Masahide Kawamoto

Prediction of reversible ischemia after revascularization: perfusion and metabolic studies with positron emission tomography

BACKGROUND Accurate noninvasive determination of myocardial viability is of paramount importance for the clinical identification of patients who will benefit most from revascularization. The preserved metabolic activity in the myocardium, as studied with positron emission tomography (PET), has been considered a gold standard for this purpose. However, recent reports show that moderate hypoperfusion or stress-induced ischemia may represent reversible ischemia. The present study was undertaken to compare the value of perfusion and metabolic studies with PET for predicting improvement in wall motion after revascularization. METHODS AND RESULTS Of 61 patients who had regional asynergy and underwent PET before revascularization, 43 patients who had successful revascularization were included in the study. Each patient underwent rest-stress 13N-ammonia perfusion scans and 18F-fluorodeoxyglucose (FDG) scan at rest while in a fasting state. Reversible ischemia was considered to be present when the resting perfusion was > or = 50% of the peak value, stress-induced hypoperfusion was present, or an increase in FDG uptake was observed. Of 130 asynergy segments, 51 segments had improved wall motion after revascularization. The positive and negative predictive values for improvement in asynergy were 48% and 87% by the rest perfusion study, 63% (P = .05 versus the rest value) and 87% by the rest-stress perfusion study, and 76% (P < .01 versus the rest value) and 92% by the FDG study. CONCLUSIONS FDG PET provided the best predictive value for improvement in wall motion after revascularization. On the other hand, 13N-ammonia PET is useful for predicting nonreversible myocardial scarring when it shows severe hypoperfusion at rest or hypoperfusion without stress-induced ischemia.

Prognostic value of an increased in flourine-18 deoxyglucose uptake in patients with myocardial infarction: Comparision with stress thallium imaging

OBJECTIVES This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Combined study with I-123 fatty acid and thallium-201 to assess ischemic myocardium: comparison with thallium redistribution and glucose metabolism.

To assess the clinical value of combined SPECT imaging with I-123-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and thallium-201 (Tl), the findings were compared with those obtained in a stress Tl study and positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in 22 patients with myocardial infarction. In 20 patients who underwent a stress Tl study, among 75 hypoperfused segments, 27 segments exhibited less BMIPP uptake than Tl (discordant segments), and the remaining 48 segments showed a similar decrease in BMIPP uptake (concordant segments). Twenty-two of 27 discordant segments (81%) exhibited redistribution on stress Tl study. On the other hand, only one of the 48 concordant segments had redistribution (p < 0.001). In 10 patients who underwent a FDG PET study, among 33 hypoperfused segments, seven segments were discordant segments, and the remaining 25 segments were concordant segments. Seven of the eight discordant segments (88%) demonstrated an increase in FDG uptake. In contrast, only five of 25 concordant segments (20%) showed increase in FDG uptake (p < 0.01). Thus, the segments showing discordant BMIPP uptake are considered to be ischemic but viable myocardium. We conclude that combined imaging with BMIPP and Tl is a useful mean for evaluating tissue viability in patients with coronary artery disease, but it may underestimate the extent of tissue viability, compared with FDG PET imaging.

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion.

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min−1 vs 0.065±0.015 min−1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080±0.018 min−1 vs 0.034±0.013 min−1 at rest) (P<0.001), with an excellent correlation with the LV Kmono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects.

Combined assessment of regional perfusion and wall motion in patients with coronary artery disease with technetium 99m tetrofosmin

BackgroundTechnetium 99m tetrofosmin is a new99mTc-labeled myocardial perfusion agent that can be labeled easily and provides excellent myocardial perfusion images. In addition, bolus administration of the tracer allows first-pass radionuclide ventriculography.Methods and ResultsThis study examined the diagnostic value of combined assessment of regional perfusion by tetrofosmin tomography and wall motion by first-pass radionuclide ventriculography both at rest and during stress in 24 patients suspected of having coronary artery disease. All patients underwent stress-rest tetrofosmin tomography, stress-delayed thallium 201 tomography, and coronary angiography. Stress tetrofosmin tomography showed abnormal perfusion in all 23 patients with angiographic evidence of coronary artery disease, whereas stress201Tl tomography showed abnormal perfusion in 22 of the 23 patients. For detection of significant (≥50% diameter stenosis) stenotic coronary arteries, the two perfusion studies showed similar sensitivities (62% with201Tl and 69% with tetrofosmin) and specificities (88% and 100%, respectively). When analysis of regional wall motion was combined with perfusion study, a slightly higher sensitivity was obtained (77%), with similar specificity. The regional wall motion score was concordant with the regional perfusion score in only 42% of the segments at rest and 50% during exercise.ConclusionsThese results suggest that stress tetrofosmin perfusion tomography and stress201Tl tomography provided similar diagnostic accuracy for detection of coronary artery disease. The combined assessment of perfusion and function that is feasible with tetrofosmin may enhance diagnostic accuracy in patients with coronary artery disease.

Significance of myocardial uptake of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid: comparison with kinetics of carbon 11-labeled palmitate in positron emission tomography.

BackgroundA radioactively labeled beta-methyl branched fatty acid analog,123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP), has been developed to probe regional myocardial fatty acid metabolism. However, the significance of BMIPP uptake in the myocardium remains unclear.Methods and ResultsTo evaluate the significance of BMIPP uptake, single-photon emission computed tomography was performed 30 minutes after injection of BMIPP, and201Tl-labeled single-photon emission computed tomography was taken on a separate day in 10 patients. Findings of BMIPP and201Tl-labeled imaging were compared with the data obtained from positron emission tomography with11C-labeled palmitate. The BMIPP uptake (percent of maximum) was significantly correlated with the early uptake (percent) and delayed uptake (percent) of11C-labeled palmitate (r=0.659 andr=0.687, respectively) (p<0.01 each), whereas it was not significantly correlated with the residual fraction (r=0.205) or the clearance half-time of the early component (r=0.138) of11C-labeled palmitate as a marker of β-oxidation of the fatty acid.ConclusionsThese data indicate that, although the myocardial uptake of BMIPP may not directly reflect β-oxidation of fatty acids, its uptake may reflect both regional myocardial blood flow and fatty acid extraction.

Assessment of myocardial fatty acid metabolism with positron emission tomography at rest and during dobutamine infusion in patients with coronary artery disease

The myocardial clearance rate of C-11 palmitate as an index of fatty acid oxidation was assessed by means of positron emission tomography (PET) at rest and during dobutamine infusion in seven normal subjects and 10 patients with coronary artery disease. In the normal subjects the clearance half time was homogeneous in the left ventricle at rest and uniformly shortened during dobutamine infusion. In the myocardium at risk, clearance half time tends to be longer in the segments with an abnormal Q wave on ECG, exhibiting regional wall motion abnormality, and supplied by severely stenosed coronary arteries, particularly during dobutamine infusion. These data indicate that fatty acid oxidation may be decreased in infarcted myocardium and associated with regional asynergy. Such an abnormality was most striking in those with severe coronary stenosis during dobutamine infusion. We conclude that PET with the use of C-11 palmitate at rest and during dobutamine is a useful means of identifying impaired fatty acid oxidation and decreased metabolic reserve in patients with coronary artery disease.

Myocardial oxidative metabolism in normal subjects in fasting, glucose loading and dobutamine infusion states

Experimental studies indicated the clearance rate constant of11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n=7), after oral glucose administration (n=4), and during dobutamine infusion (n=7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065±0.017 min< 1) and glucose loading states (0.059±0.OO8 min−1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106±0.018 min−1) (p< 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p< 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.

The use of iodinated free fatty acids for assessing fatty acid metabolism

Free fatty acid is a major substrate fuel for normal myocardium. Cardiovascular disease is frequently associated with impairment of fatty acid oxidation. Therefore assessment of fatty acid metabolism may be an important tool for the early detection of myocardial abnormalities and may provide insight into pathologic heart conditions. Although carbon 11-labeled palmitate is a well-established tracer for probing myocardial fatty acid metabolism, a variety of iodinated fatty acid compounds have been introduced for assessing fatty acid metabolism, including straight-chain and branched-chain fatty acid compounds. Straight-chain fatty acid has advantages for measuring fatty acid oxidation on the basis of tracer clearance from the myocardium. Branched-chain fatty acid can be trapped in the myocardium without futher washout and uptake in the myocardium may reflect fatty acid retention and some aspect of fatty acid metabolism. A long tracer retention period makes feasible the acquisition of single-photon emission computed tomographic images. This review examines the characteristics of both types of tracers and our recent clinical experience with β-methyliodophenyl pentadecanoic acid, which has potential for detecting and characterizing both ischemic heart disease and cardiomyopathy.

Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction ( %) were calculated as indices of β-oxydation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65 ± 5 vs 100±29 bpm, p< 0.05 and 119±12 vs 144±16 mmHg, p< 0.01, respectively). The clearance half time and the residual fraction were significantly decreased (23.4±2.6 vs 15.8±2.3 min and 67.0±2.5vs 58.6± 4.0%, p< 0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that β-oxydation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium.