Early insights of cardiac risk and treatment response with quantitative PET monitoring of coronary-specific endothelial dysfunction and myocardial perfusion reserve

Quantitative measurement of absolute myocardial blood flow and myocardial perfusion reserve offers real promise in the assessment of heart disease. Unlike cardiac CT and cardiac magnetic resonance imaging which can also provide non-invasive quantification of coronary blood flow in units of ml per min per gram tissue, positron emission tomography (PET) measurements of rest and stress coronary blood flow are based on kinetic modeling of true myocardial blood flow (MBF) which integrates flow of the entire coronary vascular tree and myocardial tracer uptake. Resting and pharmacologic vasodilator stress quantification of blood flow with Rubidium-82 and N-13 ammonia PET permit assessment of myocardial perfusion reserve, and these PET techniques are highly accurate for the detection of arteriographic stenoses. Of greatest potential clinical value of quantitative PET is its ability to detect and track serial changes of early functional markers of cardiac risk and treatment response with coronary-specific endothelial dysfunction and total vasodilator reserve prior to the development of angiographically identifiable stenosis or microangiopathy and prior to the development of visible perfusion defects of routine rest and stress myocardial perfusion tomographic scintigraphy. Important long-term prognostic significance of reduced coronary flow reserve patients with normal N-13 ammonia PET perfusion images has been recently reported by Herzog et al. The relatively mild degree and pervasive extent of endothelial dysfunction likely account for the absence of detectable perfusion defects by visual or semi-quantitative analyses of SPECT or PET images. Alterations of coronary endothelial function with cold pressor testing (CPT) reflect upstream changes of coronary pathophysiology that precede symptoms, stressinduced ECG repolarization changes, and wall motion abnormalities that characterize traditional clinical recognition of the ischemia cascade associated with the development of coronary stenoses. Ample evidence exists of the pathogenesis of coronary artery disease associated with these measurable, pre-stenotic functional abnormalities of reduced vasodilator response by cardiac PET. While resting flow remains relatively intact, the magnitude of reductions of stress-induced blood flow correlate with the degree of cardiovascular risk. Numerous reports identify progressive reduction of stress-induced myocardial blood flow along the spectrum of cardiovascular risk in patients with hyperlipidemia, diabetes, cigarette smoking, family history of a primary relative of a parent or sibling with a coronary disease event, the presence of multiple coronary risk factors and increases in coronary vascular resistance, chronic inflammation with coronary risk factors, with increased risk of developing cardiovascular events, with diffuse mild atherosclerosis prior to stenosis development with normal coronary angiograms, in early atherosclerosis, and in the regional segments without stenosis of patients with CAD. The presence of microangiopathy as seen in diabetes, hypertrophic cardiomyopathy, and vasculitis also impairs total vasodilator reserve. These scintigraphic reports correlate with contrast arteriographic observations of ‘‘paradoxical’’ vasospastic coronary vasomotor response in smooth coronary arteries induced by acetylcholine, adenosine, or CPT in patients with risk factors in the presence or in the absence of CAD. The demonstration of the vasospastic response of the conduit coronary artery in response to endothelium-specific activation by CPT or by flow mediated dilation similarly identifies the presence of occult plaque, the subsequent development within 4 years of arteriographic stenosis, From the University of Rochester Medical Center, Rochester, NY. Reprint requests: Ronald G. Schwartz, MD, MS, University of Rochester Medical Center, Box 679-N, 601 Elmwood Avenue, Rochester, NY 14642-8679, USA; ronald_schwartz@urmc.roch ester.edu. J Nucl Cardiol 2010;17:985–9. 1071-3581/$34.00 Copyright 2010 American Society of Nuclear Cardiology. doi:10.1007/s12350-010-9295-2