A novel trans-catheter heart valve system for low- to middle-income countries: need assessment, surgical feasibility and preclinical translation

My thesis covers the clinical translation of a unique initiative at a South African tertiary institution towards a comprehensive, tailor-made African answer to a global health problem affecting millions of indigent patients outside the industrialized world. Rheumatic Heart Disease is typically a disease of poverty, leading to different levels of destruction of patients' heart valves in an estimated 33 million patients of low- to middle income countries globally. Heart valve surgery is often the only life-saving remedy but seriously underprovided in developing countries. Moreover, replacement heart valve prostheses were developed for degenerative pathologies prevailing in high-income countries and poorly suited for the majority of patients suffering from rheumatic heart disease. As a clinician at the interface of the developing and developed world, I dedicated the first part of my thesis establishing the shortcomings of contemporary replacement heart valves in rheumatic patients. This included one of the rare follow-up studies in indigent patients confirming the need for a radically different concept. Providing the clinical end-goals to an engineering endeavor at the University of Cape Town to develop a replacement heart valve for rheumatic patients, the second part of my PhD focused on the in-vivo translation of this concept. In the absence of an established animal model for such a trans-catheter solution, the extensive implant series I performed achieved two goals: optimization of the devices in close interaction with the engineers and establishment of anatomical inclusion/exclusion criteria in both the sheep and pig model. Based on these accomplishments, I worked out an optimal implantation technique and demonstrated short and long-term performance of the developed heart valve devices in the animal models I established. Having successfully provided all the regulatory preclinical data required for ‘first-in-human' implants, I used a statistical analysis approach to extrapolate clinical and pre-clinical data towards size predictions for the replacement valves expected to be needed in an upcoming clinical trial while also defining anatomical exclusion criteria. I trust that this comprehensive clinical and laboratory-based PhD thesis that systematically progressed through the clinical translation process of a novel university-based development complies with the high standards defining the highest of postgraduate degrees.

Grantor dc:publisher.institution

Division of General Surgery

Year dc:date.issued

2024

Author dc:creator

• Scherman, Jacques

Advisor dc:contributor.advisor

• Zilla, Peter

• Rheumatic Heart Disease

Handle dc:identifier.uri

http://hdl.handle.net/11427/41345

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/41345