Caitlin Vink

194 Chapter 9 ENGLISH SUMMARY Chronic coronary syndrome (CCS) comprises various underlying pathophysiological mechanisms, from obstructive coronary artery disease (CAD) to endotypes of Angina with Non-Obstructive Coronary Arteries (ANOCA). These endotypes include enhanced vasoconstriction (i.e. coronary vasospasm) and impaired vasodilation (i.e. coronary microvascular dysfunction (CMD)). However, a deeper understanding of CCS and it’s relation to ANOCA is essential. Therefore, the research described in this thesis aimed to achieve the following objectives: 1. To understand the relationship between sex and various endotypes of CCS. 2. To identify the role of sex differences in ANOCA. 3. To investigate reduction of myocardial blood volume as a potential pathophysiological mechanism in ANOCA. 4. To evaluate the possibilities to non-invasively diagnose ANOCA using Cardiac Magnetic Resonance (CMR) imaging. Part 1. Endotypes of Chronic Coronary Syndrome Chronic coronary syndrome (CCS) is a clinical condition characterized by angina and can has various causes. Among these possible causes are both obstructive CAD and CMD. Differentiation between symptoms caused by obstructive CAD and those due to CMD can be challenging, often requiring multiple ischemia tests and coronary anatomy imaging to achieve the appropriate diagnosis. This distinction is particularly difficult in women, since anginal symptoms may vary depending on sex. Therefore, better insight into the distribution and phenotyping of these CCS endotypes, especially among sexes, might result into a more effective diagnostic process. In Chapter 2, we used the results from a comprehensive invasive epicardial and microvascular physiological assessment from the international ILIAS (Inclusive Invasive Physiological Assessment in Angina Syndromes) registry to explore the relationship between sexes and different endotypes of CCS, including the prevalence and long-term outcomes of obstructive CAD and CMD. We revealed a higher prevalence of obstructive CAD in men, whereas CMD was more prevalent in women. Interestingly, men with obstructive CAD who underwent revascularization had a lower risk of target vessel failure at 5 years compared to those who did not undergo revascularization. Conversely, this beneficial effect of revascularization was not observed in women. Regardless of the CCS endotype, men consistently experienced worse cardiovascular outcome compared to women. In Chapter 3 we looked into the vasodilator capacity of the coronary circulation across sexes with the recently introduced parameter microvascular resistance reserve (MRR), using data from the ILIAS registry. In this chapter, we present the impact of sex on the diagnostic and prognostic value of MRR. The diagnostic characteristics were similar in both sexes, however, the MRR was generally lower in women and therefore a lower cut-off value should be used in women. We also report an independent and significant association between continuous

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