25 Sex Differences in Chronic Coronary Syndrome: Data from the ILIAS Physiology Registry Individual patient data were collected and anonymously stored in a fully compliant cloudbased clinical data platform (Castor EDC, Amsterdam, The Netherlands). The ILIAS registry was registered at ClinicalTrials.gov (NCT04485234). For the present study, the following inclusion criteria were applied: i) Invasive coronary angiogram performed to evaluate CCS, ii) both invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) physiological indices were measured, and iii) individual patient outcome data were available. Invasive coronary assessment Invasive coronary assessment was performed according to standard techniques. Invasive physiologic measurements were performed using either separate pressure- (PressureWire, RADI medical – now Abbott Vascular, St Paul, MN, USA) and Doppler velocity sensorequipped coronary guidewires (FloWire, Endosonics – now Philips-Volcano, San Diego, CA, USA), a dual pressure- and Doppler flow velocity-equipped guidewire (ComboWire, Volcano Corp. – now Philips-Volcano, San Diego, CA, USA), or a temperature-sensitive pressure sensor-equipped guidewire (PressureWire, St Jude Medical-now Abbott Vascular, St. Paul, MN, USA). Prior to physiological assessment, intracoronary nitroglycerine (100 or 200 μg) was administered in all cases. Baseline (bAPV) and hyperemic average peak flow velocities (hAPV) were obtained from Doppler velocity measurements. The inverse of the average basal (bTmn) and hyperemic mean transit times (hTmn) was derived from resting and hyperemic thermodilution curves as described previously.10 Hyperemia was induced according to local standards by intravenous infusion of adenosine (140 μg/kg per min) or adenosine-triphosphate (ATP 150 μg/kg per min) through a peripheral or central vein, intracoronary bolus injection of adenosine (20-200mcg), or intracoronary bolus injection of nicorandil (3 mg). FFR was calculated as the ratio between mean hyperemic distal coronary pressure and mean hyperemic aortic pressure, and FFR≤0.80 was considered abnormal.11 CFR was calculated as the ratio between hyperemic and baseline coronary flow, and CFR≤2.5 was considered abnormal.12 Microvascular resistance (MR) was calculated as the ratio of distal coronary flow and distal coronary pressure during hyperemia. For MR, the hyperemic microvascular resistance index (HMR) was derived from Doppler velocity measurements and the index of microcirculatory resistance (IMR) was derived from thermodilution measurements. HMR≥2.5 13 and IMR≥25 were considered abnormal.14 Clinical follow-up To ascertain the occurrence of target vessel failure (TVF), clinical follow-up was obtained either at outpatient clinic visits or by telephone contact. TVF was a composite vessel-level endpoint, consisting of cardiac death, acute myocardial infarction not clearly attributable to a nontarget vessel, and clinically driven revascularization of the target vessel by means 2
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