Measuring left ventricular mechanical dyssynchrony from ECG-gated SPECT myocardial perfusion imaging.

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. The traditional criteria to select patients for CRT (New York Heart Association [NYHA] class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) result in at least 30% of the selected patients with no response to CRT. Recent studies with echocardiography have shown that the presence of LV dyssynchrony is an important predictor for response to CRT. However, the recent report from the predictors of response to cardiac resynchronization therapy (PROSPECT) trial suggested that under ''real-world'' conditions the current available echocardiographic techniques including tissue Doppler imaging (TDI) and myocardial strain-rate imaging are not ready for routine clinical practice to assess LV dyssynchrony. Phase analysis is a recently developed technique that allows measuring LV dyssynchrony from electrocardiogram (ECG)-gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI). This technique uses Fourier harmonic functions to approximate regional wall thickening over the cardiac cycle and to calculate regional onset of mechanical contraction (OMC) phases. These OMC phases are obtained three-dimensionally over the entire left ventricle to quantitatively assess the degree of LV dyssynchrony. This technique has been compared to TDI and shown promising results in clinical validations. The advantages of this technique over echocardiography in measuring LV dyssynchrony are its automation, its high repeatability and reproducibility. It can be applied to any conventional GSPECT MPI study with no additional procedure. In this review the phase analysis methodology is described and its up-to-date clinical validations are summarized.

Long-term outcome of patients with intermediate-risk exercise electrocardiograms who do not have myocardial perfusion defects on radionuclide imaging.

BACKGROUND: The appropriate management of patients with intermediate-risk Duke treadmill scores is not established. The purpose of this study was to determine the long-term risk of subsequent cardiovascular events in patients with an intermediate-risk treadmill score who do not have myocardial perfusion defects on radionuclide imaging. METHODS AND RESULTS: The existing databases of the nuclear cardiology laboratories of 4 academic institutions were searched retrospectively. A total of 4649 patients were identified who had intermediate-risk Duke treadmill scores (-10 to 4), normal or near-normal exercise single photon-emission computed tomographic myocardial perfusion images using either thallium-201 or technetium-99m sestamibi, and no previous coronary revascularization. Follow-up was 95% complete. Cardiovascular survival was 99.8% at 1 year, 99.0% at 5 years, and 98.5% at 7 years. Cardiac survival free of myocardial infarction was similarly high at 96.6% at 7 years. Cardiac survival free of myocardial infarction or revascularization was 87.1% at 7 years. Near-normal scans and cardiac enlargement were independent predictors of time to cardiac death. Seven-year cardiac survival was still high at 97.0% in the 357 patients with near-normal scans and normal cardiac size and somewhat lower, at 89.0%, in the 167 patients with cardiac enlargement. CONCLUSIONS: Patients with an intermediate-risk treadmill score but with normal or near-normal exercise myocardial perfusion images and normal cardiac sizes are at low risk for subsequent cardiac death and can be safely managed medically until their symptoms warrant revascularization. The appropriate management of patients with cardiac enlargement will remain a matter of clinical judgment.

Risk assessment using single-photon emission computed tomographic technetium-99m sestamibi imaging.

OBJECTIVES: This review summarizes the results of single-photon emission computed tomographic (SPECT) technetium-99m (Tc-99m) tracer imaging in patients with stable symptoms, patients with acute coronary syndromes, patients undergoing major non-cardiac surgery and patients with chest pain in the emergency department. BACKGROUND: Previous studies have examined the prognostic value of stress thallium imaging in several subsets of patients with ischemic heart disease. At present, >50% of myocardial perfusion studies are performed with technetium-labeled tracers in the United States. Furthermore, there is a shift from diagnostic to the prognostic utility of stress testing. There are important differences between technetium-labeled tracers and thallium-201. It is therefore important to review the prognostic value of technetium-labeled tracers. METHODS: We analyzed published reports in English on risk assessment using Tc-99m perfusion tracers. Results. The largest experience is in patients with stable symptoms, comprising >12,000 patients in 14 studies. In these patients, normal stress SPECT sestamibi images were associated with an average annual hard event rate of 0.6% (death or nonfatal myocardial infarction [MI]). In contrast, patients with abnormal images had a 12-fold higher event rate (7.4% annually). Both fixed and reversible defects are prognostically important, and quantitative analysis shows increased risk in relation to the severity of the abnormality. These results are similar to those obtained with thallium-201. CONCLUSIONS: Patients with stable chest pain syndromes and normal stress SPECT sestamibi images have a very low risk of death or nonfatal MI. It is highly unlikely that coronary revascularization can improve survival in such patients. Patients with abnormal images have an intermediate to high risk for future cardiac events, depending on the degree of the abnormality. Further prospective studies comparing aggressive medical therapy with coronary revascularization in these patients are warranted.

Correlation between hemodynamic changes and tomographic sestamibi imaging during dipyridamole-induced coronary hyperemia.

OBJECTIVES: The purposes of this study were to examine the effects of dipyridamole infusion on hemodynamic variables and to compare these changes with myocardial perfusion. BACKGROUND: Dipyridamole stress testing with myocardial perfusion imaging is widely used in the assessment of patients with known or suspected coronary artery disease (CAD). Few studies, however, have correlated the hemodynamic effects of dipyridamole using invasive monitoring with perfusion patterns in patients with chest pain syndromes. METHODS: Hemodynamic measurements were made in the cardiac catheterization laboratory with a Swan-Ganz thermodilution catheter before, during and after infusion of dipyridamole (142 microg/kg body weight per min for 4 min). Technetium-99m sestamibi was injected 3 min after the completion of the infusion. RESULTS: There were 20 patients with and 6 without CAD, as demonstrated by angiography. Compared with baseline values, dipyridamole resulted in an increase in pulmonary capillary wedge pressure (54 +/- 78% vs. 32 +/- 26%, p = NS), cardiac index (36 +/- 21% vs. 40 +/- 18%, p = NS) and stroke volume index (16 +/- 18% vs. 40 +/- 18%, p = NS) and a decrease in systemic vascular resistance (22 +/- 13% vs. 24 +/- 11%, p = NS), aortic pressure (2 +/- 9% vs. 0 +/- 6%, p = NS) and pulmonary vascular resistance (19 +/- 25% vs. 11 +/- 32%, p = NS) in patients with and without CAD. The peak effect of dipyridamole on heart rate, systemic vascular resistance and pulmonary capillary wedge pressure was evident at 3 min after infusion in 70% of patients. Aminophylline, given to 20 patients, improved hemodynamic variables within 2 min. The single-photon emission computed tomographic sestamibi images were normal in the 6 patients without and abnormal in the 18 patients with CAD. CONCLUSIONS: Dipyridamole-induced coronary hyperemia produces mild hemodynamic changes in patients with and without CAD; these changes are at or near peak effect at 3 min after infusion and are rapidly reversed by aminophylline.

Noninvasive characterization of stunned, hibernating, remodeled and nonviable myocardium in ischemic cardiomyopathy.

OBJECTIVES: We evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction. BACKGROUND: Myocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging. METHODS: We studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred. RESULTS: Severe regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p<0.05). CONCLUSIONS: It is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.

The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia. Economics of Noninvasive Diagnosis (END) Multicenter Study Group.

OBJECTIVES: The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality. BACKGROUND: A number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice. METHODS: We prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk. RESULTS: Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary revascularization rates were higher for low, intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates were similar (p > 0.20). CONCLUSIONS: Observational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

Exercise-rest same-day SPECT sestamibi imaging to detect coronary artery disease.

UNLABELLED: This study examined the results of exercise-rest same-day SPECT protocol in 193 patients, of whom 132 had coronary artery disease (CAD) by angiography (> or = 50% diameter stenosis), and 61 had a low pretest probability of CAD. METHODS: The rest study was combined with first-pass radionuclide angiography using the multicrystal gamma camera in 72 patients. RESULTS: The sensitivity of SPECT was 76% (25/33 patients) in patients with one-vessel, 84% in patients with two-vessel (38/45) and 98% in patients with three-vessel CAD (53/54) (P = 0.01 versus one- or two-vessel CAD). The sensitivity of SPECT in patients with CAD was higher than ST depression (88% versus 28%, P = 0.001). The exercise was submaximal in 53 patients (40%). The perfusion defects were reversible (complete or partial) in 80 patients and fixed in 36 patients. The left ventricular ejection fraction was 50 +/- 12% in patients with reversible defects (n = 44) and 39 +/- 9% in patients with fixed defects (n:19) (P = 0.0004). The normalcy rate in subjects with a low pretest probability of CAD was 95% (53 of 61 subjects). CONCLUSION: The exercise-rest same-day sestamibi protocol provides high diagnostic accuracy for CAD detection. The protocol may eliminate the need for rest studies in patients with normal exercise images, help improve laboratory throughput and lower costs.

123I-IPPA SPECT for the prediction of enhanced left ventricular function after coronary bypass graft surgery. Multicenter IPPA Viability Trial Investigators. 123I-iodophenylpentadecanoic acid.

UNLABELLED: Fatty acids are the prime metabolic substrate for myocardial energy production. Hence, fatty acid imaging may be useful in the assessment of myocardial hibernation. The goal of this prospective, multicenter trial was to assess the use of a fatty acid, 123I-iodophenylpentadecanoic acid (IPPA), to identify viable, hibernating myocardium. METHODS: Patients (n = 119) with abnormal left ventricular wall motion and a left ventricular ejection fraction (LVEF) < 40% who were already scheduled to undergo coronary artery bypass grafting (CABG) underwent IPPA tomography (rest and 30-min redistribution) and blood-pool radionuclide angiography within 3 d of the scheduled operation. Radionuclide angiography was repeated 6-8 wk after CABG. The study endpoint was a > or =10% increase in LVEF after CABG. The number of IPPA-viable abnormally contracting segments necessary to predict a positive LVEF outcome was determined by receiver operating characteristic (ROC) curves and was included in a logistic regression analysis, together with selected clinical variables. RESULTS: Before CABG, abnormal IPPA tomography findings were seen in 113 of 119 patients (95%), of whom 71 (60%) had redistribution in the 30-min images. The LVEF increased modestly after CABG (from 32% +/- 12% to 36% +/- 8%, P< 0.001).A > or =10% increase in LVEF after CABG occurred in 27 of 119 patients (23%). By ROC curves, the best predictor of a > or =10% increase in LVEF was the presence of > or =7 IPPA-viable segments (accuracy, 72%; confidence interval, 64%-80%). Among clinical and scintigraphic variables, the single most important predictor also was the number of IPPA-viable segments (P = 0.008). The number of IPPA-viable segments added significant incremental value to the best clinical predictor model. CONCLUSION: Asubstantial increase in LVEF occurs after CABG in only a minority of patients (23%) with depressed preoperative function. The number of IPPA-viable segments is useful in predicting a clinically meaningful increase in LVEF.

Evidence-based risk assessment in noninvasive imaging.

UNLABELLED: Assessment of important clinical and economic outcomes has become central to the evaluation of patient care. Outcome research is deeply rooted in epidemiology, including the use of multivariable, risk-adjusted regression analysis. In our current health care environment, these methods are increasingly being used to assess the quality of care and to profile physicians and laboratories. Nuclear medicine physicians therefore need to better understand outcome methodologies in order to evaluate patient outcomes, develop guidelines, and decide on patient management. METHODS: This review describes the methods of assessing the diagnostic and prognostic value of nuclear medicine techniques and, briefly, the methodologic limitations of sample size, frequency and type of events, and follow-up periods and the incremental value of imaging. Also described are logistic regression and Cox proportional hazards modeling. Models for risk assessment are designed to identify whether patients require conservative (i.e., low-risk) or aggressive (i.e., high-risk) treatment. Treatment selection is currently based on risk assessment and the formation of an integrated, empiric risk stratification algorithm of care. This review also includes the methods of assessing economic effectiveness and quality-of-life issues for patients examined with nuclear medicine techniques. CONCLUSION: In this era of constrained resources, low-cost outpatient-based care may be of increasing importance. High-quality evidence of the clinical and economic outcome of nuclear imaging is essential for helping health care providers and payers assess its value.

Fasting and nonfasting iodine-123-idophenylpentadecanoic acid myocardial SPECT imaging in coronary artery disease.

UNLABELLED: Iodine-123-labeled idophenylpentadecanoic acid (IPPA) metabolic imaging has been shown to be clinically useful for the identification of myocardial viability in patients with coronary artery disease and left ventricular dysfunction. Imaging is usually performed under fasting conditions since nonfasting conditions may affect myocardial uptake of 123I-IPPA. The purpose of this study was to examine the impact of dietary condition on 123I-IPPA metabolic imaging. METHODS: Forty patients with stable coronary artery disease underwent, in randomized order and on separate days, 123I-IPPA SPECT myocardial imaging under fasting and nonfasting conditions. Patients were injected with 123I-IPPA (4-5 mCi) at rest with imaging performed at 4 (initial) and 30 (delay) min. For each image (initial and delay images), 10 segments were analyzed by three experienced observers without knowledge of patient identity or dietary condition using a 5-point grading system (O = no uptake to 4 = normal uptake). A summed global score was obtained for each image by adding the scores for all 10 segments. Image quality was assessed using a 3-point grading system. RESULTS: Visual agreement for normal and abnormal segments between fasting and nonfasting conditions was 82% (kappa = 0.63). There were no significant differences in the summed global scores for both conditions. Image quality was equivalent for both conditions in 65% of cases and superior under the nonfasting condition in 25% of cases. CONCLUSION: Image quality as well as the presence, location and severity of defects are similar under fasting and nonfasting conditions with 123I-IPPA. Therefore, fasting is not necessary before 123I-IPPA SPECT imaging for the assessment of myocardial viability.

Stress myocardial perfusion imaging after coronary angioplasty.

Stress myocardial perfusion imaging is useful in patient management after coronary angioplasty. The ischemic perfusion pattern suggests the presence of residual stenosis, restenosis, down stream stenosis, side branch stenosis, and remote stenosis.

Prognostic utility of myocardial viability assessment.

Myocardial viability assessment is useful in patients with severe coronary artery disease and severe left ventricular dysfunction. Whereas most studies have focused on recovery of regional function, there are emerging data on patient outcome. Review of these data suggests that patients with chronic ischemia, cardiomyopathy, and viable myocardium who are treated medically have a worse, outcome than those treated with coronary revascularization. However, there are no prospective randomized trials. We present perspectives for future studies.

Impact of exercise single-photon emission computed tomographic imaging on appropriateness of coronary revascularization.

This study examined the predictors of early coronary revascularization in 816 patients with chest pain syndromes who had coronary artery disease by angiography and exercise single-photon emission computed tomography (SPECT) thallium imaging. Multivariate analysis of clinical, stress, nuclear, and catheterization variables revealed the presence of SPECT reversibility as the most powerful predictor (chi-square = 43) of early revascularization.

Hemodynamic effects of arbutamine.

This study examined the hemodynamic effects of arbutamine, a synthetic catecholamine, in 12 patients with and 7 patients without coronary artery disease. Arbutamine produced a balanced positive inotropic (increase in left ventricular dp/dt) and chronotropic effect (increase in heart rate).

Prognostic value of simultaneous perfusion and function assessment using technetium-99m sestamibi.

This study examines the prognostic value of simultaneous perfusion and function assessment in 412 patients. The exercise perfusion pattern was a stronger predictor of events (mostly acute nonfatal myocardial infarcts) than resting ejection fraction.

Comparison of the polar maps method and the summed stress score for predicting outcome in medically treated patients with coronary artery disease.

This study showed that quantitative analysis of SPECT perfusion images provide comparable prognostic information to summed stress score in medically treated patients with coronary artery disease.

Utility of stress single-photon emission computed tomography (SPECT) perfusion imaging in predicting outcome after coronary artery bypass grafting.

Previous studies have examined the predictors of outcome in medically treated patients with coronary artery disease (CAD). There is limited information on predictors of outcome after coronary artery bypass grafting (CABG). This study examined the predictors of outcome of 255 patients with CAD, at a mean time of 5 years after CABG for angina pectoris. The 255 patients underwent coronary angiography and stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging after CABG. During a mean follow-up of 41 +/- 28 months after stress testing, there were 34 hard events (24 cardiac deaths and 10 nonfatal myocardial infarctions). The hemodynamics during stress testing, and age and gender were not predictors of events. The SPECT variables of multivessel perfusion abnormality, perfusion deficit size, and increased lung thallium uptake were predictors of death and total events by uni- and multivariate survival analysis. There were 14 events in 45 patients (31%) with multivessel abnormality and increased lung thallium uptake, 14 events in 101 patients (14%) with either multivessel abnormality or increased lung uptake, and 6 events in 109 patients (6%) with neither of these 2 variables (p = 0.0001). The annual mortality and total event rates were 7.5% and 9.5% with both variables, 3.4% and 4.3% with either variable, and 0.6% and 1.7% with neither of the variables (p = 0.01). Thus, stress SPECT perfusion imaging is useful to stratify patients after CABG into low, intermediate, and high risk groups for future cardiac events.

Comparison of the prognostic value of qualitative versus quantitative stress tomographic perfusion imaging.

This study compared qualitative assessment of exercise thallium imaging to quantitative assessment in predicting outcome in 713 patients with 78% prevalence of coronary artery disease by coronary angiography; during a mean follow-up of 52 months, there were 106 hard cardiac events (death or nonfatal myocardial infarction). The qualitative method provided important prognostic information; however, unlike the quantitative technique, less patients were assigned to either the low- or high-risk group and proportionally more patients into the intermediate-risk group, which may limit the clinical usefulness of the technique.

Impact of stress single-photon emission computed tomography perfusion imaging on downstream resource utilization.

This study shows that in patients with intermediate pretest probability of coronary artery disease stress single-photon emission computed tomography perfusion imaging decreases the rate of coronary angiography and coronary revascularization and is economically a superior strategy to routine coronary angiography.

Predictors of outcome of medically treated patients with left main/three-vessel coronary artery disease by coronary angiography.

This study examined the prognostic value of single-photon emission computed tomography in angiographically high-risk patients with left main and/or 3-vessel coronary artery disease who were treated medically. Multivariable Cox survival analysis revealed the single-photon emission computed tomography score (based on size of perfusion abnormality, multivessel abnormality, left ventricular dilation, and lung uptake) as the only independent predictor of outcome.