Doctoral Degrees (Cardiology)
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- ItemEchocardiographic screening for subclinical rheumatic heart disease: Improving screening through simplification of the diagnostic criteria(Stellenbosch : Stellenbosch University, 2020-12) Hunter, Luke David; Herbst, Philip George; Doubell, A. F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.ENGLISH ABSTRACT: Rheumatic heart disease (RHD) remains one of the leading causes of cardiovascular morbidity and mortality in developing countries withSub-Saharan Africa being identified as an endemic area. The early detection and initiation of secondary prophylaxis in children with ‘latent’ RHD remain attractive primary health care interventions, particularly in endemic regions with no or limited access to specialist cardiac services. However, the current consensus-derived screening criteria endorsed by the World Heart Federation (WHF criteria) are overly complex, require the use of expensive echocardiographic equipment with Doppler functionality and identify a large borderline diagnostic group that demonstrates a predominantly benign outcome in longitudinal study. This raises concerns regarding the feasibility of large-scale screening in resource-poor regions and questions the utility of early echocardiographic case-detection of RHD. The primary purpose of this thesis was to critically appraise the performance of the WHF criteria and todetermine whether a set of screening criteria based on a novel, focused morphological and mechanistic evaluation would simplify the current WHF guideline and reduce the number of cases ‘misclassified’ with borderline RHD whilst maintaining a similar degree of sensitivity. A literature review was undertaken that critically appraised the performance of the current WHF criteria and its impact in African RHD screening programs. This highlighted important logistical and methodological shortcomings that have curtailed the implementation of large-scale RHD screening in RHD endemic regions. The five-year experience of a large-scale, high-risk RHD screening program (Echo in Africa [EIA] project) was analysed. The results from this project highlightRHD as an ongoing, significant healthcare challenge amongst underserved communities within the Western Cape, South Africa.The estimated prevalence of WHF ‘definite-’ and ‘borderline-RHD’ of 9.1 cases/1000 and 19.5 cases/1000 reported by EIA is significantly higher thanthatpreviously described in this region. Furthermore, a critical appraisal of the WHF criteria’s performance in the EIA cohort highlighted various redundant and ambiguous criteria that require revision.Inter-scallop separations (ISS) of the posterior mitral valve leaflet (PMVL) were described in both our high-and very low-risk populations. They were a common finding and the principal cause of WHF ‘pathological’ mitral regurgitation (MR) in the ‘borderline RHD’ group in both cohorts. This supported theirstatus as a normal and importantly, non-rheumatic variant.The reliability of the current WHF anterior mitral valve leaflet (AMVL) thickness assessment was evaluated and was demonstrated to be poor amongst readers despite controlling for systematic bias. This raised the possibility of introducing a non-measurement-based AMVL thickness evaluation. A novel screening definition of AMVL restriction was introduced, enabling the description of a variable spectrum of AMVL restriction amongst children.This definition reliably identified two subtypes of leaflet restriction: a normal, ‘gradual bowing’ variant that localised predominantly to the medial portion of the leaflet and a ‘distal tip’ variant seen to affect at least the central portion of the leaflet in all cases of WHF ‘definite RHD’ in this cohort. Finally, this thesis culminated in the development and evaluation of a novel set of morpho-mechanistic (MM) echocardiographic screening criteria for RHD. Together with an abbreviated ‘rule-out’ screening test, the MM criteria were assessed alongside the current WHF criteria in a gold standard RHD-negative cohort and a gold standard RHD-positivecohort. The MM criteria significantly reduced the false-positive rate of a borderline diagnosis inthe gold standard RHD-negative cohort (2.7/1000 vs 41.8/1000) whilst maintaining a similar screening sensitivity (99.7%) compared to the WHF criteria (95.9%) within thegold standard RHD-positivecohort. Similarly, the MM RHD ‘rule-out’ test performed well by excluding the majority of cases (98%) within the gold standard RHD-negative cohort while including all cases within the gold standard RHD-positive cohort. The work presented in this thesis addresses key research needs and gaps in our current understanding of ‘screen-detected’ latent RHD. It representsa significant contribution that will impact on policy, practice and further research in the field. The discovery that ISS of the PMVL are a normal finding and the principal cause of isolated ‘pathological’ MR in the borderline group represents a key element in solving the ‘borderline conundrum’. This discovery supported the adoption of a morpho-mechanistic screening approach over a predominantly functional MV assessment. Centred around a novel definition of AMVL restriction, the MM criteria significantly improve the specificity of RHD detection by markedly reducing the size of the borderline group. Importantly, this was achieved without a reduction in the sensitivity of the criteria when compared to the current WHF criteria. Together with a simple ‘rule-out’ test, the MM criteria bring us closer to the objective of implementing large-scale screening programs that identify children with latent RHD who will benefit from secondary prophylaxis.
- ItemEvaluating a bioprosthetic anterior mitral valve leaflet made from autologous jugular vein and expanded polytetrafluoroethylene (Gore-Tex) chordae in a sheep model(Stellenbosch : Stellenbosch University, 2016-03) Janson, Jacques; Coetzee, Andre; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Cardiology.ENGLISH ABSTRACT: The purpose of this study was to evaluate whether an autologous vein graft supported by expanded polytetrafluoroethylene (Gore-Tex) chordae can be used to replace an anterior mitral valve leaflet and whether the vein will be able to withstand the stress and strain of deformation, remain viable in the intracardiac environment and be able to adapt morphologically and grow as a valve leaflet. An autologous jugular vein graft, used as a double layer, supported by Gore-Tex chordae was used to create a functional anterior mitral valve leaflet in 21 sheep. No ring annuloplasty was used to support the annulus. The average cross-clamp time was 99 minutes (76 to 151 min) and the average bypass time was 137 minutes (109 to 188 min). One sheep died intra-operatively. The post-operative echocardiogram demonstrated laminar diastolic flow across the mitral valve with an average opening area of 2.8cm². Fourteen sheep had trace to mild mitral regurgitation (MR), 5 sheep had mild to moderate MR and 1 sheep had moderate to severe MR. The body of the vein leaflet tends to billow during systole which increases stress on the Gore-Tex chordae. Three sheep died 2 to 3 days postoperatively from mitral regurgitation due to Gore-Tex chordae that were too long, causing prolapse in 2 cases and 1 case developed a hematoma between the 2 vein layers. Seven sheep died between 1 and 6 months. Four sheep developed infective endocarditis on the mitral valve. Echocardiography at 6 months showed that the mitral regurgitation (MR) progressed with time in most of the sheep: 3 out of 11 sheep had mild MR, 5 had mild to moderate MR and 3 had moderate to severe MR. The progression of MR was due to lack of secondary chordal support of the vein leaflet and mitral annulus, leading to progressive annular dilatation, decreased leaflet coaptation length and increased tension on the primary Gore-Tex chordae. Durability of the valve should be improved by adding an annuloplasty ring and supporting the leaflet with secondary chordae. The 10 surviving sheep were euthanized between 6 to 10 months. All vein implants were examined histologically. The vein leaflet developed intimal fibroplasia and fibrous proliferation between the 2 vein layers as a response to the increased stress upon the tissue. This caused leaflet thickening, but the vein remained flexible without shortening or contracture. The 6 to 10 month vein implants showed viable endothelium and the underlying vein layers clearly showed viability with myofibroblasts, collagen and elastin. A normal healing pattern was seen at the suture lines and no calcification was seen in the vein leaflet apart from the Gore-Tex sutures. No vein growth was demonstrated. Autologous vein has the potential to be used as a valve leaflet substitute, because it remains viable in the intracardiac position for up to 10 months and is able to withstand the stress and deformation of a valve leaflet. Histologically it showed the ability to heal and to morphologically adapt to the new environment.
- ItemLupus myocarditis : diagnostic characteristics and outcome of myocardial injury(Stellenbosch : Stellenbosch University, 2020-12) Du Toit, Riette; Doubell, A. F.; Reuter, H.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.ENGLISH ABSTRACT: Lupus myocarditis is a rare but serious manifestation of systemic lupus erythematosus (SLE). Through this dissertation I have aimed to describe the outcome of both clinical as well as subclinical myocardial injury in SLE. I have also aimed to define the diagnostic characteristics of myocardial injury, identified by cardiac magnetic resonance imaging with regards to clinical, echocardiographic and cytokine profiles.
- ItemRenal denervation restores autonomic imbalance and prevents atrial fibrillation in patients with hypertensive heart disease : a pilot study(Stellenbosch : Stellenbosch University., 2020-03) Heradien, Marshall Jacobus; Brink, Paul A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Cardiology.ENGLISH ABSTRACT: Background: Atrial fibrillation (AF) is associated with increased cardiovascular morbidity and mortality, but it is uncertain if catheter-based renal denervation (RD) can reduce AF in patients with hypertensive heart disease (HHD). Methods: Patients who were ≥ 55 years old, in sinus rhythm, taking ≥ 3 anti-hypertensive drugs including a diuretic, with echocardiogram-confirmed HHD and suspected coronary artery disease, were randomised to undergo RD or sham procedure. Patients with renal impairment, significant valvular heart disease and untreated thyroid disease were excluded. The primary endpoint, the first episode of subclinical AF (SAF) lasting ≥ 6 minutes, was detected using an implantable loop recorder which was scanned every six months. Six-month follow-up (6MFU) office systolic blood pressure (SBP), cardiovascular mortality and restoration of autonomic imbalance were secondary endpoints. Results: Eighty patients were randomised: 42 underwent RD and 38 a sham procedure. After an average follow-up of three years, fewer RD patients experienced SAF: 6 of 42 patients (14.3%) vs 15 of 38 (39.5%) sham patients (odds ratio (OR), 0.26; 95% CI, 0.1 to 0.71, p = 0.01). Fast AF (ventricular rate ≥ 100 bpm) occurred in 10 sham patients (26.3%) vs 1 RD patient (2.4%): OR, 14.64; 95% CI, 1.77 to 120.91; p = 0.002). The incidence of cardiovascular death was higher in the sham than RD group (6 of 38 (15.8%) vs 1 of 42 (2.4%): OR, 7.69; 95% CI, 0.88 to 67.12; p = 0.049). Non-ST elevation myocardial infarction (NSTEMI) incidence was lower in the RD than sham group (2.3% vs 18.4%: OR, 0.108; 95% CI, 0.01–0.92; p = 0.02). The 6MFU between-group SBP difference was not significant (−3.8 mmHg; p = 0.49). Resting and one-minute recovery heart rate did not differ between groups at 6MFU. Conclusion: In patients with HHD, RD reduces subclinical and fast AF, NSTEMI and cardiovascular death independent of lowering blood pressure. RD was not associated with improvement of surrogate markers of autonomic imbalance.
- ItemThe Tygerberg Endocarditis Cohort (TEC) Study(Stellenbosch : Stellenbosch University, 2021, 2021-12) Pecoraro, Alfonso Jan Kemp; Doubell, Anton Frans; Herbst, Philippus George; Janson, Jacques Teran; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology.ENGLISH ABSTRACT: Background: The diagnosis of infective endocarditis (IE) is based on the modified Duke/ESC 2015 clinical criteria. The sensitivity of the criteria is unknown in South Africa, but high rates of blood culture negative endocarditis (BCNIE), coupled with a change in the clinical features of IE, may limit the sensitivity. Methods: The Tygerberg Endocarditis Cohort (TEC) study prospectively enrolled patients with IE between November 2019 and June 2021. A standardised protocol for organism detection, with management of patients by an Endocarditis Team, was employed. Patients with definite IE by pathological criteria were analysed to determine the sensitivity of the current clinical criteria. Results: Eighty (80) consecutive patients with IE were included of which 45 (56.3%) had definite IE by pathological criteria. In patients with definite IE by pathological criteria, 26/45 (57.8%) of patients were classified as definite IE by clinical criteria. BCNIE was present in 25/45 (55.6%) of patients and less than three minor clinical criteria were present in 32/45 (75.6%) of patients. The elevation of Bartonella serology to a major microbiological criterion of the modified Duke/ESC 2015 clinical criteria would increase the sensitivity (56.3% vs. 77.8%; p=0.07). Conclusion: The sensitivity of the modified Duke/ESC 2015 clinical criteria is lower than expected in patients with IE in South Africa, primarily due to the high rates of Bartonella-associated BCNIE. The elevation of Bartonella serology to a major microbiological criterion, similar to the status of Coxiella burnetii in the current criteria, would increase the sensitivity. The majority of patients with definite IE by pathological criteria had less than three minor criteria present.