97 Rational and Design of the MICORDIS study Figure 2. Schematic representation of the coronary circulation and different diagnostic techniques, showing measurements of CFR and microvascular resistance independent from the epicardial artery, with a ComboWire positioned in the LAD. The ComboWire consists of a Doppler-flow velocity sensor on the tip (B), and a pressure-sensor more proximal (A). Microvascular resistance can be measured using either HMR or IMR. HMR is a Doppler-based index, calculated as: Pd during hyperemia divided by the averaged peak flow velocity during hyperemia, and considered abnormal > 1.9. IMR is a bolus thermo-dilution based parameter, calculated as: Pd multiplied by the mean transit time during hyperemia, and considered abnormal > 25. Abbreviations: LAD: Left Anterior Descending coronary artery; CFR: Coronary Flow Reserve; HMR: Hyperemic Microvascular Resistance; IMR: Index of Microcirculatory Resistance; Pd: mean Distal coronary pressure Subsequently, a guide wire equipped with a pressure sensor and Doppler crystal (ComboWire, XT, Philips-Volcano, San Diego, CA) is advanced in the left anterior descending coronary artery (LAD) to perform ICFT (Figure 2). Flow velocity and intracoronary pressure are recorded throughout the procedure using a dedicated console (ComboMAP, Philips-Volcano, San Diego, CA).36, 37 CRT is performed by intracoronary administration of incremental doses (2, 20, 100, and 200 μg) of acetylcholine, an endothelium-dependent vasodilator, by manual bolus injection 10 cc of solution in 1 min through the guiding catheter engaged in LAD. The surface ECG, Doppler flow signal, coronary angiogram and the patient’s symptoms are strictly monitored during and after each bolus of acetylcholine. An optional dose of 80 μg is administered in the right coronary artery (RCA) if no spasm is observed in the LAD. After the last dose, when a positive test is obtained, or when vasospasm is not resolved within 3 min after injection, an intracoronary bolus of nitroglycerine (NTG), an endothelium-independent vasodilator, is given to counteract the acetylcholine effects, after which CAG is repeated to obtain reference coronary artery dimensions. A re-challenge of acetylcholine provocation is performed immediately after nitroglycerine administration using the same dose that induced spasm during initial testing, or with 200 μg acetylcholine in the absence of spasm. 5
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