202 Chapter 10 microbubbles are destroyed using a high MI, and video-intensity is monitored until the microbubble concentration returns to steady state, indicating myocardial replenishment (i.e. replenishment curve). The replenishment curve can be fitted to the formula y=A(1− e−βt). In this equation, A is the plateau intensity and is proportional to MBV, while β is the slope of the curve, representing the reappearance rate of the microbubbles and is proportional to the microvascular flow velocity. The product of A and ß provides a quantitative estimate of MBF.17 MCE enables the simultaneous non-invasive assessment of MBF and MBV. This capability is crucial in the diagnostic process of ANOCA, as both parameters can independently contribute to the anginal complaints. MBV is reduced in patients with type 2 diabetes, likely due to capillary rarefaction, a characteristic feature also seen in essential hypertension. These cardio-metabolic risk factors are closely linked to ANOCA.18 In this thesis, we have demonstrated that MBV is lower in ANOCA patients compared to healthy control subjects during unstimulated conditions as well as during hyperinsulinemia and dobutamine-induced stress. Furthermore, we observed a reduced MBV independent from the established ANOCA endotypes, suggesting a potential role for MBV in the pathophysiological phenomenon of ANOCA. However, MCE is a time-consuming technique that requires offline analysis by specialized technicians and is technically challenging due to its dependence on the quality of the patient’s acoustic window. Nevertheless, incorporating MBV into the classification of ANOCA endotypes can enhance the accuracy of identifying underlying etiology in ANOCA, and facilitate more effective therapeutic strategies. Achieving high sensitivity and specificity in identifying all ANOCA entities is crucial for both patients and clinicians, enabling personalized clinical approaches and improving quality of life. Part 3. Quantitative perfusion CMR in ANOCA In this thesis, we focused on all endotypes of ANOCA to gain a better understanding of the pathophysiology of the different ANOCA endotypes and to develop non-invasive methods for its stratification and diagnosis. Previous studies have investigated the use of QP in patients with obstructive CAD, and those with CMD. In patients with CMD, QP has been shown to accurately detect CMD and correlate well with invasively obtained CFR measurements. Current ESC guidelines on CCS provide a class Ib recommendation for the use of invasive coronary function testing in patients with chronic coronary syndromes and suspected ANOCA. In contrast, stress CMR holds a class IIa recommendation (not routinely recommended but should be considered) and is primarily mentioned for ruling out obstructive CAD and for research purposes in the current guidelines.4 Invasive coronary function testing (CFT) is typically performed in a single coronary artery, most commonly the left anterior descending (LAD). However, recent literature indicates that this approach is insufficient and may lead to missed diagnoses. Therefore, multivessel coronary function testing significantly enhances diagnostic yield.19 However,
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