93 Rational and Design of the MICORDIS study (i.e., hydrogen-proton-spin-lattice relaxation time) is a magnetic property of tissue that provides a quantitative biomarker of intracellular and extracellular environments of the myocardium-T1 relaxation time is prolonged with increasing myocardial water content, such as edema and infarction.32 Thus, an increased MBV could be detectable as an increase in T1-value. The MICORDIS study aims to provide insight into the role of MBV in INOCA, using a variety of stressors to test the regulation of MBV, and using several conventional and new imaging techniques to determine MBV. The main objective of the MICORDIS study is to investigate whether MBV is reduced in INOCA patients. METHODS Overview The MICORDIS trial is a single-center observational cross-sectional cohort study, comparing MBV in INOCA patients with a group of matched healthy controls (https://www. trialregister.nl/, unique identifier NTR7515). The trial will be performed at the Amsterdam University Medical Centers (UMC), location VU medical center. The study has been approved by the institutional ethics committee on human research of the Amsterdam UMC and carried out in compliance with the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act (WMO). Patient Enrollment Patients with long-standing angina, documented non-obstructive CAD and lack of response to medical therapy will be included in the study. Non-obstructive CAD is defined as signs and symptoms of myocardial ischemia and ≤50% stenosis on coronary angiography and/or fractional flow reserve (FFR) >0.80. Signs and symptoms of ischemia are defined as; (1) stable chronic (i.e., several weeks or longer) symptoms suggesting IHD, such as chest discomfort with classic (i.e., angina pectoris) and/or atypical features regarding location, intensity and provoking factors, and 2) with or without objective evidence for myocardial ischemia on ECG or a cardiac imaging study (e.g., transthoracic echocardiography (TTE), nuclear imaging or CMR) at rest or during stress induced by exercise, mental or pharmacological triggers. After informed consent is obtained, eligible candidates meeting the selection-criteria listed in Table 3, will be enrolled. 5
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