205 General discussion population. Our ongoing sub-study of the MICORDIS focuses on delta T1-mapping, employing clinically established and easily implementable T1 mapping CMR techniques to evaluate patients with ANOCA compared to healthy controls. Delta T1-mapping measures the T1 reactivity to adenosine stress. Native (pre-contrast) T1 mapping is a non-invasive, non-contrast CMR technique that has recently been shown to accurately detect changes in myocardial blood flow and volume, identify ischemia, and differentiate between normal, infarcted, ischemic, and remote myocardium. T1 mapping measures the magnetic properties of tissue, primarily detecting free water. Increased free water content in tissues, indicative of coronary vasodilatation, results in prolonged myocardial T1 times. Therefore, delta T1 mapping might enable non-invasive detection of CMD. Another novel technique for evaluating myocardial perfusion is oxygenation-sensitive CMR (OSCMR). This method shows promising results in detecting CMD and could allow for noninvasive imaging of microvascular function without using a contrast-agent. However, validation against invasive coronary flow testing (CFT) or PET is essential before it can be implemented into clinical practice. The limitation of all currently investigated non-invasive methods is that they are only able to diagnose CMD, and not coronary vasospasm. Since spontaneous coronary spasm is difficult to document, provocation tests are employer. Currently vasospasm is diagnosed by eliciting vasoconstriction by agents such as acetylcholine which causes paradoxical vasoconstriction in patients with endothelial dysfunction, while in healthy individuals it induces vasodilation. Other possible triggers for vasospasm are emotional stress, exposure to cold and stimulant drugs such as cocaine and amphetamines. Given the ethical concerns associated with some of these methods, the cold pressor test is a viable option that warrants further investigation. In this test, the hand is placed into ice water for at least one minute, and this temperature stressor could provoke coronary vasospasm. Further research should explore the relationship between vasospasm induced by acetylcholine and that triggered by the cold pressor test. If a correlation is found, the cold pressor test could potentially be used during imaging of the coronary circulation, such as with Doppler echocardiography or coronary computed tomography angiography (CCTA). In the future, CCTA could potentially offer a non-invasive method to diagnose both coronary vasospasm and CMD, since CCTA also shows promise in detecting CMD by identifying non-obstructive coronary arteries and measure the perivascular fat attenuation index which provides insights into coronary inflammation.29 Recent studies in ANOCA have indicated that CCTA combined with perivascular fat attenuation index can identify inflammatory changes that are associated with CMD (30). However, this technique is currently limited to research purposes, but could enhance our understanding of ANOCA pathophysiology in the future. Furthermore, the implementation of Artificial Intelligence (AI) in the diagnostic process of ANOCA could facilitate faster diagnosis resulting in faster treatment. AI is already implemented in specialty fields of cardiology, like the implementation of CHAT-GPT in EPIC31 and currently used to assess the prevalence of myocardial ischemia during invasive CFT in ANOCA patients (NCT06387693). By using machine learned algorithms 10
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