Recommendations of the European Association of Echocardiography: how to use echo-Doppler in clinical trials: different modalities for different purposes.

The European Association of Echocardiography (EAE) has developed the present recommendations to assist clinical researchers in the design, implementation, and conduction of echocardiographic protocols for clinical trials and to guarantee their quality. Clinical trials should be designed and conducted based on the knowledge of the pathophysiology of the clinical condition studied, the technical characteristics of the echo-Doppler modalities, and the variability of the tested parameters. These procedures are important to choose the most reliable and reproducible techniques and parameters. Quality assurance must be guaranteed by adequate training of peripheral site operators to obtain optimal echo-Doppler data and by using a core laboratory for accurate and reproducible data analysis.

Monitoring in vivo absorption of a drug-eluting bioabsorbable stent with intravascular ultrasound-derived parameters a feasibility study.

OBJECTIVES: The aim of this study was to investigate the feasibility of using quantitative differential echogenicity to monitor the in vivo absorption process of a drug-eluting poly-l-lactic-acid (PLLA) bioabsorbable stent (BVS, Abbott Vascular, Santa Clara, California). BACKGROUND: A new bioabsorbable, balloon-expanded coronary stent was recently evaluated in a first-in-man study. Little is known about the absorption process in vivo in diseased human coronary arteries. METHODS: In the ABSORB (Clinical Evaluation of the BVS everolimus eluting stent system) study, 30 patients underwent treatment with the BVS coronary stent system and were examined with intracoronary ultrasound (ICUS) after implantation, at 6 months and at 2-year follow-up. Quantitative ICUS was used to measure dimensional changes, and automated ICUS-based tissue composition software (differential echogenicity) was used to quantify plaque compositional changes over time in the treated regions. RESULTS: The BVS struts appeared as bright hyperechogenic structures and showed a continuous decrease of their echogenicity over time, most likely due to the polymer degradation process. In 12 patients in whom pre-implantation ICUS was available, at 2 years the percentage-hyperechogenic tissue was close to pre-implantation values, indicating that the absorption process was either completed or the remaining material was no longer differentially echogenic from surrounding tissues. CONCLUSIONS: Quantitative differential echogenicity is a useful plaque compositional measurement tool. Furthermore, it seems to be valuable for monitoring the absorption process of bioabsorbable coronary stents made of semi-crystalline polymers.

European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography.

The main mission statement of the European Association of Echocardiography (EAE) is 'to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe'. As competence and quality control issues are increasingly recognized by patients, physicians, and payers, the EAE has established recommendations for training, competence, and quality improvement in echocardiography. The purpose of this document is to provide the requirements for training and competence in echocardiography, to outline the principles of quality measurement, and to recommend a set of measures for improvement, with the ultimate goal of raising the standards of echocardiographic practice in Europe.

Coronary calcium significantly affects quantitative analysis of coronary ultrasound: importance for atherosclerosis progression/regression studies.

BACKGROUND: Coronary atherosclerosis is a dynamic process, which progresses differently in coronary segments containing noncalcified or calcified plaques. This may have implications for the study of the effects of therapy on progression/regression. OBJECTIVE: To test this hypothesis, we performed a post-hoc analysis on data of a randomized trial in which perindopril treatment was compared with placebo on progression/regression of atherosclerosis with regard to the degree of calcification. METHODS AND RESULTS: The intracoronary ultrasound data of 118 patients, who were enrolled in the multicentre, double-blinded randomized trial (PERSPECTIVE), were analysed. Vessel, lumen and plaque areas were measured in 711 5-mm-long matched coronary segments (perindopril 360, placebo 351). Each individual intracoronary ultrasound cross-section was binary labelled for the presence of calcium (yes/no), and the degree of calcium was assessed as a percentage of length. The segments were classified into three groups: 0-25, 25-50 and 50-100% (percentage of length) calcification. Coronary plaques with no or little calcium (0-25%) regressed on perindopril and did not change on placebo (-0.33+/-1.74 vs. -0.03+/-1.66, respectively; P = 0.04). Plaques containing moderate calcium (group 25-50%) did not change and plaques with severe amounts of calcification (group 50-100%) equally progressed. CONCLUSION: Noncalcified plaques may be amenable to regression with ACE inhibitor treatment. The method, which considers the amount of calcium content in a plaque, may lead to new insights for quantitative analysis of the effects of therapy in progression/regression studies of atherosclerosis.

Compositional volumetry of non-calcified coronary plaques by multislice computed tomography: an ex vivo feasibility study.

AIMS: Non-invasive quantitative compositional analysis of coronary plaque would be a major advantage to study coronary artery disease. This study explores the application to use the Hounsfield units (HU) distribution of coronary plaques imaged by multislice computed tomography-coronary angiography (MSCT-CA). METHODS AND RESULTS: A dedicated computer-assisted method was developed to measure the HU distribution within a coronary plaque by MSCT-CA. To test the feasibility of the method, an ex vivo left anterior descending (LAD) coronary specimen, excised during autopsy, was imaged both by non-enhanced and enhanced MSCT-CA. Quantitative histology was used as a reference. To test the feasibility of the new volumetric analytic method, the MSCT-CA data were compared with volumetric histopathology. The coronary specimen, with a heterogeneously distributed plaque composition without large areas of calcification, was histologically sampled at five different locations, 5 mm apart, where at each location 15 sections were taken at 100 microm intervals, resulting in 75 individual histology sections. Tri-chrome Masson staining was used for histology quantification of three plaque/tissue components: smooth muscle cells (SMC), collagen and calcium. MSCT plaque composition was defined as "lower-HU" or "higher-HU" plaque and "calcium" based on the HU distribution. Comparison of the MSCT defined tissue components against histology showed a good relationship without significant differences. CONCLUSIONS: This ex vivo study shows the feasibility of using the Hounsfield unit distribution to perform compositional coronary plaque volumetry by MSCT-CA. The results are encouraging.

Contrast-enhanced three-dimensional dobutamine stress echocardiography: between Scylla and Charybdis?

AIMS: Real-time three-dimensional echocardiography (RT3DE) allows quick volumetric scanning of the left ventricle (LV). We evaluated the diagnostic accuracy of contrast-enhanced stress RT3DE for the detection of coronary artery disease (CAD) in comparison with coronary arteriography as the reference technique. METHODS AND RESULTS: Forty-five consecutive patients (age 59 +/- 10, 31 males) referred for coronary angiography were examined by contrast-enhanced RT3DE. Wall motion analysis was performed off-line by dedicated software. New or worsening wall motion abnormalities were detected in 17 of 28 patients with significant CAD (sensitivity 61%), and in two of 17 patients without significant CAD (specificity 88%). The sensitivity for detection of single-vessel CAD was 8/15 patients (53%), for two-vessel CAD 4/6 (67%), and for three-vessel CAD 5/7 (71%). In 35 patients, comparison with conventional RT3DE was available. The image quality index at rest improved from 2.5 +/- 1.2 to 3.2 +/- 1.0 (P < 0.001) with contrast and at peak stress from 2.3 +/- 1.2 to 3.1 +/- 1.0 (P < 0.001). Interobserver agreement on the diagnosis of myocardial ischaemia improved from 26 of 35 studies (74%, kappa = 0.44) with conventional stress RT3DE to 30 of 35 studies (86%, kappa = 0.69) with contrast-enhanced stress RT3DE. Sensitivity increased from 50 to 55% and specificity from 69 to 85% with contrast-enhanced stress RT3DE in this subset of patients. CONCLUSION: Despite some important practical and theoretical benefits, contrast-enhanced stress RT3DE currently has only moderate diagnostic sensitivity due to several technical limitations as temporal and spatial resolution.

Partial ventricular septal defect (Pacman Heart).

Complete ventricular septal defects (VSD) can be congenital (estimated prevalence 0.5% in live births) (Roguin N, et al. High prevalence of muscular ventricular septal defect in neonates. J Am Coll Cardiol 1995;26:1545-1548) or may be a complication of acute myocardial infarction (estimated incidence in the era of thrombolysis 0.2%) [Crenshaw BS, et al. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators. Circulation 2000;101:27-32]. In this paper, we report two unique cases of partial VSD.

Three-dimensional and quantitative analysis of atherosclerotic plaque composition by automated differential echogenicity.

OBJECTIVE: To validate automated and quantitative three-dimensional analysis of coronary plaque composition using intracoronary ultrasound (ICUS). BACKGROUND: ICUS displays different tissue components based on their acoustic properties in 256 grey-levels. We hypothesised that computer-assisted image analysis (differential echogenicity) would permit automated quantification of several tissue components in atherosclerotic plaques. METHODS AND RESULTS: Ten 40-mm-long left anterior descending specimens were excised during autopsy of which eight could be successfully imaged by ICUS. Histological sections were taken at 5 mm intervals and analyzed. Since most of the plaques were calcified and having a homogeneous appearance, one specimen with a more heterogeneous composition was further examined: at each interval of 5 mm, 15 additional sections (every 100 microm) were evaluated. Plaques were scored for echogenicity against the adventitia: brighter (hyperechogenic) or less bright (hypoechogenic). Areas of hypoechogenicity correlated with the presence of smooth muscle cells. Areas of hyperechogenicity correlated with presence of collagen, and areas of hyperechogenicity with acoustic shadowing correlated with calcium. None of these comparisons showed statistical significant differences. CONCLUSION: This ex vivo feasibility study shows that automated three-dimensional differential echogenicity analysis of ICUS images allows identification of different tissue types within atherosclerotic plaques. This technology may play a role as an additional tool in longitudinal studies to trace possible changes in plaque composition.

Comparison of contrast agent-enhanced versus non-contrast agent-enhanced real-time three-dimensional echocardiography for analysis of left ventricular systolic function.

Ultrasound contrast has shown to improve endocardial border definition. The purpose of this study was to evaluate the value of contrast agent-enhanced versus non-contrast agent-enhanced real-time 3-dimensional echocardiography (RT3DE) for the assessment of left ventricular (LV) volumes and ejection fraction. Thirty-nine unselected patients underwent RT3DE with and without SonoVue contrast agent enhancement and magnetic resonance imaging (MRI) on the same day. An image quality index was calculated by grading all 16 individual LV segments on a scale of 0 to 4: 0, not visible; 1, poor; 2, moderate; 3, good; and 4, excellent. The 3-dimensional data sets were analyzed offline using dedicated TomTec analysis software. By manual tracing, LV end-systolic volume, LV end-diastolic volume, and LV ejection fraction were calculated. After contrast agent enhancement, mean image quality index improved from 2.4 +/- 1.0 to 3.0 +/- 0.9 (p <0.001). Contrast agent-enhanced RT3DE measurements showed better correlation with MRI (LV end-diastolic volume, r = 0.97 vs 0.86; LV end-systolic volume, r = 0.96 vs 0.94; LV ejection fraction, r = 0.94 vs 0.81). The limits of agreement (Bland-Altman analysis) showed a similar bias for RT3DE images with and without contrast agent but with smaller limits of agreement for contrast agent-enhanced RT3DE. Also, inter- and intraobserver variabilities decreased. In a subgroup, patients with poor to moderate image quality showed an improvement in agreement after administration of contrast agent (+/-24.4% to +/-12.7%) to the same level as patients with moderate to good image quality without contrast agent (+/-10.4%). In conclusion, contrast agent-enhanced RT3DE is more accurate in assessment of LV function as evidenced by better correlation and narrower limits of agreement compared with MRI, as well as lower intra- and interobserver variabilities.

Three-dimensional echocardiographic analysis of left ventricular function during hemodialysis.

BACKGROUND: The effects of hemodialysis (HD) on left ventricular (LV) function have been studied by various echocardiographic techniques (M-mode, 2D echocardiography). These studies are hampered by a low accuracy of measurements because of geometric assumptions regarding LV shape. Three-dimensional echocardiography (3DE) overcomes this limitation. METHODS: We tested the feasibility of 3DE assessment of LV function during HD. Conventional biplane Simpson rule (BSR) and single plane area length method (SPM) for LV function analysis were used as a reference. RESULTS: 12 HD patients were studied and in 10 (83%) a total of 80 3D datasets were acquired. In 3 patients, one dataset (4%) was of insufficient quality and excluded from analysis. Correlation between SPM, BSR and 3DE for calculation of end-diastolic (EDV, r = 0.89 and r = 0.92, respectively), end-systolic volume (ESV, r = 0.92 and r = 0.93, respectively) and for ejection fraction (EF, r = 0.90 and r = 0.88, respectively) was moderate. Limits-of-agreement results for EDV and ESV were poor with confidence intervals larger than 30 ml. Both 2DE methods underestimated end-diastolic and end-systolic volume, while overestimating ejection fraction. CONCLUSION: 3DE is feasible for image acquisition during HD, which opens the possibility for accurate and reproducible measurement of LV function during HD. This may improve the assessment of the acute effect of HD on LV performance, and guide therapeutic strategies aimed at preventing intradialytic hypotension.

Can echocardiographic findings predict falls in older persons?

BACKGROUND: The European and American guidelines state the need for echocardiography in patients with syncope. 50% of older adults with syncope present with a fall. Nonetheless, up to now no data have been published addressing echocardiographic abnormalities in older fallers. METHOD AND FINDINGS: In order to determine the association between echocardiographic abnormalities and falls in older adults, we performed a prospective cohort study, in which 215 new consecutive referrals (age 77.4, SD 6.0) of a geriatric outpatient clinic of a Dutch university hospital were included. During the previous year, 139 had experienced a fall. At baseline, all patients underwent routine two-dimensional and Doppler echocardiography. Falls were recorded during a three-month follow-up. Multivariate adjustment for confounders was performed with a Cox proportional hazards model. 55 patients (26%) fell at least once during follow-up. The adjusted hazard ratio of a fall during follow-up was 1.35 (95% CI, 1.08-1.71) for pulmonary hypertension, 1.66 (95% CI, 1.01 to 2.89) for mitral regurgitation, 2.41 (95% CI, 1.32 to 4.37) for tricuspid regurgitation and 1.76 (95% CI, 1.03 to 3.01) for pulmonary regurgitation. For aortic regurgitation the risk of a fall was also increased, but non-significantly (hazard ratio, 1.57 [95% CI, 0.85 to 2.92]). Trend analysis of the severity of the different regurgitations showed a significant relationship for mitral, tricuspid and pulmonary valve regurgitation and pulmonary hypertension. CONCLUSIONS: Echo (Doppler) cardiography can be useful in order to identify risk indicators for falling. Presence of pulmonary hypertension or regurgitation of mitral, tricuspid or pulmonary valves was associated with a higher fall risk. Our study indicates that the diagnostic work-up for falls in older adults might be improved by adding an echo (Doppler) cardiogram in selected groups.

Reproducible coronary plaque quantification by multislice computed tomography.

BACKGROUND: The aim of this study was to investigate reproducibility and accuracy of computer-assisted coronary plaque measurements by multislice computed tomography coronary angiography (QMSCT-CA). METHODS AND RESULTS: Forty-eight patients undergoing MSCT-CA and coronary arteriography for symptomatic coronary artery disease and quantitative intravascular ultrasound (IVUS, QCU) were examined. Two investigators performed the QMSCT-CA twice and a third investigator performed the QCU, all blinded for each other's results. There was no difference found for the matched region of interest (ROI) lengths (QCU 29.4 +/- 13 mm vs. QMSCT-CA 29.6 +/- 13 mm, P = 0.6; total length = 1,400 mm). The comparison of volumetric measurements showed (lumen QCU 267 +/- 139 mm(3) vs. mean QMSCT-CA 177 +/- 91 mm(3), P < 0.001; vessel 454 +/- 194 mm(3) vs. 398 +/- 187 mm(3), P <<0.001; and plaque 189 +/- 93 mm(3) vs. 222 +/- 121 mm(3); investigator 1, P = 0.02; and investigator 2, P = 0.07) significant differences. Automated lumen detection was also applied for QMSCT-CA (218 +/- 112 mm(3), P < 0.001 vs. QCU). The interinvestigator variability measurements for QMSCT-CA showed no significant differences. CONCLUSION: QMSCT-CA systematically underestimates absolute coronary lumen- and vessel dimensions when compared with QCU. However, repeated measurements of coronary plaque by QMSCT-CA showed no statistically significant differences, although, the outcome showed a scattered result. Automated lumen detection for QMSCT-CA showed improved results when compared with those of human investigators.

Efficient quantification of the left ventricular volume using 3-dimensional echocardiography: the minimal number of equiangular long-axis images for accurate quantification of the left ventricular volume.

For quantification of the left ventricular volume from 3-dimensional echocardiograms a number of cross-sectional images are used. The goal of this study was to determine the minimum number of long-axis images necessary for accurate quantification of the left ventricular volume. A strong correlation was observed between volumes obtained from magnetic resonance imaging and 3-dimensional echocardiography using 16 equiangular images (r = 0.99; y = 0.95x + 3.3 mL; standard error of the estimate = 7.0 mL; N = 30). Comparison of these results with random subsets showed a significant difference for volumes obtained with 4 and 2 equiangular images (P < .005). However, when the subsets were selected to target the eccentric region of the endocardial border this was only the case for subsets of two images (P < .001). This study demonstrates that accurate left ventricular volume quantification can be performed with as little as 8 equiangular long-axis images. By selecting the correctly oriented image set, this number can even be brought down to 4, which will further reduce the analysis time.

Harmonic 3-D echocardiography with a fast-rotating ultrasound transducer.

Although the advantages of three-dimensional (3-D) echocardiography have been acknowledged, its application for routine diagnosis is still very limited. This is mainly due to the relatively long acquisition time. Only recently has this problem been addressed with the introduction of new real-time 3-D echo systems. This paper describes the design, characteristics, and capabilities of an alternative concept for rapid 3-D echocardiographic recordings. The presented fast-rotating ultrasound (FRU)-transducer is based on a 64-element phased array that rotates with a maximum speed of 8 Hz (480 rpm). The large bandwidth of the FRU-transducer makes it highly suitable for tissue and contrast harmonic imaging. The transducer presents itself as a conventional phased-array transducer; therefore, it is easily implemented on existing 2-D echo systems, without additional interfacing. The capabilities of the FRU-transducer are illustrated with in-vitro volume measurements, harmonic imaging in combination with a contrast agent, and a preliminary clinical study.

Rapid and accurate measurement of left ventricular function with a new second-harmonic fast-rotating transducer and semi-automated border detection.

Measurement of left ventricular (LV) volume and function are the most common clinical referral questions to the echocardiography laboratory. A fast, practical, and accurate method would offer important advantages to obtain this important information. To validate a new practical method for rapid measurement of LV volume and function. We developed a continuous fast-rotating transducer, with second-harmonic capabilities, for three-dimensional echocardiography (3DE). Fifteen cardiac patients underwent both 3DE and magnetic resonance imaging (reference method) on the same day. 3DE image acquisition was performed during a 10-second breath-hold with a frame rate of 100 frames/sec and a rotational speed of 6 rotations/sec. The individual images were postprocessed with Matlab software using multibeat data fusion. Subsequently, with these images, 12 datasets per cardiac cycle were reconstructed, each comprising seven equidistant cross-sectional images for analysis in the new TomTec 4DLV analysis software, which uses a semi-automated border detection (ABD) algorithm. The ABD requires an average analysis time of 15 minutes per patient. A strong correlation was found between LV end-diastolic volume (r = 0.99; y = 0.95x - 1.14 ml; SEE = 6.5 ml), LV end-systolic volume (r = 0.96; y = 0.89x + 7.91 ml; SEE = 7.0 ml), and LV ejection fraction (r = 0.93; y = 0.69x + 13.36; SEE = 2.4%). Inter- and intraobserver agreement for all measurements was good. The fast-rotating transducer with new ABD software is a dedicated tool for rapid and accurate analysis of LV volume and function.

Benefits of coronary revascularisation in diabetic and non-diabetic patients with ischaemic cardiomyopathy: role of myocardial viability.

BACKGROUND: Diabetes mellitus in patients with coronary artery disease is associated with poor outcome. In this study, the relation between myocardial viability, diabetes, coronary revascularisation and outcome was evaluated. METHODS: 129 patients (31 diabetic, 98 non-diabetic) with ischaemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability. Patients with >or=4 viable segments were defined as viable and patients with <4 viable segments as nonviable. Left ventricular ejection fraction (LVEF) was assessed before and 9-12 months post-revascularisation. At the same time-points, LV volumes were measured to evaluate LV remodelling. Finally, cardiac events were noted during 5-year follow-up. RESULTS: The extent of viable myocardium was comparable between diabetic and non-diabetic patients. After revascularisation, LVEF increased >or=5% in 44% of diabetic and in 40% of non-diabetic patients. LVEF only improved in patients with viable myocardium. Ongoing LV remodelling occurred in 36% and 35% of diabetic and non-diabetic patients respectively, and was related to non-viability, whereas viability protected against ongoing LV remodelling, both in diabetic and non-diabetic patients. Viability was the only predictor of survival after revascularisation. CONCLUSIONS: Diabetic, viable patients with ischaemic LV dysfunction exhibit improvement in LVEF post-revascularisation with prevention of ongoing LV remodelling, similar to non-diabetic patients. Myocardial viability was also the only predictor of long-term outcome.

Clinical and prognostic implications of angina pectoris developing during dobutamine stress echocardiography in the absence of inducible wall motion abnormalities.

This study assessed the incidence, clinical correlates, and prognostic significance of angina during dobutamine stress echocardiography (DSE) in patients who did not have inducible wall motion abnormalities. We studied 2,117 patients (61 +/- 13 years of age; 1,149 men) who underwent large-dose DSE and had no new or worsening wall motion abnormalities during DSE. Follow-up events were hard cardiac events (cardiac death or nonfatal myocardial infarction) and myocardial revascularization. Angina was induced in 217 patients (10%) during stress. DSE was normal in 1,198 patients (57%), whereas 919 patients (43%) had fixed wall motion abnormalities. During a mean follow-up of 5.5 +/- 3.7 years, 143 patients (7%) died of cardiac causes and 78 (4%) had nonfatal myocardial infarction. Patients who developed angina during DSE were more likely to have a history of exertional angina (64% vs 16%, p <0.001) and had a higher wall motion score index at rest (1.29 +/- 0.5 vs 1.17 +/- 0.4, p = 0.01) compared with patients who did not have angina. Annual hard cardiac event rates were 2.2% in patients who had dobutamine-induced angina (DIA) and 2.1% in patients who did not (p = NS). Myocardial revascularization was performed more frequently in patients who had DIA than in those who did not (39% vs 14%, p <0.0001). In Cox's regression model, independent predictors of hard events were age (RR 1.03, 95% confidence interval [CI] 1.02 to 1.04), male gender (RR 1.6, 95% CI 1.1 to 2.2), smoking (RR 1.5, 95% CI 1.1 to 2.9), and wall motion score index at rest (RR 2.6, 95% CI 1.8 to 3.8). In conclusion, in patients who do not have ischemia by echocardiographic criteria during DSE, inducible angina pectoris is associated with a high incidence of revascularization during follow-up. However, the hard cardiac event rate does not differ in patients who develop DIA from those who do not.

Relation of improvement in left ventricular ejection fraction versus improvement in heart failure symptoms after coronary revascularization in patients with ischemic cardiomyopathy.

In the present study, the relation between improvement in the left ventricular ejection fraction (LVEF) and heart failure symptoms was evaluated in 100 patients with ischemic cardiomyopathy undergoing coronary revascularization. In patients with viable myocardium, the improvement in the LVEF after revascularization was accompanied by improvement in heart failure symptoms in most patients (80%); most viable patients (75%) without improvement in LVEF also showed an improvement in New York Heart Association functional class. Conversely, most nonviable patients failed to improve in LVEF or New York Heart Association class.

Effect of myocardial ischemia during dobutamine stress echocardiography on cardiac mortality in patients with heart failure secondary to ischemic cardiomyopathy.

This study assessed the effect of ischemia during dobutamine stress echocardiography (DSE) on cardiac mortality in patients with heart failure. We studied 528 patients (62 +/- 11 years of age, 402 men) who had heart failure and previous myocardial infarction or known coronary artery disease and underwent DSE. Ischemia was defined as new or worsening wall motion abnormalities or a biphasic response. End point during follow-up was cardiac death. Mean ejection fraction was 35 +/- 12%. Ischemia was detected in 407 patients (77%). During a mean follow-up of 3.2 +/- 2.4 years, cardiac death occurred in 150 patients (28%). Myocardial revascularization was performed within 4 months after DSE in 117 patients (29%) who had ischemia. Annual rates of cardiac death were 4.8% in patients who did not have ischemia, 5.5% in those who had ischemia and underwent revascularization within 4 months, and 11.8% in those who had ischemia and were not revascularized (p <0.001 vs other groups). In a multivariate analysis model, independent predictors of cardiac death were diabetes (RR 2, 95% confidence interval 1.4 to 2.9), male gender (RR 1.7, 95% confidence interval 1.2 to 3.1), low-dose wall motion score index (RR 1.4, 95% confidence interval 1.2 to 2.6), and ischemia (RR 1.9, 95% confidence interval 1.3 to 3.2). Angina was not predictive of death. In patients who had ischemia, revascularization within 4 months after DSE was associated with decreased risk of cardiac death (RR 0.43, 95% confidence interval 0.3 to 0.8). In conclusion, myocardial ischemia that is detected by DSE is associated with increased risk of cardiac death among patients who have heart failure, after adjustment for left ventricular function. Patients who had ischemia and received revascularization within 4 months had a better survival than did patients who had ischemia and did not receive revascularization. Angina had no effect on prognosis. Therefore, patients who do not have angina should not be considered a lower-risk population if they have inducible ischemia.