Adenosine-induced Coronary Hyperemia Research Articles

Is heart rate response a reliable marker of adenosine-induced coronary hyperemia?

Introduction Growing evidence supports ischemia-guided management of chest pain, with invasive and non-invasive tests reliant upon achieving adenosine-induced coronary hyperemia (defined as increased blood flow to an organ’s perfusion bed). In the non-invasive setting, surrogate markers of hyperemia, such as increases in heart rate, are often used, despite not being formally validated. We tested whether heart rate and other non-invasive indices are reliable markers of coronary hyperemia. Methods The first part involved Doppler flow-based validation of the best pressure-wire markers of hyperemia in 53 patients. Subsequently, using these validated pressure-derived parameters, 265 pressure-wire traces were analysed to determine whether heart rate and other non-invasive parameters correlated with hyperemia. Results In the flow derivation cohort, the best determinant of hyperemia came from having 2 out of 3 of: (1) Ventriculisation of the distal pressure waveform, (2) disappearance of distal dicrotic pressure notch, (3) separation of mean aortic and distal pressures. Within the 244 patients demonstrating hyperemia, non-invasive markers of hyperemia, such as change in heart rate (p = 0.77), blood pressure (p = 0.60) and rate-pressure product (p = 0.86), were poor correlates of coronary hyperemia, with only 37.3% demonstrating a ≥ 10% increase in heart rate that is commonly used to adjudge adenosine-induced hyperemia in the non-invasive setting. Conclusions We demonstrate, by correlation with Doppler-flow data, a validated method of identifying coronary hyperemia within the catheter laboratory using the pressure-wire. We subsequently show that non-invasive parameters, such as heart rate change, are poor predictors of coronary hyperemia during stress imaging protocols that rely upon achieving adenosine-induced hyperemia.

RELATIONSHIP BETWEEN AGE AND DIASTOLIC BLOOD PRESSURE TO CHANGES IN MYOCARDIAL OXYGENATION AS ASSESSED BY CARDIOVASCULAR MAGNETIC RESONANCE

myocardial apoptosis, necrosis, collagen deposition and interstitial fibrosis. These may result in myocardial stiffness and alteration of myocardial extracellular volume fraction (ECV). In this pilot study, we hypothesize that CMR-determined LV diastolic dysfunction in diabetic patients is associated with increased ECV measured by T1 mapping. METHODS: 17 DM patients (6 males, age 63 10 years old) without macrovascular diseases were examined on a 1.5T MR system. LV systolic and diastolic function was determined using a short-axis SSFP stack, T1 map and average LV myocardium T1 at preand post-contrast was derived from a T1 prep or a modified Look-Locker sequence performed in a mid-LV level. Post-contrast late gadolinium enhancement (LGE) CMR was performed 15 minutes post injection of GdDTPA. LV systolic function and LGE determination used commercial software CMR42. LV diastolic functional parameters including peak filling rate (PFR) and time to peak filling rate (TPFR) were calculated using MASS software and were blinded to T1 analysis. T1 calculation used CMR42 or a customized Matlab code. Myocardial ECV 1⁄4 (1-haematocrit) (DR1myocardium/DR1blood). Increased ECV was defined as ECV > 30%. RESULTS: The average LV functional parameters in 17 subjects were in the normal range (LVEF1⁄461 6%, LVESV1⁄445 17 ml, LVEDV1⁄4113 33 ml, LVSV1⁄468 19 ml, LVM1⁄4103 25 g). No focal LGE was observed in this patient cohort. 8 of 17 subjects had ECV> 30% (ECV1⁄438 9%) and the other 7 subjects had ECV 0.05) in LV systolic functional parameters of LVEF, LVESV, LVEDV, LVSV and LVM between the increased ECV and normal ECV group. However, a statistically significant difference (P<0.05) was observed among diastolic functional parameters of TPFR and PFR, with significantly longer TPFR (344 148 vs.156 32 ms) and lower PFR (220 50 vs. 295 74 ml/s) observed in the increased ECV group. Also a statistically significant difference (P<0.05) was observed in pre-contrast T1 measurements. CONCLUSION: Increased ECV was observed in diabetic patients with preserved systolic function and this was associated with altered LV diastolic function. The increased ECV may indicate the presence of diffuse interstitial fibrosis and myocardial stiffness, thus limiting the LV diastolic relaxation.

Assessment of significant coronary artery stenosis using blood oxygen level dependent cardiovascular magnetic resonance (BOLD-CMR)

Summary Oxygenation-sensitive CMR at 1.5T can be used to identify functionally significant coronary artery stenosis, by demonstrating a blunted response to adenosine induced hyperaemia. Image quality remains a limitation. Background Using the magnetic properties of hemoglobin, changes in myocardial tissue oxygenation can be detected with blood oxygen level dependent (BOLD) cardiovascular MRI (CMR). The study aim was to assess whether BOLD-CMR images can detect an abnormal myocardial tissue response to adenosine infusion in patients with CAD, when compared to fractional flow reserve (FFR). Methods Patients undergoing clinically indicated coronary angiography underwent BOLD CMR scans using a clinical 1.5T scanner. Three short axis BOLD cine images were captured at baseline and during adenosine-induced coronary hyperemia. The mean segmental percent signal intensity (SI) changes were calculated between baseline and hyperemia in the subendocardial myocardium using the 16-segment model. Segments were defined as ischemic or non-ischemic by FFR (cut-off <0.80). The segment with the lowest BOLD SI percent change per patient was used for analysis. Results Thirty-two patients were enrolled, 5 patients were excluded due to incomplete CMR, leaving 27 patients (age 61 ± 10 years) for analysis. There were 864 myocardial segments (baseline and adenosine) available for analysis, 289 were subtended by a coronary artery with an available FFR value. Eighty-two segments (28%) were excluded due to pre-defined criteria for poor image quality, 67% were apical. From the remaining 20 patients, 7 had ischemic FFR values and 13 had non ischemic FFR values. Using the segment with the lowest % BOLD SI change per patient there was a significant difference between ischemic -6.49% ± -8.65% and non ischemic 4.21 ± 4.94% (p=0.0023) patients. Using a cut off value of 1.1% SI change the sensitivity is 86%, specificity 69%, positive predictive value 0.6 and negative predictive value 0.9.

Functional significance of Blood Oxygen Level Dependent (BOLD) imaging in patients with coronary artery disease - a validation study using fractional flow reserve

Background/purpose Blood oxygen level-dependent (BOLD) cardiac MRI (CMR) uses the signal generated by endogenous hemoglobin in the blood supply to directly measure tissue oxygenation. Therefore it may be useful as a non-contrast enhanced, non-invasive method to detect the presence of myocardial ischemia in patients suspected of having coronary artery disease (CAD). The aim of this study was to validate whether BOLDsensitive CMR images can detect and quantify alterations in myocardial oxygen levels in patients with CAD, in comparison to the gold standard of fractional flow reserve (FFR). Methods Oxygen-sensitive BOLD CMR scans were performed in patients who were scheduled for clinically-indicated coronary angiography. BOLD images were captured during rest and adenosine-induced coronary hyperemia. The mean BOLD signal intensity (SI) percent changes were calculated between rest and hyperemia in the subendocardial myocardium at basal, mid, and apical regions. Segmental ΔSI% in the corresponding coronary territory was defined as ischemic (using a cut-off of <0.80) or non-ischemic by FFR. The BOLD segment with the lowest ΔSI% in the territory subtended by the FFR measurements was selected for statistical analysis. Bland-Altman analysis was used to assess the level of agreement between all segments analyzed by two blinded readers. Results Twenty-eight patients totaling 147 myocardial segments were available for analysis. 73 segments were excluded, with 66% of these being apical. The remaining 74 segments equated to 22 patients (60 +/- 9y, 19 males), eight of these had a normal FFR (≥ 0.80) and 14 had FFR values <0.80. Mean BOLD SI percent change was significantly less in patients with abnormal FFR values (-4.62 +/- 2.28% SEM), in comparison to patients with normal FFR values (8.54 +/- 3.08 % SEM); p=0.003. (See Figure 1 and 2). The Bland-Altman analysis indicated that the 95% limits of agreement between the two readers ranged from -23.6% to 27.8% (Figure 3).

High-Dose Adenosine Overcomes the Attenuation of Myocardial Perfusion Reserve Caused by Caffeine

We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation. Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose. Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (baseline) and after coffee ingestion (caffeine). At baseline, patients received 140 microg/kg/min of adenosine combined with low-level exercise. For the caffeine study, 12 patients received 140 microg/kg/min of adenosine (standard) and 18 patients received 210 microg/kg/min (high dose) after caffeine intake (200 mg). Myocardial perfusion was assessed semiquantitatively and quantitatively, and perfusion defect was characterized according to the presence of reversibility. Caffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 +/- 4.4 at baseline vs. 4.1 +/- 2.1 after caffeine, p < 0.001) as well as defect size (18% [3% to 38%] vs. 8% [0% to 22%], p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 +/- 4.0 at baseline vs. 7.8 +/- 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated. Caffeine in coffee attenuates adenosine-induced coronary hyperemia and, consequently, the detection of perfusion abnormality by adenosine MPS. This can be overcome by increasing the adenosine dose without compromising test tolerability.

Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts

Because adenosine is commonly used for inducing maximal coronary hyperemia in the clinic, it is imperative that adenosine-induced hyperemia (AH) resembles coronary hyperemia that can be attained by endogenous stimuli. In the present study we hypothesized that coronary reactive hyperemia (RH) is limited compared with AH due to the presence of the glycocalyx and that the AH response is therefore unable to detect glycocalyx modifications. In anesthetized open-chest dogs, blood flow and pressure were measured in the left circumflex artery. RH after 15-s occlusion was compared with an intracoronary infusion of adenosine (650 microg; AH) during control conditions and after intracoronary treatment of the glycocalyx with hyaluronidase (20.000 U, 2 x 20 min; n = 6) or heat-inactivated hyaluronidase (n = 5). During control, coronary conductance during RH was 1.49 +/- 0.15 ml.mmHg(-1).min(-1) and 76 +/- 7% of coronary conductance during AH (P < 0.05). After hyaluronidase, RH conductance increased (P < 0.01) by 43 +/- 13% and became 93 +/- 4% of AH conductance (P = NS). Heat-inactivated hyaluronidase had no effect on RH and AH conductance. Our results demonstrate that adenosine-induced coronary hyperemia profoundly exceeds RH and that the difference is virtually abolished on selective removal of the glycocalyx. It is concluded that, compared with RH, adenosine-induced coronary hyperemia is not affected by modification of the glycocalyx. This glycocalyx insensitivity should be taken into account when using adenosine-induced coronary hyperemia as a marker for vasodilating capacity to an ischemic stimulus.

Functional and Morphologic Imaging of Coronary Atherosclerosis in Living Mice Using High-Resolution Color Doppler Echocardiography and Ultrasound Biomicroscopy

This study aimed to establish non-invasive methods of assessing coronary artery morphology in normal and atherosclerotic mice in vivo. Coronary flow velocity reserve (CFVR) has been shown to correlate with coronary minimal lumen diameter (MLD) in patients with coronary artery stenosis. In mice, there are no existing non-invasive imaging techniques allowing quantitative measurement of the coronary artery morphology and function. Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In 17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10 atherosclerotic low-density lipoprotein receptor (LDLR)-/- mice, the hypoxia-induced CFVR was performed and proximal LCA MLD was measured using ultrasound biomicroscopy (UBM). Histologic sections of the LCA were collected. The adenosine dose of 160 microg/kg/min induced maximal coronary hyperemia without any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values averaged at 2.0 +/- 0.1 and 1.9 +/- 0.3, respectively, in C57BL/6 mice (p = NS). In LDLR-/- mice, CFVR and MLD ranged between 1.4 to 2.9 microm and 190 to 370 microm, respectively. Histology revealed proximal lumen-narrowing plaques in the LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD (p < 0.005, R2 = 0.8707). The CDE and UBM technique can be used to measure atherosclerosis-related lumen narrowing of the LCA in living mice. These non-invasive techniques may provide us with novel tools for following up disease status in mouse coronary arteries in a quantitative manner.

Redistribution in thallium-201 myocardial imaging soon after successful coronary stenting--tomographic evaluation during coronary hyperemia induced by adenosine.

To evaluate the clinical significance of reversible perfusion defects that were observed soon after the successful deployment of a coronary stent, 47 patients underwent thallium-201 myocardial scintigraphy and radionuclide angiography in conjunction with adenosine-induced coronary hyperemia before and after complete revascularization. Coronary angiography showed a significant decrease in the percent diameter stenosis (from 87+/-11% before stenting to -1+/-5% after stenting, p<0.01) with no major dissection, residual stenosis, or intra-stent formation of thrombus. Even after the angiographically successful procedure, reversible perfusion defects were present in 17 (36%) of the 47 patients, none of whom showed any wall motion abnormalities during the infusion of adenosine. Disease duration was significantly longer and collateral vessels were more common in the patients with than in those without thallium redistribution, whereas the other clinical, pre- and post-stent angiographic and hemodynamic factors were similar. In conclusion, reversible perfusion defects without wall motion abnormalities were demonstrated during the infusion of adenosine in approximately one-third of patients soon after coronary stenting, and were not consistently related to acute unfavorable outcomes of stent placement.

Myocardial Perfusion Imaging During Adenosine-Induced Coronary Hyperemia

Myocardial Perfusion Imaging During Adenosine-Induced Coronary Hyperemia

Relation between diastolic left ventricular function and myocardial blood volume during adenosine-induced coronary hyperemia

Adenosine infusion is accompanied by increases in coronary blood flow and myocardial bllood volume. Myocardial blood volume may produce changes in diastolic left ventricular (LV) performance by increasing myocardial turgor. Diastolic dysfunction may also be the result of myocardial ischemia. The relation between changes in LV mass and diastolic function has not been previously investigated. this study examined the relation between changes in LV mass during adenosine-induced coronary hyperemia and LV diastolic function. Serial two-dimensional and Doppler echocardiographic measurements were made before, during, and after adenosine infusion (140 μg/min for 6 min) in 21 patients with (group 1) and 10 patients without (group 2) coronary artery disease (CAD). The LV mass and transmitral diastolic filling indexes were determined from digitized images from apical four-chamber view. Adenosine infusion produced a greater increase in LV mass in group 2 than in group 1 (29% + 11% vs 9% + 6%, p < 0.0002). The ratio of transmitral early (E) to atrial (A) filling velocity ( E A ) increased 10% + 16% in group 2 and decreased 8% ± 20% in group 1 ( p < 0.02), and the velocity time integral of early filling increased 11% ± 52% in group 2 and decreased 20% ± 31% in group 1 ( p < 0.04). There was a correlation between the change in E A ratio and the LV mass ( r = 0.53, p < 0.003). Thus adenosine infusion caused a greater increase in LV mass in normal subjects than in patients with CAD. There were also changes in Doppler-derived indexes of diastolic LV function. The diastolic dysfunction in CAD cannot be entirely the result of increased myocardial turgor.

Significance of ST segment depression during adenosine-induced coronary hyperemia in angina pectoris and correlation with angiographic, scintigraphic, hemodynamic, and echocardiographic variables

Factors determining myocardial ischemia during adenosine-induced coronary vasodilation in patients with angina pectoris are not well defined. To evaluate the angiographic, scintigraphic, hemodynamic, and echocardiographic determinants of ST segment depression during adenosine infusion, 40 patients with angina pectoris underwent technetium-99m sestamibi single photon emission computed tomography and simultaneous two-dimensional echocardiography. Ischemic ST depression occurred in 18 patients (45%). Coronary angiography was performed in all patients and a coronary artery jeopardy score was determined. The sensitivity, specificity, and the predictive accuracy of adenosineinduced ST segment depression in detecting significant coronary artery disease were 53%, 100%, and 60%, respectively, while the corresponding results for detecting reversible perfusion defects were 61%, 92%, and 70%, respectively. Univariate predictors of ST segment depression included the coronary artery jeopardy score, the presence and the extent of reversible perfusion defects, the presence of three-vessel and/or left main coronary artery disease, and diastolic blood pressure at peak adenosine infusion. There was a trend ( P = 0.06) to a higher incidence of collateral vessels in patients developing ST segment depression. The coronary artery jeopardy score was found to be the only significant independent predictor of ST segment depression by stepwise multivariate logistic regression analysis. Thus, in patients with angina pectoris, the coronary artery jeopardy score, representing the extent of significant coronary artery disease, is the most important independent predictor of adenosine-induced ST segment depression. ST depression is unusual in the absence of reversible perfusion defects and is also associated with more extensive reversible defects.

Identification of high-risk patients with left main and three-vessel coronary artery disease by adenosine-single photon emission computed tomographic thallium imaging

The purpose of this study was to examine the ability of SPECT imaging with thallium-201 during adenosine-induced coronary hyperemia to detect highrisk patients with left main or three-vessel CAD. There were 339 patients: 102 with either left main or three-vessel CAD (group 1) and 237 with no CAD, one-, or two-vessel disease (group 2). By means of univariate analysis, several variables were found to differ between groups 1 and 2: Q wave myocardial infarction (35% vs 25%, p < 0.05), ST segment depression (35% vs 19%, p < 0.001), age (67 ± 9 vs 62 ± 10 years, p < 0.001), resting systolic blood pressure (142 ± 22 vs 135 ± 20 mm Hg, p < 0.01), abnormal thallium images (95% vs 74%, p < 0.0001), multivessel thallium abnormality (76% vs 39%, p < 0.0001), extent of thallium abnormality (24 ± 11% vs 19 ± 13%, p < 0.0001), and increased lung thallium uptake (39% vs 15%, p < 0.01). According to stepwise discriminant analysis, only three variables were predictors of high risk: multivessel thallium abnormality ( x 2 = 27), increased lung thallium uptake ( x 2 = 10), and ST depression ( x 2 = 5). On the basis of these variables, patients were divided into three groups with different prevalence rates for left main and three-vessel CAD: 63% in 68 patients, 30% in 137 patients, and 13% in 137 patients. Thus adenosine-thallium imaging permits stratification of patients into different risk groups; 20% of patients have a high, 40% an intermediate, and 40% a low prevalence of left main or three-vessel CAD.

Single photon emission computed tomographic teboroxime imaging with a preprocessing masking technique

We previously reported that single-head SPECT imaging with teboroxime is feasible. However, excessive hepatic uptake in some patients may interfere with image interpretation. This study examined the feasibility of improving image quality by use of a preprocessing masking technique to substract hepatic activity. A band of 10 pixels in width adjacent to the inferior cardiac silhouette was marked on the raw planar images, and then SPECT reconstruction was done with the Butterworth filter with a frequency cutoff of 0.3 cycles/cm and the power of 10. The stress and rest images were compared before and after masking in 10 patients who underwent SPECT teboroxime imaging during adenosine-induced coronary hyperemia (140 μg/kg/min for 6 minutes). SPECT imaging with a single-head detector was performed with the use of a 180-degree anterior arc (from the 45-degree left posterior oblique projection to the 45-degree right anterior oblique projection); 32 images at 8 seconds per stop were obtained (total imaging time = 6.8 minutes). All images were considered subjectively better after the masking technique was used, especially for assessment of inferior wall perfusion pattern. The maximum count in any pixel was in the hepatic region of interest before masking and in the cardiac region of interest after masking (303 ± 110 counts vs 166 ± 55 counts; p < 0.001). The difference was especially pronounced in the images that were obtained when patients were at rest (366 ± 102 counts vs 184 ± 64 counts; p < 0.001). When the polar maps were used quantitatively, the inferior counts were significantly lower after the processing (229 ± 115 counts vs 146 ± 79 counts; p < 0.001). Thus preprocessing masking of hepatic activity improves the quality of SPECT teboroxime images. This method requires only 5 additional minutes, is easy to perform, and should be routinely incorporated in image processing.

Tomographic myocardial perfusion imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia: Correlation with thallium-201 imaging

Single-photon emission computed tomographic imaging with technetium-99m teboroxime during exercise has been found to be feasible and the results correlate with those obtained with thallium-201. This study examined the feasibility of this technique and compared tomographic imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia with thallium-201 imaging. With the patient positioned on the imaging table, adenosine was infused at a rate of 140 μg/kg per min for 6 min. At 4 min, 20 to 25 mCi (740 to 925 MBq) of technetium-99m teboroxime was injected intravenously and imaging was started as soon as the infusion was completed with use of a 180 ° anterior arc and 32 stops at 10 s/stop (total imaging time 7.8 min). Rest images were obtained 60 to 90 min later with use of a similar dose of technetium-99m teboroxime. Exercise tomographic thallium images were obtained within 2 weeks of the teboroxime studies.In the 20 patients studied, the teboroxime images were normal in 2 (50%) of 4 normal subjects and abnormal in 15 (94%) of 16 patients with coronary artery diseases 4 of the 15 had a fixed defect and 11 a reversible defect. There was agreement between teboroxime and thallium studies in 16 patients (80%), in 319 (80%) of 400 segments and in 50 (83%) of 69 vascular segments (p < 0.05). In two normal subjects, an apparent fixed defect involving the inferior wall was seen on the teboroxime but not the thallium images and was thought to be due to an attenuation artifact secondary to extracardiac activity in the left lobe of the liver. There were no clinically significant adverse events.Thus, this preliminary report shows that teboroxime tomographic imaging during adenosine infusion is feasible and convenient. This method combines the strengths of both agents: a very short half-life (12 min for teboroxime and 10 s for adenosine), a rapid imaging sequence (immediately after completion of infusion), maximal coronary hyperemia and a short acquisition protocol (7.8 min). This technique should be an acceptable alternative to exercise thallium-201 imaging.

Comparison of adenosine and exercise thallium-201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging

Pharmacologic stress with dipyridamole has provided useful diagnostic, as well as prognostic, information in patients undergoing thallium-201 myocardial perfusion imaging. With its ultrashort half-life and a potent and consistent vasodilator effect, adenosine may be the coronary vasodilator of choice with myocardial perfusion imaging.Fifty-one healthy subjects and 93 patients with suspected coronary artery disease constituted the study group. In this multicenter study the comparative safety and diagnostic efficacy of single-photon emission computed tomography (SPECT) thallium imaging during adenosine-induced coronary hyperemia was compared with exercise treadmill stress. There was a mean increase in heart rate of 37% and a mean decrease in diastolic blood pressure of 5% during the adenosine infusion of 140 μg/kg per min for 6 min. Adenosine infusion was well tolerated in 95% of the subjects. Side effects requiring intervention occurred in seven subjects (5%). None of the subjects experienced a life-threatening complication.The sensitivity, specificity and predictive accuracy for detection of coronary artery disease with use of quantitative analysis was 83%, 87% and 84% for adenosine SPECT and 82%, 80% and 81% for exercise SPECT studies, respectively. Most false negative results with adenosine, as well as exercise SPECT studies, occurred in patients with single-vessel disease. The first-order concordance (no defect vs. defect) and second-order concordance (no defect vs. irreversible vs. reversible defect) was 89% and 78% between the two studies, respectively.Thus, the results of adenosine SPECT imaging are highly concordant with exercise SPECT thallium imaging. Adenosine SPECT thallium imaging provides a safe and highly accurate imaging mode for the detection of coronary artery disease.

Nuclear cardiac imaging.

Important developments in the field of nuclear cardiac imaging include increasing use of single-photon emission computed tomography; the availability of pharmacologic stress testing; the introduction of newer technetium-labeled perfusion imaging agents; and a number of other newer imaging agents and imaging techniques. Tomographic imaging improves image quality as well as sensitivity. This improvement is probably more noticeable with pharmacologic stress testing and with the newer technetium agents. A number of pharmacologic stress agents are now being used. These include dipyridamole, adenosine, and dobutamine. In our experience, thallium tomographic imaging during adenosine-induced coronary hyperemia has resulted in a high degree of accuracy in the diagnosis of coronary artery disease. Both 99mTc-sestaMIBI (hexakis-2-methoxyisobutyl-isonitrile) and 99mTc-teboroxime may be used for simultaneous assessment of perfusion and function. These agents, although similar to thallium in many aspects, differ in many other aspects as they differ from each other. For example, sestaMIBI has a long retention time, but teboroxime has a very rapid washout time. Therefore, the imaging protocols using these two agents are considerably different. Assessment of myocardial viability has been an area of interest; specifically, the use of the reinjection technique has improved the ability to differentiate between scar tissue and viable myocardium.

Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia

Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p s0̌.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects.

Single photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia: Correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography

The feasibility, safety and diagnostic accuracy of single photon emission computed tomography (SPECT) with thallium-201 imaging during adenosine-induced coronary hyperemia were evaluated in 53 patients with and 7 without coronary artery disease proved by coronary angiography. Adenosine was infused intravenously at a dose of 0.14 mg/kg body weight per min for 6 min and thallium was injected at 3 min. Adenosine caused an increase in heart rate (68 ± 12 at baseline versus 87 ± 18 beats/mm at peak effect, p < 0.0001) but no change in blood pressure. The sensitivity and specificity were 92% (95% confidence intervals 81% to 98%) and 100% (95% confidence intervals 59% to 100%), respectively; 20 (61%) of 33 patients with multivessel coronary artery disease were also correctly identified.In 30 patients, the predictive accuracy of adenosine thallium imaging was slightly higher than that exercise SPECT thallium imaging (90% versus 80%, p = NS) (95% confidence intervals 72% to 97% and 61% to 92%, respectively). In 25 patients, two-dimensional echocardiography during adenosine infusion disclosed a new wall motion abnormality in 2 (10%) of 20 patients with coronary artery disease; 80% of these patients had reversible thallium defects (p < 0.001). Side effects were mild and transient; aminophylline was used in only three patients.Thus, adenosine SPECT thallium imaging provides a high degree of accuracy in the diagnosis of coronary artery disease. The results are comparable with those of exercise SPECT thallium imaging. Most reversible defects in the adenosine study are not associated with any transient wall motion abnormality.

Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia

This study examined the implications of left ventricular (LV) dilatation and increased pulmonary thallium uptake during adenosine-induced coronary hyperemia. The lung-to-heart thallium ratio in the initial images was significantly higher in patients with coronary artery disease (CAD) than normal subjects; 0.48 ± 0.16 in 3-vessel disease (n = 16), 0.43 ± 0.10 in 2-vessel disease (n = 20), 0.43 ± 0.08 in 1-vessel disease (n = 16) and 0.36 ± 0.05 in normal subjects (n = 7) (p < 0.001, 0.09 and 0.06, respectively). There was a significant correlation between the severity and the extent of the perfusion abnormality (determined from the polar maps) and the lung-to-heart thallium ratio (r = 0.51 and 0.52, respectively, p < 0.0002). There was also a significant correlation between lung thallium washout and lung-to-heart thallium ratio (r = 0.42, p = 0.0009) and peak heart rate (r = -0.49, p < 0.0001). The LV dilatation was mostly due to an increase in cavity dimension (30% increase) and to a lesser extent (6% increase) due to increase in LV size. (The cavity dimensions were measured from the short-axis slices at the midventricular level in the initial and delayed images.) The dilation was seen in patients with CAD but not in the normal subjects. These changes correlated with the extent and severity of the thallium perfusion abnormality. Thus, adenosine-induced coronary hyperemia may cause LV dilation and increased lung thallium uptake on the basis of subendocardial ischemia.