Non-invasive characterization of cardiac microvascular disease by nuclear medicine using single-photon emission tomography

In about 10 to 30% of patients with typical angina undergoing coronary angi ography for suspicion of stenotic coronary artery disease angiographically normal coronary arteries are found. Kemp et al. in 1973 coined the term syn drome X to describe this entity. In a substantial portion of these patients pathologic findings in myocardial scintigraphy are present. Sensitivity and specificity of thallium-201 exercise imaging by visual anal ysis of images in the presence of significant coronary stenosis is 84 and 8 8%, respectively. Several investigators have reported abnormal results in r adionuclide exercise tests in patients with angiographically normal coronar y arteries. Some of these results can be explained by myocardial bridging, vasospasm, left or right bundle branch block, hypertrophic cardiomyopathy, or absorption artifacts. In the majority of cases, however, these abnormali ties are not sufficient to explain the scintigraphic findings. Formerly oft en claimed "false positive", recent studies suggest that endothelial dysfun ction might be the reason for the observed perfusion defects. When comparin g patients with angiographically unobstructed coronary arteries with and wi thout perfusion defects in stress myocardial perfusion imaging, patients wi th pathological results show a significantly lower increase of coronary flo w after intracoronary injection of the endothelial-dependent vasodilator ac etylcholine. Endothelial-independent vasodilation, however, is not impaired in these patients. In addition, intracoronary Doppler measurements reveal that perfusion defects in myocardial scintigraphy only occur if coronary bl ood flow in this perfusion area is significantly reduced. These results sug gest that regional endothelial dysfunction may cause hypoperfusion in myoca rdial perfusion imaging and underline the important role of the microcircul ation in the distribution of radiotracers. Another striking scintigraphic pattern in patients with microvascular angin a is the high incidence of reverse redistribution. These perfusion defects, apparent in images obtained 4 hours after exercise stress testing, often c annot be assigned to the perfusion territory of one of the major epicardial vessels. This results in a marked inhomogeneous radionuclide distribution pattern in resting images. The inhomogeneity is associated with a significa nt reduced resting coronary now velocity in these patients. As histological ly confirmed microvessel disease is often accompanied by slow-flow phenomen on reflecting decreased resting flow velocity, the results suggest that the inhomogeneous perfusion pattern is caused by microvascular dysfunction. Fu rthermore, the heterogeneity of nuclide distribution supports the hypothesi s that endothelial function is not homogeneous in the entire myocardial mic rocirculation, but varies considerably. In conclusion, microvascular dysfunction by itself seems to cause regional myocardial hypoperfusion, as documented by myocardial scintigraphy. When in terpreting pathological scintigraphic results in patients without significa nt epicardial stenosis, true blood flow and myocardial perfusion abnormalit ies must be assumed.