203 General discussion increasing the time of the procedure and also the number of invasive measurements also raises the associated risks, underscoring the need for non-invasive methods to assess myocardial perfusion. In our studies, we discovered a global reduction of quantitative perfusion in ANOCA patients compared to healthy controls. In line with the previous findings in regards to invasive CFT, we found heterogeneity across coronary perfusion areas suggesting invasive measurements limited to a single coronary territory may be insufficient. Similarly, heterogeneity in myocardial perfusion was observed in ANOCA patients using oxygenation-sensitive CMR (OS-CMR).20, 21 These technique uses the inherent paramagnetic properties of deoxyhemoglobin during T2*-weighted images to assess myocardial perfusion without a contrast-agent, while using vasoactive breathing maneuvers to evaluate changes in myocardial perfusion in patients with ANOCA.22 The observed heterogeneity was larger in the ANOCA patients compared to healthy controls, while no difference was found in global myocardial oxygenation. These findings, in accordance with ours, suggest that heterogeneous coronary vasomotor activity in response to an increased oxygen demand, may explain ischemic symptoms in this patient population. Stress CMR has been widely used for the assessment of myocardial ischemia. However, the implementation of dedicated ANOCA CMR sequences, such as QP or OS-CMR, requires further investigation before they can be implemented into clinical practice. For example, standard clinically-used stress CMR uses contrast-enhanced perfusion imaging to detect signal changes as contrast passes through the myocardium. Typically, this imaging is performed during vasodilatation (i.e. hyperemia induced by injection of adenosine, adenosine triphosphate (ATP), dipyridamole, or regadenoson). If no signal changes are observed, rest perfusion images are not typically obtained. This presents a challenge for implementing QP, as both rest and stress images are essential for its performance. Furthermore, the cut-off values for QP are currently based on obstructive CAD, which makes it difficult to apply them to patients with ANOCA. Consequently, varying cut-off values are employed for diagnosing CMD, and these inconsistent diagnostic thresholds makes it challenging to draw firm conclusions.23 Similar challenges are applicable to the use of OS-CMR. OS-CMR has not been validated against PET or invasive CFT.24 Therefore, studies to evaluate and validate the efficacy of ANOCA CMR sequences like QP or OS-CMR against PET are needed before considering their clinical implementation. FUTURE PERSPECTIVES Incorporating ANOCA stratification into clinical practice Due to the increasing interest in ANOCA, and specifically CMD, one of the possible endotypes of CCS, many articles have published about the prevalence of ANOCA in the past few years. Currently, the prevalence of ANOCA is described as 50-70% among 10
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