Identification of viable myocardium early after acute myocardial infarction using closed-loop arbutamine echocardiography: comparison with positron emission tomography.

OBJECTIVE: This study sought to evaluate the safety and efficacy of arbutamine echocardiography in identifying contractile reserve and predicting functional improvement early after acute myocardial infarction (AMI). METHODS AND RESULTS: Seventeen patients with first AMI underwent arbutamine echocardiography 48 to 96 hours after AMI. Arbutamine was infused by a closed-loop delivery device. The heart rate slope was 4 beats/min and the heart rate target was 20 beats/min above baseline heart rate. A follow-up echocardiogram was obtained one month later. N-13 ammonia and F-18 FDG positron emission tomographic (PET) imaging were performed 6 +/- 2 days after AMI, before coronary angiography. Mean duration of arbutamine infusion was 6 +/- 2 min. There was no complication and there were no major side effects. Myocardial viability was identified with PET in 15 of the 17 patients. Contractile reserve was observed in 10 patients during arbutamine infusion. Functional recovery was identified in 12 patients. Sensitivity, specificity and accuracy of PET and arbutamine echocardiography for predicting functional recovery were 100%, 40%, 76% and 67%, 80%, 84%, respectively. CONCLUSIONS: Low-dose arbutamine stress testing is safe early after AMI. Contractile reserve can be rapidly identified by echocardiography and is specific, but moderately sensitive for predicting reversible dysfunction.

The role of early measurement of nitrogen-13 ammonia uptake for predicting contractile recovery after acute myocardial infarction.

Previous studies have shown that the maintenance of cell membrane integrity and metabolism requires the persistence of residual myocardial blood flow. The purpose of this study was to assess the role of N-13 ammonia positron emission tomographic (PET) imaging performed early after an acute myocardial infarction for predicting functional recovery. Seventeen patients with an acute myocardial infarction were included in the study. Thirteen received thrombolytic therapy, 2 underwent immediate angioplasty of the infarct-related artery and 2 were treated with heparin. N-13 ammonia imaging was performed 6 +/- 2 days after the acute event and was followed by elective angioplasty in 13 patients. Using a 16-segment polar map display, regional N-13 ammonia uptake was expressed as a percentage of maximal segmental uptake and classified as normal (> 63%), moderately reduced (63-50%) and severely reduced (< 50%) based on values of tracer uptake obtained from healthy subjects. By echocardiographic assessment of regional wall thickening within 96 hours and at 1 month after the infarct, we examined the relationship between blood flow and functional outcome of myocardial segments in the infarct-related area. Regional wall thickening was graded on a 4-point scale: normal (1), hypokinesia (2), akinesia (3) and dyskinesia (4). Of 77 dyssynergic segments at baseline echocardiographic study, 43 had normal flow, 15 moderately reduced flow and 19 severely reduced flow. Segments with N-13 ammonia uptake > or = 50% demonstrated a significant improvement in wall thickening score at follow-up (p < 0.001), whereas segments with N-13 ammonia uptake < 50% showed no improvement in wall thickening scores (p < 0.001). The proportion of segments improving contractility by at least 1 score was significantly higher in the group of segments with N-13 ammonia uptake > 63%. The predictive value for defining functional recovery with segmental N-13 ammonia uptake > 63% was 86%. The predictive value for absence of recovery (uptake < 50%) was 54%. In conclusion, our data showed that early after an acute myocardial infarction N-13 ammonia imaging provides information regarding functional outcome.

Relation between contractile reserve and positron emission tomographic patterns of perfusion and glucose utilization in chronic ischemic left ventricular dysfunction: implications for identification of myocardial viability.

OBJECTIVES: This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion-metabolism mismatch. METHODS: In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 microg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments. RESULTS: Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion-metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake > or = 50% supplied by vessels with > or = 75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels. CONCLUSIONS: Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly < 50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.

Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine.

UNLABELLED: Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog 11C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. METHODS: Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional 11C-hydroxyephedrine uptake and blood flow, as assessed with 13N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. RESULTS: Active chronic cocaine users showed small areas of abnormal blood flow and 11C-hydroxyephedrine retention in the heart in comparison with normal volunteers. The extent of abnormalities expressed as a percent of the total polar map area averaged 2.0% +/- 2.6% and 2.5% +/- 2.7% for blood flow and 11C-hydroxyephedrine uptake, respectively. Myocardial 11C-hydroxyephedrine retention was significantly reduced by 22% in active cocaine users (0.109 +/- 0.017 min-1), as compared to normal controls (0.140 +/- 0.027 min-1). CONCLUSION: PET imaging with 11C-hydroxyephedrine permits quantitative assessment of cardiac norepinephrine transporter function in active chronic cocaine users. The results of this study suggest prolonged reduction of norepinephrine uptake and storage capacity in the cardiac sympathetic nerve terminals which may reflect the effect of repetitive elevation of norepinephrine levels induced by cocaine exposure.

Myocardial kinetics of potassium-38 in humans and comparison with copper-62-PTSM.

UNLABELLED: The aim of this study was to define the kinetics of 38K and its suitability to evaluate myocardial blood flow at rest and during pharmacological vasodilation in normal subjects. Potassium-38's kinetic characteristics were also compared to those of a 62Cu-pyruvaldehyde bis(n4-methyl-thio-semicarbazone) copper (II) (PTSM) flow tracer. METHODS: Potassium-38 and 62Cu-PTSM were injected at rest and after pharmacological vasodilation in six healthy volunteers. Dynamic PET acquisition was performed over 20 min and myocardial tracer retention calculated. Homogeneity of regional myocardial tracer distribution was also evaluated. RESULTS: High image quality of the heart was observed at rest and after dipyridamole with both tracers. Potassium-38 demonstrated prolonged myocardial retention with minimal lung and liver accumulation. In contrast to 38K, 62Cu-PTSM demonstrated high liver uptake which may hinder observation of the inferior wall of the myocardium. Copper-62-PTSM dipyridamole-to-rest retention ratio was 1.49. CONCLUSIONS: Potassium-38 and 62Cu-PTSM display suitable kinetics for the qualitative evaluation of blood flow and flow reserve in the human heart. Compared to 62Cu-PTSM, potassium-38, which does not show high liver uptake, may more accurately estimate blood flow in the inferior wall of the heart. However, accurate quantification of myocardial blood flow using 38K or 62Cu-PTSM retention appears to be limited to decreasing retention fraction at hyperhemic states.

Imaging of cardiac neuronal function after cocaine exposure using carbon-11 hydroxyephedrine and positron emission tomography.

OBJECTIVES: The aim of the study was to define the effect of cocaine on the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model. BACKGROUND: Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by the sympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labeled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of cocaine on norepinephrine reuptake by cardiac sympathetic nerve terminals. METHODS: The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to characterize norepinephrine reuptake by the sympathetic nerve terminals. Carbon-11 hydroxyephedrine was injected intravenously before, as well as at 5 min and 2.5 h after, intravenous administration of 2 mg/kg body weight of cocaine in anesthetized dogs. Hemodynamic variables and microsphere-determined cardiac blood flow were also measured before and after cocaine exposure. RESULTS: Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flow in the anesthetized animals. Compared with baseline, myocardial retention of C-11 hydroxyephedrine was significantly reduced by 78 +/- 3% (mean +/- SD) at 5 min and remained significantly reduced (28 +/- 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydroxyephedrine injection (30 min) resulted in rapid biexponential clearance of C-11 hydroxyephedrine from myocardium. CONCLUSIONS: These results suggest prolonged effects of cocaine on the sympathetic nerve terminals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetics of drugs such as cocaine.

Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES: The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND: Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS: The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS: Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.