Background Management of coronary heart disease remains a challenge even with modern advances. New anti-platelet agents which reduce thromboembolic events in patients with coronary heart disease were introduced. However, there are concerns about an increased in bleeding risk for patients taking these new anti-platelet agents. Platelet function test, such as VerifyNow, claimed to be able to predict bleeding risk. However, the evidence was limited, especially among the Asian population. This study aimed to evaluate the use of VerifyNow to assess bleeding risk. Subjects with low residual platelet reactivity, i.e. low PRU value, were hypothesized to have an increased bleeding risk. Methods This was a case control study performed in the Princess Margaret Hospital of Hong Kong. A total of 120 subjects who were taking a P2Y12 inhibitor and had a VerifyNow test were recruited. The cases were defined as subjects with a PRU value of less than or equal to 95, a threshold for increased bleeding risk as recommended by Western studies. The controls were age matched to the cases. The primary outcome was the increase in bleeding risk associated with a low PRU value at 30 days. The secondary outcome was the increase in bleeding risk associated with a low PRU value at 1 year. The use of the percentage of platelet inhibition was also evaluated as a secondary outcome. Multivariable logistic regression was used to obtain the odds ratio of the low PRU group. Results Bleeding events occurred more frequently in the low PRU group. At 30 days, 31.7% of subjects among the case had a bleeding event while 43.3% of the cases had a bleeding event at 1 year. The majority of these bleeding events were minor bleeding, such as easy bruising. After adjusting for confounders, there was no statistically significant increase in bleeding risk among those in the low PRU group at 30 days or 1 year. Subjects with a high percentage of platelet inhibition (>50%) was also not associated with a statistically significant increase in bleeding risk. Conclusion A low PRU value was not associated with an increased bleeding risk at 30 days. Thus the VerifyNow test was not shown to be useful in assessing the bleeding risk of patients in an Asian population, contrary to the findings from Western literature. A possible explanation was that the VerifyNow threshold for predicting bleeding might be higher among the Asian population. The definition for low residual platelet reactivity might be different in our locality. A larger sample size might also be needed. Further studies are needed to evaluate whether a different cut off is more optimal for the Asian population. / published_or_final_version / Public Health / Master / Master of Public Health

Submitted in fulfilment of the Master’s Degree in Clinical Technology, Durban University of Technology, 2012. / The sirolimus-eluting stent (Cypher) was the first approved drug- eluting stent by the Food and Drug Administration in April 2003. This is a stent that is based on a bare-metal stent and is coated with a layer of polymer incorporating sirolimus and releasing it by diffusion. Drug-eluting stents reduced risk of restenosis and repeat revascularization as compared with bare-metal stents. Clinical data has raised concerns that drug-eluting stents are associated with late untoward events. Objectives: The objective of this study was to test the hypothesis that stenting is safe and effective treatment for coronary artery disease. Methods and Results: Sirolimus-eluting stenting was performed in 30 patients with 34 coronary lesions. Detailed clinical follow-up data was collected by personal interview or telephone contact at 1, 6, 12 and 24 months. Patients were followed for 2 years for the occurrence of angina and cardiovascular events namely death, myocardial infarction, stent thrombosis and target lesion revascularization. The mean age of the cohort was 62.33±10.99 years; 83 percent were male, 6 percent were diabetic, 53 percent had hypertension. In spite of the overall patient and lesion complexity there were no incidences of major adverse cardiac events and all patients remained angina free out to two years. Dual antiplatelet therapy with aspirin and plavix varied from at least four weeks to one year. One patient had a bleeding event. Conclusions: Treatment of lesions with sirolimus-eluting stents is associated with a sustained clinical benefit two years after device implantation.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Master / Doctor of Medicine

Introduction There is a pressing clinical need to treat patients with acute coronary syndrome (ACS) timely and efficiently in order to improve their prognosis. Standard tools available in ED, while useful, do not comprehensively characterize ACS for either diagnosis or risk stratification. The role of CMR in ACS is emerging because it allows assessment of both myocardial composition and function. Newer CMR techniques such as: a) T2 W imaging for assessing myocardial oedema and area at risk B) pre contrast T1 mapping techniques for quantitative characterization of the tissue composition, are adding further utility for CMR in ACS. At present the clinical use of these techniques is still limited and further investigations are needed to assess their clinical applicability in ACS patients. Aims The aims of this thesis were several. Firstly we sought to establish a CMR protocol for imaging ACS patients on a 3T CMR scanner. In order to do so, we validated a novel T2 W technique for oedema imaging (T2 prep SSFP) at 3T. Second, we aimed to perform a detailed study of the time course of oedema in ACS patients in order to establish the appropriate imaging time for the assessment of area at risk. Third, by applying T2W acute oedema imaging, we sought to investigate the functional and pathological meaning of complicated remote plaques in patients with multivessel disease. Finally, we aimed to establish whether, in comparison to standard CMR techniques, novel precontrast Tl mapping allows better characterisation of the acutely injured myocardium and whether it can predict long-term functional recovery. Methods The research studies were all performed on a 3T Trio Siemens scanner. In the initial stage of the research, we validated the T2 W technique performing phantom work and scanning both volunteers and patients to assess the uniformity of signal intensity in the myocardium and to establish a threshold based method to post process the images. We then established a CMR protocol for ACS including oedema imaging, T1 mapping imaging, perfusion, functional and late gadolinium enhancement imaging. Patients with acute myocardial infarction (both ST elevation myocardial infarction (STEMI) and non STEMI) were scanned at 4 different time points after the acute event (3 scans within 2 weeks and one at 6 months). All STEMI patients underwent primary percutaneous coronary intervention (PCI) while the non-STEMI patients underwent coronary angiography and for PCI. Results We validated the T2prep SSFP technique at 3T, highlighting its limitations and establishing a threshold of mean ± 2SD to assess myocardial oedema. We found that the optimal imaging window to assess the maximal expression of myocardial oedema was within 1 week from the acute event in patients with ST elevation MI. Also, our results showed a reduction of LGE over time (from acute to chronic) in segments which also showed improvement in contractile function indicating that even segments with transmural LGE assessed in the early hours post event could be viable. By applying these techniques in acute patients with bystander disease undergoing percutaneous coronary intervention, we found that: l) T2W imaging can detect myocardial injury downstream from a vessel identified as "non culprit" 2) in 20% of NSTEMI patients, the angiographic assessment alone failed to identify the culprit vessel. Finally, we found that the diagnostic performance of acute pre-contrast Tl-mapping was at least as good as that ofT2W CMR for detecting myocardial injury. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental Tl values and the likelihood of improvement of segmental function at 6 months decreased progressively as acute Tl values increased. Conclusions In summary, we defined a stable imaging window for the retrospective evaluation of area at risk and we also indicated that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium. Furthermore, in NSTEMI patients with multivessel disease, by revealing acute myocardial damage in territories pertaining to vessels not treated acutely, we raised the issue of the need for better tools for the correct identification of the culprit vessel and to stratify patients rather than by angiographic assessment alone. Finally, we demonstrated how pre-contrast Tl mapping allows for assessment of the extent of myocardial damage and how Tl mapping might become an important complementary technique to LGE and T2W for the identification of reversible myocardial injury and the prediction of functional recovery in acute MI.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Master of Philosophy

Thesis (MBA (Business Management))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: South Africa is on the verge of major changes in the private medical sector. The government’s planned National Health Insurance has far reaching implications for all role players in the industry, as well as for the general public. This paper looks at the changes that have been made since the ANC government came to power in 1994 and then continues to look at possible models for the new National Health Insurance plan. A proposal on practicing cost-effective cardiology within this new system is made. The data of a pilot project between a private service provider and a managed healthcare company is analysed as a basis of this discussion. / AFRIKAANSE OPSOMMING: Suid-Afrika se mediese bedryf staan op die vooraand van groot veranderinge. Die regering se beplande Nasionale Gesondheidsplan het verreikende implikasies vir alle rolspelers in die bedryf, sowel as die algemene man op straat. Die dokument kyk oorsigtelik na die veranderinge wat ondergaan is sedert die ANC regering aan bewind gekom het in 1994 en gaan daarna voort om na moontlike opsies te kyk hoe die nuwe gesondheidsmodel daarna gaan uitsien. Voorstelle word gemaak oor hoe privaat kardiologie in die nuwe sisteem koste-effektief beoefen kan word. ‘n Lootsprojek van ‘n privaat diensverskaffer en ‘n bestuurde gesongheidsorg maatskappy se data word ontleed as basis vir die bespreking.

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences