Myocardial scintigraphy plays important roles in the diagnosis of coronary artery disease, prognostic risk stratification, and determination of the treatment policy. Recently, several large-scale clinical trials reported that coronary intervention was not necessarily advantageous for preventing future cardiac events in patients with stable angina. This review summarizes how we can estimate cardiac event risks based on Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), and describes that the combination of scintigraphy and other clinical features leads to more accurate stratification of prognosis and the determination of subsequent treatment policy.

We assessed the prognostic value of myocardial perfusion scintigraphy (MPS) with cadmium-zinc-telluride in addition to clinical and coronary anatomy analysis.

We prospectively enrolled 1464 patients (26% females, 69.5 ± 10.4 years) referred for stress-rest MPS. All the patients underwent invasive coronary angiography (1171, 80%) or coronary computed tomography angiography (293, 20%). We defined a composite endpoint of cardiovascular death and non-fatal MI. After an 8-year follow-up, summed stress score (SSS) had the highest accuracy in predicting primary endpoint with a ROC-derived cut-off of SSS >8 (>10% myocardium). SSS >8 portended the lowest survival probability at Kaplan-Meier analysis (P < 0.0001 for the composite endpoint and individual components). The Cox-regression analysis indicated SSS as an independent predictor of the composite endpoint, along with fasting blood glucose and total cholesterol and contrary to coronary anatomy parameters. Patients with SSS >8 treated with optimal medical therapy (OMT) had the largest area of necrosis, the lower ischaemic burden, the most compromised LV systo-diastolic function and the highest LV mass, but received a less aggressive treatment in comparison to early revascularized patients. Survival analysis revealed patients with SSS ≤8 had the greater freedom from events, irrespective of the treatment strategy, while the group with SSS >8 and OMT had the worst outcome, followed by patients with SSS >8 and early revascularization (log-rank test: all P < 0.0001).

MPS-SSS constitutes a strong independent predictor of future adverse events after adjustment for multiple clinical parameters and coronary angiography. In particular, MPS could help risk stratification of patients who did not undergo early revascularization.

The assessment of ischemia through myocardial perfusion imaging (MPI) is widely accepted as an index step in the diagnostic evaluation of stable ischemic heart disease (SIHD). Numerous observational studies have characterized the prognostic significance of ischemia extent and severity. However, the role of ischemia in directing downstream SIHD care including coronary revascularization has remained elusive as reductions in ischemic burden have not translated to improved clinical outcomes in randomized trials. Importantly, selection bias leading to the inclusion of many low risk patients with minimal ischemia have narrowed the generalizability of prior studies along with other limitations. Accordingly, an ongoing randomized controlled trial entitled ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) will compare an invasive coronary revascularization strategy vs a conservative medical therapy approach among stable patients with moderate to severe ischemia. The results of ISCHEMIA may have a substantial impact on the management of SIHD and better define the role of MPI in current SIHD pathways of care.

Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI.

From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis.

Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03-34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively].

Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population.

The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with (99m)Tc-tetrofosmin MPS.

Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45).

3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia.

Previous studies demonstrated that coronary revascularization, especially percutaneous coronary intervention (PCI), does not significantly decrease the incidence of cardiac death or myocardial infarction in patients with stable coronary artery disease. Many studies using myocardial perfusion imaging (MPI) showed that, for patients with moderate to severe ischemia, revascularization is the preferred therapy for survival benefit, whereas for patients with no to mild ischemia, medical therapy is the main choice, and revascularization is associated with increased mortality. There is some evidence that revascularization in patients with no or mild ischemia is likely to result in worsened ischemia, which is associated with increased mortality. Studies using fractional flow reserve (FFR) demonstrate that ischemia-guided PCI is superior to angiography-guided PCI, and the presence of ischemia is the key to decision-making for PCI. Complementary use of noninvasive MPI and invasive FFR would be important to compensate for each method's limitations. Recent studies of appropriateness criteria showed that, although PCI in the acute setting and coronary bypass surgery are properly performed in most patients, PCI in the non-acute setting is often inappropriate, and stress testing to identify myocardial ischemia is performed in less than half of patients. Also, some studies suggested that revascularization in an inappropriate setting is not associated with improved prognosis. Taken together, the presence and the extent of myocardial ischemia is a key factor in the management of patients with stable coronary artery disease, and coronary revascularization in the absence of myocardial ischemia is associated with worsened prognosis.

Three-dimensional cardiac magnetic resonance perfusion imaging is promising for the precise sizing of defects and for providing high perfusion contrast, but remains an experimental approach primarily due to the need for large-dimensional encoding, which, for traditional 3DFT imaging, requires either impractical acceleration factors or sacrifices in spatial resolution. We demonstrated the feasibility of rapid three-dimensional cardiac magnetic resonance perfusion imaging using a stack-of-spirals acquisition accelerated by non-Cartesian k-t SENSE, which enables entire myocardial coverage with an in-plane resolution of 2.4 mm. The optimal undersampling pattern was used to achieve the largest separation between true and aliased signals, which is a prerequisite for k-t SENSE reconstruction. Flip angle and saturation recovery time were chosen to ensure negligible magnetization variation during the transient data acquisition. We compared the proposed three-dimensional perfusion method with the standard 2DFT approach by consecutively acquiring both data during each R-R interval in cardiac patients. The mean and standard deviation of the correlation coefficients between time intensity curves of three-dimensional versus 2DFT were 0.94 and 0.06 across seven subjects. The linear correlation between the two sets of upslope values was significant (r = 0.78, P < 0.05).

Limited data are available on coronary lesion morphology for patients with false-negative radionuclide findings together with typical angina symptoms.

The study group consisted of 25 subjects with a negative pharmacological thallium (Tl)-201 single-photon emission computed tomography perfusion imaging study but typical angina symptoms and coronary artery disease (CAD) confirmed by coronary angiography. The control group included 690 subjects with a positive pharmacological Tl-201 single-photon emission computed tomography study and CAD.

The study group showed a significantly older and higher female ratio than the control group. Significant differences were found between the 2 groups in the presence of current smoking status and hypertension. A noticeably higher percentage of positive metabolic syndrome ratio, number of metabolic syndrome components, high waist-to-hip ratio percentage and high waist circumference percentage in the study group. The study group was noticeably lower in mean numbers of culprit vessel involvement and mean lesion numbers than the control group. There were more individuals with type A classification and a lower proportion of complex stenoses--which contain type B2 and C lesions--in the study group than in the control group. The study group had significantly fewer calcified stenoses and complex morphology stenoses--the latter of which include lesion morphologies with chronic total occlusion, diffuse and calcification--than the control group.

For the high probability of CAD lesions that requires interventional therapy, patients with negative myocardial scintigraphy but typical angina symptoms would be beneficial to intensive medical treatment and coronary study.

Three-dimensional (3D) first-pass myocardial perfusion imaging (MPI) is a promising alternative to conventional two-dimensional multislice MPI due to its contiguous spatial coverage that is beneficial for estimating the size of perfusion defects. Data acquisition at mid-diastole is a typical choice for 3D MPI yet is sensitive to arrhythmia and variations in R-R interval that are common in cardiac patients. End systole is the second longest quiescent cardiac phase and is known to be less sensitive to the R-R variability. Therefore, 3D MPI with systolic acquisition may be advantageous in patients with severe arrhythmia once it is proven to be comparable to diastolic MPI in subjects with negligible R-R variation. In this work, we demonstrate the feasibility of 3D MPI with systolic data acquisition in five healthy subjects. We performed 3D MPI experiments in which 3D perfusion data were acquired at both end-systole and mid-diastole of every R-R interval and analyzed the similarity between resulting time intensity curves (TIC) from the two data sets. The correlation between systolic and diastolic TICs was extremely high (mean = 0.9841; standard deviation = 0.0166), and there was a significant linear correlation between the two time intensity curve upslopes and peak enhancements (P < 0.001).

Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.

The prognostic power of myocardial perfusion imaging in patients with ischemic heart disease (IHD) has been demonstrated since planar imaging. We aimed to investigate whether gated SPECT retains this value in current cardiology if compared with a complete diagnostic work-up and with more recent prognostic indicators.

We selected from our database a cohort of 676 consecutive inpatients who underwent a complete diagnostic work-up that included gated SPECT and coronary arteriography for known or suspected IHD. Patients with acute myocardial infarction (MI), previous coronary artery bypass surgery, or overt hyperthyroidism and patients who were undergoing dialysis treatment were excluded. During follow-up (median, 37 mo), 24 patients died from cardiac causes and 19 experienced a nonfatal MI.

The following were determined to be independent predictors of event-free survival (cardiac death and nonfatal MI) in the different phases of diagnostic work-up using Cox proportional hazards regression analysis: among clinical variables, a previous MI; among laboratory examinations, serum creatinine and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels; among electrocardiographic and echocardiographic variables, left ventricular ejection fraction; and among SPECT variables, summed rest score (SRS) and summed difference score (SDS). In addition, a score of coronary stenoses at angiography was an independent predictor. When the above predictors were tested together, SRS (P < 0.0001), SDS (P = 0.0108), and serum creatinine (P = 0.0186) and LDL and HDL cholesterol levels (P = 0.0222) were the final independent predictors of event-free survival. When gated SPECT was added to the clinical, laboratory, electrocardiographic, and echocardiographic variables, the prognostic stratification significantly improved (P < 0.05); when coronary arteriography was added to gated SPECT, prognostic stratification did not further improve (P > 0.25). If the information provided by gated SPECT was made available after clinical, laboratory, electrocardiographic, echocardiographic, and angiographic variables, the prognostic stratification still improved significantly (P < 0.05). In 492 of these patients with ascertained IHD, SRS and SDS were the final independent predictors of survival. Medical treatment and coronary revascularization did not affect the prognostic information of gated SPECT.

Myocardial perfusion abnormalities at rest and after stress are still the best predictors of cardiac event-free survival in patients with known or suspected IHD, even when compared with an extensive diagnostic work-up.

We have developed a new protocol of myocardial perfusion-gated single-photon emission computed tomography (SPECT), by use of technetium-99m sestamibi (MIBI), in which SPECT imaging at rest followed by SPECT imaging after adenosine with low level ergometer stress can be conducted by use of the Monzen position within a shortened total testing time of 1 h or less. The study group consisted of 137 patients who underwent this new imaging protocol. The diagnostic quality of the images was as good as that of images obtained with the conventional method (30-60 min after the injection of MIBI). The SPECT image quality for the 137 patients was evaluated, and the percentages of images rated as excellent, good, fair, and poor were 65.3, 27.4, 5.8, and 1.5% for the rest image, and 68.2, 21.9, 8.4, and 1.5% for the stress image, respectively. The shortened total testing time reduced the physical and mental burden on the patient compared with that of conventional myocardial perfusion imaging. Because this technique allows us to perform rest and stress myocardial imaging within a short period, it is expected to be very useful in the clinical setting.

In patients with ischemic heart disease, accurate assessment of the extent of myocardial perfusion deficit may be important in predicting prognosis of clinical cardiac outcomes. The aim of this study was to compare the ability of three dimensional (3D) and of two dimensional (2D) multi-slice myocardial perfusion imaging (MPI) using cardiovascular magnetic resonance (CMR) in determining the size of defects, and to demonstrate the feasibility of 3D MPI in healthy volunteers at 3 Tesla.

A heart phantom was used to compare the accuracy of 3D and 2D multi-slice MPI in estimating the volume fraction of seven rubber insets which simulated transmural myocardial perfusion defects. Three sets of cross-sectional planes were acquired for 2D multi-slice imaging, where each set was shifted along the partition encoding direction by +/- 10 mm. 3D first-pass contrast-enhanced (0.1 mmol/kg Gd-DTPA) MPI was performed in three volunteers with sensitivity encoding for six-fold acceleration. The upslope of the myocardial time-intensity-curve and peak SNR/CNR values were calculated.

Mean/standard deviation of errors in estimating the volume fraction across the seven defects were -0.44/1.49%, 2.23/2.97%, and 2.59/3.18% in 3D, 2D 4-slice, and 2D 3-slice imaging, respectively. 3D MPI performed in healthy volunteers produced excellent quality images with whole left ventricular (LV) coverage. Peak SNR/CNR was 57.6 +/- 22.0/37.5 +/- 19.7 over all segments in the first eight slices.

3D performed better than 2D multi-slice MPI in estimating the size of perfusion defects in phantoms. Highly accelerated 3D MPI at 3T was feasible in volunteers, allowing whole LV coverage with excellent image quality and high SNR/CNR.

To compare the prognostic ability of the imaging agents 99mTc-sestamibi versus 99mTc-tetrofosmin to predict mortality outcomes in patients with documented coronary artery disease and undergoing vasodilator stress testing.

The study included 2147 consecutive patients who underwent rest and stress single photon emission computed tomographic (SPECT) examination with either 99mTc-sestamibi (n=1128) or 99mTc-tetrofosmin (n=1019). Information relating to all-cause death and cardiovascular death was collected over a 4-year study period. Unadjusted Kaplan-Meier estimates were compared for the two imaging agents. Cox proportional hazard models were examined to determine the incremental contribution of SPECT sum stress score (SSS) and the imaging agent after adjusting for clinical and demographic characteristics. Additionally, the interaction between SSS and agent was examined to determine if the effect of SSS on prognosis was different for the two agents.

Vasodilator agents were used for stress testing in all patients who received 99mTc-tetrofosmin and 99mTc-sestamibi. Despite differences in patient risk factors Kaplan-Meier estimates were similar for the two groups of patients. Resulting P-values for differences between models for the end points of (1) death from any cause and (2) cardiovascular death showed that SSS combined with clinical index was significantly better than a model that adjusted for only baseline characteristics (P<0.0001 for both endpoints). The addition of imaging agent (99mTc-tetrofosmin or 99mTc-sestamibi) to the model containing both SSS and the clinical characteristics did not show further significant improvement (P=0.62, P=0.96 for death from any cause and cardiovascular death, respectively).

The type of clinically available 99mTc-labelled myocardial perfusion agents did not affect interpretation of results for prognostic assessment.

The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method.

SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI.

ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable.

The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Recent advances in computed tomography technology have made possible angiographic images of relatively small, moving vascular structures such as the coronary arteries. Computed tomographic coronary angiography is an exciting modality which has several obvious advantages over invasive catheterization, such as its relatively noninvasive nature and rapid speed of acquisition. However, significant drawbacks still exist, including limitations of spatial and temporal resolution and radiation exposure. Computed tomographic coronary angiography appears best suited as a diagnostic modality for the patient population with a low-to-moderate pretest probability of coronary artery disease, and for specific indications such as the imaging of coronary anomalies and bypass grafts and before biventricular pacemaker placement and atrial fibrillation ablation.

This review article discusses the historical origin of cardiac radionuclide-based methods, the physiologic background that justifies their existence, as well as the basic pathophysiologic concepts of coronary artery disease and their connection with the technologic design and application of these methods. Most importantly, this review discusses the important insights that these methods have provided to the understanding of the mechanisms of ischemia, risk stratification, and both treatment choice and treatment efficacy in ischemic heart disease. Nuclear cardiology originated as an attempt to provide complementary physiologic information to the anatomic information provided by coronary angiography. To comprehend the design and applications of nuclear cardiology methods, one must have a basic understanding of coronary artery disease as an inflammatory process that may manifest as acute or chronic states. Basic concepts on myocyte metabolic pathways, coronary blood flow, ischemic cascade, ventricular remodeling, and ejection fraction become critical for this purpose. Insights into risk stratification may permit patient-tailored therapy approaches. Insights into prognosis have made nuclear cardiology a robust tool for outcome predictions, with an exceptionally high negative predictive value. Evaluation of prognosis in special patient populations such as diabetics has originated important pathophysiologic concepts. Most insights into phenomena such as myocardial hibernation, myocardial stunning, and viability have been generated by nuclear cardiology techniques. Finally, new applications of radionuclide-based methods such as molecular identification of "vulnerable" atherosclerotic plaques, "ischemic memory" using fatty acid imaging, and myocardial innervation imaging provide new avenues for insightful research.

Limited data are available on the value of quantitative stress myocardial perfusion imaging (MPI) in patients with unstable angina. In this report we sought to study the long-term prognostic value of quantitative stress MPI in patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes.

The study population consisted of 136 patients who were hospitalized at the Methodist Hospital, Houston, Tex, with unstable angina and subsequently underwent MPI before discharge. Cox proportional hazards (regression) analysis was performed to identify clinical and MPI predictors of hard cardiac events (death or nonfatal myocardial infarction). During a mean follow-up of 31 +/- 17 months, 20 patients (15%) sustained either cardiac death (n = 12) or nonfatal myocardial infarction (n = 8). The significant multivariate predictors of cardiac events were the total perfusion defect size ( P = .002), the presence of reversible perfusion defects ( P = .01), and the presence of multiple perfusion defects ( P = .03). The perfusion defect size was significantly larger in patients with events than in those without events (21% +/- 20% vs 12% +/- 14%, P = .002). Kaplan-Meier analysis showed that cardiac events were much more likely to develop in patients with defects involving 15% or more of the left ventricle than in those with defects involving less than 15% of the left ventricle ( P = .003).

In patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes, quantitative stress MPI provides powerful prognostic information that can be used in the risk stratification of these patients.

Dipyridamole thallium-201 single-photon emission computed tomography (SPECT) has not been extensively evaluated for risk stratification and the medium- to long-term prognostic value in elderly cardiac patients who are unable to exercise. The present study group comprised 210 consecutive patients aged at least 70 years with known or suspected coronary artery disease (CAD). The SPECT findings were classified as a reversible, fixed, or combined (reversible and fixed) defect. Of the 210 patients, 201 (77+/-5 years, 85 male) were successfully followed for 49+/-26 months. Thirteen (7%) patients had cardiac events: cardiac death (n=10), non-fatal myocardial infarction (n=1), or coronary artery bypass grafting (n=2). Cardiac events occurred in 3 of 112 patients with normal SPECT and in 10 of 89 patients with an abnormal scan (0.7% /year vs 2.8% /year, p=0.01). Stepwise Cox regression analysis revealed that the significant predictors of cardiac events were combined defects (relative risk 7.3) and the number of defect areas (relative risk 4.4). The predictive value of dipyridamole thallium-201 SPECT is maintained over 4 years in mixed populations of elderly CAD patients who are unable to exercise.

To determine if there was any difference in the ability of physicians to predict prognosis with technetium 99m ((99m)Tc) sestamibi or (99m)Tc tetrofosmin in a large consecutive series of patients at high risk for coronary artery disease who underwent coronary angiography.

This study included 1,818 consecutive patients who underwent a rest and stress single photon emission computed tomographic (SPECT) examination with either (99m)Tc sestamibi (n = 915) or (99m)Tc tetrofosmin (n = 903) and cardiac catheterization. A clinical index was generated and consisted of clinical and demographic variables. Information concerning death, cardiovascular death, and nonfatal myocardial infarction was 93% complete during the 1.5-year study period. Cox proportional hazards models were generated to help determine the incremental contribution of SPECT sum stress score (SSS) and the imaging agent variable to the clinical index.

Exercise was used for stress testing in 473 (52%) patients who received (99m)Tc tetrofosmin and 519 (57%) patients who received (99m)Tc sestamibi (P =.06). Cardiovascular death or myocardial infarction occurred in 130 patients. Resulting P values for chi(2) differences between models for the end points of (a) death from any cause, (b) cardiovascular death, and (c) cardiovascular death or myocardial infarction showed that SSS combined with clinical index was a significantly better model than adjusting for only baseline characteristics (P =.001, P <.001, P =.004, respectively). Incremental addition of either (99m)Tc tetrofosmin or (99m)Tc sestamibi to those models containing SSS and the clinical index did not show further significant improvement (P =.87, P =.88, and P =.26 for death from any cause, cardiovascular death, and cardiovascular death or myocardial infarction, respectively).

This study shows that the type of clinically available (99m)Tc-labeled myocardial perfusion agents should not affect interpretation of results for risk stratification and prognostic assessment.

To determine the prognostic value of a normal stress echocardiogram in the setting of a large district general non-university hospital in the United Kingdom.

Between January 1996 and December 1999, all patients who had undergone stress echocardiography were identified and those with normal results were studied. Normal stress echocardiograms were found in 252 patients, 19 of whom were lost to follow-up. Deaths and nonfatal myocardial infarctions were considered hard cardiac events and data was collected in the remaining 233 patients.

Among the 233 patients, the pre-test probability of coronary artery disease was low in 68 (27.9%) and intermediate or high in 168 (72.1%). During a follow-up period of mean (SD) 2.7 (1.1) years, death occurred in 4 patients of which 3 were consequent to acute myocardial infarctions and 1 was unexplained. One patient sustained a nonfatal infarction. Thus, the annualized mortality and hard event rates were 0.6% per patient/year and 0.8% per patient/year, respectively.

A normal stress echocardiogram portends an excellent prognosis, even in a cohort with a high proportion of patients having intermediate or high pre-test probability of coronary artery disease.

Coronary artery disease (CAD) is the main cause of death in elderly patients. Single-photon emission computed tomography (SPECT) with technetium-99m ((99m)Tc)-labeled agents is extremely useful for the diagnosis and risk stratification of CAD in the general population. However, its prognostic value for the elderly has not been established. This study examined disease outcome in 328 patients aged 74 or older, with suspected CAD who were submitted to either pharmacological (dipyridamole) or exercise stress SPECT with (99m)Tc-sestamibi, seven of whom were completely lost to follow-up. Endpoints were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death or myocardial revascularization). Mean follow-up was 34+/-15 months. During this period 24 cardiac deaths, 11 myocardial infarctions and 21 cases of revascularization were observed. Perfusion defects were found in 27.1% of patients (12.8% reversible, 6.2% partially reversible and 8.1% fixed). Abnormal studies were predominant in men, patients with chest pain and those with ST-T abnormalities in the baseline electrocardiogram (ECG) or in the exercise treadmill test. An abnormal scan was significantly associated with cardiac events (P<0.0001). Multivariate analysis revealed that a abnormal scan was the most important independent predictor of hard or total cardiac events. Event rates increased according to myocardial perfusion scintigraphy (MPS): <1.0% of hard events per year in patients with normal MPS versus 14.3% per year in those with abnormal MPS. (99m)Tc-sestamibi SPECT was demonstrated to be a powerful tool for the prognostic evaluation of elderly patients with suspected CAD.

This study was designed to assess the prognostic value of myocardial tomoscintigraphy perfusion imaging after percutaneous coronary intervention (PCI) in asymptomatic diabetic patients.

One hundred and fourteen diabetic patients were followed up during 27+/-16 (mean+/-SD) months after the myocardial tomoscintigraphy. PCI-related events were studied after myocardial tomoscintigraphy stress testing and included major cardiac events (MACE) (cardiovascular death, myocardial infarction) and revascularization (bypass surgery or new PCI). Stress myocardial tomoscintigraphy imaging was performed 5+/-5 months after PCI and ischemia was considered as present if at least 2 contiguous segments were showing reversible defects.

Persistent silent ischemia was found in 49/114 (43%) patients. No difference was observed between the two groups for MACE: four among the 65 (6%) non ischemic patients versus 2 among the 49 (4%) ischemic patients (NS). In contrast, 15 (31%) among the ischemic patients and 4 (6%) among the non ischemic patients underwent iterative revascularization (p<0.01). The relative risk of revascularization for patients with significant ischemia was 5.5 versus non ischemic patients (p<0.001).

After PCI, in asymptomatic diabetic patients followed by myocardial tomoscintigraphy a high frequency of persistent silent ischemia was found and associated with a high risk for repeat interventional procedure, although no increase in major cardiac events was observed.

Exercise thallium-201 imaging provides a noninvasive estimate of the amount of myocardium presumed to be at risk of infarcting should a complete occlusion of the coronary stenosis occur. The relationship between the size of the exercise thallium perfusion defect and the extent of myocardium supplied by a diseased coronary artery has not been established. This study evaluates that presumed correlation.

Patients were injected intravenously with technetium-99m sestamibi during acute myocardial infarction before thrombolysis or conventional therapy to quantify the myocardium at risk. Twenty-six patients who underwent risk-area assessment subsequently underwent clinically driven, predischarge, submaximal exercise imaging with thallium-201. The exercise testing was performed on day 7 +/- 2 days. A conventional polar map display was used to quantify the perfusion defect.

The myocardium at risk determined by technetium-99m sestamibi at the time of infarction was 30% +/- 20% of the left ventricle. The mean exercise thallium-201 defect was 34% +/- 22% of the left ventricle. The exercise defect tended to be slightly larger than the myocardium at risk (4% +/- 10% of the left ventricle, P =.05). There was a close correlation between the 2 measurements (r = 0.89, SE = 9.4, P <.0001).

This study shows a close correlation between the myocardium "at risk" assessed acutely by technetium-99m sestamibi and the "presumed at-risk area" determined by thallium-201 imaging on predischarge exercise testing. This finding supports the concept that the size of the exercise thallium defect caused by coronary stenosis indicates the likely size of a myocardial infarction resulting from occlusion of that stenosis.

Extension of perfusion defects is associated with outcome in patients undergoing myocardial scintigraphy. The study aimed to identify the clinical characteristics that can predict the existence of perfusion defects in more than one territory in patients referred for myocardial scintigraphy with GATED-SPECT.

A total of 193 patients undergoing myocardial scintigraphy with GATED-SPECT (99mTc-tetrofosmine) were studied. Clinical variables and scintigraphy results were studied to determine what clinical variables are associated with perfusion defects in more than one territory.

The number of territories with perfusion defects per patient was 1.1 0.8 and 29% had perfusion defects in > 1 territory. Patients with greater probability of having perfusion defects in > 1 territory were those with previous myocardial infarction (44% vs 21%, p = 0.030) and males (33% vs 10%, p = 0.006). In addition, patients with > 2 coronary risk factors had a statistical tendency to have defects in > 1 territory (47% vs 20%, p = 0.057). Only 15% of the patients with one of these three characteristics had perfusion defects in > 1 territory in comparison with 45% and 83% in those with 2 or 3 factors, respectively.

Considering 3 simple clinical characteristics (male gender, previous infarction and existence of > 2 coronary risk factors), it is possible to predict which patients are more likely to show perfusion defects in > 1 territory during GATED-SPECT myocardial scintigraphy.

Limited data suggest that stress myocardial perfusion imaging and stress echocardiography have similar prognostic value for composite cardiac events. However, it is not known whether exercise echocardiography and stress thallium are similar in their prediction of specific cardiac events, eg, death, sudden death, myocardial infarction, unstable angina, and congestive heart failure. A total of 206 patients undergoing stress echocardiography and thallium-201 single-photon emission computed tomography imaging during the same exercise test were followed-up for 5 and 10 years. Multivariate Cox regression analyses incorporating clinical, exercise stress test, echocardiographic, and nuclear imaging parameters were used to predict mortality and specific cardiac events. A moderate to large amount of ischemia (> or =4 segments on the basis of a 16-segment model) by exercise stress echocardiography was the strongest predictor of overall mortality (relative risk [RR] 6.2; P <.0001), cardiac death (RR 17.6; P =.01), congestive heart failure (RR 17.4; P =.0005) or sudden death (RR 26.8; P =.003), whereas a moderate to large fixed defect (> or =2 segments on the basis of a 6-segment model) by nuclear imaging was the strongest predictor of myocardial infarction (RR 8.1; P =.0002) or unstable angina (RR 3.0; P =.005) at 5 years. The heterogeneity in the prediction of these specific cardiac events by these 2 modalities was similarly observed at 10 years. The extent of ischemia by stress echocardiography is a better predictor of overall mortality, cardiac death, congestive heart failure, or sudden death, whereas the extent of a fixed defect by nuclear imaging is a better predictor of myocardial infarction or unstable angina.

One hundred twenty-five patients (60 +/- 10 years old, 60 women) with known (35, previous myocardial infarction) or suspected (90) coronary artery disease (CAD) and no more than 50% coronary stenoses underwent pharmacologic (48 dipyridamole and 77 dobutamine) stress echocardiography (SE) and prospective follow-up (36 +/- 22 months) for cardiac death, nonfatal infarction, and unstable angina. The ability of clinical and SE variables to predict the outcome was assessed by the Cox model. A significant increase in the global chi-square of the model indicated an incremental prognostic value. Nine events occurred: 2 fatal and 5 nonfatal infarctions and 2 hospitalizations for unstable angina. Hypertension, positive SE, and peak wall motion score index were multivariate predictors of outcome, but SE provided an 87.5% increase in the global chi-square (P <.001). Patients with positive SE had a significantly lower event-free survival compared with those with negative SE. Therefore, we conclude that SE provides incremental prognostic information in patients with chest pain without critical coronary artery disease.

Left ventricular function is an important prognostic indicator in patients with coronary artery disease. The electrocardiogram gated, myocardial, single photon emission tomography (SPECT) program is coming into wide use. This program permits measurement of end diastolic volume, end systolic volume, and ejection fraction. This study was designed to show whether the measurement of ejection fraction by using (99c)Tc tetrofosmin gated SPECT at rest could give additional information to the interpretation of perfusion. Exercise 99mTc tetrofosmin SPECT and gated (99c)Tc tetrofosmin SPECT at rest were performed in 33 patients with or suspected of having coronary artery disease. Left ventricular ejection fraction was calculated from reconstructed gated SPECT at rest with a software quantitative gated SPECT. The results showed a poor correlation between segmental ejection fraction and segmental perfusion in stress and rest. There was an increasing probability of reversibility as the ejection fraction increased, while there was a greater chance of a fixed defect as the ejection fraction decreased. It is concluded that gated SPECT using (99c)Tc tetrofosmin provides clinically satisfactory functional data that, in combination with the perfusion information, will improve diagnostic and prognostic accuracy without an increase in cost or radiation dose to patients.

Increased lung uptake of thallium-201 (Tl-201) and technetium-99m (Tc-99m) MIBI in myocardial perfusion imaging is a reliable marker of left ventricular dysfunction. The goal of our study was to establish whether the lung-to-heart (L/H) uptake ratio with a newer cardiac imaging agent, Tc-99m tetrofosmin, can also provide valuable information about left ventricular function. We studied 60 patients with recent coronary artery diseases (CAD) undergoing first-pass radionuclide ventriculography to calculate left ventricular ejection fraction (LVEF) and myocardial perfusion imaging to calculate the L/H ratio. Group A consisting of 30 CAD patients with higher LVEF (> or =40%) had a significantly lower L/H ratio than group B consisting of 30 CAD patients with abnormal LVEF (<40%) during exercise and rest. In groups A and B, the exercise and rest L/H ratios did not differ significantly. However, a statistically significant inverse correlation was found between the L/H ratio and LVEF during exercise and rest among the 60 patients. L/H ratios, measured by 99mTc-tetrofosmin imaging, provide clinically useful information with which to predict left ventricular dysfunction in CAD patients.

A 2-tiered noninvasive cardiac risk stratification algorithm was first evaluated in a test population with planar thallium myocardial perfusion imaging and subsequently in a validation population using single-photon emission computed tomographic (SPECT) thallium myocardial perfusion imaging. This study examines if SPECT imaging was as predictive of cardiac death as planar imaging and also if SPECT imaging predicted nonfatal cardiac events in the patient population. Renal transplant candidates were evaluated using a 2-tiered noninvasive cardiac risk stratification algorithm. The first tier of risk assessment utilized 5 variables: age >50 years, insulin-dependent diabetes mellitus, abnormal electrocardiogram, and a history of either angina or congestive heart failure. Patients without risk factors were considered low risk and underwent no further cardiac evaluation. Patients with > or =1 risk factor were considered high risk and underwent a second tier of risk assessment with planar (n = 95) or SPECT (n = 112) imaging. In the test population, 13 of 16 cardiac deaths (81%) occurred in high-risk patients with abnormal planar studies. In the validation group, all cardiac deaths (5 of 60) and nonfatal cardiac events (13 of 60) occurred in high-risk patients with abnormal SPECT studies. SPECT imaging was at least as predictive as planar imaging and also predicted nonfatal as well as fatal cardiac events. Pretransplant risk stratification by clinical variables identified low-risk patients who may not require further cardiac evaluation and high-risk patients with normal SPECT imaging who may not require angiography.

In myocardial perfusion imaging, multiple-vessel involvement of coronary artery disease (CAD) sometimes makes diagnosis difficult. Transient left ventricular (LV) dilatation on Tl-201 myocardial SPECT is a useful finding that enables the clinician to identify patients with multiple-vessel disease. The aim of this study was to confirm the utility of measuring transient LV dilatation for the detection of multiple-vessel CAD in exercise Tc-99m tetrofosmin myocardial SPECT. The participants were 55 CAD patients and 20 controls who underwent Tc-99m tetrofosmin myocardial SPECT exercise and resting imaging. During exercise, 370 MBq (10 mCi) Tc-99m tetrofosmin was injected. Exercise images were obtained 30 minutes after injection. At 210 minutes after injection, 740 MBq (20 mCi) Tc-99m tetrofosmin was administered intravenously. The rest SPECT images were acquired 30 minutes later. Thirty-six radii at every 10 degrees were generated from the center of short-axis images. An area surrounded by 36 maximal points of the myocardial Tc-99m tetrofosmin counts on each radius was calculated for exercise and rest images. The area surrounded by the 36 maximal points in the same slice of the exercise and rest images was assigned the variables A (Ex) and A(R), respectively. The transient dilatation index (TDI) of the left ventricle was calculated using the formula mean A (Ex)/A(R) in the apical, middle, and basal myocardial short-axis images. In the controls, the TDI was 0.970 +/- 0.021. In patients with CAD, the TDIs of one-vessel disease, two-vessel disease, and three-vessel disease were 1.034 +/- 0.032, 1.093 +/- 0.046, and 1.131 +/- 0.076, respectively. The TDIs were significantly greater in patients who had more occluded coronary arteries (P < 0.01). If the mean + 2SD of the TDI (1.012) in controls were assumed to be the normal upper limit, the sensitivity, specificity, and accuracy of this method in detecting two-vessel or three-vessel disease would be 91.4%, 76.9%, and 84%, respectively. The TDI is a useful index for evaluating subendocardial ischemia non-invasively and detecting multiple-vessel disease clinically.

The aim of this study was to determine whether exercise echocardiography provides incremental data for risk stratification of patients with a low pretest probability of coronary artery disease.

The study included patients referred for exercise echocardiography whose probability of coronary artery disease was 25% or less. We calculated an exercise wall motion score index (on a 1-5 scale), an indicator of the extent and severity of exercise-induced abnormalities. The primary outcomes of the study were subsequent cardiac events (cardiac death and nonfatal myocardial infarction).

We studied 571 men and 1047 women; their mean (+/- SD) age was 55 +/- 13 years. During a median follow-up of 3 years, there were 19 cardiac events (6 cardiac deaths and 13 nonfatal myocardial infarctions); an additional 37 patients underwent coronary revascularization. In a multivariate analysis of clinical, exercise electrocardiographic, and echocardiographic parameters, exercise wall motion score index (hazard ratio [HR] = 2.1 per 0.5 units; 95% confidence interval [CI]: 1.3 to 3.4), and age (HR = 2.0 per decade; 95% CI: 1.2-2.8) were independently associated with the risk of cardiac events. Although exercise echocardiographic variables contributed significantly (P = 0.01) to a model of the risk of adverse events, only 9 (47%) of the 19 patients with cardiac events were identified by an abnormal exercise echocardiogram.

Among patients with low pretest probability of coronary artery disease by clinical criteria, exercise echocardiography identifies some, but not all, patients at risk of future events. Because of the low event rate, routine application of exercise echocardiography in a patient with a low pretest probability does not appear to be cost-effective and therefore cannot be recommended.