Implementation of technetium-99m MIBI SPECT imaging guidelines: optimizing the two day stress-rest protocol

Objectives. In a previous study in 460 patients, we found that in patients with suspected or known coronary artery disease undergoing stress-rest technetium-99m sestamibi (MIBI) SPECT myocardial perfusion imaging, rest SPECT imaging could be withhold in approximately 20% of patients because of a completely normal stress study. The present study was set up to evaluate the consequences of the implementation of this finding in a subsequent population of patients, and to set standards for the variety of protocols now used for MIBI SPECT imaging. Methods. Within a period of 4 months, 235 consecutive patients referred for MIBI SPECT scintigraphy were studied. All patients had stable cardiac chest pain and underwent symptom-limited exercise MIBI SPECT perfusion imaging. The stress SPECT images were reconstructed and evaluated immediately after acquisition of the images. In case of a clearly normal stress SPECT study, rest imaging was cancelled. Results. Twenty-six of 235 patients (11%) had a completely normal stress MIBI SPECT study and the rest SPECT imaging procedure could be subsequently cancelled. In 20 patients (9%) the stress SPECT was inconclusive, and in 189 (80%) of patients stress imaging was clearly abnormal. In the first month of the study, the nuclear medicine physicians and cardiologists would interprete only 6% of the stress images as normal, while this number increased to 13% after 9 weeks, with a mean of 11% for the whole investigation period of 4 months. Conclusion. In patients undergoing stress MIBI SPECT imaging, it was found justified to cancel rest MIBI SPECT imaging in at least 11% of patients because of a completely normal stress SPECT. As 9% of the images were inconclusive, the number of normal stress images could theoretically increase to 20% if reliable measures are taken to improve reading accuracy. This number is in close agreement with the number of normal stress studies previously reported by our institution and would lead to a considerable reduction of radiation dose, costs, and increased convenience for an important subset of patients.     

Normal limits for left ventricular ejection fraction and volumes determined by gated single photon emission computed tomography--a comparison between two quantification methods

To compare gender-related normal limits for left ventricular (LV) ejection fraction (EF), end-diastolic and end-systolic volumes (EDV and ESV), obtained using two myocardial perfusion-gated single photon emission computed tomography (SPECT) quantification methods. A total of 185 patients were retrospectively selected from a consecutive series of patients examined for coronary artery disease (CAD) or for management of known CAD. Patients were included in the study group if they had normal or probably normal results with stress and rest perfusion imaging and if the combined interpretation of perfusion studies and gated rest studies showed no signs or suspicion of myocardial infarction. The gated SPECT studies were performed using a 2-day stress/gated rest Tc-99m sestamibi protocol. All patient studies were processed using CAFU and quantitative-gated SPECT (QGS), the two software packages for quantification of gated SPECT images. The lower normal limits for EF were higher for CAFU compared with QGS for both women (59% versus 53%) and men (54% versus 47%). The upper normal limits for EDV were also higher for CAFU compared with QGS for both women (133 versus 107 ml) and men (182 versus 161 ml). The differences between the software packages were small for ESV (women 44 versus 44 ml; men 69 versus 74 ml). Gender-specific normal limits need to be applied for LV EF and volumes determined by gated SPECT. Separate criteria for abnormal LV EF and EDV need to be used for women and men depending on the software package used.     

Should imaging at stress always be followed by imaging at rest in Tc-99m MIBI SPECT?

Objectives. We addressed the question whether in patients with cardiac chest pain referred for stress myocardial perfusion scintigraphy, Tc-99m MIBI SPECT stress imaging should always be followed by a rest imaging procedure. Background. Using Tc-99m MIBI imaging a stress-rest sequence is usually performed implying that the resting study always follows the stress study irrespective of the results of the stress study. As a normal stress study would eliminate a subsequent resting study, it appears desirable to potentially define certain subsets of patients in whom a normal stress study can be expected in order to determine a more selective referral approach to the nuclear medicine department. The consequences of such a more streamlined approach would less impose on the logistics of the department of nuclear medicine, with decrease of investigation time, radiation dose, and costs in a time of retrenchment in the medical sector. Methods. A consecutive series of 460 patients (mean age 58.2 years) was studied who were stratified to 269 patients without prior myocardial infarction, and to 191 patients with documented evidence of a previously sustained mycoardial infarction. All patients underwent Tc-99m MIBI SPECT imaging according to a two-day stress-rest protocol. Results. Patients with and without a previous myocardial infarction showed suboptimal overall predictive accuracies for the exercise electrocardiograms (58% and 60%, respectively). In the total group of 460 patients, 94 (20%) patients showed a normal stress-rest Tc-99m MIBI SPECT; this occurred in 86/269 (32%) patients without a previous myocardial infarction and in only 8/191 (4%) patients with a previous myocardial infarction. Conclusions. Patients with a stress defect at Tc-99m MIBI SPECT imaging should always undergo a resting SPECT study irrespective of the clinical and stress electrocardiographic findings. As patients without a previous myocardial infarction had a normal stress SPECT study in almost one-third (32%) of patients compared to only 4% in patients with a previous myocardial infarction, it may be useful to employ different referral and imaging strategies i.e. a stress-only versus a stress-rest procedure. To schedule referring patients differently according to the presence or absence of a previously sustained myocardial infarction may be cost-saving, less demanding for the nuclear medicine personnel, and patient-convenient. In addition, a stress-only imaging procedure reduces radiation exposure to the individual patient.     

Myocardial flow reserve derived by dynamic perfusion single-photon emission computed tomography reflects the severity of coronary atherosclerosis

A novel single-photon emission computed tomography (SPECT) camera was developed to evaluate dynamic myocardial perfusion flow. However, it is unclear whether myocardial flow reserve (MFR) derived by dynamic perfusion SPECT using the novel SPECT camera (D-SPECT) reflects the severity of coronary atherosclerosis. In the present study, we therefore examined the relationship between MFR using D-SPECT and severity of coronary lesions. The study population comprised 40 patients who underwent both a myocardial dynamic perfusion SPECT study and invasive coronary angiography. The severity of coronary atherosclerosis was evaluated using the Gensini score. All patients underwent a rest/stress SPECT imaging protocol using Tc-99m-sestamibi, and dynamic acquisition was performed. Stress and rest flow was evaluated, and the global and regional MFR was calculated. Global MFR showed a significant negative correlation with Gensini score (r?=???0.345, p?=?0.037). Multiple linear regression analysis showed that only global MFR was independently related to Gensini score (p?=?0.018). Regional MFR was significantly lower in regions with ?90% ≤ stenotic lesions compared with regions with <?90% stenotic lesions (p?=?0.009). Global MFR derived by dynamic perfusion SPECT using D-SPECT reflects the severity of coronary atherosclerosis. Further, regional MFR is modulated by severe coronary artery stenotic lesions.     

Effect of caffeine on myocardial perfusion imaging using single photon emission computed tomography during adenosine pharmacologic stress

Approximately 6 million cardiac stress tests are performed annually in the United States, of which 2.4 million are pharmacologic stress tests using agents such as adenosine. Adenosine induces differential coronary hyperemia in normal coronary arteries versus coronary arteries with atherosclerosis, allowing single photon emission computed tomography (SPECT) imaging to identify reduced coronary flow in segments subtended by diseased coronary arteries. The potential attenuation of pharmacologic effects of adenosine in the presence of caffeine is why patients are routinely instructed to abstain from caffeine for 12 to 24 hours prior to administration of an adenosine stress test. Failure to abstain from caffeine results in cancellation or delaying of cardiac stress testing, resulting in procedural delays and its impact on patient throughput. Recent studies have evaluated such interaction and suggested a lack of clinically significant effect of caffeine on adenosine-induced hyperemia during myocardial SPECT imaging. This article reviews the clinical pharmacology of caffeine, adenosine, and dipyridamole and effect of caffeine on myocardial stress testing using adenosine and dipyridamole in clinical cardiovascular medicine. The limited published data are conflicting, but some recent publications suggest that myocardial perfusion SPECT imaging using adenosine may not be clinically significantly altered by routine consumption of caffeine, such as a cup of coffee. Although prospective randomized studies would be required to obtain a definitive answer to this question, it appears on the basis of some of the studies reviewed in this article that caffeine consumption prior to myocardial perfusion imaging may not necessitate cancellation or rescheduling of adenosine stress testing.     

Real-time cine and myocardial perfusion with treadmill exercise stress cardiovascular magnetic resonance in patients referred for stress SPECT

Background

To date, stress cardiovascular magnetic resonance (CMR) has relied on pharmacologic agents, and therefore lacked the physiologic information available only with exercise stress.

Methods

43 patients age 25 to 81 years underwent a treadmill stress test incorporating both Tc99m SPECT and CMR. After rest Tc99m SPECT imaging, patients underwent resting cine CMR. Patients then underwent in-room exercise stress using a partially modified treadmill. 12-lead ECG monitoring was performed throughout. At peak stress, Tc99m was injected and patients rapidly returned to their prior position in the magnet for post-exercise cine and perfusion imaging. The patient table was pulled out of the magnet for recovery monitoring. The patient was sent back into the magnet for recovery cine and resting perfusion followed by delayed post-gadolinium imaging. Post-CMR, patients went to the adjacent SPECT lab to complete stress nuclear imaging. Each modality''s images were reviewed blinded to the other''s results.

Results

Patients completed on average 9.3 ± 2.4 min of the Bruce protocol. Stress cine CMR was completed in 68 ± 14 sec following termination of exercise, and stress perfusion CMR was completed in 88 ± 8 sec. Agreement between SPECT and CMR was moderate (κ = 0.58). Accuracy in eight patients who underwent coronary angiography was 7/8 for CMR and 5/8 for SPECT (p = 0.625). Follow-up at 6 months indicated freedom from cardiovascular events in 29/29 CMR-negative and 33/34 SPECT-negative patients.

Conclusions

Exercise stress CMR including wall motion and perfusion is feasible in patients with suspected ischemic heart disease. Larger clinical trials are warranted based on the promising results of this pilot study to allow comparative effectiveness studies of this stress imaging system vs. other stress imaging modalities.     

Comparison of thallium-201 SPECT redistribution patterns and rubidium-82 PET rest-stress myocardial blood flow imaging

To compare regional thallium-201 SPECT redistribution patterns with rubidium-82 PET, we studied 81 patients with both imaging modalities. Sixty patients had significant coronary artery disease. All patients underwent PET imaging after dipyridamole infusion, while SPECT imaging was performed after exercise stress (38 patients) and dipyridamole (43 patients). Sixty-eight percent of patients with prior infarct had fixed defects on SPECT, compared to 39% with PET. Sixty-one percent of patients with prior infarct had PET perfusion defects which exhibited ‘reflow’ or normal rubidium-82 tracer uptake (p < 0.05 vs. SPECT). Similar results were seen in patients without prior infarct (26% fixed defects on SPECT vs. 12% for PET, p < 0.05). Regional analysis showed that 57% of fixed SPECT defects corresponded to PET defects with reflow or normal rubidium-82 uptake, while 78% of ‘fixed’ PET defects corresponded to fixed SPECT defects. PET reflow and normal rubidium-82 uptake in sites of fixed thallium-201 SPECT perfusion defects suggest that imaging modalities employing separate tracer injections at rest and after stress, such as rubidium-82 PET, may be more specific in the assessment of myocardial viability, especially in patients with prior myocardial infarction.     

Shortened acquisition time or reduced-activity dose for gated myocardial perfusion SPECT with new reconstruction algorithm

To confirm that shortened acquisition time or reduced-activity dose in single-photon emission computed tomography (SPECT) myocardial perfusion imaging reconstructed with Astonish software (AS) does not compromise image quality or diagnostic accuracy. One hundred patients referred for SPECT myocardial perfusion imaging were prospectively studied. The patients were randomly selected to receive the full-dose protocol (group A, n = 54) or the half-dose protocol (group B, n = 46). The patients of group A underwent a 2-day stress/rest protocol. After half-time acquisition, they underwent a full-time acquisition for stress and rest SPECT. Group B underwent a 1-day stress/rest protocol. During peak stress, all patients received an intravenous injection of ^99mTc-methoxyisobutylisonitrile (MIBI; 5.2 ± 0.6 mCi). After the full-time stress acquisition, the patients underwent a double-time stress acquisition. If the stress image showed a defect, a patient received ^99mTc-MIBI (19.5 ± 1.7 mCi) at rest on the same day. The rest SPECT acquisition protocol was the same in both groups. The low count (LC) and high count (HC) were acquired for each patient. AS and filtered back projection (FBP) reconstructed each set of raw data. Image quality of perfusion was assessed on a four-point scale. Perfusion parameters and function parameters were calculated by quantitative perfusion SPECT and quantitative gated SPECT. Mean image quality for LC-AS and HC-AS (3.5 ± 0.5 and 3.7 ± 0.5, respectively) was superior to HC-FBP (3.1 ± 0.4) in group A (for all, p < 0.001). LC-AS and HC-AS (3.5 ± 0.5 and 3.6 ± 0.5, respectively) in group B were superior to HC-FBP (3.1 ± 0.3) (for all, p < 0.001). LC-AS, HC-AS and LC-FBP showed high diagnostic concordance with HC-FBP (kappa value was 0.92, 0.92, and 0.94, respectively; all p < 0.001). Cardiac SPECT studies can be acquired with half of the scan time or reduced radioactivity dose and reconstructed by using the AS algorithm without compromising image quality.     

Prognostic evaluation in obese patients using a dedicated multipinhole cadmium-zinc telluride SPECT camera

The purpose of this study is to evaluate the prognostic value of myocardial perfusion SPECT obtained in CZT cameras (CZT–SPECT) with multipinhole collimation in obese patients. CZT–SPECT may be technically challenging in the obese, and its prognostic value remains largely unknown. Patients underwent single-day, rest/stress (supine and prone) imaging. Images were visually inspected and graded as poor, fair or good/excellent. Summed stress and difference scores (SSS and SDS, respectively) were converted into percentages of total perfusion defect and of ischemic defect by division by the maximum possible score. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m² and classified as class I (BMI 30–34.9 kg/m²), II (BMI 35–39.9 kg/m²), or III (BMI ≥ 40 kg/m²). Patients were followed-up by telephone interview for the occurrence of all-cause death, myocardial infarction or revascularization. A Cox proportional hazards analysis was used to assess the independent predictors of death. Among 1396 patients, 365 (26.1 %) were obese (mean BMI 33.9 ± 3.6; 17.5 % class I, 3.4 % class II, and 3.4 % class III). Image quality was good/excellent in 94.5 % of the obese patients. The annualized mortality rates were not significantly different among obese and non-obese patients, being <1 % with normal CZT–SPECT, and increased with the degree of scan abnormality in both obese and non-obese patients. Age, the use of pharmacologic stress and an abnormal CZT–SPECT, but not obesity, were independent predictors of death. In obese patients, single-day rest/stress CZT–SPECT with a multipinhole camera provides prognostic discrimination with high image quality.     

Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography using low mechanical index power modulation technique allows for simultaneous myocardial perfusion and wall motion analysis. RTP-adenosine stress echocardiography (ASE) could be an alternative to dobutamine-atropine stress echocardiography; more tolerable for the patients and possibly similarly accurate. We aimed to evaluate RTP-ASE for the detection of myocardial ischaemia, compared to 99mTc-sestamibi single-photon emission computed tomography (SPECT). METHODS: Patients with suspected coronary artery disease, admitted to SPECT evaluation, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using infusion of Sonovue (Bracco, Milano, Italy) before and during ASE. Two separate readers performed off-line analysis of myocardial perfusion and wall motion by RTP-ASE. A perfusion defect was the principal marker of ischaemia. Wall motion assessment was used to evaluate ischaemia in segments with perfusion artefacts. Each segment was attributed to one of the three main coronary vessel areas of interest: the left anterior descending (LAD); the left circumflex (LCx) and the right posterior descending (RPD). Normal SPECT at stress was judged normal at rest. RESULTS: In 33 patients, 99 coronary territories were analysed by SPECT and RTP-ASE. SPECT showed evidence of ischaemia in 9 of 33 patients. For the detection of ischaemia, the overall level of agreement between RTP-ASE and SPECT was 92% in all segments. The level of agreement was 88% in LAD, 97% in LCx and 91% in RPD segments. CONCLUSION: Real-time perfusion-adenosine stress echocardiography using power modulation could be an accurate and feasible tool for evaluation of ischaemia in patients with suspected coronary artery disease. The results from this study need confirmation by a study of a larger patient sample.     

Contrast Echocardiography: Current Applications and Future Perspectives

Contrast echocardiography is an established imaging method and an essential tool in every state of the art echocardiographic laboratory. It has also been the subject of several major clinical and research studies during the last year. This article addresses the impact of these studies on the clinical use of contrast echocardiography. Most recent studies have been performed with commercially available ultrasound contrast agents, which cross the pulmonary vasculature and are used for assessment of the left heart. The principle licensed indication for these contrast media is the delineation of left ventricular (LV) borders, masses, and aneurysms. The superiority of 2-dimensional contrast echocardiography over nonenhanced 2-dimensional imaging has been confirmed for assessment of LV volumes and ejection fraction, and there is growing evidence for the use of contrast 3-dimensional echocardiography. Two studies have demonstrated the usefulness of contrast-enhanced TEE for detection of thrombi in the left atrial appendage. The improved endocardial definition seen with ultrasound contrast media can also be used for strain analysis on selected systems. In stress echocardiography, contrast has been used for myocardial perfusion imaging in addition to assessment of regional LV wall motion. A large European multicenter study has demonstrated Sonovue-enhanced myocardial contrast echocardiography to be more sensitive than nuclear single photon emission computed tomography (SPECT) for the detection of significant coronary artery disease. Two further studies are discussed, which have demonstrated the impact of isolated perfusion defects on patients’ outcome. In addition, several publications have supplemented existing evidence regarding the safety of commercially available contrast agents. Recent studies continue to establish the usefulness and safety of contrast echocardiography for the currently licensed indications. There is also now good evidence for the use of myocardial contrast echocardiography as an alternative to nuclear imaging.     

Quantification of Myocardial Blood Flow with CZT SPECT Imaging: Is It Ready for Clinical Use?

Purpose of Review

Myocardial blood flow (MBF) quantification with positron emission tomography (PET) is well validated and has established diagnostic and prognostic value for patient management. New cardiac dedicated solid-state single-photon emission tomography (SPECT) cameras using cadmium-zinc-telluride (CZT) crystals have better temporal and spatial resolution and increased count sensitivity than conventional SPECT systems and can measure MBF. We review recent validation studies using CZT technology for measurement of MBF and assess its readiness for clinical application.

Recent Findings

One preclinical study showed the accuracy of MBF measured using the CZT technology and conventional radiotracers versus microsphere data. Clinical studies have demonstrated the feasibility in patients and excellent correlations with coronary angiography and flow-wire studies, and PET imaging.

Summary

Measurement of MBF is possible with SPECT CZT systems and has been validated. Further studies are necessary to confirm the incremental value of MBF measurements with SPECT CZT to standard relative perfusion imaging for diagnostic accuracy and risk stratification.

     

运动核素心肌灌注断层显像评估PTCA疗效

本文总结31例经皮冠状动脉腔内血管成形术(PTCA)前后作运动核素心肌灌注断层显像,PTCA前冠状动脉平均狭窄82.58±16.04%,术后为17.7±6.21%,26例(83.9%)运动心肌灌注断层显像显示PTCA术后心肌缺血完全消失及明显改善。90.3%病例PTCA术后运动试验较术前进步。认为运动心肌灌注断层显像可做为判断PTCA疗效的有效方法。     

An automatic approach to the analysis, quantitation and review of perfusion and function from myocardial perfusion SPECT images

We have developed a software suite that automatically selects, analyses, quantitates and displays all the key image data in a myocardial perfusion SPECT study. Methods: The files automatically selected (upon specification of the patient name) are rest and stress projections, rest and stress short axis and gated short axis files, and all ‘snapshot’ files. The projection data sets are presented in cine mode for evaluation of patient motion, while the lung/heart ratio at rest and stress is calculated from regions of interest (ROIs) that are automatically derived and overlayed on the LAO 45 images. Left ventricular (LV) cavity volumes at rest and stress are calculated from the short axis data sets, and the related transient ischemic dilation (TID) ratio derived and displayed. Quantitative measurements of global (ejection fraction) and regional function parameters are performed from the gated short axis dataset. All algorithms use the C++, X-Windows and OSF-Motif standards. The overall suite executes in less than 1 minute on a SunSPARC5 with 32 Mb of RAM and no proprietary hardware. Results: The software was validated on 144 patients (118 rest²⁰¹ Tl/post-stress ^99mTc-sestamibi, 18 post-stress ^99mTc-sestamibi, 8 rest ²⁰¹Tl) acquired on a 90° dual detector (ADAC Vertex, 91 patients) and a triple detector camera (Picker Prism 3000, 53 patients). Overall, the individual algorithms for the analysis of projection, short axis and gated short axis images were successful in 622/660 (94.2%) of the images. In 80.5% of the patients (73/91+43/53) all algorithms executed successfully, without significant difference in success rates for²⁰¹ Tl versus ^99mTc-sestamibi images. Conclusion: Our automated approach to myocardial perfusion SPECT analysis and review is highly successful, intrinsically reproducible, and can produce time and cost savings while improving accuracy in a clinical or teleradiology-type environment.     

The clinical use of imaging techniques with exercise testing

The addition of nuclear imaging techniques to basic exercise electrocardiography (ECG) has provided significant diagnostic and prognostic information in the evaluation of patients with suspected coronary artery disease. During the last decade, new classes of isotopes (technetium-and rubidium-based perfusion agents) and refinements in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have become better accepted. These new studies have added to the diagnostic armamentarium available to physicians, but at considerable costs with an estimated 4.8 million procedures performed this year. Nuclear imaging techniques can assess myocardial blood flow (perfusion imaging) or function (ventriculography). Another imaging modality, stress echocardiography, has also achieved widespread acceptance with clinical guidelines for its use published in 1997. This review addresses these imaging techniques in diagnostic evaluation of the patient with suspected coronary artery disease.     

Transient ischemic dilatation of the left ventricle with severe post stress left ventricular dysfunction in the setting of severe aortic stenosis and normal coronary arteries

Transient ischemic dilatation (TID) of the left ventricle observed during single photon myocardial perfusion emission computed tomography (SPECT) is an important non-perfusion finding that may not only suggest underlying significant (usually multi-vessel) coronary artery disease (CAD) but also an independent prognostic factor of adverse outcomes regardless of abnormal or normal perfusion finding. We present a patient with no significant epicardial coronary disease who had significant TID and considerable decrease in the left ventricular ejection fraction with left ventricular dilatation after a rest-stress Tc-99 tetrofosmin SPECT study in the setting of severe aortic stenosis. With the advent of gated SPECT imaging the additive value of determining rest and post stress EF, as demonstrated in this case, aided in the recognition of TID and transient decrease in the left ventricular ejection fraction. These are not necessarily related to obstructive epicardial coronary disease, but are a result of severe aortic valve disease causing subendocardial ischemia in the setting of multilple other non-ischemic etiologies of TID such as left ventricular hypertrophy and diabetes mellitus.     

Comparison of 1- and 2-day protocols for myocardial SPECT: a Monte Carlo study

BACKGROUND: Myocardial perfusion single-photon emission computed tomography (SPECT) is carried out by combining a rest and a stress study that are performed either on one day or two separate days. A problem when performing the two studies on 1 day is that the residual activity from the first study contributes to the activity measured in the second study. AIM: Our aim was to identify and evaluate trends in the quantification parameters of myocardial perfusion images as a function of separation time between rest and stress. METHODS: A digital phantom was used for the generation of heart images and a Monte Carlo-based scintillation camera program was used to simulate SPECT projection images. In our simulations, the rest images were normal and the stress images included lesions of different types and localization. Two programs for quantification of myocardial perfusion images were used to assess the different images in an automated and objective way. RESULTS: The summed difference scores observed with the 2-day protocol were 3 +/- 1 (mean +/- SD) higher for AutoQUANT and 2 +/- 1 higher for 4D-MSPECT compared with those observed with the 1-day protocol. The extent values were 2% points higher for the 2-day protocol compared with the 1-day protocol for both programs. CONCLUSIONS: There are differences in the quantitative assessment of perfusion defects depending on the type of protocol used. The contribution of residual activity is larger when a 1-day protocol is used compared with the 2-day protocol. The differences, although small, are of a magnitude that results in a clear shift in quantification parameters.     

Evaluation of ASPIRE trial: a Phase III pivotal registration trial,using intracoronary administration of Generx (Ad5FGF4) to treat patients with recurrent angina pectoris

The ASPIRE study (a randomized, controlled, parallel group, multicenter study to evaluate the efficacy and safety of Ad5FGF-4 using adenosine single-photon emission computed tomography (SPECT) myocardial perfusion imaging in patients with stable angina pectoris) (ClinicalTrials.gov Identifier: NCT01550614) is a 100-patient, controlled, randomized, multicenter study conducted in six centers in Russia. This trial will assess the therapeutic efficacy of Generx (Ad5-FGF4) using rest and stress SPECT following a one-time, catheter-based administration. Adenovirus-based antianginal therapy represents an interesting option but the difficulties observed in the various trials carried out to date illustrate the complexity of the issue. Large and well-designed studies should be encouraged to provide definitive answers to this important research question.     

High prevalence of (99m)tc-tetrofosmin reverse perfusion pattern in patients with myocardial infarction and angiographically smooth coronary arteries

Background: There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA) Objectives: To evaluate myocardial perfusion imaging in a series of patients with MI and NCA. Methods: Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI. Results: In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest. Conclusions: Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.     

Abnormal electron beam computed tomography results: the value of repeating myocardial perfusion single-photon emission computed tomography in the ongoing assessment of coronary artery disease

OBJECTIVE: To determine whether asymptomatic patients with atherosclerosis, indicated by the presence of coronary artery calcium on electron beam computed tomography, are at enough risk for progression of disease to justify a repeated stress single-photon emission computed tomography (SPECT) examination after an initial normal to low-risk perfusion study. PATIENTS AND METHODS: We retrospectively identified patients who had abnormal results on electron beam computed tomography (coronary artery calcium score > 0) and normal to low-risk results on SPECT (defined as a summed stress score of 0-3) within a 3-month period from January 1, 1995, to October 31, 2002. Of the 504 identified patients, 285 remained after exclusion criteria were applied. Of the 285 patients, 69 (mean +/- SD age, 58.2 +/- 7.6 years; 91% male) underwent at least 1 repeated myocardial perfusion SPECT imaging study within 4 years of their initial assessment as normal or at low risk without recurrence of symptoms. The value of repeated SPECT imaging was assessed by detection of a substantial change in the repeated SPECT study and by documentation of a clinical event (death, nonfatal myocardial infarction, or revascularization). Follow-up was 100% complete at a mean of 4.3 +/- 1.6 years. RESULTS: Only 4 patients (6%) had a substantial progression in their SPECT risk category; substantial changes on the SPECT scans occurred only in patients with a coronary artery calcium score greater than 100. Three patients underwent revascularization, yielding a 5-year rate for survival free of revascularization of 94% (95% confidence interval, 88%-100%). No deaths or nonfatal myocardial infarctions were reported. CONCLUSION: The principal findings of this study indicate that asymptomatic patients with initial normal or low-risk results from stress SPECT performed because of abnormal coronary artery calcium scores who remain asymptomatic are at low risk of death, myocardial infarction, or coronary revascularization. Three patients underwent revascularization by percutaneous coronary intervention despite the absence of symptoms. A substantial change in SPECT results (defined as progression from normal or low-risk summed stress score to intermediate- or high-risk summed stress score) affected 6% of patients and was not associated with any adverse hard events (nonfatal myocardial infarction or death).