96 Chapter 5 The study protocol is executed on two separate days (Figure 1). On day A, INOCA patients will undergo a CAG with ICFT to identify patients with epicardial and/or microvascular spasm and/or CMD. Patients and controls will undergo a stress CMR scan, including quantitative perfusion imaging and T1-mapping. Furthermore, all study-participants receive questionnaires including the Seattle Angina Questionnaire (SAQ), Hospital Anxiety and Depression scale (HADS), Perceived Stress Scale (PSS) and Pittsburg sleep quality index (PSQI) to assess angina-burden and mental-health status. Also sex-differences are investigated within groups. The women in the study will also receive a female-specific questionnaire developed for the Heart-study by the UMC Utrecht.33 This questionnaire includes specific questions about menstruation, pregnancy and postmenstrual phase. On day B both study groups will undergo myocardial contrast echocardiography (MCE) to examine MBV, an microvascular function test using the EndoPAT (Peripheral Artery Tonometer, Itamar Medical, Israel) for noninvasive assessment of microvascular function. Blood is collected and used to determine circulating endothelial colony forming cells (ECFC’s) which represent endothelial precursors cells and contribute to de novo blood vessel formation in vivo.34 Circulating endothelial cells are established markers for endothelial damage, and may therefore also be used to identify biomarkers for INOCA.35 A smaller sample of blood is stored and frozen for future experiments. All analyses of non-invasive imaging are performed by an investigator blinded to the results of the ICFT. Invasive CAG and ICFT Invasive CAG and ICFT are performed in INOCA patients only. Prior to invasive angiography, patients are asked to withhold from calcium channel blocker, β-blockers and long-acting nitrates use for two days. Short-acting nitrates can be used freely during this period to overcome intercurrent chest pain episodes. A baseline CAG is performed according to local practice to rule out obstructive CAD, where FFR can be measured to exclude hemodynamic relevance for lesions of intermediate angiographic severity.
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