Myocardial201Tl washout after combined dipyridamole submaximal exercise stress: Reference values from different patient groups

Dipyridamole stress is favorable in patients unable to exercise maximally for²⁰¹Tl myocardial scintigraphy. Aside from an analysis of uptake defects, proper washout analysis can be limited by heart rate variations when isolated dipyridamole stress is used. Heart rate standardized²⁰¹Tl washout kinetics after a combined dipyridamole and submaximal exercise stress protocol (CDSE), feasible in elderly patients as well as in patients with peripheral artery disease, were therefore studied to investigate the²⁰¹Tl washout after CDSE in differently defined patient groups: Group I comprised 19 patients with documented heart disease and angiographically excluded coronary artery disease (CAD); group II contained 17 patients with a very low likelihood of CAD determined by both normal exercise radionuclide ventriculography and normal²⁰¹Tl uptake. Group III comprised 56 patients with a 50% pretest likelihood of CAD but normal²⁰¹Tl uptake. Mean washout values were nearly identical in all groups. Despite similar uptake patterns, however, washout standardized by CDSE was significantly lower than the normal washout values after maximal treadmill exercise. Thus an obviously lower²⁰¹Tl washout after CDSE than after maximal treadmill exercise must be considered if washout analysis criteria after dipyridamole are applied to evaluate ischemic heart disease. Nevertheless, heart rate elevation achieved by additional submaximal exercise stress seems necessary, adequate and clinically safe for standardisation of washout analysis in dipyridamole²⁰¹Tl scintigraphy.     

Myocardial imaging with dipyridamole: Comparison of the sensitivity and specificity of 201Tl versus MUGA

Myocardial imaging was performed at rest and after dipyridamole infusion using ²⁰¹Tl and ⁹⁹Tc^m-gated blood pool studies (MUGA). Of 38 patients studied, 21 had coronary artery disease (CAD) and 17 were normal. With ²⁰¹Tl imaging, 19 of 21 patients with CAD (sensitivity 88%) showed perfusion defects during dipyridamole. Of 17 normals 6 (specificity 65%) showed clear perfusion defects during dipyridamole. With MUGA, 2 of 15 patients with CAD (sensitivity 13%) developed abnormal wall motion during dipyridamole; both patients developed ST depression >1 mm. Of 10 normals none developed abnormal wall motion. Twenty six of 38 patients developed angina during dipyridamole, which was reversed by aminophylline in 24 of 26. We suggest that dipyridamole infusion is effective for ²⁰¹Tl-perfusion imaging, and easily performed, but is not suitable for MUGA studies where ischaemia is the required end-point.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of 201Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as less than or equal to 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37% +/- 2.11%. The regional washout in the 70 degrees LAO view (46.65% +/- 1.10%) was significantly higher than in the anterior and 30 degrees LAO views (43.44% +/- 1.50% and 43.02% +/- 1.45%, respectively). Profiles of uptake and washout of 201Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201Tl derived from healthy volunteers who underwent the same combined protocol.     

Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging

BACKGROUND: Caffeine binds to the A2 receptors and inhibits adenosine's action of vasodilation or dipyridamole-induced vasodilation. Patients scheduled for (201)Tl myocardial perfusion using pharmacologic stress with dipyridamole or adenosine are advised to abstain from caffeine for 24 h before the test. This article reports on the residual serum caffeine levels of 36 patients after 24-h caffeine abstention and the clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. METHODS AND RESULTS: Heart rate, diastolic blood pressure, and systolic blood pressure were recorded before and after dipyridamole infusion. Sixty-six percent of the patients had detectable plasma caffeine but all values were within the range of 0.1-0.8 mg/L. No statistically significant change in diastolic and systolic blood pressures after dipyridamole infusion has been observed. The mean heart rate was increased by 18% after dipyridamole infusion in patients with zero caffeine, and the heart rate increase was inversely correlated with the serum caffeine levels (r = -0.22) with 81% confidence. CONCLUSION: A serum caffeine level of 2 mg/L is predicted to be the lower limit for false-negative dipyridamole (201)Tl myocardial perfusion. The increase of heart rate after dipyridamole infusion could be the simple indicator for the serum caffeine level. Rescheduling of the patient study or further adenosine challenge is necessary only if the heart rate increase is <5% after dipyridamole or adenosine infusion.     

Inadequate exercise leads to suboptimal imaging. Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level exercise unmasks ischemia in symptomatic patients with non-diagnostic thallium-201 scans who exercise submaximally

This study was undertaken to establish the additional value of 201TI imaging after dipyridamole in combination with low-level exercise in 15 symptomatic patients with non-diagnostic 201TI scans, who exercised submaximally. Most patients had angina, ST-segment depression and even exertional hypotension and were referred for stress 201TI testing for determining the functional significance of known coronary artery disease. Six patients with a normal exercise 201TI test and one patient with an apical defect only were found to have 37 segments (of 105 segments) with reversible perfusion defects after dipyridamole infusion. One patient showing two reversible defects after exercise had five reversible segments after dipyridamole. Seven patients with fixed defects in 28 segments after exercise and two with small areas of border zone ischemia in seven additional (sub)segments, demonstrated fixed in defects in only nine segments but reversible defects in 40 segments after dipyridamole. Quantitative analysis resulted in 24.8 +/- 28.5 (mean value) sample points below -2 s.d. of the mean normal uptake after exercise, which increased to 72 +/- 26.5 after dipyridamole infusion (p less than 0.005). The washout analysis resulted in a mean value of 5.5 +/- 8.1 sample points below -2 s.d. after exercise, increasing to 33.3 +/- 22.1 after dipyridamole (p less than 0.005). Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level upright bicycle exercise may unmask scintigraphic evidence for ischemia in symptomatic patients who would otherwise have non-diagnostic imaging studies during submaximal exercise.     

Regadenoson in Europe: first-year experience of regadenoson stress combined with submaximal exercise in patients undergoing myocardial perfusion scintigraphy

Purpose

Regadenoson was approved for clinical use in Europe in 2011. Since then, it has become the default form of stress at our institution. We have assessed the side-effect profile and tolerability of regadenoson in patients undergoing clinically indicated myocardial perfusion scintigraphy between July 2011 and July 2012.

Methods

Clinical, stress and imaging data were recorded prospectively. Symptoms during stress were recorded and defined as mild, moderate or severe. An adverse event was defined as any symptom that persisted for more than 30 min or that required investigation or treatment.

Results

Of 1,764 consecutive patients, 1,581 (90 %) received regadenoson combined with submaximal exercise unless contraindicated. Symptoms were common (63 %) but transient and well-tolerated. The severity of symptoms was recorded in most patients as mild (84 %). Dyspnoea (36 %) and chest discomfort (12 %) were the commonest side effects. Adverse events were reported in eight patients (0.5 %), thought to be vasovagal in seven of these. All patients recovered fully without sequelae. There were no deaths, myocardial infarction or hospital admissions. Regadenoson stress was performed in 206 patients (12 %) with asthma or chronic obstructive pulmonary disease (COPD) without bronchospasm or any other major side effect.

Conclusion

We studied the symptom profile of regadenoson in the largest European cohort to date. Regadenoson combined with submaximal exercise was well tolerated, notably also in patients with asthma or COPD. The majority of regadenoson-related adverse events were vasovagal episodes without sequelae.     

Myocardial sestamibi single-photon emission tomography: Variations in reference values with gender, age and rest versus stress?

Reference data files support the evaluation of myocardial perfusion single-photon emission tomography (SPET). The aim of this study was to create a large reference data base for technetium-99m sestamibi SPET, age and gender matched to the general patient population. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a likelihood of coronary artery disease of less than 5% underwent rest and maximal exercise^99mTc-sestamibi SPET with a 2-day protocol and 180° elliptical rotation. The normalized activity values of^99mTc-sestamibi in the inferior wall differed significantly between men and women. Age variations were found for men in the anterior wall. Normalized activity values in all four walls were strikingly similar during rest and stress. Our results suggest that the use of reference files in^99mTc-sestamibi SPET requires a gender- and, for males, possibly an age-matched reference population. Different reference files at rest and during stress might not be necessary.     

Myocardial uptake and clearance of T1-201 in healthy subjects: comparison of adenosine-induced hyperemia and exercise stress

Pharmacologic stress testing with dipyridamole is useful in patients undergoing thallium-201 myocardial perfusion scintigraphy who cannot adequately exercise. Because dipyridamole increases coronary blood flow by reducing the metabolism of adenosine, the authors compared the uptake and clearance of T1-201 following exercise stress testing (EST) and resting intravenous infusion of adenosine (AI) in crossover fashion in 20 healthy men. No perfusion defects or areas of redistribution were noted in any of the scans. Mean absolute myocardial T1-201 uptake was 1.3 times greater with AI than with EST. Mean absolute extracardiac uptake was 2.0 times greater with AI. Mean T1-201 myocardial clearance was virtually the same in all AI and EST views. During AI, 70% of the subjects experienced subjective side effects, mean arterial blood pressure decreased by 15%, and heart rate increased by 48%. The effects of adenosine on T1-201 kinetics in the myocardium are similar to those of EST. Adenosine may be useful as a pharmacologic stress agent in patients undergoing T1-201 myocardial perfusion scintigraphy.     

Symptom-limited exercise combined with dipyridamole stress: Prognostic value in assessment of known or suspected coronary artery disease by use of gated SPECT imaging

Background  Combining vasodilator and exercise stress reduces noncardiac side effects, improves image quality, and enhances the detection of ischemia, compared with suboptimal exercise or vasodilator stress alone. However, prognostic data with combined protocols are limited. Methods and Results  Consecutive patients (n=2064) who underwent symptom-limited exercise and dipyridamole stress with gated single-photon emission computed tomography (SPECT) imaging, without early revascularization, were studied. Subsequent cardiac death or nonfatal myocardial infarction was related to exercise and gated SPECT variables. Cox proportional hazards regression modeling was performed to identify predictors of adverse outcome. Annualized event rates in patients with normal and abnormal images were 0.96% and 2.71%, respectively (P<.001). With abnormal imaging, annualized event rates were 0.86% and 3.13% in patients with average to high and fair or poor functional capacity, respectively (P=.019). Abnormal imaging, a severely reduced post-stress ejection fraction, transient ischemic dilation, and fair or poor functional capacity emerged as predictors of adverse outcome. Accordingly, patients were stratified into low-risk, intermediate-risk, and high-risk cohorts with annualized event rates of 0.94%, 2.24%, and 8.19%, respectively (P<.001 in any two-way comparison). Conclusions  A protocol that combines symptom-limited exercise and dipyridamole stress with gated SPECT imaging provides highly effective risk stratification for adverse outcomes. This study was supported in part by a grant from Bristol-Myers Squibb Medical Imaging, Billerica, Mass. Financial disclosure: G.V.H. receives grant support and is on the speaking board of Bristol-Myers Squibb Medical Imaging.     

Myocardial viability assessment in patients with highly impaired left ventricular function: comparison of delayed enhancement, dobutamine stress MRI, end-diastolic wall thickness, and TI201-SPECT with functional recovery after revascularization

This study compared different magnetic resonance imaging (MRI) methods with Tl²⁰¹ single photon emission computerized tomography (SPECT) and the gold standard for viability assessment, functional recovery after coronary artery bypass grafting (CABG). Twenty patients (64±7.3 years) with severely impaired left ventricular function (ejection fraction [EF] 28.6±8.7%) underwent MRI and SPECT before and 6 months after CABG. Wall-motion abnormalities were assessed by stress cine MRI using low-dose dobutamine. A segment with a nonreversible defect in Tl²⁰¹-SPECT and a delayed enhancement (DE) in an area >50% of the entire segment, as well as an end-diastolic wall thickness <6 mm, was defined as nonviable. The mean postoperative EF (n=20) improved slightly from 28.6±8.7% to 32.2±12.4% (not significant). Using the Tl²⁰¹-SPECT as the reference method, end-diastolic wall thickness, MRI-DE, and stress MRI showed high sensitivity of 94%, 93%, and 84%, respectively, but low specificities. Using the recovery of contractile function 6 months after CABG as the gold standard, MRI-DE showed an even higher sensitivity of 99%, end-diastolic wall thickness 96%, stress MRI 88%, and Tl²⁰¹-SPECT 86%. MRI-DE showed advantages compared with the widely used Tl²⁰¹-SPECT and all other MRI methods for predicting myocardial recovery after CABG.