT of children less than fourteen years, could not show a difference in freedom from reoperation between homografts harvested more than twenty-four hours post mortem and those harvested less than twenty-four hours post mortem. As the Bloemfontein homograft bank is presently the only homograft bank in South Africa, it embarked on a number of experimental studies in the ovine model in order to validate its practise and by implication, also that of cadaver based programmes. Four studies are presented evaluating the impact of increased post mortem harvest times and cryopreservation on homograft tissue integrity and in vivo performance. In the first study, the impact of increased post mortem homograft harvest times is described in cryopreserved ovine pulmonary homografts harvested twenty-four hours, fourty-eight hours and seventy-two hours post mortem. In the in vitro studies evaluating the morphology and tissue strength before implantation, no differences could be observed between the groups up to seventy-two hours post mortem harvest times. In the in vivo study no differences could be discerned in clinical performance, immunological processes, morphology, tissue strength and calcification after 180 days implantation. It was concluded that post mortem harvest times of pulmonary homografts can safely be extended up to seventy-two hours. In the second study, the morphology of unprocessed and cryopreserved pulmonary homograft leaflets with post mortem harvest times up to seventy-two hours was described. The impact of cryopreservation on leaflets per se was described in a control group as well as in tissue harvested at twenty-four hours, fourty-eight hours and seventy-two hours post mortem. Once again, no impact of extended post mortem harvest times could be perceived, except for increased oedema on TEM in the seventy-two hour group. Picrosirius red staining demonstrated that cryopreservation had a compressing and flattening impact on collagen in all groups. Disruption of collagen was observed on TEM in all cryopreserved groups. It demonstrated that cryopreservation had an immediate impact on tissue morphology and produced more ultrastructural tissue disruption than extending post mortem harvest times. In the third study, the impact of increased post mortem harvest times was studied in vitro comparing unprocessed and cryopreserved leaflets in relation to tissue strength. No difference in strength using tensile strength, Young’s modulus and thermal denaturation temperture, could be observed between the control group and the twenty-four hour, fourty-eight hour and seventy-two hour groups in the unprocessed leaflets. In addition, no difference could be discerned between leaflets processed and cryopreserved after twenty-four hours, fourty-eight hours and seventy-two hours post mortem harvesting. Tensile strength was potentially reduced by cryopreservation when compared to unprocessed leaflets, but did not reach statistical significance in all instances. In the final study, a fourty-eight hour post mortem homograft harvested group was processed and cryopreserved for implantation. This mimicks the clinical circumstances of cadaver programmes. The objective of this study was to evaluate the stability of homografts’ leaflet tissue after two periods of implantation. Control tissue (processed, cryopreserved and thawed) was compared to tissue explanted after two weeks and after 180 days in the ovine model. Despite the disruptive effect of cryopreservation demonstrated by TEM in all groups, the tissue remained stable throughout the period with normal clinical function and minimal calcification at 180 days. Through these studies conducted in the ovine model in order to provide experimental evidence for the safe extension of cold post mortem harvest times, it was concluded that in vitro and in vivo studies could not reveal detrimental effects on tissue integrity up to at least fourty-eight hours and possibly to seventy-two hours post mortem harvesting. The safety of fourty-eight hour post mortem harvested and thereafter cryopreserved pulmonary homografts was specifically studied in order to mimic the human clinical scenario wherein the stability of the homografts was confirmed in two study periods. It is concluded that these studies provide experimental scientific evidence to increase post mortem homograft harvest times to at least fourty-eight hours. Furthermore, these studies collectively provide experimental support for the re-evaluation of human cadaver homograft donor banks in order to attenuate international homograft shortages.
  • Thumbnail Image
    ItemOpen Access
    Processed pulmonary homografts in the right ventricle outflow tract: an experimental study in the juvenile ovine model
    (University of the Free State, 2020-02) Van den Heever, Johannes Jacobus; Smit, F. E.; Dohmen, P. M.
    The availability of pulmonary homografts with improved biomechanical properties, tissue stability, reduced calcification and improved durability for right ventricular outflow tract (RVOT) reconstruction is desired. In paediatric patients, a valve with growth potential will be advantageous. Extending the post-mortem ischaemic time will enlarge the donor pool. Cryopreservation of homografts remains the gold standard, but it damages the extracellular matrix (ECM) and reduces the cellularity, contributing to early valve degeneration. Decellularization of homografts might reduce immunogenicity, promote recellularization and tissue remodeling, maintain mechanical stability and improve clinical outcomes. The decellularization process should not compromise the durability and strength of the homograft, and alternative stabilization of the scaffold might be required. The current study evaluated the effect of the further processing of pulmonary homografts, following a 48 h cold ischaemic postmortem harvesting time, on the structural integrity and function when implanted in the RVOT position in the juvenile ovine model. Sheep pulmonary homografts (n = 30) were subjected to 48 h cold ischaemia to simulate the clinical homograft donor circumstances, and equally divided into three groups. Homografts in group 1 were cryopreserved, decellularized in group 2 and decellularized, GA-fixed and detoxified in group 3. Decellularization consists of a multi-detergent and enzymatic protocol with numerous washout steps, and additional fixation and detoxification were done with EnCap technology. The study was divided into three parts. In study 1, the histological (DAPI, H&E, von Kossa, Modified von Gieson, SEM, TEM) and mechanical (TS and YM) properties of the processed homografts (n = 15, 5 per group) were compared. Study 2 involved implantation of cryopreserved and decellularized pulmonary homografts (n = 5 per group) in the RVOT of juvenile sheep for 180 days, monitored with echocardiography and compared on histology, mechanical properties and calcification after explantation. Study 3 involved the same parameters, however, decellularized and decellularized plus EnCap treated homografts (n = 5 per group) were implanted and compared. Cryopreserved homografts demonstrated collapsed and disrupted/fractured collagen with cells and cellular remnants. Homografts in the decellularized group were acellular with large interfibrillar spaces and a loosely arranged collagen network, while decellularized plus EnCap treated homograft were acellular with a compacted collagen network. Decellularization did not reduce tensile strength and tissue stiffness, but EnCap treatment did increase tissue stiffness. Implanted cryopreserved homografts demonstrated significant regurgitation due to leaflet thickening and retraction, loss of interstitial cells, calcification and increased tissue stiffness. Decellularized homografts showed increased annulus diameter with trivial regurgitation, excellent haemodynamics, remained soft and pliable, recellularized extensively with young fibroblasts exhibiting rough endoplasmic reticulum, and mitigated calcification. Decellularized and EnCap treated homografts became rigid and stenotic, showed poor haemodynamic characteristics, development of bacterial endocarditis and premature death, no leaflet recellularization, and fibrous encapsulation. Cryopreserved homografts remain the valve of choice for RVOT reconstruction surgery, however, cryopreservation causes cell death and collagen disruption, and loss of cellularity and calcification during implantation, which will result in early valve degeneration. Our proprietary decellularization protocol proved to be effective for complete decellularization of pulmonary homografts with a post-mortem ischaemic time of 48 h, while maintaining a well-organized collagen matrix and tissue strength and stiffness. Implanted decellularized homografts repopulated extensively without signs of inflammation, maintained structural integrity and strength, calcification was mitigated, and the potential for remodeling and growth in size with somatic growth was observed. Additional fixation of the decellularized homograft scaffold will be counterproductive in growing individuals, and should only be performed on adult size homografts where valve growth is not required. GA-fixation restricts valve repopulation with host cells and tissue remodeling, and defies the purposes and advantages of decellularization. Additional fixation may not be necessary when using decellularization methods that achieve complete acellularity without altering the ECM structure and mechanical properties of homografts. Successful decellularization of donor homograft heart valves and other collagenous tissues holds exciting new prospects and possibilities for tissue processing, and can open a new era in supply of substitution valves and tissues with improved properties and advantages to medical patients in South Africa.
  • Thumbnail Image
    ItemOpen Access
    Infective endocarditis in central South Africa in the HIV era- a surgical perspective
    (University of the Free State, 2021) Gwila, Taha H.; Smit, F. E.; Botes, L.; Hanekom, H. A.
    Introduction: Infective endocarditis (IE) remains an evolving disease with a persistently high mortality and morbidity. In Africa, it is predominantly a disease of the young in contrast to the developed world. South Africa represents a very high prevalence of HIV at 21.67% of global HIV infections. Other factors in South Africa include the high prevalence of rheumatic valvular heart disease, low socio-economic status and poverty makes the patient population completely different from the developed world. The primary aim was to determine the influence of HIV infection on infective endocarditis patients in central South Africa. The secondary aim was to compare the HIV positive patients and HIV negative patients in the context of this disease. Objectives: To determine the demographics, presentation, indication for surgery, microorganisms, and outcomes of HIV positive versus HIV negative patients presenting with Infective endocarditis. Methods: Retrospective, analytical cohort study that reviewed the records of adult patients who were tested for HIV and treated surgically for infective endocarditis between 2009 to 2019. Data was compared between the two groups using chi-square or Fisher exact tests for categorical variables. Median and interquartile ranges were used for continuous variables and frequencies and proportions for categorical variables. Significance was set as p < 0.05. Results: From the 141 IE patients who underwent surgery for IE, 105 patients were tested for HIV, 31% (n=33) tested positive. The mean age for both groups was comparable 38.87 versus 39.51 years. Eighty-eight percent (n=29) of positive patients were on HAART. In both groups, there was a male preponderance, 55% vs 46% and 56% vs 44% respectively. The majority of HIV positive (91%) and negative patients (71%) were of African descent, more than 50% of both groups presented with NYHA III&IV, both groups had a medium-high risk of developing IE (HIV (+) 72%; HIV (-) 62%). Prevention of embolization was the main indication for surgery in HIV (+) group and heart failure in the negative group. In both groups a greater proportion of patients had left sided native valve endocarditis 95% and RHD was predominantly the underlying pathology 60%, requiring mechanical prostheses mainly in the mitral 46% and aortic 33% position. Right sided endocarditis represents <5% and only 2 out 105 patients confirmed IVDA’s, Staphylococcus and Streptococcus dominated cultured organisms with staphylococcus species being more frequent, culture negative endocarditis remains high in both groups, with 47% HIV (-) group vs 33%. Morbidity was limited in both groups 12% vs 11% with no major difference. The overall mortality was higher in the HIV (+) group (39% vs 34%); however, the in-hospital mortality was higher in the HIV (-) group (17% vs 12%). Conclusion: Infective endocarditis remains a deadly disease with high short- and long-term mortality. HIV infection has minimal to no impact on perioperative and in- hospital morbidity and mortality, left heart endocarditis is the dominant disease within the HIV patients due to the rheumatic valvular heart disease as opposed to right heart endocarditis. The high prevalence of culture negative endocarditis warrants further investigation. Given the low number of patients in this cohort study, further prospective studies need to be conducted to establish a statistical significance between the HIV (+) and (-) groups.
  • Thumbnail Image
    ItemOpen Access
    Critical analysis of rheumatic mitral valve surgery outcomes in central South Africa
    (University of the Free State, 2021) De-huis, Thabo J.; Smit, F. E.; Botes, L.; Hanekom, Manie
    Introduction: Rheumatic heart disease (RHD) is still an important cause of acquired heart disease affecting children and young adults from poor socio-economic backgrounds. The most common presentation of RHD is mitral valve disease requiring surgical intervention. The study aim was firstly to describe peri-operative risk factors, procedures performed and surgical outcomes after mitral valve surgery for RHD in Central South Africa. Secondly, to compare these results in patients presenting with mitral regurgitation to those presenting with mitral stenosis and mixed mitral valve disease. Methods: Patients undergoing mitral valve surgery for RHD, with or without concomitant tricuspid valve repair between January 2009 and December 2019 were identified from the departmental database. The lesions were grouped into mitral stenosis (MS), mitral regurgitation (MR), and mixed mitral (MX) disease. Statistical analyses was performed using the IBM SPSS program, version 26.0. A p-value of 0.05 or less was considered statistically significant. Results: A total of 242 patients were included in the study of which 75.2% (n=182) were female. Black patients represented 74.4% (n=180), whites 13.6% (n=33) with Asian and mixed races at 12% (n=29). The mean age of the study population was 43.7 years. Distribution of patients according to the lesions was 25.6% (n=62) for MS, 45.0% (n=109) for MR and 29.3% (n=71) for MX disease. Patients presenting in NYHA status III and IV formed 44% of the MR group and 44% of the MS group and for 28% for the MX group. Calculated EuroSCORE > 5 was 29.4% (n=18) in the MS group, 29% (n=32) in the MR group, and 9.9% (n=7) in the MR group. For the MS group, 96.7% (n=60) had mitral valve replacement and only 2.8% (n=2) were repaired (valvotomy); whilst in the MR and MX groups the replacement vs repair rate was 90.3% (n=93) and 94% (n=63) vs 9.7% (n=10) and 5.6% (n=4) respectively. The MS group had the highest number of concomitant tricuspid valve repair at 58.0% (n=36) as compared to MR (38.5%) and MX (35.2%) groups. There was no statistical difference across the groups with regards to the post-operative stroke rate (1%) as well as the rate of in-hospital complications (14%). In-hospital mortality for the entire cohort was 3.8% (n=9), with 4.8% (n=3) for the MS, 3.7% (n=4) in the MR group and 2.8% (n=2) in the MX group. Of the 242 patients in the study 82 did not have their follow up at the UAH clinic. For the 160 patients followed up at UAH clinic, the median follow-up time was 2.68 years, with 35 patients having had follow-up visits > 5 years. Conclusion: Patients received mitral valve surgery had RHD and were young females from poor socio-economic backgrounds with an average age in the 4th decade of life. MR was the most common lesion with replacement being the most performed operation in our unit. The post-operative complications rate as well as the in-hospital mortality were comparable to the published literature.
  • Thumbnail Image
    ItemOpen Access
    Impact of three different processing techniques on the strength and structure of juvenile pulmonary homografts
    (MDPI, 2022) Van den Heever, Johannes J.; Jordaan, C. J.; Lewies, Angelique; Goedhals, Jacqueline; Bester, Dreyer; Botes, Lezelle; Dohmen, Pascal M.; Smit, Francis E.
    Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on the strength and structure of ovine pulmonary homografts harvested 48 h post-mortem. Cells and cellular remnants were present for the cryopreserved group, while the decellularized groups were acellular. The decellularized group had large interfibrillar spaces in the extracellular matrix with uniform collagen distribution, while the additional fixation led to the collagen network becoming dense and compacted. The collagen of the cryopreserved group was collapsed and appeared disrupted and fractured. There were no significant differences in strength and elasticity between the groups. Compared to cryopreservation, decellularization without fixation can be considered an alternative processing technique to maintain a well-organized collagen matrix and tissue strength of homografts.