204 Chapter 10 women versus 30-50% in men referred for CAG.4 However, no exact numbers are known, and these studies often only included women and lack to give insight in the sexdifferences of the prevalence of ANOCA. The NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT) registry is one of the studies that is currently being conducted and should provide more insight into the extend and prevalence of the disease in the Netherlands. Meanwhile, the prevalence of some of the different ANOCA endotypes is likely underestimated, particularly for CMD. CMD is associated with various (cardio)vascular diseases. In addition to the previously mentioned link between CMD and obstructive CAD, the occurrence of CMD may explain the increased severe risk of cardiovascular complications in COVID-19, such as myocardial injury leading to the release of cardiac troponins. Acute COVID-19 can infect endothelial cells, causing endothelial injury and inflammation.25 Furthermore, CMD seems associated with hypertensive disorders of pregnancy, with a higher incidence of these hypertensive disorders observed in patients with CMD later in life.18, 26 Even in Takotsubo, an acute form of myocardial dysfunction triggered by stress, both CMD and microvascular spasm have been implied as the mechanism leading to reversible left ventricular dysfunction.27 Gaining more insights into the extent of ANOCA will enable the development of a more effective therapeutic approach. A crucial step to obtain this insight will be more ad-hoc invasive testing to determine the endotypes of ANOCA, in patients undergoing CAG. Currently, patients are first evaluated for obstructive CAD, and when anginal complaints persists, patients are referred for an invasive CFT to evaluate vasomotor dysfunction, usually at a specialized tertiary center. This approach is time consuming, expensive and creates a barrier for patients. When no obstructive CAD is observed, physicians should continue ad-hoc with invasive CFT to assess vasomotor dysfunction. Studies testing the effectiveness of this stepwise approach, are the ILIAS ANOCA trial (NTR NL9474) and the AID-ANGIO study.28 Incorporating the stratification of ANOCA through invasive coronary function testing into clinical practice is essential to bridge the existing knowledge gap regarding its prevalence and risk factors thereby advancing our understanding of this disease. Better non-invasive diagnostic ways to diagnose ANOCA Most clinical studies on ANOCA use invasive strategies to evaluate coronary blood flow. However, conventional stress tests or dobutamine TTE often fail to detect the subtle microvascular dysfunction seen in ANOCA. To overcome these limitations and reduce barriers for ANOCA stratification, more specialized, non-invasive imaging techniques are essential. Imaging is already crucial in diagnosing many cardiovascular diseases, and developing ANOCA-dedicated imaging seems to be the way forward for more accurate evaluation. In our study, we used MCE to image the coronary microcirculation and investigate ANOCA. However, MCE is a challenging technique, with several patientspecific factors affecting echo quality, such as a poor acoustic window or inability to hold their breath for 10 seconds. Additionally, the technique is very time-consuming. Considering all these factors, MCE is not (yet) suitable for clinical implementation. Other techniques for investigating myocardial blood volume should be explored in the ANOCA
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