Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.

AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification.

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 [111In]In-DOTATATE; [111In]In-DOTA-JR11; [67Ga]Ga-Pentixafor; [111In]In-DANBIRT; and [111In]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 [111In]In-EC0800; followed by [111In]In-DANBIRT; [67Ga]Ga-Pentixafor; [111In]In-DOTA-JR11; and [111In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm2, respectively). Binding of [111In]In-DANBIRT and [111In]In-EC0800 was highest across plaque phenotypes, binding of [111In]In-DOTA-JR11 and [67Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [111In]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. [111In]In-EC0800 and [111In]In-DANBIRT appear most suitable for plaque detection, while [67Ga]Ga-Pentixafor and [111In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.

Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11.

BACKGROUND: Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST2 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 [111In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [111In]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 [111In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [111In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST2 expressing cells. CONCLUSIONS: The results of this study indicate DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation.

Nuclear Imaging of Post-infarction Inflammation in Ischemic Cardiac Diseases - New Radiotracers for Potential Clinical Applications.

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.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach.

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 (SST2). 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 [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0-14,Asp0,Tyr3]-octreotate ([99mTc]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 SST2 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 SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]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. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Sex Differences in the Performance of Cardiac Computed Tomography Compared With Functional Testing in Evaluating Stable Chest Pain: Subanalysis of the Multicenter, Randomized CRESCENT Trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease).

BACKGROUND: Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. METHODS AND RESULTS: The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women (P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women (P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). CONCLUSIONS: Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393028.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial.

AIMS: To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS: Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION: For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Computed tomography coronary imaging as a gatekeeper for invasive coronary angiography in patients with newly diagnosed heart failure of unknown aetiology.

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.

Factors affecting sensitivity and specificity of diagnostic testing: dobutamine stress echocardiography.

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.

Side-by-side viewing of anatomically aligned left ventricular segments in three-dimensional stress echocardiography.

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.

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.

The mild form of mucopolysaccharidosis type I (Scheie syndrome) is associated with increased ascending aortic stiffness.

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.

[Real-time 3-dimensional echocardiography: can there be one more dimension?]. / Real-time 3-dimenziós echokardiográfia--lehet egy dimenzióval több?

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.

Role of parasternal data acquisition during contrast enhanced real-time three-dimensional echocardiography.

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.

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.

A comparison between QLAB and TomTec full volume reconstruction for real time three-dimensional echocardiographic quantification of left ventricular volumes.

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.

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.