Revival of an old stressor: Dobutamine-stimulation for PET myocardial perfusion imaging in patients with end-stage liver disease?

Excerpt

In patients with end-stage liver disease (ESLD), the exclusion of hemodynamically obstructive coronary artery disease (CAD) and normal left ventricular function with e.g., stress-rest scintigraphic myocardial perfusion imaging (MPI) commonly constitutes a pre-requisite to be listed for liver transplantation.1,2 An indeed, perioperative risk and clinical outcome may be affected by the CAD process in liver transplant recipients.2 Most ESLD patients may not be able to sufficiently exercise on the treadmill to reach 85% of predicted maximal heart rate and/or more than 5 METS for a sufficient diagnostic yield with MPI.3,4 In such patients, pharmacologic stress testing with either vasodilator stress such as with regadenoson, dipyridamole, or adenosine, or with β1-stimulated increase in heart rate and contractility by dobutamine remain viable options to induce hyperemic myocardial blood flow (MBF) increases.5 The mechanism of these pharmacologic agents to stimulate hyperemic MBFs are distinct different. For example, pharmacologic vasodilation of the coronary arteriolar resistance vessels with regadenoson will lead to sub-maximal or maximal hyperemic flow increases uncoupled from the metabolic demand of the left ventricle.6 In the presence of flow-limiting CAD lesions, relative differences in radiotracer uptake or perfusion heterogeneity can be noted as the hyperemic MBF increases in the myocardial region subtended by an obstructive CAD lesion will be less than in the remote myocardial region without significant coronary obstruction.7,8 Such observed differences in regional radiotracer uptake is a sensitive approach for the identification of flow-limiting CAD burden but it may not necessarily cause classical ischemia as evidenced by corresponding wall motion abnormalities.9 Conversely, dobutamine-stimulation with increases in heart rate and contractility increase MBFs indirectly by elevations in myocardial metabolic and thus oxygen demand leading to a metabolically mediated vasodilation of the coronary microcirculation. Consequently, impaired coronary flow increases in response to dobutamine-stimulation due to a flow-limiting epicardial lesion is more likely to cause a perfusion deficit associated with classical ischemia induced wall motion abnormality or myocardial stunning due to a mismatch between increased metabolic demand and insufficient oxygen supply. Given these mechanistic differences in pharmacologic induced hyperemic MBF increases among vasodilator—and dobutamine stressors, cardiac PET flow studies revealed distinct higher hyperemic MBF values with pharmacologic vasodilation of the coronary arteriolar vessels than with dobutamine-stimulation.10^–12 For example, Jagathesan et al. 5 reported of hyperemic MBF increases and MFR in the normal range, as determined with ¹⁵O-water PET, but significantly higher for flow increase stimulation with the vasodilator adenosine than with dobutamine (hyperemic MBFs: 4.04 ± 0.51 vs 3.18 ± 0.96 ml/g/min and MFR: 3.36 ± 0.48 vs 2.62 ± 0.57; P < 0.05, respectively). Such observations may provide a rationale for the commonly observed higher sensitivities of pharmacologic vasodilator versus dobutamine stress scintigraphic MPI, while dobutamine stress stimulation afforded a higher specificity in CAD detection and characterization.13,14 …