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Type: Thesis
Title: Clinical studies of patients with acute coronary syndromes in the absence of obstructive coronary artery disease.
Author: Cutri, Natalie
Issue Date: 2011
School/Discipline: School of Medicine
Abstract: Background: Although there is extensive data on patients with obstructive coronary artery disease in relation to clinical manifestations, health outcomes and genetic predisposition, little is known about these features in patients with Non-obstructive Coronary Artery Disease (NoCAD), despite these patients representing 20-30% of patients undergoing angiography. Objectives: This thesis examined the clinical features, health outcomes and genetic polymorphisms in patients with NoCAD. The specific objectives include (1) comparing the health outcomes of NoCAD patients who present with an acute coronary syndrome (ACS) to those who have a stable chest pain pattern; (2) examining the prevalence of acute ischaemic electrocardiographic (ECG) changes in patients with the coronary slow flow phenomenon (CSFP) admitted with an ACS; and (3) to investigate the frequency of an endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) polymorphism in patients with: (a) chest pain and NoCAD and, (b) the CSFP. Summary of Thesis Chapters: Chapter 1 summarises the relevant background for the studies described in this thesis. Chapter 2 examines health outcomes, including health related quality of life (HRQoL) measures, in ACS versus stable chest pain presentations in patients with NoCAD, over 12 months follow-up. HRQoL measures were assessed using both a generic (Short-Form-36) and disease-specific (Seattle Angina Questionnaire) instrument. This study found no significant differences in health outcomes between the two clinical cohorts. Chapter 3 assesses evidence of myocardial ischemia, utilising continuous ST/T wave monitoring to examine the frequency of ST/T wave fluctuations during an ACS in patients with the CSFP compared to healthy control subjects. This study found 92% of patients with the CSFP showed ECG evidence of myocardial ischaemia on continuous ST monitoring during an ACS presentation, with significant ST segment and T-wave fluctuations occurring in 24% and 86% of CSFP patients; respectively. In comparison, ST/T wave fluctuations were observed in 5% of healthy control subjects. Chapter 4 is a case-control study that investigates the frequencies of the eNOS (T-786C) and ET-1 (+138A del/ins) polymorphisms in patients with: (a) chest pain and NoCAD and (b) the CSFP. There were no significant differences in the frequency of each polymorphism associated with patients diagnosed with chest pain and NoCAD. However, the frequency of the +138 del/ins polymorphism from the ET-1 gene was significantly more prevalent in the CSFP patients compared to the control groups. Conclusion: This thesis has demonstrated that NoCAD patients who present with an ACS have similar health outcomes to those with stable chest pain. Patients with the CSFP frequently present with an ACS and this is associated with dynamic ST/T wave fluctuations and in particular T-wave inversion. The underlying pathogenesis of the CSFP requires further study; however, endothelin appears to have an important role. Consistent with this mechanism, this study found an increased prevalence of the +138 del/ins polymorphism from the ET-1 gene in patients with the CSFP. We therefore postulate that endothelin-1 (possibly derived from inflammatory cells) produces acute microvascular vasoconstriction in patients with the CSFP resulting in myocardial ischaemia and thus an ACS presentation. Further studies are required to assess this hypothesis.
Advisor: Beltrame, John Francis
Adams, Robert John
Kucia, Angela
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2011
Keywords: chest pain; non-obstructive; acute coronary syndromes; small vessel disease; coronary slow flow phenomenon
Provenance: Copyright material removed from digital thesis. See print copy in University of Adelaide Library for full text.
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