lschaemia With No Obstructive Coronary Artery Disease (INOCA): Insights Into Assessment and Obstructive Sleep Apnoea Association

Abstract

The evolution of myocardial ischaemia started with clinicopathological correlation of typical angina symptoms, traditionally, with flow-limiting atherosclerotic coronary artery disease (CAD). Notwithstanding, ischaemia with no obstructive coronary artery disease (INOCA) is increasingly recognised as a separate phenomenon, that impacts cardiac-related morbidity and financial burden on health services.1-6 Obstructive sleep apnoea (OSA) is recognized to be a risk factor of cardiovascular disease through a number of postulated mechanisms that encompasses hemodynamic, autonomic and inflammatory disturbances.7-12 This thesis evaluates OSA as a risk factor of INOCA and explore the prospect of assessing INOCA non-invasively via advanced echocardiography. Literatures review in chapter 1 provide comprehensive understanding of CAD, including the latest definition of chronic coronary syndrome (CCS), basic mechanisms of coronary ischaemia, the prevalence, prognosis and diagnosis of INOCA, with emerging invasive coronary physiology assessment and potential non-invasive technology. The current evidence illustrating the potential commonality in mechanisms and association of OSA with INOCA, is explored. Chapter 2 focused on more detail, of the association between OSA and structural and functional CAD. OSA is independently associated with CAD. The pathogenesis of atherosclerosis remains complex and poorly understood. CPAP therapy has been linked with reduction in major adverse cardiovascular events in a recent meta-analysis, albeit pivotal randomised controlled trials failed to demonstrate its significance. INOCA, a relatively new entity, remains unexplored in its association with OSA nor the effects of CPAP therapy. In chapter 3, information of the prevalence and clinical predictors of OSA in patients with anginal symptoms who have undergone coronary angiogram in a South Australia registry is provided. This study shows INOCA to be an independent predictor of OSA; especially in those presenting with stable angina; in addition to established risk factors for OSA. In chapter 4, we examined the relationship of obstructive sleep apnoea in patients experiencing angina with no obstructive coronary artery disease, with invasive coronary physiology study as a pilot study. The next two chapters are aimed to determine the ability to evaluate INOCA noninvasively with advanced echocardiography, given the invasiveness of current diagnostic criteria requiring instrumentations of the apparently ‘normal’ coronary arteries. Chapter 5 demonstrates the importance of establishing the extent of myocardial ischaemia in the diagnosis, management and prognostication of coronary artery disease. Stress echocardiography modality is easily available, cost effective and radiation free. Myocardial ischaemia prediction, utilising non-invasive speckle tracking derived global longitudinal strain (GLS), providing a novel prospect.13,14 Chapter 6 provides a pilot study information on correlation between GLS derived contractile reserve (CR) and the invasive coronary microvascular measures, specifically coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR), in INOCA. This study found that there were more CR at 5mcg/kg/min of dobutamine infusion between normal and abnormal coronary haemodynamic indices which suggest hibernating myocardium contractility recruitment. This was not seen on the higher dose of dobutamine. However, the results were limited by small numbers and echocardiographic technique remain at the mercy of suitable image quality.