Cardiology

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Browsing Cardiology by browse.metadata.advisor "Doubell, Anton F."

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    Development of an improved approach to transcatheter heart valve heart valve replacement in younger patients
    (Stellenbosch : Stellenbosch University, 2024-03) Weich, Hellmuth Stephan von Heyderhoff; Doubell, Anton F.; Smit, Francis E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.
    ENGLISH ABSTRACT: Rheumatic heart disease [RHD] globally affects four times as many people as degenerative aortic valve stenosis, yet all the current transcatheter aortic valves are aimed at treating degenerative disease in mostly affluent societies. There is a lack of access to cardiac surgery in low- to middle income countries where RHD is prevalent and affects mostly younger patients. Less invasive transcatheter alternatives may improve this but current devices are not appropriate because they are not designed to anchor in less calcified anatomy and the bioprosthetic tissue used for their leaflets are not durable in younger patients. We aimed to address three challenges faced in the development of a TAVI valve suitable for use in younger patients, namely more accurate positioning of the device, better anchoring of the device and better durability. We postulated that a novel non-occlusive balloon [NOB] has the potential to deliver a balloon expandable transcatheter heart valve [THV] to the aortic position with greater accuracy and stability than current [occlusive] balloons. Such a balloon was tested in an acute sheep experiment. The balloon could be inflated in the aortic valve position without compromising the animals’ hemodynamics. The NOB holds promise for a deployment device for balloon expandable THVs in younger patients with less calcified aortic valves. We designed and 3D printed a novel anchor stent to improve anchorage in the aortic valve position. The aim of the stent was as a docking station for a THV, but the principle could potentially be applied to a THV itself. The stent anchored securely in an ex-vivo study but deployment in an ovine experiment was unpredictable. Our failure to anchor it however identified a number of areas for improvement allowing us to propose an alternate design to overcome these obstacles. Our team developed a THV and collaborated with the Frater Centre at the University of the Free State which has extensive experience with pericardial tissue processing. Our approach for improved durability of the bovine pericardial leaflet tissue in young people focused on reducing glutaraldehyde exposure and decellularization of the tissue. We manufactured 3 sets of THVs [one decellularized according to the Frater Center’s technique (DE), one decellularized in the same way but fixed with very low dose monomeric glutaraldehyde (DF) and one with an industry standard (Glycar ®) fixed with high dose glutaraldehyde]. These valves were implanted for 6 months in an ovine right ventricular outflow conduit. At explant, the DF and DE valves outperformed the Glycar ® valves in a number of areas: better hemodynamic performance and strength; no inflammatory response; no pannus formation in DE and limited on DF tissue; no calcification of either DE or DF. The most notable finding was that the DE tissue had no cellular ingrowth [essentially inert] but despite this, was not mechanically inferior to the two glutaraldehyde fixed tissues and comparable to the same tissue prior to implant. This finding is unique and warrants validation in longer term implants and higher pressure environments. Based on our results, these two novel tissues has the potential to perform better in younger patients. This work brings us three steps closer to finding a THV that can be accurately delivered, implanted in a stable position and prove to be durable in younger patients.
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    Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy
    (Stellenbosch : Stellenbosch University, 2022-12) Robbertse, Pieter-Paul Strauss; Herbst, Philip G; Doubell, Anton F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.
    ENGLISH ABSTRACT: HIV-associated cardiovascular disease (CVD) exists on a spectrum, is poorly understood, and may be highly heterogenous. In low- and middle income countries, HIV-associated cardiomyopathy (HIVAC) remains prevalent; yet, little research is available on antiretroviral treatment (ART) naïve persons from these regions. The study of subclinical CVD may increase our appreciation of HIV-related pathology. Purpose and methods The dissertation’s purpose was to explore subclinical HIV-associated CVD. Our experience with the diagnosis and management of symptomatic HIVAC, and the questions that arose from this, served as motivation for the development of this prospective research project assessing for subclinical HIVAC in people living with HIV (PLWH). Cardiovascular magnetic resonance imaging (CMR), supplemented by additional modalities, was employed in a cohort study of newly diagnosed, ART naïve PLWH in South Africa. Contemporary, HIV uninfected persons were recruited as a control group. Cardiovascular findings were compared between the research groups at enrolment and at 9 months after the initiation of ART. Key findings Distinct similarities exist between symptomatic and subclinical HIVAC, characterised by dilated and thickened left ventricles (LV), decreased systolic function, and tissue characterisation suggesting myocardial oedema. ART improved but did not normalise these abnormalities. The finding of inflammation in our asymptomatic cohort suggests that HIVAC exists along a spectrum, ranging from asymptomatic cardiac inflammation to end stage dilated cardiomyopathy. Inflammation is therefore likely to be the central pathology as supported by CMR imaging biomarkers, biochemical markers of inflammation, and highly prevalent pericardial effusions in our HIV cohort. The cross-sectional analysis of the cohort study revealed altered structure, function, tissue characteristics, biochemical signatures, and aortic stiffness in PLWH compared with controls. The features of dilated ventricles in PLWH with increased LV mass and deceased biventricular systolic function were associated with myocardial tissue abnormalities. These included elevated native T1, T2, and extracellular volume mapping (ECV). Furthermore, PLWH had a high prevalence of cardiac fibrosis and aortic stiffness, already present at the time of HIV diagnosis. Significant associations with the HIV viral load were demonstrable between the LV and right ventricular (RV) ejection fractions and markers of myocardial oedema. Cardiac biochemical biomarkers of myocardial stretch, remodelling, and fibrosis showed promise as surrogates for CMR imaging biomarkers. The prospective data of PLWH showed that, despite the decrease in systemic inflammation and myocardial oedema, the LV size and systolic function did not improve. Coupled with tissue characterisation evidence of persistent myocardial fibrosis, this suggests irreversible cardiac injury, partially to ART. Conclusion At the time of HIV diagnosis, the hearts of PLWH demonstrated subclinical abnormalities. ART improved, but did not completely normalise these abnormalities. Myocardial oedema and fibrosis were present, supporting the current inflammatory hypothesis of HIV. The subclinical myocardial abnormalities resemble cases of symptomatic HIVAC, and may represent a stage in the evolution towards more advanced CVD. In the absence of long-term clinical outcomes, the aortic stiffness and cardiac biomarker findings suggest increased cardiovascular risk in our cohort. This body of work provides robust data that lays the foundation for further research on the cardiovascular risk and clinical outcomes of subclinical CVD in PLWH.