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Background: Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers., Methods: Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology., Results: On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype., Conclusion: Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit., (© 2021. The Author(s).)

Background: Imaging Somatostatin Subtype Receptor 2 (SST 2 ) expressing macrophages by [DOTA,Tyr 3 ]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST 2 targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection., Methods and Results: Atherosclerotic ApoE -/- mice (n = 22) fed an atherogenic diet were imaged by SPECT/CT two hours post injection of [ 111 In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [ 111 In]In-DOTA-JR11 was visible in all mice, with a target-to-background-ratio (TBR) of 2.23 ± 0.35. Post-mortem scans after thymectomy and ex vivo scans of the arteries after excision of the arteries confirmed plaque uptake of the radioligand with TBRs of 2.46 ± 0.52 and 3.43 ± 1.45 respectively. Oil red O lipid-staining and ex vivo autoradiography of excised arteries showed [ 111 In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST 2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [ 111 In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST 2 expressing cells., Conclusions: The results of this study indicate DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation., (© 2020. The Author(s).)

Purpose: Many radioligands have been developed for the visualization of atherosclerosis by targeting inflammation. However, interpretation of in vivo signals is often limited to plaque identification. We evaluated binding of some promising radioligands in an in vitro approach in atherosclerotic plaques with different phenotypes., Methods: Tissue sections of carotid endarterectomy tissue were characterized as early plaque, fibro-calcific plaque, or phenotypically vulnerable plaque. In vitro binding assays for the radioligands [ 111 In]In-DOTATATE; [ 111 In]In-DOTA-JR11; [ 67 Ga]Ga-Pentixafor; [ 111 In]In-DANBIRT; and [ 111 In]In-EC0800 were conducted, the expression of the radioligand targets was assessed via immunohistochemistry. Radioligand binding and expression of radioligand targets was investigated and compared., Results: In sections characterized as vulnerable plaque, binding was highest for [ 111 In]In-EC0800; followed by [ 111 In]In-DANBIRT; [ 67 Ga]Ga-Pentixafor; [ 111 In]In-DOTA-JR11; and [ 111 In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm 2 , respectively). Binding of [ 111 In]In-DANBIRT and [ 111 In]In-EC0800 was highest across plaque phenotypes, binding of [ 111 In]In-DOTA-JR11 and [ 67 Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [ 111 In]In-DOTATATE was the lowest across plaque phenotypes. The areas positive for cells expressing the radioligand's target differed between plaque phenotypes for all targets, with lowest percentage area of expression in early plaque sections and highest in phenotypically vulnerable plaque sections., Conclusions: Radioligands targeting inflammatory cell markers showed different levels of binding in atherosclerotic plaques and among plaque phenotypes. Different radioligands might be used for plaque detection and discerning early from vulnerable plaque. [ 111 In]In-EC0800 and [ 111 In]In-DANBIRT appear most suitable for plaque detection, while [ 67 Ga]Ga-Pentixafor and [ 111 In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.

Acute myocardial infarction is one of the leading causes of death in the western world. Despite major improvements in myocardial reperfusion with sophisticated percutaneous coronary intervention technologies and new antithrombotic agents, there is still no effective therapy for preventing post- infarction myocardial injury and remodeling. Death of cardiomyocytes following ischemia results in "danger signals" that elicit an inflammatory reaction to remove cell debris and form scar tissue. Optimal healing of the damaged myocardial tissue requires a coordinated cellular response for sufficient wound healing and scar formation. However, if this inflammatory reaction is overactive or incompletely resolved, adverse left ventricular remodeling and heart failure may occur. Treatment aimed at the modulation of the post-MI inflammatory response has been widely pursued and investigated. Although improved infarct healing was shown in many experimental preclinical studies, to date, clinical trials using anti-inflammatory treatment strategies have been far less successful. Clearly, a need exists for predicting and selecting patients at risk and selecting the most appropriate therapy for individual patients. To this end, imaging of the post-MI response has been a topic of significant interest. In this review, we first discuss the clinical complications resulting from myocardial inflammation following AMI and the need for non-invasive imaging techniques using radiolabeled tracers. We then discuss the inflammatory reaction cascade following acute myocardial infarction, the inflammatory reaction cascade following acute myocardial infarction focusing on inflammatory cell types involved herein, and potential imaging targets for identifying these cells during the inflammatory process. In addition, we discuss specific characteristics and limitations of various preclinical animal models for ischemic heart disease since they are crucial in the development and evaluation of the imaging techniques. Finally, we discuss the need for non-invasive imaging approaches using radiolabeled tracers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer's capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST 2 ). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed., Methods: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [ 111 In]In-DOTA-butylamino-NorBIRT ([ 111 In]In-Danbirt) and [ 99m Tc]Tc-[N 0-1 4 ,Asp 0 ,Tyr 3 ]-octreotate ([ 99m Tc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST 2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images., Results: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST 2 . [ 111 In]In-Danbirt and [ 99m Tc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [ 111 In]In-Danbirt and [ 99m Tc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses., Conclusion: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [ 111 In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Background: 111 In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated 111 In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice., Methods and Results: ApoE -/- mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of 111 In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111 In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with 111 In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111 In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with 111 In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111 In-DANBIRT uptake and CD68 and LFA-1 expressing cells., Conclusions: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation.

This review addresses nuclear SPECT and PET imaging in small animals in relation to the atherosclerotic disease process, one of our research topics of interest. Imaging of atherosclerosis in small animal models is challenging, as it operates at the limits of current imaging possibilities regarding sensitivity, and spatial resolution. Several topics are discussed, including technical considerations that apply to image acquisition, reconstruction, and analysis. Moreover, molecules developed for or applied in these small animal nuclear imaging studies are listed, including target-directed molecules, useful for imaging organs or tissues that have elevated expression of the target compared to other tissues, and molecules that serve as substrates for metabolic processes. Differences between animal models and human pathophysiology that should be taken into account during translation from animal to patient as well as differences in tracer behavior in animal vs. man are also described. Finally, we give a future outlook on small animal radionuclide imaging in atherosclerosis, followed by recommendations. The challenges and solutions described might be applicable to other research fields of health and disease as well.

Aims: To evaluate the accuracy of cardiac computed tomography (CT) in distinguishing CAD and non-CAD heart failure (HF) and its effectiveness as a gatekeeper for invasive coronary angiography (ICA)., Methods and Results: We prospectively included 93 symptomatic patients with newly diagnosed HF of unknown aetiology (59 men; mean age 53 ± 13) and EF <45%, and/or fractional shortening <25%, and/or end-diastolic LV diameter >60 mm (men) or >55 mm (women). In all patients, the CT calcium score (CTCS) was determined. CTCS = 0 excluded CAD HF. Additional CT coronary angiography (CTCA) was performed if CTCS >0. ICA was used as the gold standard for distinguishing between CAD and non-CAD HF in patients with >20% luminal diameter narrowing on CTCA. CAD HF was defined as >50% luminal diameter narrowing in either (i) the left main coronary artery or proximal left anterior descending coronary artery or (ii) in multiple coronary arteries. Diagnostic accuracy and follow-up data (20 ± 16 months) were collected for all patients. CTCS = 0 ruled out CAD HF in 43 patients (46%). The CT algorithm had 100% sensitivity, 95% specificity, 67% positive predictive value, and 100% negative predictive value for detecting CAD HF. Patients with CTCS = 0 or non-CAD HF on CTCA had no coronary events during follow-up, and ICA could have been safely avoided in 76 out of 93 patients (82%)., Conclusion: In patients with HF of unknown aetiology, cardiac CT combining CTCS and CTCA has high accuracy for detecting CAD HF and can be used effectively as a gatekeeper for ICA.

Background: Clinical characteristics of patients, angiographic referral bias, and several technical factors may all affect the reported diagnostic accuracy of tests. The aim of this study was to assess their influence on the diagnostic accuracy of dobutamine stress echocardiography (DSE)., Methods: The medical literature from 1991 to 2006 was searched for diagnostic studies using DSE and meta-analysis was applied to the 62 studies thus retrieved, including 6881 patients. These studies were analyzed for patient characteristics, angiographic referral bias, and several technical factors., Results: The sensitivity of DSE was significantly related to the inclusion of patients with prior myocardial infarctions (0.834 vs 0.740, P < .01) and defining the results of DSE as already positive in case of resting wall motion abnormalities rather than obligatory myocardial ischemia (0.786 vs 0.864, P < .01). Specificity tended to be lower when patients with resting wall motion abnormalities were included in a study (0.812 vs 0.877, P < .10). The presence of referral bias adversely affected the specificity of DSE (0.771 vs 0.842, P < .01)., Conclusion: This analysis suggests that the reported sensitivity of DSE is likely higher and the specificity lower than expected in routine clinical practice because of the inappropriate inclusion of patients with prior myocardial infarctions, the definition of positive results on DSE, and the negative influence of referral bias. However, in the patient subset that will be sent to coronary angiography, the opposite results can be expected.

Background: Dobutamine stress echocardiography (DSE) suffers from high interobserver and inter-institution variability in the diagnosis of myocardial ischemia. Therefore, we developed a three-dimensional (3D) analysis tool that makes it possible to anatomically align 3D rest and stress data systematically, to generate optimal, nonforeshortened standard anatomical cross sections and to analyse the images synchronized and side-by-side., Aim of the Study: To investigate whether this 3D analysis tool could improve interobserver agreement on myocardial ischemia during 3D DSE., Methods: The study comprised 34 consecutive patients with stable chest pain who underwent both noncontrast and contrast 3D DSE. Two observers scored segmental wall motion using a conventional analysis and the novel analysis with the new 3D tool., Results: The two observers agreed on the presence or absence of myocardial ischemia in 81 of 102 coronary territories (agreement 79%, kappa (kappa) 0.28) during noncontrast 3D imaging and 92 of 102 coronary territories (agreement 90%, kappa 0.65) during contrast-enhanced 3D imaging. With the new 3D analysis software these numbers improved to 98 of 102 coronary territories (agreement 96%, kappa 0.69) during noncontrast 3D imaging and 98 of 102 coronary territories (agreement 96%, kappa 0.82) during contrast-enhanced 3D imaging., Conclusion: The use of a 3D DSE analysis tool improves interobserver agreement for myocardial ischemia both for noncontrast and contrast images.

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.

Dobutamine stress magnetic resonance imaging is considered the superior stress modality to detect wall motion abnormalities. In this report we demonstrate the strengths of a newly developed stress modality: dobutamine stress contrastenhanced real-time three-dimensional echocardiography. This stress modality may become a competitor of stress magnetic resonance imaging allowing fast acquisition and an unlimited number of left ventricular cross sections. Unfortunately, at the moment adequate imaging with stress realtime three-dimensional echocardiography is only possible in a minority of cardiac patients. (Neth Heart J 2008;16:217-8.).

Mucopolysaccharidosis type I (MPS IS) is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase, which is involved in the degradation of sulfated glycosaminoglycans (GAGs). The deficiency results in the intra-and pericellular accumulation of the GAGs heparan sulfate and dermatan sulfate. Eight adult patients with typical features of MPS IS aged 31.5 +/- 6.8 years (five men) were included and compared to age-and gender-matched controls. With transthoracic echocardiography, cyclic ascending aortic diameter changes were measured and ascending aortic elastic properties were calculated to characterize aortic elasticity. In MPS IS patients, aortic stiffness index was significantly increased (23.1 +/- 10.4 vs 3.9 +/- 1.5, P < 0.001), while aortic distensibility was significantly decreased (1.6 +/- 0.8 vs 4.6 [corrected] +/- 1.9 cm(2)/dynes [corrected] 10(-6), P < 0.001) compared to age-and sex-matched controls. The results of the present study demonstrate that in addition to the known cardiac complications, MPS IS patients have an impairment of ascending aortic elasticity. Further follow-up studies are needed to examine arterial elasticity using other methods in this patient population, and to detect possible effects of enzyme replacement therapy.

There is an essential importance of non-invasive imaging methods for evaluation of cardiac patients. Theoretically, the heart can be examined exactly, if due to its nature assessed in three dimensions (3D) concerning the heart cycle. In recent studies it has been confirmed that the second-generation real-time three-dimensional echocardiography offers optimal opportunity for three-dimensional evaluation of cardiac structures. Real-time three-dimensional echocardiography is a valuable tool for exact evaluation of ventricular and atrial volumes and ventricular masses. Valves and congenital abnormalities can be analysed 'en-face' with this new methodology. The usefulness of this method with stress protocols has been confirmed. The aim of the present review is to demonstrate advantages of this new promising method showing recent technological limitations as well.

Background: Recent technical developments have resulted in high-resolution real time three-dimensional echocardiography (RT3DE). The purpose of this study was to investigate the beneficial role of parasternal-acquired images in addition to apical-acquired images during contrast stress RT3DE., Methods: The study comprised 30 consecutive patients (52 +/- 11 years, 18 males) with chest pain referred for routine stress testing. The contrast RT3DE images were acquired from the apical and parasternal window with a Sonos 7500 echo system attached to a X4 matrix array transducer., Results: From the apical and parasternal acquisition, 464 segments (91%) and 267 segments (52%) could be analyzed, respectively (P < 0.001). From the apical window, more basal segments were not analyzable (22 of 180, 12% vs. 24 of 330, 7%; P = 0.06). From the parasternal window, more apical segments were not analyzable (117 of 150, 78% vs. 126 of 360, 35%; P < 0.01). The mean image quality index of the 464 analyzable segments from the apical-acquired images was 2.43. Fourteen of 180 basal segments (8%), 12 of 180 midventricular segments (7%) and 2 of 150 apical segment (1%) were only available with parasternal data acquisition. In addition to these 28 segments, 79 segments (15%) already visualized from the apical window improved in quality. The overall mean image quality index, now assessed from 492 (96%) of all segments, using both the apical and parasternal acquired data, improved to 2.74 (P < 0.05)., Conclusions: Addition of parasternal to apical acquisition of contrast RT3DE data can decrease the number of nonvisualized segments and improve mean image quality.

Background: Mitral annulus assessment is of great importance for the diagnosis and treatment of mitral valve disease. The present study sought to assess the value of real-time three-dimensional echocardiography for the assessment of true mitral annulus diameter (MAD)., Methods: One hundred and fifty patients (mean age 38 +/- 18 years) with adequate two-dimensional (2D) echocardiographic image quality underwent assessment of MAD(2D) and MAD(3D) (with real-time three-dimensional echocardiography). In a subgroup of 30 patients true MAD was validated with magnetic resonance imaging (MRI)., Results: There was a good interobserver agreement for MAD(2D) (mean difference = -0.25 +/- 2.90 mm, agreement: -3.16, 2.66) and MAD(3D) (mean difference = 0.29 +/- 2.03, agreement = -1.74, 2.32). Measurements of MAD(2D) and MAD(3D) were well correlated (R = 0.81, P < 0.0001). However, MAD(3D) was significantly larger than MAD(2D) (3.7 +/- 0.9 vs. 3.3 +/- 0.8 cm, P < 0.0001). In the subgroup of 30 patients with MRI validation, MAD(3D) and MAD(MRI) were significantly larger than MAD(2D) (3.3 +/- 0.5 and 3.4 +/- 0.5 cm vs. 2.9 +/- 0.4 cm, both P < 0.001). There was no significant difference between MAD(MRI) and MAD(3D)., Conclusion: MAD(3D) can be reliably measured and is superior to MAD(2D) in the assessment of true mitral annular size.

Objectives: To compare the interobserver variability and accuracy of two different real time three-dimensional echocardiography (RT3DE) analyzing programs., Methods: Forty-one patients (mean age 56 +/- 11 years, 28 men) in sinus rhythm with a cardiomyopathy and adequate 2D image quality underwent RT3DE and magnetic resonance imaging (MRI) within one day. Off-line left ventricular (LV) volume analysis was performed with QLAB V4.2 (semiautomated border detection with biplane projections) and TomTec 4D LV analysis V2.0 (primarily manual tracking with triplane projections and semiautomated border detection)., Results: Excellent correlations (R(2) > 0.98) were found between MRI and RT3DE. Bland-Altman analysis revealed an underestimated LV end-diastolic volume (LV-EDV) for both TomTec (-9.4 +/- 8.7 mL) and QLAB (-16.4 +/- 13.1 ml). Also, an underestimated LV end-systolic volume (LV-ESV) for both TomTec (-4.8 +/- 9.9 mL) and QLAB (-8.5 +/- 14.2 mL) was found. LV-EDV and LV-ESV were significantly more underestimated with QLAB software. Both programs accurately calculated LV ejection fraction (LV-EF) without a bias. Interobserver variability was 6.4 +/- 7.8% vs. 12.2 +/- 10.1% for LV-EDV, 7.8 +/- 9.7% vs. 13.6 +/- 11.2% for LV-ESV, and 7.1 +/- 6.9% vs. 9.7 +/- 8.8% for LV-EF for TomTec vs. QLAB, respectively. The analysis time was shorter with QLAB (4 +/- 2 minutes vs. 6 +/- 2 minutes, P < 0.05)., Conclusions: RT3DE with TomTec or QLAB software analysis provides accurate LV-EF assessment in cardiomyopathic patients with distorted LV geometry and adequate 2D image quality. However, LV volumes may be somewhat more underestimated with the current QLAB software version.

Objective: We evaluated two different commercially available real-time 3-dimensional echocardiographic semiautomated border detection algorithms for left ventricular (LV) volume analysis in patients with cardiomyopathy and distorted LV geometry., Methods: A total of 53 patients in sinus rhythm with various types of cardiomyopathy (mean age 56 +/- 11 years, 28 men) and adequate 2-dimensional image quality were included. The real-time 3-dimensional echocardiographic multiplane interpolation (MI) and full volume reconstruction (FVR) methods were used for LV volume analysis. Magnetic resonance imaging was used as the reference method., Results: A strong correlation (R(2) > 0.95) was found for all LV volume and ejection fraction measurements by either real-time 3-dimensional echocardiographic method. Analysis time was shorter with the FVR method (6 +/- 2 vs 15 +/- 4 minutes, P < .01) as compared with the MI method. Bland-Altman analysis showed greater underestimation of end-diastolic and end-systolic volumes by MI compared with FVR. For the MI method a bias of -24.0 mL (-15.0% of the mean) for end-diastolic volume and -11.3 mL (-18.0% of the mean) for end-systolic volume was found. For FVR analysis these values were -9.9 mL (-6.0% of the mean) and -5.0 mL (-9.0% of the mean), respectively. Ejection fraction was similar for the MI and FVR method with a mean difference compared with magnetic resonance imaging of 0.6 (1.0%) and 0.8 (1.3%), respectively., Conclusion: In patients with cardiomyopathy, distorted LV geometry, and good 2-dimensional image quality, the FVR method is faster and more accurate than the MI method in assessment of LV volumes.

Objective: We sought to assess mitral annular (MA) size and function in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) using real-time 3-dimensional (3D) echocardiography (RT3DE)., Methods: The study included 30 patients with HCM, 20 patients with DCM, and 30 control subjects. RT3DE measurements included end-systolic and end-diastolic MA area (MAA) (MAA(3D)), MA diameter(3D), MA fractional area change (MAFAC), and MA fractional shortening. In subgroup of 50 patients, magnetic resonance imaging (MRI) was used for MAA(MRI) and MA diameter(MRI) measurement., Results: End-diastolic MAA(3D) was larger in HCM than in control group (P < .0001). Higher MAFAC and MA fractional shortening were present in HCM than in control group (P = .001 and P = .006, respectively). End-systolic and end-diastolic MAA(3D) in DCM were higher than in HCM and control groups (P < .0001). Lower MAFAC and MA fractional shortening were present in DCM than in HCM and control groups (P < .0001). MAFAC correlated well with left ventricular function in control subjects (r = 0.94, P < .0001), whereas correlation was less in DCM (r = 0.53, P = .02) and HCM (r = 0.42, P < .01). RT3DE and MRI measurements were comparable., Conclusion: RT3DE assessment of MA size and function in control subjects and patients with cardiomyopathy is accurate and well correlated with MRI.

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.

Dobutamine stress echocardiography (DSE) has good diagnostic accuracy for the diagnosis of coronary artery disease (CAD). However, in most published diagnostic studies, patients are predominantly men. In women, diagnostic accuracy may be lower because of a lower prevalence and extent of CAD, a higher incidence of dobutamine stress-induced hypotension (resulting in less stress or even nondiagnostic test results), smaller left ventricular chamber size, and the beneficial effects of estrogens on the induction of myocardial ischemia. To determine the diagnostic accuracy of DSE in women, 14 diagnostic studies published through 2006 were identified through a Medline search. For a total of 901 patients, the weighted mean sensitivity and specificity were 72% and 88%, respectively. In 7 studies directly comparing results in women and men, conflicting results were reported. However, pooled data showed nearly identical values for sensitivity and specificity in women and men. Additionally, in 6 studies directly comparing DSE results in women with those of stress nuclear scintigraphy, DSE was as sensitive and more specific to detect CAD (90% vs 70%, p <0.0001). The excellent specificity of DSE in women was also confirmed by excellent normalcy rates, ranging from 92% to 100% in women, with a <5% pretest probability of CAD. In conclusion, despite some theoretical limitations, DSE has reasonable sensitivity and excellent specificity for the detection of CAD in women. Considering the diagnostic problems of exercise electrocardiography and nuclear scintigraphy in women, stress echocardiography may be the stress modality of choice in women because of its superior diagnostic specificity.

Dobutamine stress echocardiography is an accepted tool for the diagnosis of coronary artery disease. Some investigators have claimed that 3-dimensional imaging improves the diagnostic accuracy of dobutamine stress echocardiography. The purpose of the present investigation was to examine the role of contrast echocardiography in the improvement of segmental quality and interobserver agreement during stress real-time 3-dimensional echocardiography (RT3DE). The study comprised 36 consecutive patients with stable chest pain referred for routine stress testing. Three-dimensional images were acquired with an RT3DE system with an X4 matrix-array transducer. All available reconstructed 2-dimensional segments were graded as optimal, good, moderate, or poor. Wall motion was scored as normal, mild hypokinesia, severe hypokinesia, akinesia, or dyskinesia. At peak stress, 466 of the 612 segments (76%) could be analyzed during conventional RT3DE. With contrast-enhanced RT3DE, the number of available segments increased to 553 (90%). The image quality index during conventional RT3DE was 2.2, whereas with contrast-enhanced RT3DE, it was 3.1. With conventional RT3DE, 2 independent observers agreed on the diagnosis of myocardial ischemia in 85 of 108 coronary territories (79%, kappa = 0.26). With contrast-enhanced RT3DE, agreement increased to 95 of 108 coronary territories (88%, kappa = 0.59). Study agreement on myocardial ischemia was present in 26 of 36 studies (72%, kappa = 0.43) with conventional RT3DE and in 32 of 36 studies (89%, kappa = 0.77) with contrast-enhanced RT3DE. In conclusion, during stress RT3DE, contrast-enhanced imaging significantly decreases the number of poorly visualized myocardial segments and improves interobserver agreement for the diagnosis of myocardial ischemia.

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., ((c) 2007 S. Karger AG, Basel.)

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.

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.

Purpose: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) beta-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with the high-LET alpha-emitter, 213Bi, was evaluated., Experimental Design: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic efficacy of 213Bi-DOTATOC (specific activity 7.4 MBq/microg) were investigated. Biodistribution studies to determine somatostatin receptor specificity were done in Lewis rats at 1 and 3 hours postinjection. Histopathology of various organs was used to evaluated toxicity and safety. Therapeutic efficacy of 4 to 22 MBq 213Bi-DOTATOC was determined in a rat pancreatic carcinoma model., Results: Radiolabeling of the 213Bi-DOTATOC was achieved with radiochemical purity >95% and an incorporation yield > or = 99.9%. Biodistribution data showed specific binding to somatostatin receptor-expressing tissues. Administration of free 213Bi, compared with 213Bi-DOTATOC, resulted in higher radioactivity accumulation at 3 hours postinjection in the kidneys [34.47 +/- 1.40% injected dose/g (ID/g) tissue versus 11.15 +/- 0.46%, P < 0.0001] and bone marrow (0.31 +/- 0.01% ID/g versus 0.06 +/- 0.02%, P < 0.0324). A significant decrease in tumor growth rate was observed in rats treated with >11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P < 0.025). Treatment with >20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving <11 MBq (P < 0.02)., Conclusions: 213Bi-DOTATOC showed dose-related antitumor effects with minimal treatment-related organ toxicity. No acute or chronic hematologic toxicities were observed. Mild, acute nephrotoxicity was observed without evidence of chronic toxicity. 213Bi-DOTATOC is a promising therapeutic radiopharmaceutical for further evaluation.

Objective: The purpose of this study was to assess the (1) feasibility of real-time three-dimensional echocardiography (RT-3DE) data acquisition and (2) volumes and function of the abnormal left ventricle (LV) in adult patients with congenital heart disease (CHD), compared with magnetic resonance imaging (MRI) data., Methods: Thirty-two patients (59% were male) with CHD were evaluated on the same day by MRI and RT-3DE. Acquisition of RT-3DE data sets was feasible in 29 of the 32 patients (91%). The time of 3D data acquisition was 4 +/- 2 minutes, and LV analysis was 17 +/- 5 minutes per patient for manual border tracing., Results: A good correlation was observed between RT-3DE with manual border detection and MRI for LV end-diastolic volume (r = 0.97), LV end-systolic volume (r = 0.98), and LV ejection fraction (r = 0.94)., Conclusion: RT-3DE is feasible for volumetric analysis of the abnormal LV allowing accurate determination of LV volume and ejection fraction compared with MRI in adult patients with CHD.

This is the first study to assess the feasibility and accuracy of real-time 3-dimensional echocardiography (RT-3DE) for the measurements of left ventricular (LV) mass in patients with congenital heart disease (CHD) compared with magnetic resonance imaging (MRI). Twenty patients (60% men) with CHD were evaluated by MRI and RT-3DE on the same day. Their mean age was 29 +/- 8 years (range 19 to 49). RT-3DE was performed with a Philips Sonos 7500 echocardiographic system and LV mass analyses with the assistance of TomTec software. The results for LV mass obtained by manual tracing were compared with Signa 1.5-T MRI data. The acquisition of RT-3DE data sets was feasible in all 20 patients. Nine patients (45%) had good, 5 patients (25%) moderate, and 6 patients (30%) poor image quality of the 3-dimensional data set. The time of 3-dimensional data acquisition was 4 +/- 2 minutes. Off-line image processing and tracing required approximately 11 +/- 3 minutes. A very good correlation was observed between RT-3DE data with sufficient image quality and MRI (r = 0.98, y = 0.96x + 4.1, SEE 9.8 g), with a mean difference of 2.0 +/- 20 g. Interobserver agreement was excellent (r = 0.99, y = 0.97x + 3.81), with a mean difference of -1 +/- 11 g. In conclusion, the assessment of LV mass from RT-3DE data is feasible in patients with CHD. The mass of an abnormally shaped left ventricle can be determined with high accuracy and low interobserver variability in patients with good or moderate echocardiographic image quality.

Purpose: Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied., Subjects and Methods: We studied 136 patients (mean age 64+/-12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate)., Results: Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5+/-2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P=.01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P=.004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model., Conclusion: Myocardial ischemia during pacemaker stress echocardiography is an independent predictor of cardiac death and all-cause mortality in patients with a permanent pacemaker.

Background: Dobutamine stress echocardiography (DSE) was shown to provide incremental prognostic information. However, its role in the prediction of mortality in elderly persons is not well defined. We assessed the value of DSE in the prediction of mortality and hard cardiac events during long-term follow-up in patients older than 65 years., Methods: We studied 1434 patients >65 years old (mean age 72 +/- 3 years) who underwent DSE for evaluation of coronary artery disease. Ischemia was defined as new or worsening wall motion abnormalities. Follow-up events were total mortality and hard cardiac events (cardiac mortality and nonfatal myocardial infarction). Multivariable Cox regression analysis was used to identify the independent predictors of follow-up events., Results: Ischemia was detected in 675 patients (47%). Five hundred six patients (35%) had a normal study, and 253 (18%) had fixed wall motion abnormalities. During a mean follow-up of 6.5 years, 532 (37%) deaths occurred, of which 249 (17%) were due to cardiac causes. A nonfatal myocardial infarction occurred in 45 patients (3%). Independent predictors of all-cause mortality in a multivariate analysis model were age (hazard ratio [HR] 1.06; 95% confidence interval [CI], 1.05-1.08), male sex (HR 1.5; 95% CI, 1.2-1.8), hypertension (HR 1.2; 95% CI, 1.1-1.4), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.4; 95% CI, 1.1-1.8), rest wall motion abnormalities (HR 1.07; 95% CI, 1.06-1.09), and ischemia (HR 1.3; 95% CI, 1.1-1.6). Independent predictors of hard cardiac events were age (HR 1.07; 95% CI, 1.05-1.09), male sex (HR 1.3; 95% CI, 1.1-1.7), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.6; 95% CI, 1.2-2.2), rest wall motion abnormalities (HR 1.13; 95% CI, 1.12-1.16), and ischemia (HR 2.1; 95% CI, 1.5-2.8)., Conclusion: DSE provides independent prognostic information to predict all-cause mortality and hard cardiac events in elderly patients.

Rationale and Objectives: We propose a semiautomatic endocardial border detection method for three-dimensional (3D) time series of cardiac ultrasound (US) data based on pattern matching and dynamic programming, operating on two-dimensional (2D) slices of the 3D plus time data, for the estimation of full cycle left ventricular volume, with minimal user interaction., Materials and Methods: The presented method is generally applicable to 3D US data and evaluated on data acquired with the Fast Rotating Ultrasound (FRU-) Transducer, developed by Erasmus Medical Center (Rotterdam, the Netherlands), a conventional phased-array transducer, rotating at very high speed around its image axis. The detection is based on endocardial edge pattern matching using dynamic programming, which is constrained by a 3D plus time shape model. It is applied to an automatically selected subset of 2D images of the original data set, for typically 10 equidistant rotation angles and 16 cardiac phases (160 images). Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastole and end-systole volumes. Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastolic (ED) and end-systolic (ES) volumes., Results: The semiautomatic border detection approach shows good correlations with MRI ED/ES volumes (r = 0.938) and low interobserver variability (y = 1.005x - 16.7, r = 0.943) over full-cycle volume estimations. It shows a high consistency in tracking the user-defined initial borders over space and time., Conclusions: We show that the ease of the acquisition using the FRU-transducer and the semiautomatic endocardial border detection method together can provide a way to quickly estimate the left ventricular volume over the full cardiac cycle using little user interaction.

Objectives: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE)., Design: Observational study., Setting: Tertiary referral centre., Patients: 931 patients who experienced stress induced myocardial ischaemia during DSE., Results: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001)., Conclusions: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate.

Three-dimensional (3-D) echocardiography has been an important research goal ever since the introduction of two-dimensional (2-D) echocardiography. Most approaches towards 3-D echocardiography were off-line and based on the sequential rotational scanning and acquisition of multiple cross-sectional images together with external or internal reference systems. These approaches were limited by long acquisition and analysis time in combination with poor image quality. Recently, improvements in the matrix array technology have significantly increased spatial and temporal resolution of second-generation real-time 3-D transducers. Clinical use of modern 3-D echocardiography is boosted by the marked reduction in acquisition time and the unique possibility of on-line rendering on the ultrasound system. The integration and future quantification of new parameters together with on-line review allows new insights into cardiac function, morphology and synchrony that offer great potentials in the evaluation of right and left global and regional function, diagnosis of small areas of ischemia, congenital and valvular heart disease and effects of biventricular pacing in dilated heart asynchrony. This report will review current and future applications of 3-D data acquisition, emphasizing the real-time methods and clinical applications of the new matrix array transducer.

The presence of myocardial ischemia during dobutamine stress echocardiography is independently associated with an increased risk of all-cause mortality in women after adjustment for clinical data. This association is observed in patients who have proved coronary artery disease and in patients who have no history of coronary artery disease.

Many imaging modalities have been evaluated for the diagnosis of left ventricular noncompaction (LVNC). Echocardiography with color Doppler flow imaging is currently the diagnostic modality of choice. In this study, the usefulness of contrast echocardiography to diagnose LVNC was examined, and the diagnostic criteria were evaluated.

Objectives: The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography (DSE)., Background: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied., Methods: We studied 2,276 men and 1,105 women with known or suspected coronary artery disease who underwent DSE. Follow-up events were cardiac death and nonfatal myocardial infarction (MI)., Results: Dobutamine stress echocardiography was normal in 687 men (30%) and 483 women (44%) (p <0.0001). Ischemia on DSE was present in 1,194 men (52%) and 416 women (38%) (p <0.001). During a mean follow-up of 7 +/- 3.4 years, there were 894 (26%) deaths (442 attributed to cardiac causes) and 145 (4%) nonfatal MIs. The annual cardiac event rate was 2.5% in men and 1.2% in women with normal DSE. Independent predictors of cardiac events in patients with normal DSE using a Cox proportional hazards regression analysis were male gender (hazard ratio [HR]: 1.7 [range 1.1 to 2.8]), age (HR: 1.02 [range 1.01 to 1.04]), history of heart failure (HR: 3.4 [range 1.5 to 7.9]), previous MI (HR: 1.7 [range 1.1 to 2.8]), and diabetes (HR: 2.4 [range 1.3 to 4.5]). Independent predictors of cardiac events in patients with an abnormal DSE were age (HR: 1.03 [range 1.02 to 1.04]), history of heart failure (HR: 1.7 [range 1.3 to 2.1]), diabetes (HR: 1.4 [range 1.1 to 1.8]), heart rate at rest (HR: 2.8 [range 1.4 to 5.8]), wall motion abnormalities at rest (HR: 1.06 [range 1.04 to 1.09]), and ischemia on DSE (HR: 1.04 [range 1.02 to 1.07]). Myocardial ischemia was an independent predictor of cardiac events in both men and women., Conclusions: Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities.

Background: Detection of myocardial viability is crucial for clinical treatment of patients with ischemic cardiomyopathy. Currently, quantitative information for the evaluation of systolic and diastolic function of viable tissue is limited. Our aim was to compare quantitatively systolic and diastolic function in viable and nonviable dysfunctional myocardium in patients with ischemic cardiomyopathy., Methods: A total of 93 patients (mean age, 62 +/- 10 years) underwent dobutamine stress echocardiography to assess myocardial viability. Pulsed-wave tissue Doppler imaging (TDI) was used to assess systolic ejection velocity (V(S)) and early (V(E)) and late (V(A)) diastolic velocities at rest and at low-dose dobutamine infusion (10 microg/kg per minute) in viable and nonviable dysfunctional regions. Analysis was repeated after dividing study population in patients >or=65 years old (n = 40) and <65 years old (n = 53)., Results: Pulsed-wave TDI demonstrated that V(S) was comparable in dysfunctional viable and nonviable regions at rest (V(S), 6.3 +/- 1.9 cm/s vs 6.3 +/- 2.0 cm/s, respectively, P = .93). However, at low-dose dobutamine challenge, V(S) was significantly higher in viable regions (8.5 +/- 2.7 cm/s vs 7.8 +/- 2.4 cm/s, P = .002). Viable regions had higher V(E) at rest compared with nonviable regions (8.4 +/- 2.5 cm/s vs 7.5 +/- 2.8 cm/s, P = .003). Myocardial velocities were significantly higher in patients >or=65 years old, both in viable and nonviable regions., Conclusions: Quantification of myocardial motion by pulsed-wave TDI demonstrates that at low-dose dobutamine stress, systolic velocity is markedly improved in viable myocardium, indicating the presence of contractile reserve in viable regions. A superior early diastolic filling at rest can also differentiate viable from nonviable myocardium.

Background: Dobutamine stress echocardiography (DSE) is an accepted test for the diagnosis of coronary artery disease (CAD), despite its wide diagnostic accuracy., Aim: Which factors cause test variability of DSE for the diagnosis of CAD., Methods: In a retrospective analysis of 46 studies in 5,353 patients, the potential causes of diagnostic variability were systematically analyzed, including patient selection, definition of CAD, chest pain characteristics, confounding factors for DSE (left ventricular hypertrophy, left bundle branch block, female gender), work-up bias (present when patient's chance to undergo coronary angiography is influenced by the result of DSE), review bias (present when DSE is interpreted in relation to CAG), DSE protocol and definition of a positive DSE., Results: Diagnostic variability was related to definition of a positive test, but not related to the definition of CAD or DSE protocol. However, only three of eight methodological standards for research design found general compliance. Differences in the selection of the study population (quality of echocardiographic window, angina pectoris), handling of confounding factors and analysis of disease in individual coronary arteries were observed. Lack of data on analysis of relevant chest pain syndromes and handling of nondiagnostic test results hampered further evaluation of these standards., Conclusion: Methodological problems may explain the wide range in diagnostic variability of DSE. An improvement of clinical relevance of DSE testing is possible by stronger adherence to common and new methodological standards.

The presence of a right bundle branch block (RBBB) is associated with increased mortality. We studied the role of dobutamine stress echocardiography for the prognostic stratification of patients with RBBB. The presence of an abnormal dobutamine stress echocardiography was the strongest predictor of cardiac events and provided incremental prognostic information to clinical and stress test data.

Objective: To assess the prognostic value of dobutamine stress echocardiography (DSE) in patients with previous myocardial revascularisation., Design: Prospective study., Setting: Tertiary referral centre in Rotterdam, the Netherlands., Patients: 332 consecutive patients with previous percutaneous or surgical coronary revascularisation underwent DSE. Follow up was successful for 331 (99.7%) patients. Thirty eight patients who underwent early revascularisation (

Objective: To assess a new approach for guiding and hemodynamic optimization of resynchronization therapy, using three-dimensional (3D) transthoracic echocardiography., Background: Resynchronization therapy for heart failure provides the greatest hemodynamic benefit when applied to the most delayed left ventricular (LV) site. Currently, the ideal LV pacing site is selected according to acute invasive hemodynamic assessment and/or tissue Doppler imaging., Methods: A total of 16 patients with advanced heart failure and an implanted biventricular pacemaker were included in this study. Transthoracic apical LV images at equidistant intervals were obtained using a prototype, fast-rotating second harmonic transducer to reconstruct 3D LV datasets during sinus rhythm (SR), right ventricular (RV) apical and biventricular pacing mode. A semi-automated contour analysis system (4D LV analysis, TomTec, Germany) was used for segmental wall motion analysis and identification of the most delayed contracting segment and calculation of global LV function., Results: Data acquisition duration was 10 s and analyzable 3D images were obtained in 12 patients. Of these patients, data during SR were available in 9 and during biventricular pacing in 11. The greatest contraction delay during SR was found in the anterior and antero-septal segments in five of nine patients. Biventricular pacing resulted in reduction of the contraction delay in seven of eight patients. The global LV function did not change significantly., Conclusion: 3D echocardiography with appropriate analytic software allows detection of the most delayed LV contracting segment and can be used to select the optimal pacing site during resynchronization therapy.