Improved diagnostic accuracy of planar imaging with technetium 99m-labeled tetrofosmin compared with thallium-201 for the detection of coronary artery disease.

BACKGROUND: Receiver operating characteristic (ROC) curve analysis provides detailed information about the performance of a diagnostic test. METHODS AND RESULTS: As part of a multicenter phase III trial, 160 patients with known or suspected coronary artery disease underwent planar stress-rest 99mTc-labeled tetrofosmin and stress-redistribution 201Tl imaging within 14 days of each other, to compare the diagnostic accuracy of these imaging modalities by ROC curve analysis. Coronary arteriography was used as the reference standard and greater than 70% stenosis was considered significant. ROC curve analysis showed improved detection of coronary artery disease with 99mTc-labeled tetrofosmin compared with 201Tl, with ROC curve areas of 0.765 versus 0.644, respectively (p = 0.02). 99mTc-labeled tetrofosmin also better identified single-vessel disease in those without previous myocardial infarction (ROC curve areas of 0.684 vs 0.510 for 99mTc-labeled tetrofosmin and 201Tl, respectively; p = 0.04) and enhanced the detection of multivessel disease in those with previous myocardial infarction (ROC curve areas of 0.764 vs 0.638, respectively; p = 0.02). CONCLUSIONS: Detailed assessment of diagnostic performance by ROC curve analysis shows that, for planar imaging, 99mTc-labeled tetrofosmin enhances the detection of coronary artery disease compared with 201Tl.

Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction.

OBJECTIVES: To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS: 45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS: Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS: Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction.

Myocardial perfusion imaging with 99mTc tetrofosmin. Comparison to 201Tl imaging and coronary angiography in a phase III multicenter trial. Tetrofosmin International Trial Study Group.

BACKGROUND: Our objective was to compare the sensitivity and specificity of tetrofosmin, a new 99mTc-labeled myocardial perfusion imaging agent for the detection of myocardial perfusion abnormalities, with those of 201Tl and coronary angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging could provide data comparable to those of 201Tl imaging. Myocardial perfusion imaging plays an important role for the evaluation of coronary artery disease. Newer 99mTc-labeled agents offer several advantages over 201Tl, the conventional myocardial perfusion imaging agent. Tetrofosmin is a new 99mTc-labeled agent with promising results in preliminary studies. METHODS AND RESULTS: Two hundred fifty-two patients with suspected coronary artery disease were enrolled in 10 centers in the United States and Europe. All patients underwent exercise and rest myocardial perfusion imaging with 99mTc-tetrofosmin using two separate injections of the radiotracer 4 hours apart on the same day. Planar images were obtained in three standard views 15 to 60 minutes after radiotracer injection. Patients also underwent standard exercise and redistribution planar 201Tl imaging within 2 weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low likelihood of coronary artery disease underwent exercise and rest tetrofosmin imaging. Coronary angiograms were available in 181 patients with suspected coronary artery disease. All radionuclide images were processed in the central core laboratory and interpreted blindly by a panel of four experienced readers. 201Tl images and tetrofosmin images were read separately. Discrepancies were resolved by consensus. The workload, peak heart rate, and double products were comparable during exercise for both imaging agents. Technically acceptable paired 201Tl and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin images were generally of good quality, with low extracardiac activity, and easy to interpret. Patients were categorized as showing normal, ischemia, infarction, or mixture with each imaging modality. Precise concordance for each of these categories was 59.4% (kappa = 0.44; 95% CI, 0.35 to 0.53). When patients were categorized as normal or abnormal, the concordance was 80.4% (kappa = 0.55; 95% CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior, inferior, lateral, and apical) was categorized as normal versus abnormal, the concordance varied from 81% to 90%. When similar comparison was made for the specific category of abnormality, the concordance was 64% to 84%. When coronary angiography was used as the criterion, the sensitivity and positive and negative predictive accuracy of tetrofosmin and 201Tl were comparable. The normalcy rate of tetrofosmin images in the healthy subjects with low likelihood of coronary artery disease was 97%. CONCLUSIONS: 99mTc tetrofosmin is a new myocardial imaging agent with favorable imaging characteristics with results comparable to those of 201Tl.

Reverse redistribution of thallium-201 represents a low-risk finding in thrombolysed patients following myocardial infarction.

The aim of the study was to evaluate the prevalence and clinical significance of reverse redistribution on thallium-201 imaging in post-myocardial infarction patients who have undergone thrombolytic therapy. Sixty-two patients aged 35-79 (mean 60) years with proven myocardial infarction who had undergone thrombolysis were studied 6 weeks post infarction. Standard stress and 4-h redistribution imaging was performed with 201Tl following treadmill exercise. Separate day rest injection of 201Tl was given after sublingual nitroglycerine; imaging was performed at 1 h. Planar images were acquired in three standard views and semiquantitative segmental analysis of the images was performed from the unprocessed images. All patients had radionuclide ventriculography for the assessment of left ventricular ejection fraction and wall motion abnormality. Thirty-three patients also had coronary angiography. 201Tl scintigraphy revealed fixed defects in 19 patients, reversible defects in 22, and reverse redistribution in 21. Those with reverse redistribution had a significantly higher exercise capacity (P < 0.01). Mean (SD) left ventricular ejection fraction was 46 (12)% for those with fixed defects, 47 (9)% for those with reversible defects and 45 (15)% for patients with reverse redistribution (P = NS). The regional wall motion abnormality score was 8 (5), 11.8 (2.2) and 14.2 (6) respectively in patients with reverse redistribution, redistribution alone and fixed defects. Regions with reverse redistribution revealed less regional wall motion abnormality compared to the other two groups (P < 0.01). Fifteen patients demonstrated significant 201Tl uptake in the region showing reverse redistribution, with rest injection of 201Tl following sublingual nitroglycerine, suggesting viable myocardium in that region.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic value of simultaneous stress dobutamine sestamibi single-photon-emission computerized tomography and echocardiography in the detection of coronary artery disease.

The relative value of exercise electrocardiography, simultaneous dobutamine technetium 99m-sestamibi (MIBI) single-photon-emission computerized tomography (SPECT), and echocardiography were evaluated for the diagnosis of coronary artery disease in patients with chest pain. Sixty-one consecutive patients underwent exercise electrocardiography and simultaneous graded dobutamine echocardiography and MIBI imaging. All patients underwent coronary arteriography. The exercise electrocardiogram was found to be a poor predictor of coronary artery disease (p not significant). Individually, MIBI SPECT and echocardiography were significantly predictive of coronary artery disease (p < 0.001). According to logistic regression analysis, the combined imaging modalities significantly increased the prediction of coronary artery disease for any vessel (p < 0.001), for multiple vessels (p < 0.001), and for the left anterior descending (p < 0.001), for right coronary artery (p < 0.001), and for left circumflex arteries (p < 0.01), compared with either MIBI SPECT or echocardiography alone. The results suggest a synergism in the detection of coronary artery disease when MIBI SPECT and echocardiography are combined during dobutamine stress.

Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction.

To compare the measurement of left ventricular ejection fraction obtained by two-dimensional echocardiography and by radionuclide ventriculography in patients following acute myocardial infarction, 49 consecutive patients with acute myocardial infarction underwent echocardiography and radionuclide ventriculography on the same day, pre-discharge. Left ventricular ejection fraction was assessed by two blinded observers for each method and reproducibility was also assessed for each technique. The limits of agreement for the differences in ejection fraction (%) between the two methods was--11.4, 12.2; the mean difference 0.4 was not significantly different from zero. The limits of agreement for the intra- and inter-observer differences in ejection fraction by radionuclide ventriculography were--9.4, 7.6 and -8.6, 11.0, respectively; the mean differences--0.9 and 1.2 were not significantly different from zero. The limits of agreement for the intra- and inter-observer differences by echocardiography were--5.8, 6.6 and--8.9, 9.5 respectively; the mean differences 0.4 and 0.3 were not significantly different from zero. Thus, two-dimensional echocardiography compares well with radionuclide ventriculography for the assessment of ejection fraction without the disadvantage of radiation.

Reverse redistribution: fact or fiction?

It has been well documented that it is not uncommon for a thallium-201 perfusion defect to develop or become more evident on delayed exercise thallium scintigraphic imaging, as compared with the initial image immediately following stress. The pathophysiology and clinical significance of the phenomenon are currently unclear. Literature on this subject is reviewed, and it is concluded that reverse redistribution of 201Tl in the post-myocardial infarction patient is indeed a "fact". In this context it represents a low-risk condition and may imply successful thrombolysis, patent infarct-related coronary artery, improved wall motion at the infarct site and retained myocardial viability in that segment.

Antihypertensive efficacy of twice daily controlled release diltiazem using 24 hour intra-arterial blood pressure monitoring.

The aim of the study was to examine the efficacy of a new controlled release formulation of diltiazem administered in a twice-daily dose in patients with essential hypertension using 24 hour intra-arterial ambulatory blood pressure monitoring. Sixteen patients (2 female) of mean age 53 years with mild to moderate essential hypertension, defined as a supine resting diastolic cuff blood pressure > or = 95 mm Hg, were recruited to a sequential dose ranging study of controlled release (CR) diltiazem. After a six week run-in period without any anti-hypertensive medication, intraarterial blood pressure monitoring with 60 degrees tilt, isometric handgrip and bicycle exercise testing were performed. Patients were then treated for one week with CR diltiazem 120 mg b.i.d. If supine resting diastolic cuff blood pressure fell by < 10 mm Hg compared to the last run-in value and remained > 90 mm Hg, the dose was increased to 240 mg b.i.d. for a week, and if necessary to 360 mg b.i.d. for a week. Patients continued for further one month on the dose of CR diltiazem at which they achieved target blood pressure reduction. At the end of this maintenance treatment, 24 hour intra-arterial blood pressure monitoring was repeated. Twelve patients were satisfactorily controlled on 120 mg b.i.d. CR diltiazem, three on 240 mg twice daily and one on 360 mg twice daily. During rest and exercise, blood pressure and heart rate were significantly lower after treatment with CR diltiazem than before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate of change of left ventricular ejection fraction during exercise is superior to the peak ejection fraction for predicting functionally significant coronary artery disease.

OBJECTIVE: To detect and characterise rapid temporal changes in the left ventricular response to exercise in patients with ischaemic heart disease and to relate these changes to the functional severity of coronary artery disease. BACKGROUND: The gamma camera does not allow the detection of rapid changes in cardiac function during exercise radionuclide ventriculography, the monitoring of which may improve the assessment of patients with ischaemic heart disease. METHODS: A miniature nuclear probe (Cardioscint) was used to monitor continuously left ventricular function during exercise in 31 patients who had coronary angiography for suspected coronary artery disease. A coronary angiographic jeopardy score was calculated for each patient. RESULTS: The coronary jeopardy score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during exercise from 46% to 34%. Patients were divided into two groups based on the response of their ejection fraction to exercise. In 14 patients (group I), the peak change in ejection fraction coincided with the end of exercise, whereas in the other 17 patients (group II) the peak change in ejection fraction occurred before the end of exercise, resulting in a brief plateau. The peak change in ejection fraction and the time to its occurrence were independent predictors of coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001 for time to that change). The rate of change in ejection fraction was the strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the peak change in ejection fraction was a poor predictor severity of coronary disease (r = -0.28, NS), whereas the time to peak and the rate of change in ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In group II the peak, the time to the peak, and the rate of change in ejection fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r = -0.83, p < 0.01). CONCLUSION: The rate of change of ejection fraction during exercise can be assessed by continuous monitoring of left ventricular function with the nuclear probe, and is the best predictor of functionally significant coronary artery disease.

Comparison of myocardial perfusion imaging with technetium-99m tetrofosmin versus thallium-201 in coronary artery disease.

Technetium-99m (Tc-99m) tetrofosmin, a new myocardial perfusion imaging agent, was evaluated at exercise and rest in 50 patients with documented coronary artery disease to determine myocardial kinetics, redistribution and ideal imaging time. Planar imaging was performed at 5, 30, 60, 90, 120 and 240 minutes after an injection of Tc-99m tetrofosmin (8 to 10 mCi) at peak graded ergometric exercise. Reinjection (24 to 30 mCi) was performed at rest, 4 hours after the stress injection and also on a separate day, and imaging was repeated. All patients underwent thallium-201 (Tl-201) exercise and redistribution (4-hour) imaging. Perfusion defect to normal, and heart to lung ratios were calculated for exercise Tc-99m tetrofosmin images at each time point. The mean +/- SD defect to normal ratios were 0.75 +/- 0.10, 0.75 +/- 0.10, 0.74 +/- 0.09, 0.73 +/- 0.10, 0.73 +/- 0.10 and 0.72 +/- 0.10 at 5, 30, 60, 90, 120 and 240 minutes, respectively (p = NS), suggesting absence of redistribution. There was a significant increase in lung uptake of Tl-201 during exercise (p < 0.05), but not with Tc-99m tetrofosmin (p = NS). Washout of Tc-99m tetrofosmin was calculated in a subset of patients (n = 23). Rapid background clearance enabled postexercise diagnostic imaging as early as 5 minutes after injection. Myocardial retention curves after rest injection suggested that the optimal time for imaging was approximately 30 minutes later. Slow myocardial washout (4%/hour after exercise and 0.6%/hour after rest injection) enabled diagnostic images to be obtained up to 4 hours after each study.(ABSTRACT TRUNCATED AT 250 WORDS)