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Severely reduced left ventricular (LV) ejection fraction (EF) derived from 2D echocardiographic (2DE) images is associated with increased mortality and used to guide therapeutic choices. Global longitudinal strain (GLS) is more sensitive than LVEF to detect abnormal LV function, and accordingly may help identify patients with mildly-to-moderately reduced LVEF who are at a similarly high cardiovascular (CV) risk. We hypothesized that 3D echocardiographic (3DE) measurements of EF and GLS, which are more reliable and reproducible, may have even better predictive value than the 2DE indices, and compared their ability to identify such patients. We retrospectively studied 104 inpatients with 2DE-derived LVEF of 30-50% who underwent transthoracic echocardiography during 2006-2010 period, had good quality images, and were followed-up through 2016. Both 2DE and 3DE images were analyzed to measure LVEF and GLS. Kaplan-Meier survival curves were generated for two subgroups defined by the median of each parameter as the cutoff. Of the 104 patients, 32 died of CV related causes. Cox regression revealed that 3D GLS was the only variable associated with CV mortality. Kaplan-Meier curves showed that 2D LVEF, 2D GLS and 3D EF were unable to differentiate patients at higher CV mortality risk, but 3D GLS was the only parameter to do so. Because 3D GLS is able to identify patients with mildly-to-moderately reduced LVEF who are at higher CV mortality risk, its incorporation into clinical decisions may improve survival of those who would benefit from therapeutic interventions not indicated according to the current guidelines.

Women with hypertensive disorders of pregnancy have an increased risk of subsequent heart failure and cardiovascular disease when compared with women with normotensive pregnancies. Although the mechanisms underlying these findings are unclear, elevated levels of the biomarker activin A are associated with myocardial dysfunction and may have predictive value. We hypothesized that elevated levels of antepartum activin A levels would correlate with postpartum cardiac dysfunction in women with hypertensive disorders of pregnancy. We prospectively studied 85 women to determine whether increased antepartum activin A levels were associated with cardiac dysfunction at 1 year postpartum as measured by global longitudinal strain. Thirty-two patients were diagnosed with preeclampsia, 28 were diagnosed with gestational or chronic hypertension, and the remainder were nonhypertensive controls. Activin A levels were measured with ELISA both in the third antepartum trimester and at 1 year postpartum. Comprehensive echocardiograms including measurement of global longitudinal strain were also performed at enrollment and at 1 year postpartum. Antepartum activin A levels correlated with worsening antepartum global longitudinal strain ( r =0.70; P =0.0001). Across the entire cohort, elevated antepartum activin A levels were associated with the development of abnormal global longitudinal strain at 1 year (C statistic 0.74; P =0.004). This association remained significant after multivariable adjustment for clinically relevant confounders (C statistic 0.93; P =0.01). Postpartum activin A levels also correlated with increasing left ventricular mass index ( P =0.02), increasing mean arterial pressures ( P =0.02), and decreasing E' values ( P =0.01). Activin A may be a useful tool for identifying and monitoring patients at risk for postpartum development of cardiovascular disease., (© 2018 American Heart Association, Inc.)

Background: Although 3D echocardiography (3DE) allows accurate and reproducible quantification of cardiac chambers, it has not been integrated into clinical practice because it relies on manual input, which interferes with workflow. A recently developed automated adaptive analytics algorithm for simultaneous quantification of left ventricular and atrial (LV, LA) volumes was found to be accurate and reproducible in patients with good images. We sought to prospectively test its feasibility and accuracy in consecutive patients in relationship with image quality and reader experience., Methods: Three hundred consecutive patients underwent 3DE. Image quality was graded as poor, adequate, or good. Images were analyzed by an expert echocardiographer to obtain LV volumes and ejection fraction (EF) and LA volume using the automated analysis (HeartModel, Philips, Andover, MA) with and without editing the endocardial boundaries and using conventional manual tracing (QLAB, Philips, Andover, MA) blinded to the automated measurements as a reference. In a subgroup of 100 patients, automated analysis was repeated by two readers without 3DE experience., Results: Automated analysis failed in 31/300 patients (10%). Patients with poor image quality (n = 72, 24%) showed suboptimal agreement with the reference technique, especially for LVEF. Importantly, patients with adequate (n = 89, 30%) and good (n = 108, 36%) images showed small biases and excellent correlations without border corrections, which were further improved with editing. In contrast, border corrections by inexperienced readers did not improve the agreement with reference values., Conclusions: Automated 3DE analysis allows accurate quantification of left-heart size and function in 66% of consecutive patients, while in the remaining patients, its performance is limited/unreliable due to image quality. Border corrections require 3DE experience to improve the accuracy of the automated measurements. In patients with sufficient image quality, this automated approach has the potential to overcome the workflow limitations of the 3D analysis in clinical practice., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to test the feasibility and accuracy of an automated algorithm that simultaneously quantifies 3-dimensional (3D) transthoracic echocardiography (TTE)-derived left atrial (LA) and left ventricular (LV) volumes and left ventricular ejection fraction (LVEF). Conventional manual 3D TTE tracings and cardiac magnetic resonance (CMR) images were used as a reference for comparison., Background: Cardiac chamber quantification from 3D TTE is superior to 2D TTE measurements. However, integration of 3D quantification into clinical practice has been limited by time-consuming workflow and the need for 3D expertise. A novel automated software was developed that provides LV and LA volumetric quantification from 3D TTE datasets that reflect real-life manual 3-dimensional echocardiography measurements and values comparable to CMR., Methods: A total of 159 patients were studied in 2 separate protocols. In protocol 1, 94 patients underwent 3D TTE imaging (EPIQ, iE33, X5-1, Philips Healthcare, Andover, Massachusetts) covering the left atrium and left ventricle. LA and LV volumes and LVEF were obtained using the automated software (HeartModel, Philips Healthcare) with and without contour correction, and compared with the averaged manual 3D volumetric measurements from 3 readers. In protocol 2, automated measurements from 65 patients were compared with a CMR reference. The Pearson correlation coefficient, Bland-Altman analysis, and paired Student t tests were used to assess inter-technique agreement., Results: Correlations between the automated and manual 3D TTE measurements were strong (r = 0.87 to 0.96). LVEF was underestimated and automated LV end-diastolic, LV end-systolic, and LA volumes were overestimated compared with manual measurements. Agreement between the automated analysis and CMR was also strong (r = 0.84 to 0.95). Test-retest variability was low., Conclusions: Automated simultaneous quantification of LA and LV volumes and LVEF is feasible and requires minimal 3D software analysis training. The automated measurements are not only comparable to manual measurements but also to CMR. This technique is highly reproducible and timesaving, and it therefore promises to facilitate the integration of 3D TTE-based left-heart chamber quantification into clinical practice., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We evaluate in this paper different strategies for the construction of a statistical shape model (SSM) of the left ventricle (LV) to be used for segmentation in cardiac magnetic resonance (CMR) images. From a large database of LV surfaces obtained throughout the cardiac cycle from 3D echocardiographic (3DE) LV images, different LV shape models were built by varying the considered phase in the cardiac cycle and the registration procedure employed for surface alignment. Principal component analysis was computed to describe the statistical variability of the SSMs, which were then deformed by applying an active shape model (ASM) approach to segment the LV endocardium in CMR images of 45 patients. Segmentation performance was evaluated by comparing LV volumes derived by ASM segmentation with different SSMs and those obtained by manual tracing, considered as a reference. A high correlation (r(2)>0.92) was found in all cases, with better results when using the SSM models comprising more than one frame of the cardiac cycle., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Implantable device leads can cause tricuspid regurgitation (TR) when they interfere with leaflet motion. The aim of this study was to determine whether lead-leaflet interference is associated with TR severity, independent of other causative factors of functional TR., Methods: A total of 100 patients who underwent transthoracic two-dimensional and three-dimensional (3D) echocardiography of the tricuspid valve before and after lead placement were studied. Lead position was classified on 3D echocardiography as leaflet-interfering or noninterfering. TR severity was estimated by vena contracta (VC) width. Logistic regression analysis was used to identify factors associated with postdevice TR, including predevice VC width, right ventricular end-diastolic and end-systolic areas, fractional area change, right atrial size, tricuspid annular diameter, TR gradient, device lead age, and presence or absence of lead interference. Odds ratios were used to describe the association with moderate (VC width ≥ 0.5 cm) or severe (VC width ≥ 0.7 cm) TR, separately, using bivariate and stepwise multivariate logistic regression analysis., Results: Forty-five of 100 patients showed device lead tricuspid valve leaflet interference. The septal leaflet was the most commonly affected (23 patients). On bivariate analysis, preimplantation VC width, right atrial size, tricuspid annular diameter, and lead-leaflet interference were significantly associated with postdevice TR. On multivariate analysis, preimplantation VC width and the presence of an interfering lead were independently associated with postdevice TR. Furthermore, the presence of an interfering lead was the only factor associated with TR worsening, increasing the likelihood of developing moderate or severe TR by 15- and 11-fold, respectively., Conclusion: Lead-leaflet interference as seen on 3D echocardiography is associated with TR after device lead placement, suggesting that 3D echocardiography should be used to assess for lead interference in patients with significant TR., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Three-dimensional echocardiographic (3DE) analysis provides better measurements of left ventricular (LV) volumes, ejection fraction, myocardial deformation, and dyssynchrony. Many studies have shown that this technique has high intrainstitutional reproducibility. However, interinstitutional reproducibility is low, limiting its adoption. The aim of this study was to determine if standardization of training could reduce the interinstitutional variability in 3DE data analysis., Methods: In total, 50 full-volume, transthoracic 3DE data sets of the left ventricle were analyzed by two readers. Measurements obtained included LV volumes, ejection fraction, global longitudinal strain, and two dyssynchrony indices. The cases represented a wide spectrum of ejection fraction. After initial analysis of 21 studies, readers formally met to standardize their analytic approach on six additional cases. Five months after the intervention, 23 new cases were analyzed. Paired t tests were performed to identify systematic institutional differences in measurements. Interinstitutional variability was quantified using intraclass correlation coefficients and variability., Results: Before the intervention, there was a systematic bias in LV volumes, which was eliminated after intervention. Intraclass correlation coefficients showed that the intervention improved agreement in measurements of LV volumes, strain, and dyssynchrony between the two centers and decreased variability., Conclusions: A simple intervention to standardize analysis can reduce interinstitutional variability of measurements obtained from 3DE analysis. This intervention is needed before the use of 3DE measurement in multicenter trials and to increase the reproducibility of such measurements in routine clinical practice., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Currently, no real-time three-dimensional echocardiographic (RT3DE) indices are recommended by the official guidelines for the assessment of diastolic dysfunction (DD). We hypothesized that recent developments in RT3DE imaging technology that allow dynamic quantification of both left ventricular (LV) volume and 3D myocardial deformation, could be utilized to objectively assess DD. Transthoracic RT3DE datasets were acquired (Philips iE33, X5 transducer, frame rate 19 ± 4) in 76 subjects, including 20 normal controls (NL), 16 mild DD, 20 moderate DD and 20 severe DD (grade 1, 2 and 3, respectively, using ASE guideline). Images were analyzed using prototype software (TomTec) that performs 3D speckle tracking to generate time curves of LV volume and segmental myocardial strain. Indices of diastolic LV function were calculated: volume at 25, 50 and 75 % of filling duration (FD) in percent of end-diastolic volume (volume index, LVVi), and rapid filling volume (RFV) fraction. Temporal indices included: FD in % of RR, and rapid filling duration (RFD) in % of FD. Additionally, longitudinal, radial and circumferential strains at 25, 50 and 75 % of FD were calculated. Inter-groups differences were tested using ANOVA. LVVi and RFV fraction showed a biphasic pattern with the severity of DD characterized by an initial decrease (grade 1), a pseudo-normalization (grade 2), and then an increase above normal (grade 3). FD progressively decreased with severity of DD. RFD was significantly increased in all 3 groups compared to NL. After normalization by peak systolic values, all three strain components showed a linear pattern with the severity of DD, suggesting potential clinical usefulness. This is the first study to show that current RT3DE technology allows combined quantitative analysis of LV volume and 3D myocardial strain, which is sensitive enough to demonstrate differences in myocardial relaxation in patients with different degrees of DD.

Background: Sickle cell disease (SCD) is a hemoglobinopathy that affects one in 500 African Americans. Although it is well established that patients with SCD have left ventricular (LV) diastolic dysfunction, it is not clear whether they have subtle LV systolic dysfunction despite preserved ejection fraction (EF). We used three-dimensional speckle tracking echocardiography (3DSTE) to assess changes in both systolic and diastolic LV function in SCD., Methods: Transthoracic real time 3D images were obtained (Philips iE33) in 56 subjects, including 28 stable outpatients with SCD (age 33 ± 7 years) and 28 normal controls (age 35 ± 9 years). 3DSTE was performed using prototype software (4DLV Analysis, TomTec) to obtain LV volume and deformation time curves, from which indices of systolic and diastolic LV function were calculated., Results: In SCD patients, 3DSTE-derived LV filling parameters were significantly different from normal controls, reflecting an increase in both rapid and atrial filling volumes and prolonged active relaxation, depicted by a decrease in filling volume fractions at fixed times and an increase in rapid filling duration. Global LV systolic function was not only preserved but increased compared to controls, as reflected by significantly increased global longitudinal strain. Importantly, twist angle and torsion as well as radial and circumferential components of 3D strain were similar in both groups., Conclusions: 3DSTE was able to confirm diastolic dysfunction, as expected in some patients with SCD. However, 3DSTE strain analysis did not reveal any changes in LV systolic function. These findings provide novel insight into the pathophysiology of the cardiovascular complications of SCD., (© 2012, Wiley Periodicals, Inc.)

Background: Myocardial strain is useful in the evaluation of left ventricular function using high-frame rate two-dimensional (2D) speckle-tracking echocardiography (STE). Three-dimensional (3D) STE allows 3D measurement of myocardial deformation, which is potentially more accurate, because it is not affected by through-plane motion. However, the low frame rates of 3D STE are a potential limitation that has not been studied to date. Whereas with 2D STE, high frame rates are necessary because speckles may move out of the imaging plane, it was hypothesized that because they always remain within the scan volume, they should be tracked with 3D STE, even if frame rates are considerably lower., Methods: Twenty-seven subjects were studied, including 16 normal volunteers and 11 patients with nonischemic dilated cardiomyopathy, who underwent 2D (frame rate, 62 ± 9 frames/sec) and 3D echocardiographic imaging. In normal subjects, 3D imaging was performed at four different frame rates, achieved by varying the number of beats used for full-volume acquisition (six, four, two, and one). In the patients with dilated cardiomyopathy, 3D imaging was performed using a four-beat acquisition. The principal components of strain and the corresponding strain rates were calculated in 16 myocardial segments and averaged. Both 2D and 3D images were analyzed using TomTec software to avoid analysis-related differences., Results: In normal subjects, strain and strain rate values were the same for 3D STE with six-beat and four-beat full-volume data sets, corresponding to 25 and 18 frames/sec, respectively. In contrast, 3D STE with one-beat and two-beat data sets, corresponding to 5 and 10 frames/sec, respectively, resulted in significantly lower values. Strain and strain rate values derived from six-beat and four-beat 3D data sets were not significantly lower than 2D STE-derived values, indicating that there was no loss of information due to lower frame rates. In patients with dilated cardiomyopathy, both 2D STE-derived and 3D STE-derived strain values were significantly reduced compared with normal hearts. The differences between 2D STE-derived and 3D STE-derived strain values echoed those noted in the normal subjects., Conclusions: Three-dimensional speckle-tracking echocardiographic assessment of myocardial deformation is not compromised by low frame rates when derived from 18 or 25 frames/sec data sets but is underestimated with lower frame rates., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Left ventricular (LV) compliance is an important determinant of LV function and can be affected by a variety of cardiovascular conditions. In particular, diastolic dysfunction is associated with altered LV compliance. However, the evaluation of LV compliance is complex. Although the end-diastolic pressure-volume relationship (EDPVR) allows a direct, accurate evaluation of LV compliance, it requires invasive measurements. The aim of this study was to test the feasibility of noninvasive estimation of the EDPVR as a tool to evaluate LV compliance using three-dimensional echocardiography., Methods: Sixty-eight subjects were studied, including 23 normal controls, 22 patients with increased LV compliance due to dilated cardiomyopathy, and 23 patients with reduced LV compliance secondary to isolated diastolic dysfunction as defined using current American Society of Echocardiography guidelines. The EDPVR was calculated for each subject using a nonlinear model with echocardiographic estimates of end-diastolic pressure and volume. For both the isolated diastolic dysfunction and dilated cardiomyopathy groups, predicted end-diastolic volumes at predetermined pressure values (5, 10, 20, and 30 mm Hg) were compared with values in normal controls., Results: Compared with controls, noninvasive estimates of the EDPVR resulted in predicted end-diastolic volumes that were lower in the isolated diastolic dysfunction group and higher in the dilated cardiomyopathy group (P < .0001 for all four pressure levels). In addition, a stepwise trend of decreased compliance was noted for the different grades of diastolic dysfunction., Conclusions: This is the first study to demonstrate the feasibility of noninvasive estimation of the LV EDPVR and its ability to differentiate normal from abnormal LV compliance using three-dimensional echocardiography., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Most techniques previously used to assess left ventricular (LV) end-systolic elastance (E(es)) and ventricular-arterial coupling (C(LV-A)) relied on invasive measurements and data acquisition over a wide range of loading conditions. Our goals were to 1) assess the feasibility of noninvasive assessment of E(es) and C(LV-A) using real-time three-dimensional echocardiography (RT3DE) and arterial tonometry; 2) test the ability of this approach to detect changes in LV contractility; and 3) study its reproducibility. We studied pharmacologically induced changes in inotropic state (5 and 10 μg·kg(-1)·min(-1) dobutamine) in normal volunteers (N = 8) and compared 10 normal volunteers with 10 patients with dilated cardiomyopathy (DCM; ejection fraction < 35%). RT3DE LV images, calibrated carotid artery tonometry, and Doppler tracings were obtained to noninvasively estimate E(es) and C(LV-A), using two alternative calculations. Dobutamine caused a significant stepwise increase in blood pressure, heart rate, ejection fraction, and E(es) and a decreased C(LV-A). In patients with DCM, E(es) was significantly reduced and C(LV-A) elevated, compared with controls. Both inter- and intraobserver variability were good for all measured parameters, as reflected by intraclass correlation coefficients (>0.8) and coefficients of variation (<20%). While both E(es) estimates showed significant differences between DCM patients and controls, one estimate resulted in no overlap and better reproducibility (interobserver intraclass correlation coefficient: 0.83 vs. 0.47, coefficients of variation: 20 vs. 29%). This is the first study to test the feasibility of using RT3DE-derived LV volumes in conjunction with arterial tonometry to noninvasively quantify LV elastance and C(LV-A). This approach was found to be sensitive enough to detect expected differences in LV contractility and reproducible. Due to its noninvasive nature, this methodology may have clinical implications in various disease states.

Background: Myocardial deformation measurements using two-dimensional speckle-tracking echocardiography (STE) are known to vary among vendors. The intervendor agreement of three-dimensional (3D) deformation indices has not been studied. The goals of this study were to determine the intervendor agreement of 3D STE-based measurements of left ventricular (LV) deformation parameters to investigate the intrinsic variability of these measurements and identify the sources of intervendor differences., Methods: Real-time full-volume images obtained in 30 subjects with normal LV systolic function using two vendors' equipment (V1 and V2) on the same day were analyzed by two independent observers using two software packages (S1 and S2). Agreement between three technique combinations (V1/S1, V2/S2, and V1/S2) and their intrinsic reproducibility (interobserver and intraobserver agreement) were assessed using intraclass correlation coefficients. Parameters of LV deformation included global longitudinal strain, twist, 3D displacement, and 3D strain and its radial, longitudinal, and circumferential components., Results: For all three combinations, intertechnique agreement was poor (intraclass correlation coefficient < 0.4), always beyond the intrinsic variability. For all measured parameters, the intertechnique agreement was better when the same software package was used with images from different vendors (V2/S2 vs V1/S2) than when images from same vendor were analyzed using different software (V1/S2 vs V1/S1)., Conclusions: Three-dimensional STE-derived LV deformation parameters are highly vendor dependent, and the discordance levels are beyond intrinsic measurement variability of any of the tested combinations of imaging equipment and analysis software. This intervendor discordance must be taken into account when interpreting 3D deformation data., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Left ventricular (LV) ejection fraction (EF) by transthoracic two-dimensional echocardiography is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) qualitatively correlates with EF and can be measured in patients with poor image quality and dropout. The authors hypothesized that speckle-tracking echocardiography (STE)-derived MAD could quantify EF accurately and tested this hypothesis using cardiac magnetic resonance (CMR) as a reference., Methods: One hundred eighteen patients undergoing clinical transthoracic echocardiography were screened, and 110 whose mitral annuli was sufficiently well-defined irrespective of LV endocardial visualization underwent CMR within 6 days (85 of 110 in 1 day). Reference CMR EF values were obtained using standard methodology. STE was used to track annular motion throughout the cardiac cycle in the apical 2-chamber and 4-chamber views. To establish the relationship between MAD and CMR EF and to obtain a formula to estimate EF from MAD, regression analysis was performed in a study group of 60 patients with a wide range of EFs. This formula was then used in an independent test group of 50 patients by comparing estimated MAD EF against CMR EF values using Pearson's correlation and Bland-Altman analyses., Results: In the study group, STE MAD correlated highly with CMR EF and resulted in a formula relating MAD to EF. In the test group, estimated EF correlated well with CMR EF (4-chamber, R(2) = 0.64; 2-chamber, R(2) = 0.55), with near-zero bias and acceptable limits of agreement. Intraobserver and interobserver variability were between 5.8% and 12.7%., Conclusions: STE MAD is a clinically useful tool for quick, easy, robust, and accurate estimates of EF irrespective of LV endocardial definition., (2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Although 2-dimensional (2D) speckle tracking echocardiography has been shown to be useful in the assessment of regional left ventricular function, it is limited by the assumption that speckles can be tracked frame-to-frame within the imaging plane, even though the cardiac motion is 3-dimensional (3D). Our goal was to evaluate new 3D-speckle tracking echocardiographic (STE) software by (1) comparing the regional wall motion measurements against 2D-STE images, and (2) testing its ability to identify regional wall motion abnormalities. The 2D images and real-time 3D data sets (Toshiba) obtained from 32 subjects were analyzed to measure segmental radial and longitudinal displacements and rotation, as well as the radial, longitudinal, and circumferential strains. The intertechnique comparisons included regression and Bland-Altman analyses. Additionally, cardiac magnetic resonance images (Siemens 1.5 T) acquired the same day were reviewed by an expert who classified the segments as normal or abnormal. The values of each 3D-STE index were compared between the normal and abnormal segments. The 3D-STE and 2D-STE indexes did not correlate well (r = 0.16 to 0.76) and showed wide limits in intertechnique agreement (2 SD: 5 to 6 mm for displacements, 14 degrees rotation, 17% to 52% strains) despite only minimal biases, indicating that these 2 techniques are not interchangeable. In normal segments, 3D-STE showed greater displacements, reflecting the out-of-plane motion component; smaller SDs, indicating tighter normal ranges; and a gradual decrease in radial and longitudinal displacement and a reversal in rotation from the base to the apex. In the abnormal segments, all 3D-STE indexes were reduced, reaching significance for 5 of 6 indexes. In conclusion, this is the first study to evaluate the new 3D-STE technique for measurement of regional wall motion indexes. Our findings have demonstrated its superiority over 2D-STE.

Objectives: This study sought to establish normal values for real-time 3-dimensional echocardiography (RT3DE)-derived left ventricular (LV) dyssynchrony index (LVDI) and determine its age dependency, and to compare dyssynchrony in patients with normal LV function and patients with dilated cardiomyopathy (DCM), with and without left bundle branch block (LBBB)., Background: Cardiac resynchronization therapy is known to be ineffective in one-third of patients with heart failure, highlighting the need for alternative techniques to assess LV dyssynchrony., Methods: Datasets from RT3DE were analyzed to calculate LVDI using 16- and 17-segment models. First, 135 normal subjects were studied to establish LVDI abnormality threshold (mean + 2 SD) and to study the relationship with age. Then, 3 groups of patients (N = 16 each: DCM with and without LBBB, normal LV function with LBBB) were compared with 50 age-matched normal control subjects., Results: In normal subjects, the 16-segment model resulted in a lower LVDI abnormality threshold than the 17-segment model (4.0% vs. 4.5%). In patients with normal LV function, LVDI was significantly lower than in those with DCM, irrespective of LBBB. Although LBBB resulted in a nearly 2-fold increase in LVDI in patients with normal LV function, its effects were nonsignificant in DCM. All patients with DCM and ejection fraction <35% had abnormally high LVDI, likely as a result of low signal-to-noise ratio in low-amplitude regional volume curves hampering accurate determination of regional ejection time., Conclusions: Normal values established in this study resulted in indiscriminate diagnosis of abnormal dyssynchrony in all patients with reduced LV function. The value of RT3DE-derived LVDI in the evaluation of dyssynchrony in patients with reduced LV function needs to be critically reassessed because of the inability to accurately detect end-ejection in low-amplitude regional volume curves. Alternative indices of dyssynchrony need to be developed to address this limitation.

Background: The recent development of 3-dimensional (3D) surface detection algorithm of the endocardial and epicardial surfaces from real-time 3D echocardiographic (RT3DE) datasets allows direct semiautomated quantification of left ventricular mass (LVM). Our aims were to (1) evaluate the accuracy of RT3DE measurements of LVM using this algorithm against cardiac magnetic resonance (CMR) reference and (2) compare RT3DE LVM with conventional M-mode, 2-dimensional (2D), and RT3DE-guided biplane measurements., Methods: A total of 205 patients were studied in 2 protocols: (1) RT3DE and CMR imaging was performed on the same day in 55 subjects; (2) in an additional 150 subjects, RT3DE, 2D, and M-mode images were acquired. In both protocols, RT3DE endocardial and epicardial surfaces were semiautomatically identified at end diastole (QLab, Philips Medical Systems, Andover, MA) to calculate LVM. CMR, 2D, and M-mode-derived LVM were obtained using standard techniques., Results: A significant correlation (r = 0.95) was noted between RT3DE and CMR-derived LVM with a small bias of -2 g. M-mode-derived LVM measurements (175 +/- 64 g) were significantly larger than RT3DE LVM (123 +/- 39 g, bias: 52 g) with moderate correlation (r = 0.76). No significant differences in LVM were noted between 2D (125 +/- 42 g) and RT3DE values (bias: 1.2 g) with good correlation (r = 0.91, P < .001). However, the best correlation was noted between RT3DE and RT3DE-guided biplane LVM values (r = 0.95, P < .001, bias: -4.6 g). Intraobserver, interobserver variability, and test-retest variability of the RT3DE measurements were 9%, 12%, and 6%, respectively., Conclusion: RT3DE imaging using the 3D surface detection algorithm allows accurate and reproducible measurements of LVM. RT3DE-guided biplane technique can be used as an accurate time-saving alternative in clinical practice.

We studied the usefulness and reproducibility of real-time 3-dimensional (3D) echocardiography (RT3DE) for evaluating left ventricular (LV) dyssynchrony, and compared its results with Doppler tissue image (DTI) indices. Full-volume RT3DE data sets and 2-dimensional DTI from apical window were obtained in 122 participants. Using fast 3D border detection software, time to minimum systolic volume (Tmsv) was semiautomatically calculated in each region from a 17-segment model. Several dyssynchrony indices were then calculated: Tmsv-16SD, the SD of Tmsv in 16 of 17 segments, excluding the apical cap; Tmsv-12SD, the SD of Tmsv of 6 basal and 6 middle segments; and Tmsv-6SD, the SD of Tmsv of 6 basal segments. These dyssynchrony indices of RT3DE were then compared with two dyssynchrony indices measured by DTI: time to peak systolic velocity (TTPV)-12SD, the SD of time to peak systolic velocity of 12 LV segments; and time to cross over point of temporal axis (TTCO)-12SD, the SD of time to crossover point of temporal axis. RT3DE data was quantitatively analyzed in 117 of 122 patients. Tmsv-16SD (35 +/- 34 milliseconds) was significantly longer compared with Tmsv-12SD (27 +/- 30 milliseconds, P < .001) or Tmsv-6SD (23 +/- 28 milliseconds, P < .001). Tmsv-16SD increased significantly with the severity of LV systolic dysfunction. Fair correlation was noted among TTPV-12SD, TTCO-12SD, and Tmsv-16SD (r = 0.71, r = 0.73) and between Tmsv-16SD and LV ejection fraction (r = 0.80). Concordance rate between TTPV-12SD and Tmsv-16SD for detecting LV dyssynchrony was 79%. The corresponding value between TTCO-12SD and Tmsv-16SD was 80%. In conclusion, Tmsv-16SD correlated well with DTI-derived LV dyssynchrony indices. In addition to LV remodeling, fast border detection RT3DE provides useful parameters for evaluating LV dyssynchrony.

Background: Quantitative information on regional left ventricular volumes from real-time three-dimensional echocardiographic (RT3DE) images has significant clinical potential but needs validation., Aim: To validate these measurements against cardiac magnetic resonance (CMR) and test the feasibility of automated detection of regional wall motion (RWM) abnormalities from RT3DE data., Methods: RT3DE (Philips) and CMR (Siemens) images were obtained from 31 patients and analysed by using prototype software to semiautomatically calculate indices of regional left ventricular function, which were compared between RT3DE and CMR (linear regression, Bland-Altman). Additionally, CMR images were reviewed by an expert, whose RWM grades were used as a reference for automated classification of segments as normal or abnormal from RT3DE and from CMR images. For each modality, normal regional ejection fraction (REF) values were obtained from 15 patients with normal wall motion. In the remaining 16 patients, REFs were compared with thresholds that were derived from patients with normal wall motion and optimised using receiver operating characteristic analysis., Results: RT3DE measurements resulted in good agreement with CMR. Regional indices calculated in patients with normal wall motion varied between segments, but overall were similar between modalities. In patients with abnormal wall motion, RWM was graded as abnormal in 74% segments. CMR and RT3DE thresholds were similar (16-segment average 55 (10)% and 56 (7)%, respectively). Automated interpretation resulted in good agreement with expert interpretation, similar for CMR and RT3DE (sensitivity 0.85, 0.84; specificity 0.81, 0.78; accuracy 0.84, 0.84, respectively)., Conclusion: Analysis of RT3DE data provides accurate quantification of regional left ventricular function and allows semiautomated detection of RWM abnormalities, which is as accurate as the same algorithm applied to CMR images.

Objective: Regional left ventricular function can be assessed by real-time 3-dimensional echocardiography (RT3DE) in patients with good image quality. Our goals were to: (1) test the feasibility of RT3DE quantification of regional wall motion (RWM) in patients with poor acoustic windows who require contrast for endocardial visualization; and (2) validate these measurements against cardiac magnetic resonance (CMR) reference., Methods: RT3DE datasets and CMR images were obtained in 24 patients. In 16 of 24 patients with suboptimal endocardial definition, RT3DE imaging was repeated with intravenous contrast and triggering at end systole and end diastole. RT3DE datasets were analyzed using custom software designed to semiautomatically detect and segment the endocardial surface and calculate RWM values. CMR images were analyzed using commercial software to obtain reference values for RWM., Results: In 8 of 24 patients with good endocardial definition, RT3DE values of RWM correlated well with CMR (r = 0.73) with a small bias (-1.0 mm). In the remaining 16 patients, analysis of nonenhanced RT3DE datasets yielded lower correlation with CMR (r = 0.61) and a slightly greater bias (-1.5 mm). The agreement with CMR improved significantly (r = 0.76, bias -1.1 mm) with contrast enhancement., Conclusions: The agreement between RT3DE and CMR values of RWM is directly related to RT3DE image quality. In patients with poor acoustic windows, dual-triggered contrast enhancement improves the accuracy of RWM quantification to a level similar to that noted in patients with good images without contrast.

Background: Two-dimensional (2D) contrast-enhanced dobutamine stress echocardiography (DSE) is used clinically to diagnose stress-induced wall-motion abnormality (WMA). We hypothesized that contrast-enhanced real-time 3-dimensional (3D) DSE could improve the detection rate of WMA, because from a single full-volume acquisition, multiple segments can be visualized., Methods: We acquired both 2D and 3D DSE in 78 patients with known or suggested coronary artery disease (mean age: 65 years; 44 men). Dobutamine was infused using a standard protocol, and atropine added, if required. For 2D DSE, the intravenous contrast agent was injected at each stage and images displayed in a quadscreen format. For 3D DSE, contrast harmonic 3D data sets (full volumes) were acquired at baseline and peak stress. Using custom software, 3 short-axis views (from apex to base) were created, and wall motion scored using a wall-motion score index using a 16-segment model. A positive stress test was defined as new or worsened WMA or fixed abnormality during stress., Results: Heart rate increased from 72 +/- 13 to 133 +/- 15/min (86 +/- 11% of age-predicted). A total of 1248 segments were analyzed at each stage for both modalities. A single segment at baseline and 5 segments at peak stress could not be assessed with contrast 2D DSE. In contrast, 88 segments at baseline and 39 segments at peak stress could not be assessed with contrast 3D DSE. With 3D DSE, the majority of uninterpretable segments were in the anterior and lateral walls. Significant correlations were noted between wall-motion score index by 2D and 3D DSE at baseline (r = 0.78) and peak stress (r = 0.83). The concordance rate (positive/negative findings) between modalities was 69% (54/78) on a patient basis and 88% (206/234) on a perfusion territory basis. When using 2D DSE results as the gold standard, sensitivity and specificity for detecting WMA by 3D DSE was 58% and 75%, respectively. Sensitivity and specificity values were 67% and 94% for the right coronary artery, 53% and 81% for the left anterior descending coronary artery, and 88% and 100% for the left circumflex coronary artery territory, respectively., Conclusion: Contrast-enhanced 3D DSE was feasible in the majority of patients. However, the moderate concordance between both modalities was a result of: (1) difficulties in visualizing the anterolateral segments because of the relatively large imprint of the transducer; and (2) lower frame rates with 3D DSE resulting in the erroneous diagnosis of dyssynchrony.

Background: We hypothesized that color encoding of endocardial motion could aid less-experienced readers in detection of wall-motion abnormalities at rest and stress in patients with poor acoustic windows., Methods: Color-encoded images (color kinesis) were obtained at rest and peak dobutamine stress in 4 standard views during intravenous infusion of contrast agent in 117 patients with poorly visualized endocardium. In 101 of 117 patients (86%), in whom contrast enhancement allowed endocardial tracking, images were reviewed by two expert readers without color overlays. Each reader graded regional wall motion as normal, abnormal, or uninterpretable, and their consensus grades served as a gold standard. The same images were then reviewed and graded with and without color overlays by 3 cardiology fellows. The accuracy of the interpretation was calculated against the gold standard separately for the 3 vascular territories (left anterior descending, left circumflex, and right coronary arteries) and averaged for the 3 fellows., Results: With the addition of color encoding: (1) the number of uninterpretable segments decreased by 55% at rest and 61% at peak stress; and (2) all 3 fellows reached higher levels of accuracy in all 3 vascular territories both at rest (6%-82% average) and at stress (73%-80%)., Conclusion: The addition of color encoding of wall motion to contrast-enhanced images obtained in patients with poor acoustic windows during stress tests improves the interpretation of regional left ventricular function by less-experienced readers.

Determination of ejection fraction (EF) in clinical practice typically involves manual tracing of endocardial borders. This method is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) has been shown to correlate well with EF. Previously, this method involved tedious analysis of M-mode tracings. We developed and studied a new technique that is ultrasound beam angle-independent for automated detection of MAD, based on a tissue tracking algorithm. A regression formula was derived in a study group to predict EF from MAD measurements and tested prospectively in a separate group of patients. We found that our technique provides accurate, ultra-fast estimation of EF with lower inter- and intraobserver variability when compared with manually traced biplane EF.

Background: Real-time 3D echocardiographic (RT3DE) data sets contain dynamic volumetric information on cardiac function. However, quantification of left ventricular (LV) function from 3D echocardiographic data is performed on cut-planes extracted from the 3D data sets and thus does not fully exploit the volumetric information. Accordingly, we developed a volumetric analysis technique aimed at quantification of global and regional LV function., Methods and Results: RT3DE images obtained in 30 patients (Philips 7500) were analyzed by use of custom software based on the level-set approach for semiautomated detection of LV endocardial surface throughout the cardiac cycle, from which global and regional LV volume (LVV)-time and wall motion (WM)-time curves were obtained. The study design included 3 protocols. In protocol 1, time curves obtained in 16 patients were compared point-by-point with MRI data (linear regression and Bland-Altman analyses). Global LVV correlated highly with MRI (r=0.98; y=0.99x+2.3) with minimal bias (1.4 mL) and narrow limits of agreement (+/-20 mL). WM correlated highly only in basal and midventricular segments (r=0.88; y=0.85x+0.7). In protocol 2, we tested the ability of this technique to differentiate populations with known differences in LV function by studying 9 patients with dilated cardiomyopathy and 9 normal subjects. All calculated indices of global and regional systolic and diastolic LV function were significantly different between the groups. In protocol 3, we tested the feasibility of automated detection of regional WM abnormalities in 11 patients. In each segment, abnormality was detected when regional shortening fraction was below a threshold obtained in normal subjects. The automated detection agreed with expert interpretation of 2D WM in 86% of segments., Conclusions: Volumetric analysis of RT3DE data is clinically feasible and allows fast, semiautomated, dynamic measurement of LVV and automated detection of regional WM abnormalities.

The Tei index is a combined measurement of systolic and diastolic left ventricular (LV) performance and may be more useful for the diagnosis of global cardiac dysfunction than either systolic or diastolic measures alone. We sought to determine whether the Tei index could be accurately calculated from LV area waveforms generated with automated border detection. Twenty-four patients were studied in 3 groups: systolic dysfunction, diastolic dysfunction, and normal. The Tei index was calculated both from Doppler tracings and from analysis of LV area waveforms. Excellent agreement was found between Doppler-derived timing intervals and the Tei index with those obtained from averaged LV area waveforms. A significant difference was seen in the Tei index, computed with both Doppler and automated border detection techniques, between the normal group and those with LV systolic dysfunction and subjects with isolated diastolic dysfunction. This study validates the use of LV area waveforms for the automated calculation of the Tei index.