Jaekyeong Heo

Safety profile of adenosine stress perfusion imaging: Results from the adenoscan multicenter trial registry

OBJECTIVES The purpose of this study was to determine the safety of adenosine infusion at 140 micrograms/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 radionuclide perfusion imaging, it has proven efficacy for the diagnosis of coronary artery disease in patients unable to exercise. Because the ultrashort half-life (< 10s) allows dose titration and rapid reversal of side effects, it may be safer than other available pharmacologic agents. METHODS Patients were prospectively entered at 21 clinical sites. Information on safety and adverse events during and immediately after adenosine infusion was maintained in the Adenoscan Multicenter Trial Registry. RESULTS The infusion protocol was completed in 80% of patients, required dose reduction in 13% and was terminated early in 7%. Interpretable imaging studies were obtained in 98.7% of patients, and 0.8% of patients received aminophylline. Minor and well tolerated side effects were reported in 81.1% of patients. There were no deaths, one myocardial infarction, seven episodes of severe bronchospasm and one episode of pulmonary edema. Transient atrioventricular (AV) node block occurred in 706 patients (first-degree in 256, second-degree in 378 and third-degree in 72) and resolved spontaneously in most patients (n = 508) without alteration in the adenosine infusion. There were no sustained episodes of AV block. Patients > 70 years of age had an increased risk of developing AV block (age < 70, 7.05% vs. > or = 70, 9.44%, p = 0.001, relative risk 1.37). CONCLUSIONS Adenosine infusion is safe. Vasodilator and negative dromotropic side effects are generally well tolerated. Serious side effects are relatively rare, and they reverse with termination of adenosine infusion. Interpretable radionuclide studies were obtained in 98.7% of patients and aminophylline reversal was seldom required.

Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease

OBJECTIVES The objective of this study was to examine the independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in patients with angiographically defined coronary artery disease. BACKGROUND Previous studies showed the importance of exercise thallium-201 in risk stratification. However, most of these studies used planar imaging techniques. METHODS Follow-up data were obtained in 316 medically treated patients with coronary artery disease. Cox proportional hazards regression models were used to examine the independent and incremental prognostic values of clinical, exercise, thallium and cardiac catheterization data. RESULTS There were 35 events (cardiac death or nonfatal myocardial infarction) at a mean follow-up time of 28 months. Univariate analysis showed that gender (chi-square = 5.1), exercise work load (chi-square = 3.1), extent of coronary artery disease and left ventricular ejection fraction (chi-square = 14.8) and thallium variables (chi-square = 22.7) were prognostically important. The thallium data provided incremental prognostic value to catheterization data (chi-square = 33.7, p < 0.01). The extent of the perfusion abnormality was the single best predictor of prognosis (chi-square = 14). Patients with a large perfusion abnormality had a worse prognosis than that of patients with a mild or no abnormality (Mantel-Cox statistics = 10.6, p < 0.001). CONCLUSIONS In medically treated patients with coronary artery disease, exercise SPECT thallium imaging provides independent and incremental prognostic information even when catheterization data are available. The extent of the perfusion abnormality is the single most important prognostic predictor.

Effect of exercise level on the ability of thallium-201 tomographic imaging in detecting coronary artery disease: Analysis of 461 patients

This study examined the effect of the level of exercise on the ability of thallium-201 imaging with single photon emission computed tomography (SPECT) to detect coronary artery disease. Patients in group 1 (n = 164) achieved adequate exercise end points, defined as positive exercise electrocardiograms or greater than or equal to 85% of maximal predicted heart rate. Patients in group 2 (n = 108) had submaximal exercise. The SPECT thallium-201 images showed perfusion defects in 74%, 88%, and 98%, respectively, of patients with one, two and three vessel coronary artery disease in group 1, compared with 52%, 84% and 79%, respectively, of such patients in group 2 (p less than 0.05). Perfusion defects showed partial or complete redistribution consistent with ischemia in 56%, 80% and 88%, respectively, of patients with one, two and three vessel coronary artery disease in group 1 compared with 35%, 58% and 56%, respectively, of such patients in group 2 (p = 0.08, less than 0.03 and less than 0.001, respectively). Of 58 patients with normal coronary angiograms or less than 50% diameter stenosis, 36 (62%) had normal SPECT images. In a separate group of 131 patients with less than 5% pretest probability of coronary artery disease, the specificity was 93%. The sensitivity of exercise SPECT imaging in group 1 was higher than that of ST segment depression (p less than 0.001). Thus, the level of exercise affects the results of SPECT thallium imaging in the localization and evaluation of the extent of coronary artery disease and the detection of ischemia.

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/min at peak effect, p less than 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 of 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 less than 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.

Use of technetium-99m isonitrile (RP-30A) in assessing left ventricular perfusion and function at rest and during exercise in coronary artery disease, and comparison with coronary arteriography and exercise thallium-201 SPECT imaging

This study compared the results of stress and rest single-photon emission computed tomography imaging of myocardial perfusion using technetium-99m isonitrile (RP-30A) with the results of stress and redistribution tomographic thallium imaging and the results of coronary arteriography in 39 patients, 11 without and 28 with coronary artery disease (CAD). Each patient underwent 2 exercise studies at identical workload, heart rate and double product. In a subset of 13 patients, concomitant evaluation of left ventricular (LV) function using first-pass radionuclide angiography with a multi-crystal camera also was performed with bolus injections of isonitrile. Isonitrile had similar sensitivity (82 vs 82%, difference not significant), a slightly--but not significantly--higher specificity (100 vs 82%) and similar predictive accuracy (87 vs 82%) to thallium-201. The tracer uptake was assessed in 20 segments/study. There was concordance between the isonitrile and thallium-201 images in 723 of the 780 segments (93%) (kappa = 0.83 +/- 0.02). In general, the isonitrile images were considered of better quality than the thallium-201 images. All 10 patients with CAD who underwent concomitant first-pass radionuclide angiography had either perfusion abnormalities or an abnormal ejection fraction response to exercise. Thus, technetium-99m isonitrile provides a reliable method of assessment of CAD with a sensitivity, specificity and predictive accuracy comparable to that of exercise thallium-201 imaging. Additional advantages include better image quality and the ability to obtain concomitant assessment of LV function with the use of first-pass radionuclide angiography.

Pharmacologic stress testing: Mechanism of action, hemodynamic responses, and results in detection of coronary artery disease

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.

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 less than 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 less than 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 less than 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.

Prognostic value of rest-redistribution tomographic thallium-201 imaging in ischemic cardiomyopathy

The relation between the presence of viable myocardium by rest-redistribution thallium imaging and prognosis is not well defined. This study examined the prognostic value of rest-redistribution single-photon emission computed tomographic imaging with thallium-201 in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Patients were divided into 2 groups: group 1 patients (n = 47) were treated medically and group 2 patients (n = 38) underwent coronary revascularization. The 2 groups were comparable in the extent of CAD and in LV ejection fraction. Thallium images showed normal tracer uptake in 1 group 1 and 3 group 2 patients, fixed defects in 26 group 1 and 18 group 2 patients, and both reversible and fixed defects in 20 group 1 and 17 group 2 patients (p = NS). Based on analysis of 20 segments/patient, reversible defects were seen in 4 +/- 4 segments/patient in group 1 and 5 +/- 5 segments/patient in group 2 (p = NS). Viable myocardium (defined as normal tracer uptake, reversible defects, or mild fixed defects) was seen in 14 +/- 4 segments/patient in group 1 and 15 +/- 5 segments/patient in group 2 (p = NS). During a mean follow-up of 31 months, there were 16 group 1 (34%) and 6 group 2 (16%) deaths. The annual mortality rate was 13% in group 1 and 6% in group 2. Actuarial survival analysis showed better survival in group 2 than in group 1 (p = 0.056). Thus, viable myocardium in patients with CAD and LV dysfunction is associated with poor prognosis with medical therapy. Coronary revascularization improves prognosis.

Prognostic value of myocardial perfusion imaging in predicting outcome after renal transplantation.

Cardiovascular disease is a significant cause of morbidity and mortality after renal transplantation. Pretransplant screening in a subset of these patients for occult coronary artery disease (CAD) may improve outcome. The objective of this study was to examine the outcome of 600 patients after renal transplantation for end-stage renal disease. Prospective outcome data were collected on 600 consecutive patients who had renal transplantation between 1996 and 1998 at our institution at 42 +/- 12 months after surgery. Stress single-photon emission computed tomographic (SPECT) myocardial perfusion imaging was performed in 174 patients before surgery, 136 (78%) of whom had diabetes mellitus. There were a total of 59 events: 17 cardiac deaths, 14 nonfatal myocardial infarctions, and 28 noncardiac deaths. There were 12 cardiac events and 11 noncardiac deaths among those who had SPECT myocardial perfusion imaging. In a multivariate analysis that included important risk factors, age (p = 0.03 and 0.003, respectively) and diabetes (p = 0.02 and 0.005, respectively) were the predictors of total events and cardiac events in patients who did not undergo stress SPECT perfusion imaging. In the subgroup who had stress perfusion imaging, an abnormal perfusion SPECT study was the only predictor of cardiac events (p = 0.006). The 42-month cardiac event-free survival rate was 97% in patients with normal SPECT images and 85% in patients with abnormal SPECT images (RR 5.04, 95% confidence interval 1.4 to 17.6, p = 0.006). Thus, there is a 2.8% event rate per year after renal transplantation, and approximately 50% of these events are noncardiac. In high-risk patients (most of whom had diabetes) with preoperative stress perfusion imaging, those with normal images had significantly lower cardiac events than those with abnormal images. These results have important implications in patient screening and postoperative management.

Identification of extensive coronary artery disease in women by exercise single-photon emission computed tomographic (SPECT) thallium imaging

OBJECTIVES The aim of this study was to examine the ability of exercise single-photon emission computed tomographic (SPECT) thallium imaging to identify high risk women with left main or three-vessel coronary artery disease using a stepwise discriminant analysis. BACKGROUND Previous studies have used statistical methods to identify high risk men with coronary artery disease. Only limited data are available in women. METHODS Exercise SPECT thallium imaging and coronary arteriography were performed for evaluation of chest pain in 243 women. Group 1 comprised 58 women with left main or three-vessel coronary disease and group 2 comprised 185 women with no or one- or two-vessel disease. Stepwise discriminant analysis was used to determine predictors of left main or three-vessel disease. RESULTS On univariate analysis, women in group 1 were older (p < 0.03) and had a lower exercise work load (p < 0.02), lower exercise heart rate (p < 0.004), higher prevalence rate of diabetes mellitus (p < 0.0003) and more multivessel thallium abnormality (p < 0.0001) compared with women in group 2. On multivariate analysis, only multivessel thallium abnormality (F = 43) and exercise heart rate (F = 6) were independent predictors of left main or three-vessel coronary disease. A model based on these two variables separated the women into three risk groups: 99 patients with 9%, 70 patients with 23% and 74 patients with 45% prevalence of left main or three-vessel disease (p < 0.0001). CONCLUSIONS High risk women with left main or three-vessel coronary disease can be identified by exercise SPECT thallium imaging.