Search

Background. Limited data are available on the value of quantitative stress myocardial perfusion imaging (MPI) in patients with unstable angina. In this report we sought to study the long-term prognostic value of quantitative stress MPI in patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes. Methods and Results. The study population consisted of 136 patients who were hospitalized at the Methodist Hospital, Houston, Tex, with unstable angina and subsequently underwent MPI before discharge. Cox proportional hazards (regression) analysis was performed to identify clinical and MPI predictors of hard cardiac events (death or nonfatal myocardial infarction). During a mean follow-up of 31 ± 17 months, 20 patients (15%) sustained either cardiac death (n = 12) or nonfatal myocardial infarction (n = 8). The significant multivariate predictors of cardiac events were the total perfusion defect size (P = .002), the presence of reversible perfusion defects (P = .01), and the presence of multiple perfusion defects (P = .03). The perfusion defect size was significantly larger in patients with events than in those without events (21% ±20% vs 12% ± 14%, P = .002). Kaplan-Meier analysis showed that cardiac events were much more likely to develop in patients with defects involving 15% or more of the left ventricle than in those with defects involving less than 15% of the left ventricle (P = .003). Conclusions. In patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes, quantitative stress MPI provides powerful prognostic information that can be used in the risk stratification of these patients. (J Nucl Cardiol 2005;12:32-6.)

References 1331 The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or full revision is needed. Guidelines for the Clinical Use of Cardiac Radionuclide Imaging were originally

Transcoronary ethanol septal ablation (TESA) is a novel treatment for obstructive hypertrophic cardiomyopathy (HOCM). Our objective was to evaluate the use of gated single photon emission computed tomography (SPECT) in patients with HOCM and the effects of TESA on myocardial perfusion.We performed gated SPECT and Doppler echocardiography before and 6 weeks after TESA in 30 patients with severe HOCM. The lung-to-heart and septal-to-lateral wall count-activity ratios were calculated. Before ablation, SPECT showed perfusion abnormalities in only 6 patients. Asymmetric septal hypertrophy was noted in 21 patients (70%). In patients with a lung-to-heart ratio greater than 0.50 before ablation, the ratio decreased from 0.56 +/- 0.04 to 0.45 +/- 0.08 after ablation (P.01). The septal-to-lateral wall ratio also decreased significantly after ablation. Mean Doppler pressure gradient across the left ventricular outflow tract decreased from 52 +/- 39 mm Hg to 13 +/- 13 mm Hg (P.01) immediately after ablation and to 10 +/- 21 mm Hg 6 weeks later (P.01). There were no significant changes in left ventricular ejection fraction by gated SPECT after the procedure. SPECT studies done after ablation showed fixed septal defects in 29 of 30 patients (96.7%). The defects involved the basal and mid septum in 100% and 38% of patients, respectively, and ranged in size from 2% to 30% of the left ventricle (mean, 8.8% +/- 7.0%).TESA is an effective technique for relieving left ventricular outflow obstruction in patients with HOCM. Myocardial gated SPECT can identify the presence and location of infarction after TESA.

Nuclear cardiology, echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography (cardiac CT), positron emission computed tomography (PET), and coronary angiography are im...

The objectives of this study were 2-fold: (1) to determine the tolerance of adenosine perfusion tomography with the use of an abbreviated (3-minute) infusion in comparison to the standard (6-minute) infusion, and (2) to assess the relative diagnostic accuracy of a 3-minute adenosine infusion in patients referred for arteriography. An abbreviated adenosine infusion may decrease the frequency and duration of side effects and be a more cost-effective alternative.We prospectively randomized 599 patients undergoing adenosine myocardial perfusion tomography to either a 3-minute or 6-minute adenosine infusion at 140 microg/kg per minute. Among the 599 enrolled patients, 142 subsequently underwent coronary angiography. Patients randomized to the 3-minute adenosine infusion tolerated the procedure better than those randomized to the standard infusion (P.01). Flushing, headache, neck pain, and atrioventricular block were all significantly less frequent (P.01) with the abbreviated infusion. Moreover, patients receiving the abbreviated infusion had less hypotension and tachycardia (P.05). The sensitivity of the test for detection of coronary artery disease was 88% for both the 3- and 6-minute infusions. In patients with abnormal scan results, perfusion defect size was slightly larger in those receiving a 6-minute infusion versus those receiving a 3-minute infusion (P =.05).An abbreviated 3-minute adenosine infusion, in combination with perfusion tomography, has similar sensitivity for detection of coronary artery disease and is better tolerated than the standard 6-minute infusion.

Previous studies that investigated the effects of coronary collateral circulation on myocardial perfusion were compromised by inclusion of patients with multivessel coronary artery disease, incomplete occlusion, prior myocardial infarction, or a combination of these. In this study we ascertained the relationship between angiographic collateral circulation and myocardial perfusion only in patients with total occlusion of a single coronary artery, in the absence of myocardial infarction or significant stenosis in the other coronary arteries.Seventy-one consecutive patients underwent stress myocardial single photon emission computed tomography within 90 days of angiography. Collateral circulation was present in 49 patients and absent in 22 patients. All but 2 patients had abnormal perfusion by single photon emission computed tomography imaging, with a mean defect size of 19% +/- 12%, and most (83%) had reversible perfusion defects. Defect count activities improved from stress to rest (or redistribution) (45% +/- 13% to 59% +/- 14%, P.001). Abnormal myocardial perfusion occurred with similar frequency in patients with collateral circulation and in those without it. Total defect size was 19% +/- 12% in patients with and 18% +/- 11% in those without collateral circulation (P = not significant). The extent of reversibility and defect count activity during stress and rest were similar in patients with collateral circulation and in those without it.In patients with a single-vessel total coronary occlusion and without myocardial infarction, stress-induced myocardial ischemia is almost always present, irrespective of presence or absence of angiographic collaterals. These data lend support to the premise that collateral circulation is rather insufficient to prevent stress-induced ischemia, although it can preserve myocardial viability.

There is scanty information on the angiographic and myocardial perfusion correlates of dobutamine-induced ST-segment elevation.We studied 39 patients who exhibited ST-segment elevation during dobutamine perfusion tomography and had recent coronary angiography performed (ie, within 3 months of the dobutamine study). Baseline characteristics, extent of coronary artery disease, relationship of Q waves to ST-segment elevation, ischemic burden, and angiographic findings were assessed. Twenty-nine patients (74%) had prior myocardial infarction, and 77% had abnormal Q waves at baseline. Ninety-three percent of patients had abnormal perfusion imaging. Eighty percent of patients had multivessel coronary artery disease. The left ventricular ejection fraction by contrast ventriculography was 35% +/- 7% (mean +/- SD), the perfusion defect size was 32% +/- 15%, and 73% of patients had some degree of myocardial ischemia. A predominance of ischemia (50% reversibility) occurred in 38% of patients with Q waves and in 70% of those without Q waves. There was also good agreement between the site of ST-segment elevation and the site of ischemia by perfusion imaging (79%) and between the site of ST-segment elevation and the location of the vessel with significant coronary stenosis (95%).Patients with dobutamine-induced ST-segment elevation have a depressed left ventricular ejection fraction, a high frequency of multivessel disease, and markedly abnormal myocardial perfusion tomography. In patients with ST-segment elevation and abnormal Q waves, substantial scarring and superimposed ischemia coexist, whereas in patients without Q waves, ST-segment elevation usually denotes severe ischemia.

OBJECTIVES We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WM) simultaneously and in real time. METHODS One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM were assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%, respectively) with the highest accuracy (86%). CONCLUSIONS The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. Methods and Results —Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. α- and β-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compared with normal segments and were most pronounced in those without contractile reserve ( P r =0.37 and −0.39, respectively). Conclusions —Thus, graded and reciprocal changes in α- and β-adrenergic receptor densities occur in viable, hibernating myocardium and may account in part for the observed depression in resting myocardial function and preserved contractile reserve in this entity.

Background —We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A 2A agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. Methods and Results —A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to 201 Tl (0.5 mCi) and 99m Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion ( P P P P P =NS), and transmural 201 Tl and 99m Tc-sestamibi count-activity ratios (0.48±0.11 and 0.51±0.09, respectively) were also comparable ( P =NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. Conclusions —CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of 201 Tl and 99m Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

OBJECTIVES The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl-201) scintigraphy. BACKGROUND Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution Tl-201 tomography before revascularization and a repeat resting echocardiogram ≥2 months later. RESULTS Global wall motion score index decreased from 2.38 ± 0.73 to 1.94 ± 0.82 after revascularization (p 0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a Tl-201 maximal uptake of ≥60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum Tl-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to Tl-201 scintigraphy. Importantly, a simple measurement of EDWT ≤0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Background —Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. Methods and Results —Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS P Conclusions —CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Background —Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure. Methods and Results —We evaluated 20 patients with coronary disease (64±13 years old, ejection fraction 28±7.5%) with DE (up to 40 μg · kg −1 · min −1 ), rest-redistribution 201 Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%, P P =0.03), and less interstitial fibrosis (2% versus 28%, P P P P =0.016), and higher thallium uptake (64% versus 35.5%, P P =0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis ( r =−0.83, P Conclusions —Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.

We compared estimates of left ventricular ejection fraction (LVEF) assessed by gated single photon emission computed tomography (SPECT), using both technetium-99m sestamibi and thallium-201, with those obtained by first-pass radionuclide angiography (FPRNA) in patients with a broad spectrum of LVEF and perfusion abnormalities.Sixty-three patients were randomly selected to undergo a dual isotope gated SPECT study (rest Tl-201 followed by adenosine Tc-99m sestamibi scintigraphy). Studies were processed by use of the Cedars quantitative gated SPECT software. FPRNA was acquired during an intravenous bolus injection of Tc-99m sestamibi and processed with a commercially available software.The estimates of LVEF were similar (P = NS) with Tl-201 gated SPECT (54% +/- 15%), Tc-99m gated SPECT (54% +/- 16%), and FPRNA (54% +/- 12%). There was an excellent correlation between Tc-99m and Tl-201 gated SPECT (Pearson's r = 0.92, P.0001). There were also good linear correlations between Tc-99m sestamibi gated SPECT and FPRNA (Pearson's r = 0.85, P.0001), as well as between Tl-201 gated SPECT and FPRNA (Pearson's r = 0.84, P.0001). In the 16 patients with LVEF50%, Tc-99m sestamibi gated SPECT and FPRNA (Pearson's r = 0.84, P.0001) and Tl-201 gated SPECT and FPRNA (Pearson's r = 0.92, P.0001) correlated well.LVEF can be accurately assessed by gated SPECT with either Tc-99m sestamibi or Tl-201 in properly selected patients with normal or depressed left ventricular function.

Whether left ventricular function can be assessed accurately by gated single photon emission computed tomography (SPECT) in patients with myocardial infarction and severe perfusion defects is not well known.Twenty-five patients with an acute myocardial infarction underwent 99mTc-labeled tetrofosmin (99mTc-tetrofosmin) gated SPECT and cine magnetic resonance imaging (MRI). Wall motion was assessed in 13 left ventricular segments using a 5-point scoring system ranging from 3 (normal) to -1 (dyskinetic). Exact agreement for wall motion scores between gated SPECT and MRI was excellent (92%, kappa = 0.82). Furthermore, correlations between the two techniques were also good for end-diastolic volume (r = 0.81, P.0001), end-systolic volume (r = 0.92, P.0001), and ejection fraction (r = 0.93, P.0001).In patients with a recent myocardial infarction, 99mTc-tetrofosmin gated SPECT provides reliable evaluation of global and regional ventricular function and volumes.

Objectives. We sought to determine the effects of nicotine patch therapy, when used to promote smoking cessation, on myocardial ischemia in patients with coronary artery disease.Background. Nicotine patches substantially increase quit rates among cigarette smokers, but their safety in patients with myocardial ischemia who are attempting to quit smoking is unknown.Methods. This is a prospective study using exercise thallium-201 single-photon emission computed tomography (SPECT) to assess serial changes in the total and ischemic myocardial perfusion defect size at baseline while patients were smoking and during treatment with 14- and 21-mg nicotine patches. Entry criteria required that patients 1) smoked ≥1 pack of cigarettes per day; 2) had known coronary artery disease; and 3) had myocardial ischemia (i.e., ≥5% reversible perfusion defect) on SPECT. All patients performed symptom-limited treadmill exercise, and the baseline SPECT study served as its own control. We interpreted and computer quantified the SPECT images with no knowledge of the testing sequence.Results. Thirty-six of the 40 enrolled patients had exercise SPECT at baseline and during treatment with at least 14-mg nicotine patches. These patients had an initial perfusion defect size of 17.5 ± 10.6% while smoking an average of 31 ± 11 cigarettes per day for 40 ± 12 years. A significant reduction in the total perfusion defect size (p < 0.001) was observed from baseline (17.5 ± 10.6%) to treatment with 14-mg (12.6 ± 10.1%) and 21-mg (11.8 ± 9.9%) nicotine patches. This reduction occurred despite an increase in treadmill exercise duration (p < 0.05) and higher serum nicotine levels (p < 0.001). There was a significant correlation between the reduction in defect size and exhaled carbon monoxide levels (p < 0.001) because patients reduced their smoking by ∼74% during the trial.Conclusions. Nicotine patches, when used to promote smoking cessation, significantly reduce the extent of exercise-induced myocardial ischemia as assessed by exercise thallium-201 SPECT.(J Am Coll Cardiol 1997;30:125–30)

Objectives. We determined the influence of angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism on the extent of myocardial ischemia in patients with acute myocardial infarction. Background. The I/D polymorphism, which in part controls plasma and tissue expression of ACE, has been implicated in predisposition to myocardial infarction and ventricular remodeling. Methods. I/D genotyping, predischarge adenosine–thallium-201 perfusion tomography and radionuclide angiography were performed in 113 patients (72 men, 41 women) with a diagnosis of acute myocardial infarction. A subgroup of 96 patients also underwent coronary angiography. Results. Genotypes DD, ID and II were present in 27, 56 and 30 patients, respectively. There was no significant difference in the baseline characteristics of patients, total creatine kinase, peak MB fraction, Killip class, mean ejection fraction or the number of diseased vessels in patients with the DD, ID or II genotype. However, the size of the total and the reversible perfusion defects was greater in those with DD than in those with ID or II genotype (total defect size [mean ± SD] 33.7 ± 22.5%, 29.5 ± 19.2% and 22.2 ± 16.0%, respectively [p = 0.022]; reversible defect size 18.0 ± 16.0%, 12.1 ± 11.6% and 8.2 ± 7.8%, respectively [p = 0.006]). Occlusion of the infarct-related artery was also more common in patients with DD genotype (odds ratio 3.9, 95% confidence interval 1.4 to 11.0). Multivariate analysis showed that the I/D genotype was an independent predictor of perfusion defect size and patency of the infarct-related artery (p = 0.001). Conclusions. DD genotype was associated with a larger ischemic defect and occlusion of the infarct-related artery. Patients with DD genotype, having a larger ischemic defect, are expected to be at a greater risk for subsequent cardiovascular events. (J Am Coll Cardiol 1997;29:1468–73)

Objectives. We sought to study the accuracy of exercise perfusion scintigraphy in patients with an implanted apical right ventricular pacemaker. Background. The specificity of exercise perfusion scintigraphy is decreased in patients with a left bundle branch block. Patients with a permanent ventricular pacemaker have a similar conduction abnormality that may also potentially result in similar false positive perfusion defects. Methods. One hundred five patients with a right ventricular pacemaker underwent exercise thallium-201 tomography and coronary angiography within 7 days of each other. Patients with a previous myocardial infarction were excluded. Results. Patients were classified into four groups according to the agreement or disagreement between the thallium tomographic and coronary angiographic results. Only 8% of patients with normal results by both techniques were continuously paced during exercise, compared with 78% of patients with normal angiographic results but abnormal scintigraphic results. The mean defect size was 12% in the latter group. Most of the false positive defects were localized to the inferoposterior (71%), apical (50%) and inferoseptal (28%) walls. Conclusions. Patients who are paced in the right ventricular apex and who continue to be paced throughout exercise have a high incidence of false positive thallium-201 single-photon emission computed tomographic defects. (J Am Coll Cardiol 1997;29:1221–5)

Objectives. We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 μg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation.Background. Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated.Methods. Eighteen patients (aged [±SD] 57 ± 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated ≥6 weeks after revascularization.Results. Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 ± 14% to 45 ± 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65).Conclusions. In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.(J Am Coll Cardiol 1997;29:985–93)© 1997 by the American College of Cardiology

Background Recent observations suggest that administration of nitrates before 201 Tl reinjection enhances the detection of reversible myocardial hypoperfusion. Methods and Results Ninety-six patients who underwent exercise-redistribution 201 Tl single photon emission computed tomography (SPECT) and had persistent defects at 4-hour redistribution imaging were prospectively randomized into a double-blind protocol in which they received a reinjection of 201 Tl (1.0 mCi) 5 minutes after either placebo or 0.8 mg sublingual nitroglycerin administration, followed by repeat SPECT imaging. Of the 69 patients who had coronary angiography, all except one had significant coronary stenoses. The overall extent of perfusion defect and the reversible component assessed by polar maps of the stress-redistribution images were similar in patients who received nitroglycerin or placebo. Among the 66 patients with persistent defects in the redistribution images, 58% of those receiving nitroglycerin showed improved reversibility after reinjection, compared with 33% of patients receiving placebo ( P P P Conclusions Nitrate-augmented 201 Tl reinjection significantly, albeit modestly, improves detection of defect reversibility, especially in patients with coronary collateral circulation.

Background The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201 Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. Methods and Results Thirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 μg·kg −1 ·min −1 ) and rest-redistribution 201 Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at ≥6 weeks. Before revascularization, resting 201 Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201 Tl uptake increased only in segments that showed a biphasic response (from 66±12% to 78±13%; P Conclusions In patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201 Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.

Among 23,059 patients who underwent exercise myocardial tomography between 1985 and 1994 at our institution, there were 817 (3.5%) with a strongly positive exercise electrocardiogram and normal myocardial tomograms. Among these, 52 patients had no conditions known to be associated with a false-positive exercise electrocardiogram and no previous coronary revascularization, and underwent coronary angiography. Of the 32 patients with significant coronary stenoses, 50% had 1-vessel disease and only 22% had 3-vessel disease (p

Objectives. This study sought to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block.Backgroud. Patients with left bundle branch block often have septal perfusion defects during exercise perfusion tomography that mimic defects caused by coronary artery disease. These defects appear to be less frequent during pharmacologic stress using adenosine or dipyridamole. Data are scanty on the value of dobutamine tomography in these patients.Methods. We studied 383 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 5-year span. Perfusion tomography was performed in conjunction with exercise in 206 patients, adenosine in 127 and dobutamine in 50. Coronary angiography was performed within 1 month of the nuclear study in 77, 50 and 27 patients, respectively.Results. Exercise, adenosine and dobutamine tomography had similar sensitivity and specificity for the detection of >50% stenosis in the left circumflex (74% and 96%; 50% and 100%; 63% and 91%, respectively) and right coronary arteries (96% and 86%; 82% and 91%; 79% and 100%, respectively) and similar sensitivity for left anterior descending coronary artery stenosis (88%, 79% and 100%, respectively). However, the false-positive rate for septal defects was higher by exercise tomography (26 [46%] of 57) than by pharmacologic methods (5 [10%] of 48, p < 0.001), and there was no significant difference between adenosine (4 [11%] of 35) and dobutamine (1 [8%] of 13, p = 0.7). The specificity and predictive value of a positive test response for left anterior descending coronary artery stenosis were 36% and 51% for exercise compared with 81% and 85% for adenosine (p ≤ 0.001) and 80% and 90% for dobutamine (p < 0.05), respectively.Conclusions. In patients with left bundle branch block, pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients.

Background . Based on physical properties, 99m Tc-labeled perfusion agents offer several advantages over 201 T1 for myocardial perfusion imaging. The results of in vivo and experimental studies, along with preliminary experience in human subjects, have shown 99m Tc-labeled furifosmin to be a promising new perfusion tracer. The purpose of this study was to evaluate the safety of a new myocardial perfusion agent, 99m Tc-labeled furifosmin (Q12), and determine the concordance of furifosmin perfusion scintigraphy to 201 T1 imaging. In addition, we sought to determine the normalcy rate of myocardial scintigraphy with furifosmin. Methods and Results . One hundred fifty patients constituted the study group in this multicenter trial. Patients underwent exercise testing with furifosmin injected at peak exercise, and tomographic imaging was begun 15 to 30 minutes afterward. After a separate injection, resting images were obtained 3 to 4 hours later. Thallium scintigraphy was performed within 2 weeks of the furifosmin scans, after a similar exercise workload. Patients with a low likelihood of coronary artery disease ( n = 39) also underwent furifosmin imaging. All images were processed and displayed in uniform manner and interpreted by a panel of readers. No adverse effects or clinically important laboratory alterations were related to furifosmin imaging. Image quality was slightly better with furifosmin than with thallium. The overall concordance between the perfusion studies was 86% (kappa value = 0.669). The normalcy rate for furifosmin scintigraphy was 100%. Conclusions . 99m Tc-labeled furifosmin is a promising new 99m Tc-labeled myocardial perfusion agent, providing diagnostic results similar to those obtained with 201 T1.

201Tl myocardial perfusion imaging is presently done by several possible strategies. Stress/delayed redistribution, stress/redistribution/reinjection, and rest/redistribution imaging can be useful in the clinical assessment of myocardial viability. Unfortunately, the extent of myocardial viability may still be underestimated even by 201Tl reinjection imaging, compared with 18F-fluorodeoxyglucose positron emission tomography. 99mTc-labeled sestamibi imaging provides results similar to those of 201Tl imaging in the detection of coronary artery disease, but several previous studies suggest that stress/rest 99mTc-labeled sestamibi imaging significantly underestimates myocardial viability. Recently it has been reported that the administration of nitrates, before 201Tl reinjection, improves detection of defect reversibility. Several studies also suggested that administration of nitrates before the injection of 99mTc-labeled sestamibi significantly improved detection of reversibility with this agent, whereas additional studies showed further that this combination improves the predictive accuracy for recovery of left ventricular function and perfusion after coronary revascularization, compared with a standard rest 99mTc-labeled sestamibi study. Nitrate administration before the injection of 201Tl and 99mTc-labeled sestamibi may thus be a potentially attractive alternative for the evaluation of myocardial viability. Although the available results are encouraging, further studies are needed to evaluate the clinical value of 201Tl and 99mTc-labeled sestamibi imaging, in combination with nitrates, for predicting recovery of left ventricular dysfunction.

Thallium-201 single photon emission computed tomography (SPECT) is superior to planar imaging for localizing native coronary stenoses, but has not yet been studied for assessing graft patency late after coronary artery bypass graft surgery (CABG). Accordingly, we studied 50 patients (40 males), aged 58 +/- 9 years (mean +/- SD), who presented for evaluation of angina (30 patients), atypical chest pain (20 patients), and other symptoms (9 patients), late after CABG (51 +/- 47 months). Patients with prior myocardial infarction were excluded. The mean ejection fraction was 58 +/- 17%. All patients underwent coronary angiography within 3 weeks of symptom-limited exercise thallium-201 SPECT. There were 119 grafts, of which 48 had50% stenosis by angiography. Thallium-201 SPECT detected 40 of these 48 (83%) stenosed grafts. The sensitivity of thallium-201 SPECT for detecting any graft stenosis was higher than that of the exercise electrocardiogram in patients with typical recurrent angina (84% vs 24%, p0.0001), as well as in those with atypical symptoms (70% vs 50%, p = 0.0039). The sensitivity of thallium-201 SPECT for correctly localizing the graft stenosis site was 82% for the left anterior descending, 92% for the right coronary, and 75% for the circumflex coronary artery. In conclusion, exercise thallium-201 SPECT is an excellent method to detect and localize graft stenosis late after CABG; it is far superior to the exercise electrocardiogram alone, both in patients with and without typical recurrent angina.

Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary prevention trials for reducing mortality in patients surviving myocardial infarction who have complex ventricular ectopy or nonsustained ventricular tachycardia, or both. In an attempt to explore the lowest dose of amiodarone with antiarrhythmic and hemodynamic activity, we studied 48 patients (mean age 53 +/- 11 years, ejection fraction 23 +/- 9%, clinical heart failure in 85%) with nonsustained ventricular tachycardia. This was a 3-month, randomized, parallel, double-blind pilot study comparing placebo (n = 16) with amiodarone 50 mg/day (n = 15) and 100 mg/day (n = 17). Patients randomized to amiodarone received a mean loading dose of 422 mg/day for the first study week. At the end of the 12 weeks, amiodarone (100 mg) significantly reduced ventricular premature complexes (177 +/- 64 to 98 +/- 38/hour), couplets (8 +/- 3 to 4 +/- 2/hour), and runs of nonsustained ventricular tachycardia (13 +/- 7 to 3 +/- 2/day), all p0.01 versus baseline. In addition, 10 of 14 patients taking 100 mg/day had total suppression of nonsustained ventricular tachycardia compared with 4 of 15 taking placebo, p = 0.021. Left ventricular ejection fraction improved byor = 7% (absolute) in 11 of 29 patients taking amiodarone as compared with only 1 of 15 placebo patients (p = 0.02). In these 11 patients with the greatest measurable hemodynamic improvement, amiodarone significantly increased ejection fraction (21 +/- 7% to 33 +/- 11%, p0.01), stroke volume index (28 +/- 9 to 40 +/- 7 ml/m2, p0.01) and decreased end-systolic volume index (116 +/- 48 to 92 +/- 44 ml/m2, p0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Controversy exists with regard to the diagnostic accuracy and optimal technique of myocardial perfusion imaging after coronary angioplasty. Exercise treadmill testing is inexpensive, with adequate predictive value for restenosis and clinical events in patients with single vessel coronary angioplasty with a normal rest electrocardiogram (ECG). Myocardial tomography has advantages for assessing patients with multivessel coronary angioplasty. Exercise stress imaging is generally preferable to pharmacologic stress in patients without physical limitations after angioplasty. Delayed thallium-201 imaging and reinjection protocols may be useful to reconcile whether residual ischemia exists in “fixed” perfusion defects. Appropriately timed stress myocardial perfusion imaging 2 to 4 weeks after procedurally successful coronary angioplasty can document improved cardiac functional capacity and reduced ECG and imaging evidence of myocardial ischemia. Although routine serial postangioplasty evaluations cannot be recommended, stess myocardial imaging may be valuable in subjects with defective anginal nocioception or extensive myocardium at risk in the area subtended by the angioplasty vessel.

Objectives. This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. Background. Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. Methods. This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving ≥5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (±SD) of 6.1 ± 1.8 days after randomization. Results. Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (−8.9 ± 11.1%) compared with placebo-treated patients (−1.8 ± 6.1%, p = 0.04), which was most apparent in those with the largest (≥20%) baseline perfusion defects (−11.4 ± 13.4% vs. 1.0 ± 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a ≥10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomiztd to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. Conclusions. Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia.

Pharmacologic stress testing has gained wide acceptance as an alternative to exercise stress testing when combined with myocardial perfusion scintigraphy and has expanded the applicability of cardiac imaging to the large number of patients who wither cannot exercise or are limited to a submaximal effort. The pharmacologic stressors presently available are either coronary vasodilators (e.g., adenosine, dipyridamole) or beta-agonists (e.g., dobutamine). This article summarizes the physiologic principles underlying pharmacologic stress imaging and its clinical utility in evaluating patients with suspected coronary artery disease.

Objectives. The purpose of this study was to determine the safety of adenosine infusion at 140 μg/kg per min in conjunction with radionuclide imaging in 9,256 consecutive patients.Background. Adenosine produces maximal myocardial hyperemia directly with a rapid onset of action. In addition, when used in conjunction with radtonuclide perfusion imaging, it has proven efficacy for the diagnosis of coronary artery disease in patients unable to exercise. Because the ultrashort half-life (70 years of age had an increased risk of developing AV block (age

Pharmacologic stress testing may be used in the diagnosis of coronary artery disease and risk assessment. The stress agents may be divided into those that produce primary coronary vasodilation (dipyridamole, adenosine, or adenosine triphosphate) and those that produce secondary vasodilation as a result of increase in myocardial oxygen demand (dobutamine and arbutamine). Assessment of myocardial perfusion and function can be made by single-photon imaging, positron emission tomography, two-dimensional echocardiography, magnetic resonance imaging, and contrast angiography. For assessment of myocardial perfusion, either thallium 201-labeled or technetium-labeled perfusion imaging agents may be used. This article will focus on the mechanisms of action, hemodynamic responses, and results of pharmacologic imaging in detecting coronary artery disease. The use of pharmacologic stress testing in risk assessment will be discussed in a separate article.

The diagnostic accuracy, safety and tolerance of adenosine thallium scintigraphy have been reported using a 2-site intravenous infusion with either a titrated or fixed-dose protocol. A single-site infusion would considerably simplify the test procedure, but its safety must be established before it can be recommended. Accordingly, 400 consecutive patients who had adenosine and thallium-201 administered through the same intravenous line were classified into 2 groups. Group I (n = 201) patients received a 7-minute titrated intravenous infusion of adenosine, with an initial dose of 50 micrograms/kg/min that increased at 1-minute intervals to a maximum of 140 micrograms/kg/min. Group II (n = 199) patients received a fixed dose of adenosine at 140 micrograms/kg/min for 6 minutes. Adenosine significantly (p0.001) increased heart rate and decreased systolic blood pressure by similar amounts in both groups. Adverse effects occurred more often (88 vs 71%, p0.001) and started earlier (2.8 vs 3.6 minutes, p0.001) in group II. There was no significant difference in the occurrence of second- and third-degree atrioventricular block between the 2 groups (4.0 vs 5.0%); however, chest pain, flushing and nausea were all more frequent in group II. Severe side effects were seldom seen in either group and occurred in 9 group I and 8 group II patients. Scintigraphic findings were similar in both groups. Transient perfusion defects were seen more often in patients with than without second- or third-degree atrioventricular block (42 vs 21%, p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives. The aim of this study was to assess the feasibility, safety and diagnostic accuracy of a high dose dobutamine infusion in conjunction with thallium-201 single-photon emission computed tomography in 144 patients (72 men and 72 women with a mean age of 65 ± 10 years) unable to perform exercise or pharmacologic vasodilator stress testing. Background. Dobutamine increases myocardial oxygen consumption by increasing heart rate, contractility and arterial blood pressure. In addition, it causes myocardial blood flow heterogeneity and thus may be a useful stress for noninvasive detection of coronary artery disease. Methods. Dobutamine was administered intravenously at incremental doses of 5, 10, 20, 30 and up to 40 μg/kg per min at 3-min intervals. After 1 min of the maximal dose, 3 mCi of thallium-201 was injected and the infusion was continued for an additional 2 min. Thallium-201 tomography was performed 5 to 10 min after termination of the infusion and 4 h later. The images were visually assessed for the presence and vascular location of perfusion defects and the extent of thallium redistribution. Coronary angiography was performed in 84 patients, with a >50% stenosis considered significant. Results. Dobutamine significantly (p = 0.0001) increased the heart rate (from 75 ± 14 beats/min to 120 ± 23 beats/min), systolic blood pressure (from 136 ± 23 mm Hg to 148 ± 35 mm Hg) and the rate-pressure product (from 10,144 ± 2,517 to 17,858 ± 4,349) from baseline to peak infusion rate, respectively. Most patients (75%) experienced side effects during the infusion, but 74% tolerated a dobutamine dose of 40 μg/kg per min and 97% a dose of 30 μg/kg per min. The more common side effects were typical (26%) and atypical (5%) chest pain, palpitation (29%), flushing (14%), headache (14%) and dyspnea (14%). The overall sensitivity of dobutamine tomography was 86% in the patients who underwent coronary angiography and 84% in those with single-vessel, 82% in those with double-vessel and 100% in those with triple-vessel disease. Seventy-eight percent of vessels with severe (≥70%) stenoses were identified with dobutamine tomography. The specificity of dobutamine tomography was 90% for patients and 86% for individual vessels. Conclusions. A high dose dobutamine infusion in conjunction with thallium tomography appears to be a well tolerated and accurate method for diagnosing coronary artery disease in patients unable to perform exercise or vasodilator pharmacologic stress testing.

BACKGROUND We prospectively investigated whether adenosine 201Tl tomography (SPECT) could determine the extent of coronary artery disease, the presence of jeopardized myocardium, and the risk for in-hospital cardiac events in 120 clinically stable patients early (5 +/- 3 days) after myocardial infarction. METHODS AND RESULTS All patients had coronary angiography and SPECT in close proximity. Adenosine SPECT identified 99% of infarct-related arteries and 82% of severely stenosed (> or = 70%) noninfarct arteries. Multivessel disease was accurately predicted in 69% of patients. Sixty-five percent of stenosed noninfarct arteries had matching thallium perfusion defects, and 92% of these were reversible. The specificity of adenosine SPECT was > 90%. Thallium redistribution occurred often within infarct (59%) and noninfarct (92%) zones. The patency status of the arteries, however, did not predict the presence or extent of jeopardized myocardium. The perfusion defect size was larger (p = 0.0001) in patients with (45 +/- 18%) than in those without (22 +/- 15%) in-hospital cardiac events. Furthermore, 90% of patients with events had a > or = 20% perfusion defect compared with only 38% of those without events (p = 0.0001). The positive-predictive accuracy for developing a cardiac event was 70% when the perfusion defect size was > 30%. The ischemic defect also was larger in patients with (19 +/- 14%) than in those without (10 +/- 10%) events (p = 0.001). The positive- and negative-predictive values for developing early postinfarction angina were 43% and 91%, respectively, when the ischemic defect was > 12%. CONCLUSIONS In selected low-risk survivors of myocardial infarction, early quantitative adenosine SPECT is safe and accurate in detecting and localizing coronary stenoses, assessing the extent of jeopardized myocardium, and determining subsequent risk for in-hospital cardiac events.

Adenosine is a purine base compound which is of fundamental importance in many physiologic processes in the body, including vasodilation in most arterial vascular beds. Adenosine produces maximal or near-maximal coronary vasodilation by interacting with the adenosine A2 receptors in the cell wall, on a dose dependent fashion. The mechanism of thallium-201 myocardial perfusion defects induced by adenosine scintigraphy is a heterogeneity of myocardial blood flow due to a greater coronary flow increase in the normal arteries and a lesser increase in the stenotic arteries. The ultra-short half-life of adenosine (< 10 sec) necessitates continuous intravenous administration at a dose of 140 μg/kg/min for six min. The excellent safety record of this regimen has been demonstrated in several thousand patients in the United States. Side effects occur in most patients during adenosine infusion. Chest pain occurs often and in some cases may be due to a true coronary steal phenomenon. In the author's experience, first degree AV block occurs in approximately 10% and second or third degree AV block in approximately 4% of the patients, and are due to the negative dromotropic effect of adenosine on the AV node. On the positive side, these untoward effects are very short-lived and typically disappear within one or two minutes after discontinuing the adenosine infusion. No serious complications or fatalities have been observed to date with this test. The cumulative experience with adenosine thallium-201 scintigraphy indicates high sensitivity and specificity in the diagnosis of coronary artery disease. Recent data also suggest it may be an excellent technique to assess a patient's prognosis early after a myocardial infarction. Adenosine-induced coronary vasodilation, in combination with thallium-201 or the new technetium-99m perfusion agents, holds great promise in the assessment of patients with coronary artery disease. © 1993 Wiley-Liss, Inc.

To determine if magnetic resonance imaging (MRI) can be used to detect tissue viability in segments with persistent 201T1 defects early following acute myocardial infarction, 24 patients underwent MRI and adenosine 201T1 single photon emission computed tomography (SPECT) imaging at approximately 6 days. Infarction was demonstrated on MRI using a velocity-compensated, T2-weighted spin-echo pulse sequence. Wall thickening was assessed using a gradient-echo pulse sequence obtained in the same anatomic position. Viable myocardium was defined by MRI as a segment with increased signal intensity and preserved wall thickening. A fixed defect on the 201T1 SPECT images was defined as the absence of any redistribution 4 hours after the 201T1 infusion. Of 11 patients with redistribution on the 201T1 images in the infarction region, 10 (91%) had preserved wall thickening by MRI. Of 13 patients with fixed defects on the 201T1 images in the infarction region, 6 (46%) had preserved wall thickening by MRI. Of 7 patients with absent thickening, all had one or more segments with absent perfusion on redistribution imaging. Wall thickening tended to occur in patients who received thrombolytic therapy or who underwent revascularization procedures prior to imaging. The results of the present study suggest that spin-echo MRI with motion compensation can be used to identify viable myocardium in patients with fixed defects on 201T1 SPECT following acute myocardial infarction.

Objectives. The study was designed to compare pharmacologic and exercise stress during thallum-201 single-photon tomography in a multkenter prospective crossover trial.Background. Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients.Methods. The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thalium tomograpltic tests performed 30 days apart, one during intravenous administration of adenosine (140 μg/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics.Results. Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p < 0.0001) and 11.1 (p < 0.00001), respectively. The agreement by computer quantification was 86% with kappa amd Z statistics of 0.709 (p < 0.0001) and 12.2 (p < 0.00001), respectively. Agreement on localisation of the perfusion defect to a specfic coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p < 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p < 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued.Conclusions. Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine.

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.

BACKGROUND Exercise echocardiography (digital cine-loop technique) and 201Tl single-photon emission computed tomography (SPECT) were performed simultaneously in 292 patients being evaluated for coronary artery disease. METHODS AND RESULTS Pretreadmill and posttreadmill echocardiographic images of diagnostic quality were obtained in 289 patients, and the left ventricle was divided into anterior, inferior, and lateral regions. Any wall motion or perfusion abnormality observed within each region was classified as totally reversible, fixed, or partially reversible. Exercise echocardiography and SPECT were normal in 137 patients and abnormal in 118 (88% agreement). Equal numbers of regional abnormalities were detected by one test when missed by the other. The two tests had an 82% agreement in detecting the same type of finding within the regions analyzed. SPECT detected more reversible abnormalities than echocardiography, whereas echocardiography detected more fixed abnormalities than SPECT: Regions with a fixed abnormality by echocardiography frequently showed partial reversibility of a perfusion defect by SPECT: Nearly one third of regions with fixed perfusion defects by SPECT demonstrated normal resting function or reversible abnormalities by echocardiography. Sensitivity for coronary artery disease by angiography (greater than or equal to 50% diameter stenosis) in 112 patients was similar for the two tests, ranging from 58% and 61% (echocardiography and SPECT, respectively) for one-vessel disease to 94% for three-vessel disease. The specificities for echocardiography and SPECT were 88% and 81%, respectively. CONCLUSIONS Exercise echocardiography had a diagnostic accuracy comparable to that of SPECT for the detection of regional abnormalities produced by significant coronary artery disease. A greater number of abnormal regions were detected with the combined use of both tests.

To assess the feasibility, safety and diagnostic accuracy of adenosine infusion combined with echocardiography, 73 patients with suspected or known coronary artery disease underwent echocardiography at baseline and during a maximal intravenous adenosine infusion of 140 micrograms/kg per min. Compared with baseline values, adenosine caused an increase in heart rate, a decrease in systolic and diastolic blood pressure and a slight but significant increase in rate-pressure product. The echocardiographic images were digitized and randomly assigned in a quad-screen format for nonbiased interpretation. An ischemic response, defined as a new or worsening wall motion abnormality, developed in 25 patients; a fixed wall motion abnormality was present in 27 and no abnormality in 21. All patients underwent coronary angiography. The sensitivity of adenosine echocardiography for greater than or equal to 75% coronary artery diameter stenosis was 85% (46 of 54), with a specificity of 92% in patients with normal coronary arteries. In the 35 patients with a normal baseline electrocardiogram the sensitivity was 60%; 9 (82%) of 11 patients with multivessel disease were correctly identified. The sensitivity for adenosine electrocardiography (greater than or equal to 1-mm ST depression) was 35% with a specificity of 100%. Side effects were transient and mild; aminophylline was used in two patients. Thus, ischemic changes can be induced in patients with coronary artery disease with intravenous adenosine that, combined with echocardiography, is sensitive for the assessment of ischemic heart disease, particularly in patients with multivessel disease.

Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans.Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis.At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 ± 3.1% vs. 8 ± 2.3%, p < 0.02; and −1.6 ± 0.4 vs. −2.9 ± 0.2 SD/chord, p < 0.05). Tomographic infarct size expressed as a percent of the left ventricle was also reduced in Fluosol-treated patients (3.5 ± 2.2% vs. 18.3 ± 4.7%, p < 0.05). No significant differences in collateral blood flow, extent of coronary artery disease or residual stenosis after angioplasty were observed.This preliminary study suggests that myocardial reperfusion injury may be an important factor in limiting myocardial salvage in patients undergoing reperfusion. These findings have important clinical implications because adjunctive therapy may further amplify the beneficial effects of mechanical or pharmacologic reperfusion. Additional prospective randomized trials must be done to confirm and extend these preliminary results.

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as >50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double- and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement.

Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 ± 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 ± 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 ± 14.0 to 91.8 ± 15.9 beats/mill (p < 0.001) and decreased systolic blood pressure from 137.8 ± 26.8 to 120.7 ± 26.1 mm Hg (p < 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p < 0.05). First-and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients.Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred. These data attest to the excellent safety of adenosine infusion as an adjunct to thallium-201 scintigraphy in humans even within a few days of acute myocardial infarction.

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is ≥7% units for left ventricular ejection fraction, ≥45 ml/m2for end-diastolic volume index, ≥35 ml/m2for end-systolic volume index, ≥20 ml/m2for stroke volume index and >1.25 liters/min per m2for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation >25% of the time. The criteria presented are applicable to clinical practice because they allow precise interpretation of hemodynamic changes measured by gated radionuclide angiography in individual patients whether the change is due to altered clinical status or to a medical intervention.

Adenosine is a ubiquitous purine base that has many physiological actions in the body, including arterial vasodilation in all vascular beds, with the exception of the kidneys. Myocardial ischemia causes an immediate breakdown of adenosine triphosphate and generates adenosine, thereby producing coronary vasodilation and restoring flow. Adenosine produces vasodilation by interacting with the adenosine receptors in the cell wall. Exogenously administered adenosine has a very short half-life ( 201 TI scintigraphy shows high sensitivity and specificity for coronary artery disease (CAD) detection, comparable with those of exercise or dipyridamole scintigraphy. Thus, adenosine-induced coronary vasodilation, in combination with 201 TI or the new technetium 99m perfusion agents, is a promising new test for assessment of patients with CAD.

Pharmacologic coronary vasodilation as an adjunct to myocardial perfusion imaging has become increasingly important in the evaluation of patients with coronary artery disease, in view of the large number of patients who cannot perform an adequate exercise test or in whom contraindications render exercise inappropriate. Adenosine is a very potent coronary vasodilator and when combined with thallium 201 scintigraphy produces images of high quality, with the added advantages of a very short half-life (less than 10 seconds) and the ability to adjust the dose during the infusion, which may enhance safety and curtail the duration of side effects. The reported sensitivity and specificity of adenosine thallium 201 scintigraphy for the detection of coronary artery disease are high and at least comparable with imaging after exercise or dipyridamole administration.

Exercise thallium-201 perfusion scintigraphy has been used extensively over the last decade for the detection and localization of coronary artery disease. Single-photon emission computed tomography (SPECT) is a refinement of presently available techniques, offering improved identification over planar imaging of individual vessel stenosis and quantification of the extent of abnormally perfused myocardium. In this review, the planar and SPECT techniques are discussed in light of the most recently published large patient series, and with regard to the many factors that affect the sensitivity and specificity of perfusion imaging in identifying coronary artery disease. The clinical implications of exercise perfusion scintigraphy and its future applications in cardiology practice are discussed.