Rob Beanlands

The Effects of β1-Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction A Double-Blind, Placebo-Controlled, Positron-Emission Tomography Study

Background—The mechanism for the beneficial effect of β-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVo2). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. Methods and Results—The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanal...

Redistribution of Myocardial Blood Flow With Topical Nitroglycerin in Patients With Coronary Artery Disease

BACKGROUNDnUnlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease.nnnMETHODS AND RESULTSnMyocardial perfusion with [13N]ammonia was estimated from dynamic time-activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n = 10) or a placebo patch (n = 10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [13N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (> 2 SDs from average counts/pixel in maximally perfused zones) in [13N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [18F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [13N]ammonia retention following either placebo (0.61 +/- 0.14 to 0.62 +/- 0.12 min-1) or GTN (0.75 +/- 0.22 to 0.74 +/- 0.19 min-1). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9 +/- 12.6% to 94.9 +/- 17.8%; P < .05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [13N]ammonia retention in nonischemic zones was observed with GTN (1.01 +/- 0.31 to 0.93 +/- 0.26 min-1).nnnCONCLUSIONSnThis study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN.

Can Nitrogen-13 Ammonia Kinetic Modeling Define Myocardial Viability Independent of Fluorine-18 Fluorodeoxyglucose?

OBJECTIVESnThe hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET.nnnBACKGROUNDnUptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue.nnnMETHODSnSixteen patients, > 3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention.nnnRESULTSnFluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 +/- 27% [mean +/- SD]; scar 37 +/- 16%, p < or = 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 +/- 0.20 ml/min per g, scar: 0.36 +/- 0.16 ml/min per g, p < or = 0.01; VD: 3.9 +/- 1.3 and 2.0 +/- 1.07 ml/g, respectively, p < or = 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow > 0.45 ml/min per g; 100% and 70% for VD > 2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively.nnnCONCLUSIONSnIn this cohort, patients having regions with flow < or = 0.45 ml/min per g or VD < or = 2.0 ml/g had scar. Viable myocardium had both flow > 0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.