206 Chapter 10 trained on large international multicenter registries, one could choose the best fitting diagnostic method, whether invasive or non-invasive, based on risk stratification and likelihood of diagnosis. Furthermore, the post-processing of diagnostic tests, such as placing regions of interest on the MCE to quantify MBV, is currently time-consuming and prone to interobserver variability since it is mostly performed manually. However, it should be noted that the adoption of AI into the clinical field should be a cooperation between a machine learning engineer and a clinical physician, to ensure that the data is medically accurate and the algorithm is properly trained. Stratified treatment of ANOCA The management of ANOCA is based on counseling on lifestyle factors and controlling risk factors such as hypertension, diabetes, smoking and dyslipidemia. However, there are only a few randomized controlled trials (RCTs) that adequately evaluate individual therapies in ANOCA. Consequently, ANOCA patients often undergo a prolonged trial-anderror process with multiple medications, exposing them to the risk of a lot of side effects. This process can be challenging for both patients and physicians, posing the question for the possibility of a better targeting of medication. Currently, during invasive CFT, patients undergo an acetylcholine rechallenge following a positive result for vasospasm. During this rechallenge, a repeated dosage of acetylcholine is administered after intracoronary nitroglycerin. This approach not only helps differentiating between epicardial and microvascular spasm, but also provides insights into the effectiveness of nitroglycerin as treatment. To help the process towards stratified medication, other medication could be added to the re-challenge alongside nitroglycerine. Examples of such medications used in the treatment of ANOCA, available for intracoronary and/or intravenous administration, include calcium-channel blockers, nicorandil, molsidomine, and ranolazine. Expanding the acetylcholine rechallenge test to include various medication could be the first step towards tailored treatment in ANOCA patients. Further exploration of the underlying pathophysiological pathways of the different ANOCA endotypes is crucial to design effective interventions. Future trials on the management of ANOCA should investigate tailored treatment strategies based on these distinct endotypes. For example, the recent EDIT-CMD trial has shown that while diltiazem did not demonstrate benefit in CMD, it did reduce the prevalence of epicardial spasm. Ongoing investigations like the ViVa-trial, testing vericiguat, and the EDIT-2 trial, investigating bosentan, aim to improve therapeutic approaches in ANOCA specific endotypes. Another possible mechanism to target in the treatment of ANOCA might be the endothelial inflammation. A potential drug could be colchicine, which is used as anti-inflammatory drug in many other cardiovascular conditions and targets the IL-1β/IL-6/CRP pathway to reduce endothelial inflammation and improve vascular function.32 Another possibility is to explore the drug-delivery form of the medication. In our study we have used microbubbles to detect CMD. However, an innovative approach of drug-
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