Endothelial and Microvascular Dysfunction by PET as Markers of the Earliest Stage of CAD
Coronary endothelial dysfunction is closely associated with microvascular dysfunction, and CAD or its risk factors may be familial as an independent risk factor and predicts future coronary events or clinically manifest disease up to 10 years later. The three principle methods for assessing coronary endothelial function reflect different aspects of its complex multifaceted behavior with specific limitations in their clinical application.
The method using intracoronary acetylcholine requires coronary arteriography and provides information only on epicardial coronary arteries, not endothelial function of the microvasculature that is an essential component of preclinical coronary atherosclerosis. Forearm arterial vasodilation during reactive hyperemia by ultrasound is non-invasive but does not correlate specifically with coronary endothelial dysfunction. The cold pressor test involves complex sensory and efferent vasomotor control mechanisms separately from endothelial function with substantial variability in normal subjects that may limit its diagnostic utility in individuals.
Coronary endothelial dysfunction is heterogeneous within different locations of a single coronary artery and among coronary arteries affecting both the macro and micro-circulation. This heterogeneous coronary endothelial dysfunction causes heterogenous arteriolar vasoconstriction at resting conditions apparent on resting PET perfusion images as a 'moth-eatenÔÇÖ appearance that may improve after dipyridamole or adenosine stress, resulting in more homogeneous perfusion in areas without flow-limiting stenosis, illustrated in Figure 6 at baseline and after intense treatment of risk factors. The automated quantification of relative activity on baseline to follow-up resting scans is shown on the upper right graph and the corresponding baseline to follow-up stress comparisons on the lower right graph. This diffuse patchy heterogeneous resting myocardial perfusion by PET may be quantified objectively by Markovian homogeneity analysis and/or its improvement during dipyridamole stress. These perfusion patterns by PET are powerful predictors of even mild stress perfusion abnormalities, more than standard risk factors, consistent with coronary microvascular dysfunction as an early marker of CAD.