Adenosine SPECT Research Articles

Abstract 16903: Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging vs. Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging for Predicting Major Adverse Cardiovascular Events - The CORE320 Multicenter Study

Background: Noninvasive risk stratification in patients with suspected coronary artery disease (CAD) is critical for implementing appropriate strategies to prevent major adverse events (MACE). We aim to compare the survival and accuracy of combined CT angiography (CTA) and CT myocardial stress perfusion imaging (CTP) with combined invasive coronary angiography (ICA) and stress SPECT myocardial perfusion imaging for predicting MACE in patients with suspected CAD. Methods: The CORE320 prospective multicenter study enrolled 381 patients, between 45-85 years of age, who were clinically referred for ICA. Overall, 379 participants had all imaging including coronary CTA, adenosine stress CTP, SPECT and ICA plus complete 2 year follow-up data. An independent panel adjudicated all adverse events. MACE was defined as late revascularization (beyond 30 days of index ICA), myocardial infarction, cardiac death, hospitalization for chest pain or congestive heart failure, and arrhythmia. Kaplan-Meier survival analysis was performed and area under the receiving operating characteristic curve (AUC) was used to determine test accuracy. Results: MACE (45 late revascularizations, 5 myocardial infarctions, 1 cardiac death, 8 hospitalizations for chest pain or congestive heart failure, and 1 arrhythmia) occurred in 51 of 379 patients. The 2 year MACE event free rate for combined CTA/CTP findings was 95% (-) vs. 82% (+) (Figure, p<0.001) and similar to combined ICA/SPECT (p<0.001). Event rates for CTA/CTP vs. ICA/SPECT for either positive or negative results were not significantly different (p=0.126 and p=0.284, respectively). The overall AUC of combined CTA and CTP vs. combined ICA and SPECT for identifying MACE at 2 years was also similar: 68 (95%CI: 62-75) vs. 71 (95%CI: 65-79), respectively, p=0.357. Conclusion: Combined CTA and CTP yields similar prediction of 2 year MACE (especially revascularization) and diagnostic accuracy compared to standard ICA and SPECT.

High Concordance Between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates.

Mental stress can trigger myocardial ischemia, but the prevalence of mental stress-induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress-induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Thirty-four coronary artery disease patients (mean age±SD, 62±10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179±65 mL at rest and increased to 217±71 after mental stress and 229±86 after adenosine (P<0.01 for both). Resting end systolic volume was 129±60 mL at rest and increased to 158±66 after mental stress (P<0.05) and 171±87 after adenosine (P<0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30±12 at baseline, 29±11 with mental stress, and 28±10 with adenosine (P=not significant). There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both conditions. Psychosocial stressors during daily life may contribute to the ischemic burden of CHF patients with coronary artery disease.

Regadenoson provides perfusion results comparable to adenosine in heterogeneous patient populations: A quantitative analysis from the ADVANCE MPI trials

BackgroundTotal and reversible left ventricular (LV) perfusion defect size (PDS) predict patient outcome. Limited data exist as to whether regadenoson induces similar perfusion abnormalities as observed with adenosine. We sought to determine whether regadenoson induces a similar LV PDS as seen with adenosine across varying patient populations. Methods and ResultsADVANCE MPI were prospective, double-blind randomized trials comparing regadenoson to standard adenosine myocardial perfusion tomography (SPECT). Following an initial adenosine SPECT, patients were randomized to either regadenoson (N = 1284) or a second adenosine study (N = 660). SPECT quantification was performed blinded to randomization and image sequence. Propensity analysis was used to define comparability of regadenoson and adenosine perfusion results. Baseline clinical and SPECT results were similar in the two randomized groups. There was a close correlation between adenosine and regadenoson-induced total (r2 = 0.98, P < .001) and reversible (r2 = 0.92, P < .001) PDS. Serial differences in total (0.00 ± 3.51 vs −0.11 ± 3.46, P = .51) and reversible (0.15 ± 3.79 vs 0.07 ± 3.33, P = .65) PDS were also comparable in patients randomized to regadenoson vs adenosine, respectively, and irrespective of age, gender, diabetic status, body mass index, or prior cardiovascular history. By propensity analysis, regadenoson-induced total PDS was significantly larger than observed with adenosine. ConclusionThis is the first study to show that regadenoson induces similar, if not larger, perfusion defects than those observed with adenosine across different patient populations and demonstrates the value of quantitative analysis for defining serial changes in SPECT perfusion results. Regadenoson should provide comparable diagnostic and prognostic SPECT information to that obtained with adenosine.

Hemodynamic response, arrhythmic risk, and overall safety of Regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic obstructive pulmonary disease and bronchial asthma patients

Regadenoson (REG) is a A2a receptor selective pharmacologic SPECT imaging agent. Its safety in unselected chronic obstructive pulmonary disease (COPD) or asthma (AM) undergoing SPECT imaging has not been well evaluated. We retrospectively identified 228 patients (COPD n = 126 and AM n = 102, Grp 1) undergoing REG SPECT from Jan to Nov 2009 and compared to 1,142 patients without COPD and AM (control, Grp 2). A standard 400 μg REG bolus was used and gated Tc-99 m tetrofosmin SPECT done. Patient demographics, REG SPECT data, side effects, arrhythmia occurrences, and any exacerbation of COPD or AM leading to treatment, hospitalization or death were evaluated. The side effect profile of Grp 1 was also compared to a historical cohort who underwent intravenous dipyridamole thallium-201 imaging and adenosine SPECT. Both groups were comparable with regards to baseline characteristics. There was 0% incidence of clinical exacerbation of COPD or AM after REG. COPD patients had more non-significant arrhythmias (58.3% vs. Grp 2, 43%, P = 0.004). There was 0% incidence of any atrio-ventricular block and only 2 instances of brief supraventricular tachycardia. When compared to the historical cohort of COPD who underwent IV dipyridamole thallium imaging, COPD in Grp 1, had more dyspnea and flushing and when compared to COPD/AM patients who underwent adenosine SPECT, Grp 1 pts had more of flushing and headache (24.9% vs. 2.8%, P = <0.001) but less of bronchospasm (1.3% vs. 6.9%, P = 0.022) and AV block (0% vs. 4.2%, P = 0.014). REG SPECT can be safely performed in COPD and AM population.

Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy

Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is unclear. We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients [35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12]. Follow-up was performed at 12-18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ(2)= 3932, P < 0.001; interaction P < 0.021). Further modelling revealed that after excluding patients with scar >10% total myocardium, %I identified a survival benefit in all patients. In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.

Safety of adenosine pharmacologic stress myocardial perfusion imaging in orthotopic cardiac transplant recipients: a single center experience of 102 transplant patients

Denervation super-sensitivity to adenosine is well described in cardiac transplant (CT) patients particularly early after transplant. The safety and hemodynamic effects of adenosine SPECT (A-SPECT) has not been described in a large series of CT patients. Single center retrospective study of 102 CT patients undergoing A-SPECT were compared to an age-gender matched patients in a 2:1 fashion who underwent A-SPECT in the same time period. Multivariate logistic regression model were used to identify independent predictors of advanced AV block. The average time from CT to A-SPECT was 8.5±4.5years. Average age was 57years with 80% males. In comparison to the control group, adenosine infusion was associated with a higher incidence of sinus pause (4.9% vs. 0%), 2nd (11.8% vs. 4.9%) and 3rd degree AVB (2.9% vs. 0%) in CT patients (all P<0.05). Prior use of aspirin and baseline 1st degree AVB were significant independent predictors of adenosine induced AVB. Baseline right or left bundle branch block, beta-blockers, calcium blockers or digoxin were not associated with occurrence of AVB. Only 1.9% of A-SPECT studies were terminated due to bradyarrythmia with 1 patient requiring aminophylline. There were no significant immediate or long term adverse events in these patients. Adenosine pharmacologic stress is associated with a higher incidence of AVB and sinus pause in CT patients reflecting persistence of super sensitivity late after CT. Nevertheless these bradyarrythmias are transient without any sequelae suggesting that A-SPECT can be performed safely in CT patients.

Comparison of dobutamine stress echocardiography, dobutamine SPECT, and adenosine SPECT myocardial perfusion imaging in patients with end-stage renal disease

ObjectivesWe sought to assess and compare the diagnostic accuracy and prognostic value of dobutamine stress echocardiography (DSE), dobutamine SPECT, and adenosine SPECT myocardial perfusion imaging (MPI) in patients with end-stage renal disease (ESRD). BackgroundThe optimal stress imaging modality for patients with ESRD has not yet been determined. MethodsForty-nine patients with ESRD underwent DSE, dobutamine SPECT MPI, and adenosine SPECT MPI. The primary endpoint of the trial was concordance between stress tests with respect to the presence or absence of ischemia. ResultsAgreement on the presence or absence of ischemia between adenosine SPECT MPI and DSE was 69% (kappa = .25, P = NS). Agreement on the presence or absence of ischemia between adenosine and dobutamine SPECT MPI was 77% (kappa = .37, P = <.009). Summed stress scores for adenosine and dobutamine SPECT MPI studies were highly correlated (r = .9, P = <.0001). DSE and SPECT MPI results provided incremental prognostic information when added to clinical variables. ConclusionsThere is moderate concordance between DSE and adenosine SPECT MPI in ESRD patients referred for stress testing. Interobserver agreement was higher for SPECT MPI compared to DSE. Based on these observations, the optimal approach for diagnosing severe coronary artery disease and assessing risk in patients with ESRD has yet to be determined, but appears to warrant further investigation.

Abstract 6131: Regadenoson Induces Perfusion Defects of Comparable Extent and Severity as Adenosine: A Quantitative Analysis from the ADVANCE 2 Trial

The quantified total and ischemic left ventricular (LV) perfusion defect size (PDS) is an important determinant of subsequent patient outcome. Therefore it is important to determine whether a new stressor agent induces similar perfusion abnormalities as a standard stressor agent such as adenosine. The ADVANCE 2 was a double-blind randomized trial comparing image results in patients undergoing standard adenosine (Ad) SPECT who were then randomized to either a second Ad SPECT (N=260) or SPECT following pharmacologic stress with Regadenoson (Reg) (N=493). All raw data of gated SPECT images (2 sets/patient) were reconstructed and reoriented in a standard fashion. Quantitative SPECT was performed using a previously validated automated program which determined the extent and severity of left ventricular (LV) perfusion defect size (PDS) and the extent of scintigraphic ischemia. PDS severity was defined as mild, moderate or severe based on the relation to normal pixel count activity (&gt;50%, 26–50%, and 0–25%, respectively). Quantification was performed blinded to randomization and image sequence. Baseline perfusion results were similar (p&gt;.05) between patients randomized to Ad vs Reg with respect to total (10.2±14.8 vs 11.5±15.8), ischemic (4.2±7.8 vs 4.6±8.9) and scar (6.0±10.7 vs 6.9±11.3) LV PDS. Results are summarized in the table below. Linear regression analysis showed a close correlation between Ad vs Reg for total (r=0.97, p&lt;.0001) and ischemic (0.94, p&lt;.0001) LV PDS. In this large database, quantitative SPECT analysis demonstrates that Regadenoson induces a comparable extent and severity of perfusion abnormality as induced with standard adenosine stress. This implies that similar prognostic information should be obtainable with Regadenoson stress as observed with adenosine.

Abstract 5754: Cardiac CT Angiography vs. SPECT Perfusion Imaging for the Evaluation of Patients with Acute Chest Pain

BACKGROUND: Over 5 million individuals present to EDs with acute chest pain each year, many of which are hospitalized for serial EKGs and cardiac enzymes followed by stress SPECT imaging. A potential alternative to SPECT is cardiac CT, which provides for the immediate and direct evaluation of coronary artery patency. We sought to determine the concordance between these modalities and the ability of CT to exclude ischemia in patients presenting with acute chest pain. METHODS: We enrolled 368 subjects without a history of hemodynamically significant CAD who presented to the ED with acute chest pain yet had negative initial EKGs and cardiac enzymes. All subjects underwent 64-slice cardiac CTA, the results of which were blinded to caregivers, then were admitted for standard care including diagnostic testing, as deemed clinically warranted by the caregivers. CTA exams were scored as being diagnostically positive or negative for significant stenosis (&gt;50% luminal narrowing) or as non-diagnostic. SPECT exams were scored as diagnostically pos or neg for ischemia or scar or as non-diagnostic (e.g., secondary to submaximal workload or artifact). RESULTS: 151 of the 368 subjects (54±11 yrs, 56% men) had an exercise (n=109), adenosine (n=41), or dobutamine (n=1) SPECT exam as part of their clinical care. 115 (76%) of the SPECT exams were read as diagnostic (7 pos for ischemia, 2 pos for scar, and 106 neg), while 36 (24%) were non-diagnostic. In contrast, 135 of the 151 (89%) of the CT exams were read as diagnostic (17 pos, 118 neg), while only 16 (11%) were non-diagnostic (p &lt;0.001). Among the 105 patients that had both diagnostic CT and SPECT exams, there was agreement between the modalities in 97/105 (92%) of patients. With SPECT defined as the standard for detecting ischemia, absence of significant stenosis on a diagnostic CT had a 98% NPV for excluding ischemia. CONCLUSION: Cardiac CT appears to be as feasible as SPECT imaging in patients with acute chest pain but inconclusive initial ED evaluation and may have a lower rate of non-diagnostic exams. Consistent with the known high NPV of CCT, absence of significant stenosis on cardiac CT predicted the absence of SPECT based ischemia in 98% of subjects. Thus, cardiac CT may be sufficient to exclude ischemia in patients with acute chest pain.

Incremental prognostic power of adenosine SPECT myocardial perfusion imaging in high risk patients for coronary artery disease: A comparison with cardiac catheterization data

Incremental prognostic power of adenosine SPECT myocardial perfusion imaging in high risk patients for coronary artery disease: A comparison with cardiac catheterization data

Adenosine sestamibi SPECT post-infarction evaluation (INSPIRE) trial: A randomized, prospective multicenter trial evaluating the role of adenosine Tc-99m sestamibi SPECT for assessing risk and therapeutic outcomes in survivors of acute myocardial infarction

Background Preliminary studies indicate that adenosine myocardial perfusion single photon tomography (SPECT) can safely and accurately stratify patients into low and high risk groups early after acute myocardial infarction (AMI). Methods and results INSPIRE is a prospective, randomized multicenter trial which enrolled 728 clinically stable survivors of AMI. Following baseline adenosine sestamibi gated SPECT, patients were classified as low, intermediate or high risk based on the quantified total and ischemic left ventricular (LV) perfusion defect size (PDS). A subset of high risk patients with a LV ejection fraction ≥35% were randomized to a strategy of either intensive medical therapy or coronary revascularization. Adenosine SPECT was repeated at 6-8 weeks to determine the relative effects of anti-ischemic therapies on total and ischemic PDS (primary endpoint). All patients were followed for one year. The baseline demographic, clinical and scintigraphic characteristics of the study population are presented. Adenosine SPECT was performed within 1 day of admission in 12% of patients and in 64% by Day 4. Conclusion The unique study design features of INSPIRE will further clarify the role of adenosine sestamibi SPECT in defining initial patient risk after AMI and in monitoring the benefits of intensive anti-ischemic therapies.

Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease.

In the past decade, significant advances have been made in the ability to image the heart with radionuclide tracers under stress and resting conditions in patients with suspected or known coronary artery disease (CAD) for the detection of ischemia, determination of prognosis, assessment of myocardial viability, preoperative risk assessment for patients undergoing noncardiac surgery, and evaluation of the efficacy of revascularization in patients undergoing coronary artery bypass surgery or an interventional procedure.1 For many years, planar imaging and SPECT with 201Tl constituted the only scintigraphic techniques available for detecting CAD and assessing prognosis in patients undergoing stress perfusion imaging. The major limitation of 201Tl scintigraphy is the high false-positive rate observed in many laboratories, which is attributed predominantly to image attenuation artifacts and variants of normal that are interpreted as defects consequent to a significant coronary artery stenosis. Although quantification of 201Tl images improves specificity, the false-positive rate remains problematic, particularly in women and in obese patients. Breast attenuation artifacts in women are sometimes difficult to distinguish from perfusion abnormalities secondary to inducible ischemia or myocardial scar. In recent years, new 99mTc-labeled perfusion agents have been introduced into clinical practice to enhance the specificity of SPECT and to provide additional information regarding regional and global left ventricular systolic function via ECG gating of images. It was immediately apparent that the quality of images obtained with these new 99mTc-labeled radionuclides was superior to that of images obtained with 201Tl because of the more favorable physical characteristics of 99mTc imaging with a gamma camera. With 99mTc, doses of ≈10 to 20 times higher than those that are feasible with 201Tl can be administered, yielding images with higher count density. 99mTc demonstrates less scatter and attenuation than 201Tl, which is associated …

Direct comparison between adenosine and ATP TL-201 myocardial SPECT in the same subjects

Direct comparison between adenosine and ATP TL-201 myocardial SPECT in the same subjects

“Pacemaker stress” with SPECT, a comparable method to adenosine SPECT to detect coronary artery disease in permanent pacing

“Pacemaker stress” with SPECT, a comparable method to adenosine SPECT to detect coronary artery disease in permanent pacing

Adenosine SPECT to assess anti-ischemic drug therapy vs coronary revascularization following acute myocardial infarction: A prospective randomized trial

Adenosine SPECT to assess anti-ischemic drug therapy vs coronary revascularization following acute myocardial infarction: A prospective randomized trial

Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction.

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. 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%. 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.

Intravenous Adenosine (Adenoscan) Versus Exercise in the Noninvasive Assessment of Coronary Artery Disease by SPECT

Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.