A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve

AIMS: To validate a novel method for assessment of coronary endothelium-dependent microvascular function and compare this index with the adenosine-derived coronary flow reserve (CFR). METHODS AND RESULTS: We validated use of intra-coronary pressure wire-derived thermodilution to assess changes in coronary flow compared to Doppler flow-wire/quantitative coronary angiography- (QCA) derived data in response to the endothelial agonist substance-P (endothelium-dependent response). There was a close correlation between Doppler/QCA- and thermodilution-derived assessment of endothelium-dependent microvascular function (r = 0.76; P < 0.001). Next, pressure wire-based thermodilution was employed to sequentially compare CFR (hyperaemia achieved with adenosine-140 microg/kg/mL) with changes in coronary flow in response to substance-P (20 pmol/min intra-coronary infusion; 2 min) in 65 unobstructed coronary arteries. There was no correlation between CFR and coronary endothelium-dependent microvascular response (r = 0.08; P = 0.50). Both indices were in turn compared with clinical markers of endothelial dysfunction, namely Framingham risk score (FRS-a marker for cardiovascular risk factor clustering, hence an indirect clinical measure of endothelial dysfunction) and presence/absence of diabetes. Patient's FRS correlated with coronary endothelium-dependent microvascular response (r = -0.48; P < 0.001), but not with CFR (r = 0.14; P = 0.25). Diabetic patients had greater endothelial dysfunction than non-diabetics (P < 0.001) whereas CFR was not influenced by diabetes (P = 0.10). CONCLUSION: A simple pressure wire-based thermodilution technique can be used to assess coronary endothelium-dependent microvascular function. Adenosine-derived CFR does not adequately interrogate the endothelium-dependent component of coronary microvascular function.