LAUSR

Quantitative myocardial blood flows (MBF) by PET are entering the practice of nuclear cardiology. Flow responses to pharmacologic vasodilation measured in absolute units together with myocardial flow reserves (MFR) have improved the detection of functionally obstructive coronary artery disease, especially in patients with multivessel disease. They also have become powerful predictors of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, acute coronary syndrome and hospital admission for heart failure. Applied globally to the myocardium, vasodilator-stimulated flows probe the responsiveness of the entire coronary circulation and provide a measure of its overall vascular health. The ‘‘global myocardial flow reserve (MFR)’’ as the ratio of global hyperemic to rest MBF therefore reflects the composite effects of coronary morphological and functional alterations that exert resistance to increases in coronary flow. A benchmark value of 2.0 for the MFR has emerged from multiple follow up investigations in patients after PET MPI and flow measurements, a threshold value that discriminates between high and low risk of cardiac death and of MACE. MFRs of B 2.0 in patients with obstructive coronary disease, visualized as inducible perfusion defects on MPI and verified by invasive or noninvasive coronary angiography, can guide decisions on treatment strategies. For example, event-free survival improved significantly more after early revascularization than on medical treatment alone in patients with severely reduced MFRs (i.e., 1.2 or lower), but did not differ between revascularization and medical treatment in patients with less severely reduced MFRs (i.e.,[ 1.4). Of note, some evidence exists for MFR as a guide to the type of revascularization. For example, two studies report significantly better event-free survival outcomes after CABG than after PCI. However, impaired MFRs without obstructive coronary disease remain therapeutically challenging because pathophysiologic mechanisms of the impaired vasodilator flow response are not fully understood. Impairments of MFR without obstructive disease are frequently present in patients referred to PET evaluation because of clinical signs of ischemia including angina and ischemic ECG changes. Nearly 50% of patients with normal stress MPI on PET and thus without evidence of obstructive CAD had global MFRs B 2.0 or B 1.8 and thus were at high risk for MACE including death. Defined broadly as coronary microvascular dysfunction (CMD) without obstructive disease, it is prevalent among patients with cardio-metabolic syndromes (i.e., obesity, pre-diabetes, diabetes mellitus), with chronic renal disease, or with heart failure with preserved ejection fraction (HFpEF) and occurs more frequently in women than in men. The underlying pathophysiology still awaits clarification. Whether functional or structural alterations confined to the microcirculation fully account for the MFR impairment has remained uncertain. In fact, a synergy of multiple adverse players may interfere with the normal coronary reactivity. Apart from structural alterations of the microcirculation like arteriolar remodeling and rarefaction, diffuse atherosclerosis or non-obstructive disease of the epicardial conduit vessel may also contribute to reducing the vasodilator-induced flow response. Depending on the reactivity of the downstream resistance vessels, a gradual distal-toproximal coronary pressure gradient in diffusely diseased arteries may reach levels of ischemia with distal to proximal coronary pressure gradients of B 8.0, equivalent to FFRs for discrete but functionally significant stenoses. Their effect on MBF is seen on perfusion images as a gradual decline of flow in the base-to-apex direction. Purely functional disturbances may further add to the impairment of the flow response. For example, pharmacologic inhibition of NO synthesis in normal Reprint requests: Heinrich R. Schelbert, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA; [email protected] J Nucl Cardiol 2021;28:2459–61. 1071-3581/$34.00 Copyright 2021 American Society of Nuclear Cardiology.