Coronary Microvascular Function assessment
Noninvasive quantification of coronary microvascular function was performed using myocardial contrast echocardiography (MCE).9 This has previously been shown to correlate with PET derived myocardial blood flow.10 Briefly, MCE was performed using ultrasound machine iE33 (Phillips Medical Systems) and SonoVue (Bracco Research SA) as the contrast infusion given at constant infusion. Real time echocardiographic images were recorded within 3-4 minutes in the apical 4, 2, and 3-chamber views with low-power settings at mechanical index of 0.1. SonoVue was at an infusion rate of 60 ml/h via peripheral intravenous access with VueJect infusion syringe pump (Bracco Research, SA). Thereafter, rate was maintained between 48 and 60 ml/h to maximise image quality. Machine settings were held constant throughout each participants study post optimisation. Flash-impulse imaging using high mechanical index of 1.0 was performed to achieve complete myocardial bubble destruction, after which 10 end-systolic frames were recorded in each apical view. Dipyridamole was infused at 0.56 mg/kg over a 4-minute period after acquisition of resting images. Post stress images were recorded within 3 to 4 minutes after an interval of 2 minutes. Quantitative analysis was performed offline using QLab V7.0 (Philips Medical Systems) blinded to patient demographic and CTCA data. Quantitative assessment of myocardial perfusion was performed for 10 consecutive end-systolic frames after microbubble destruction. A region of interest was placed over the thickness of the myocardium. Plots of peak myocardial contrast intensity (linearly related to myocardial blood volume A cm3) versus pulsing intervals (representing time) were automatically constructed to fit the mono-exponential growth function: y=A (1 - e-Bt) where B is the instantaneous initial slope of the resulting curve and represents myocardial blood velocity (sec-1) and the product of A and B yields a reliable measure of myocardial blood flow (MBF) (cm3.sec-1).
MBFR was measured as previously defined as the ratio of post-dipyridamole (stress) MBF to baseline MBF, dividing the stress MBF by the baseline MBF for the same segment.9 A 16-segment model was used excluding the basal segments in view of contrast attenuation and analyzing the 10 remaining mid- and apical cardiac segments. A segment was excluded if there was artefact, inadequate microbubble destruction, attenuation or a wide variation in contrast intensity. Segmental MBFR was calculated by dividing peak MBF with resting MBF of the same segment. MBFR was the average MBFR of all segments. CMD was defined as MBFR<2.0.9