Development of an improved approach to transcatheter heart valve heart valve replacement in younger patients

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dc.contributor.advisorDoubell, Anton F.en_ZA
dc.contributor.advisorSmit, Francis E.en_ZA
dc.contributor.authorWeich, Hellmuth Stephan von Heyderhoffen_ZA
dc.contributor.otherStellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.en_ZA
dc.date.accessioned2024-03-07T10:56:43Zen_ZA
dc.date.accessioned2024-05-08T10:50:19Zen_ZA
dc.date.available2024-03-07T10:56:43Zen_ZA
dc.date.available2024-05-08T10:50:19Zen_ZA
dc.date.issued2024-03en_ZA
dc.descriptionThesis (PhD)--Stellenbosch University, 2024.en_ZA
dc.description.abstractENGLISH 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.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Rumatiese hartsiekte [RHS] affekteer wêreldwyd vier keer soveel mense as wat degeneratiewe aorta stenose doen. Al die transkateter aorta klep [sogenaamde TAVI] prosteses is egter gemik op die behandeling van degeneratiewe siekte in die meer welgestelde gemeenskappe. Daar is ‘n beduidende tekort aan toegang tot hartklep chirurgie in lae- en middel inkomste lande waar RHS prevalent is en meestal jonger pasiënte affekteer. Minder indringende transkateter alternatiewe mag die oplossing wees, maar is tans nie toepaslik nie aangesien hulle nie ontwerp is om in die minder verkalkte anatomie te anker nie en die bioprostetiese weefsel wat vir hul klepsuile gebruik word, is nie duursaam genoeg in jonger mense nie. Ons het ons ten doel gestel om ‘n TAVI klep te ontwikkel wat geskik is vir jonger mense en drie van die struikelblokke van hierdie tipe klep teiken: meer akkurate posisionering van die toestel, beter anker in die aorta annulus en beter duursaamheid. Ons het gepostuleer dat ‘n unieke nie-obstruktiewe ballon [NOB] die potensiaal het om ʼn ballon ontplooibare transkateter hartklep [THK] in die aorta posisie te ontplooi met groter akkuraatheid as standaard obstruktiewe ballonne. Die ballon is onwikkel en getoets in ‘n akute skaap eksperiment. Die ballon kon in die aorta posisie ontplooi word sonder om die diere se hemodinamika te kompromitteer. Ons het ʼn unieke anker stent ontwikkel wat deur ‘middel van laagvervaardiging [‘3D printing’] geproduseer is. Die doel daarvan was om in die aorta posisie te anker en as ‘n dokstasie vir ‘n THK te dien. Die stent het sekuur ge-anker in ‘n ex vivo eksperiment, maar ontplooiing in die aorta annulus van skape was onvoorspelbaar. Ons onvermoë om dit te anker het egter etlike areas geïdentifiseer waar verbeteringe aangebring kan word om hierdie hindernisse te oorkom. Ons groep het ‘n THK ontwikkel en gekollaboreer met die Frater Sentrum van die Universiteit van die Vrystaat wat gevestigde ervaring het met die ontwikkeling en prosessering van bioprostetiese materiaal. Om die weefsel meer duursaam in jonger mense te maak, het ons gefokus op verminderde blootstelling van die weefsel aan glutaraldehied [GA] en desellulering van die weefsel. Ons het 3 stelle THKe vervaardig: drie wat volgens die Frater Sentrum se unieke proses gedeselluleer is (DE); drie wat op soortgelyke wyse gedeselluleer is maar ook gefikseer is met baie lae dosis GA (DF) en drie met ‘n industrie standaard (Glycar ®) weefsel wat met hoë dosis GA gefikseer is. Hierdie kleppe is vir 6 maande in skaap regterhart uitvloeibane ingeplant. Met eksplantasie is gevind dat die DE en DF kleppe betekenisvol beter as die Glycar ® kleppe gedoen het in ‘n aantal opsigte: beter hemodinamiese funksionering en sterkte; geen inflammatoriese respons; geen pannus vorming in DE en baie beperk in DF en geen verkalking in beide DF en DE. Die mees uitstaande bevinding is dat die DE weefsel geen sellulêre ingroei gehad het en dus inert was. Ten spyte hiervan was dit nie meganies ondergeskik tot die twee weefsel wat met GA gefikseer is nie en vergelykbaar met dieselfde [DE] weefsel pre-inplantering. Hierdie is ‘n unieke bevinding en regverdig verdere validering in langer termyn inplantings en in ‘n hoë druk omgewing. Gebaseer op ons bevindinge, behoort hierdie twee nuwe weefsels meer toepaslik te wees vir gebruik in jonger pasiënte. Hierdie werk verteenwoordig drie treë nader aan ʼn oplossing vir ʼn THK wat meer akkuraat geplaas kan word, in ʼn meer stabiele posisie ge-anker kan word en meer duursaam sal wees in jonger pasiënte.af_ZA
dc.description.versionDoctorateen_ZA
dc.embargo.terms2024-09-26
dc.format.extentxii, 82 pages : illustrationsen_ZA
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/130793
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshRheumatic heart diseaseen_ZA
dc.subject.lcshAortic valve -- Stenosisen_ZA
dc.subject.lcshHeart valves -- Diseasesen_ZA
dc.subject.lcshDegeneration (Pathology)en_ZA
dc.subject.lcshUCTDen_ZA
dc.titleDevelopment of an improved approach to transcatheter heart valve heart valve replacement in younger patientsen_ZA
dc.typeThesisen_ZA
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