The relation between left ventricular ejection fraction and perfusion defect size by gated SPECT myocardial perfusion imaging in patients with coronary artery disease.

AIM: Left ventricular (LV) ejection fraction (EF) and perfusion defect size (PDS) provide independent and incremental prognostic information in patients with coronary artery disease (CAD). The purpose of this study was to examine the correlation between EF and PDS. METHODS: LVEF and PDS were measured in 96 consecutive patients with CAD and abnormal perfusion scan using well-validated automated programs. The PDS was expressed as % of LV myocardium as total (reversible plus fixed), fixed or reversible. RESULTS: The EF was 49±15% (range 17-84), the total PDS was 29±15% (2-77) and the fixed PDS was 20±13% (2-58). The end-diastolic volume (EDV) was 131±59 mL (29-342) and end-systolic volume (ESV) was 72±51 mL (4-283). There were moderate but significant correlations between EF and total PDS (r=-0.46, P<0.0001) and fixed PDS (r=-0.45, P<0.0001) but not with reversible PDS. In the subgroup analysis, the correlations were stronger in patients with history of prior coronary artery bypass grafting than without, and higher in men than women. The highest correlations were seen between EF and EDV in both men and women (r=-0.68 and -0.74 respectively, P<0.0001 each), and between EF and ESV (r =-0.80, P<0.0001). CONCLUSION: Although there is a statistically significant correlation between PDS and EF, the correlation is not strong. This observation provides supportive evidence of why PDS and EF provide incremental prognostic information. It also supports the incremental prognostic merits of LV volume measurements.

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.

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.

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.

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.

Noninvasive strategies for the estimation of cardiac risk in stable chest pain patients. The Economics of Noninvasive Diagnosis (END) Study Group.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.

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.

Comparison of dobutamine echocardiography, dobutamine sestamibi, and rest-redistribution thallium-201 single-photon emission computed tomography for determining contractile reserve and myocardial ischemia in ischemic cardiomyopathy.

Both dobutamine stress echocardiography (DSE) and myocardial perfusion scintigraphy are used to assess myocardial viability. Few studies have compared the data on myocardial viability and ischemia by low and peak dose DSE and myocardial perfusion imaging in the same patients. Fifty-four patients (45 men and 9 women aged 65 +/- 9 years) with ischemic cardiomyopathy (mean ejection fraction 24 +/- 9%) underwent rest 4-hour redistribution thallium-201 single-photon emission computed tomography (SPECT), low and peak dose DSE, and dobutamine sestamibi SPECT. A total of 864 segments were analyzed (16 segments/patient). Wall motion abnormality was present in 796 segments (92%), and contractile reserve during dobutamine infusion was seen in 400 of these segments (50%). Contractile reserve was seen in 331 of 509 hypokinetic segments (65%) and 69 of 287 akinetic/dyskinetic segments (24%) (p <0.001). Contractile reserve was more frequent in segments with normal thallium uptake (64%), reversible thallium defects (42%), or mild to moderate fixed thallium defects (48%) than severely fixed defects (22%) (p <0.05 each). Concordant information about viability by thallium imaging and DSE was obtained in 62% of segments. Dobutamine sestamibi ischemia was seen in 518 of 796 segments (65%) compared with 265 segments (33%) by DSE (p <0.001). Scintigraphic ischemia was noted in 126 of 195 segments (65%) demonstrating biphasic response, 129 of 205 segments (63%) showing sustained improvement, 42 of 70 segments (60%) deteriorating during dobutamine infusion, and 221 of 326 (68%) demonstrating no change (p = NS). Thus, in patients with ischemic cardiomyopathy, contractile reserve is more frequent in hypokinetic segments than akinetic/dyskinetic segments. The number of segments with normal or near-normal thallium uptake or with scintigraphic ischemia is significantly greater than the number of those capable of increasing contractile function or demonstrating an ischemic response during dobutamine echocardiography.

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.

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.

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.

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.