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BACKGROUND: Current echocardiographic guidelines recommend that tricuspid regurgitation (TR) severity be graded into three categories, following assessment of specific parameters. Findings from recent trials have shown that the severity of TR frequently far exceeds the current definition of severe. We postulated that a grading approach that emphasizes outcomes could be useful to identify patients with severe TR at increased risk of mortality. METHODS: We identified 284 patients with echocardiograms demonstrating severe functional TR, defined as vena contracta (VC) ≥0.7 cm. Demographics and mortality data were obtained from the medical records. Patients were divided into Study (n=122 patients with 3D images) and Validation (n=162) cohorts. VC was measured in both the right ventricular (RV) inflow and apical-4 chamber views and averaged. For the Study cohort, tricuspid annular (TA), RV end-diastolic (basal, mid, long axis) dimensions, tricuspid leaflet tenting height and area, RV free-wall longitudinal strain (Epsilon Imaging), and RV volumes (TomTec) were measured from 2D and 3D datasets, respectively. A K-partition algorithm was used in the Study cohort to derive a mortality-related cutoff VC value, above which TR was termed “massive”. The ability of this VC cutoff to identify patients at greater mortality risk was then tested in the Validation cohort using Kaplan-Meier survival analysis. RESULTS: In the Study cohort, VC>0.92 cm (”massive” TR) was optimally associated with worse survival. TA and RV size were larger in the Massive group (p

Increased vascular stiffness is known to be an independent predictor of mortality in patients with heart failure with reduced ejection fraction (HFrEF). The effects of sacubitril–valsartan on vascular structure and function have not been systematically studied in this patient population. We hypothesized that aortic distensibility (AD) and fractional area change (AFAC), as assessed by 2D transthoracic echocardiography (TTE), would improve over time in HFrEF patients on sacubitril–valsartan therapy, due to the vasodilatory properties of the medication. We prospectively studied 30 patients with HFrEF (25 < EF < 40%) on optimal guideline-directed medical therapy who were subsequently started on sacubitril–valsartan. Patients underwent serial 2D TTE imaging at baseline, 3 and 6 months following therapy initiation. Ascending aortic diameters were measured 3 cm above the aortic valve in the parasternal long-axis view and used to calculate AD and AFAC, two markers of vascular compliance. For reference, we also measured AD and AFAC in 30 healthy, age and gender-matched controls at a single time point. Normal controls had significantly higher values of AD and AFAC than HFrEF patients at baseline (AD: 4.0 ± 1.1 vs. 2.2 ± 0.9 c m(2)dyne(−1)10(−3), p < 0.0001 and AFAC: 18.8 ± 3.7% vs. 10.3 ± 4.3%, p < 0.0001). In HFrEF patients on sacubitril–valsartan, both indices of aortic compliance progressively improved towards normal from baseline to 6 months: AD from 2.2 ± 0.9 to 3.6 ± 1.5 cm(2)dyne(−1)10(−3) (p < 0.0001) and AFAC from 10.3 ± 4.3 to 13.7 ± 4.1% (p < 0.0001). In conclusion, AD and AFAC are decreased in patients with HFrEF and gradually improve with sacubitril–valsartan treatment. The echocardiographic markers used in this study may become a useful tool to assess the effectiveness of sacubitril–valsartan therapy in HFrEF patients.

Tricuspid annular (TA) size, assessed by 2D transthoracic echocardiography (TTE), has a well-established prognostic value in patients undergoing mitral valve surgery, with TA dilatation triggering simultaneous tricuspid annuloplasty. While TA dilatation is common in patients with dilated atria secondary to atrial fibrillation, little is known about the mechanisms of TA dilatation in patients with sinus rhythm (SR). This study aimed to identify echocardiographic parameters most closely related to the TA size as a potential tool for identification of patients prone to developing TA enlargement. 120 patients with SR underwent clinically indicated TTE, including 30 patients with normal hearts and 90 patients diagnosed with at least one right heart abnormality, defined as: right ventricular (RV) or right atrial (RA) dilatation, ≥ moderate tricuspid regurgitation (TR) and elevated systolic pulmonary artery pressure (sPAP). RA and RV end-diastolic and end-systolic volumes (EDV, ESV) and function were measured using commercial 3D software (TomTec). 3D RV long and short axes were used as surrogate indices of RV shape. Degrees of TR and sPAP were estimated by 2D TTE. 3D TA sizing was performed at end-diastole using 3D custom software. Linear regression analysis was used to identify variables best correlated with TA size, followed by multivariate analysis to identify independent associations. The highest correlations were found between TA area and: RA ESV (r = 0.73; p

Three-dimensional echocardiography (3DE) allows accurate and reproducible measurements of right ventricular (RV) size and function. However, widespread implementation of 3DE in routine clinical practice is limited because the existing software packages are relatively time-consuming and skill demanding. The aim of this study was to test the accuracy and reproducibility of new machine learning- (ML-) based, fully automated software for three-dimensional quantification of RV size and function.Fifty-six unselected patients with a wide range of RV size and function and image quality, referred for clinically indicated cardiac magnetic resonance (CMR) imaging, underwent a transthoracic 3DE exam on the same day. End-systolic and end-diastolic RV volumes (ESV, EDV) and ejection fraction (EF) were measured using the ML-based algorithm and compared with CMR reference values using Bland-Altman and linear regression analyses.RV function quantification by echocardiography was feasible in all patients. The automatic approach was accurate in 32% patients with analysis time of 15 ± 1 seconds and 100% reproducible. Endocardial contour editing was necessary after the automated postprocessing in the remaining 68% patients, prolonging analysis time to 114 ± 71 seconds. With these minimal adjustments, RV volumes and EF measurements were accurate in comparison with CMR reference (biases: EDV, -25.6 ± 21.1 mL; ESV, -7.4 ± 16 mL; EF, -3.3% ± 5.2%) and showed excellent reproducibility reflected by coefficients of variation7% and intraclass correlations ≥0.95 for all measurements.The new ML-based 3DE algorithm provided accurate and completely reproducible RV volume and EF measurements in one-third of unselected patients without any boundary editing. In the remaining patients, quick minimal editing resulted in reasonably accurate measurements with excellent reproducibility. This approach provides a promising solution for fast three-dimensional quantification of RV size and function.

Background The prevalence of isolated cleft mitral valve (MV; no concomitant congenital heart disease or degenerative MV disease) with significant mitral regurgitation (MR) diagnosed using two-dimensional echocardiography (2DE) has been reported to be very low. Three-dimensional echocardiography (3DE) has enabled a more comprehensive visualization of the MV and detailed understanding of the mechanisms of MR and can potentially reveal isolated cleft MV that is not recognized with 2DE. The aim of this study was to determine, using 3DE, the prevalence, location, and associated MV annular and left ventricular characteristics of isolated cleft MV, in the absence of associated congenital heart disease, in patients with significant MR. Methods A total of 1,092 patients with unexplained moderate or greater MR on two-dimensional transthoracic echocardiography who were referred for three-dimensional transesophageal echocardiography between 2005 and 2017 (n = 626) were retrospectively studied. Left ventricular dimensions and function were determined, and quantitative MR assessment and three-dimensional analysis of the MV annulus was performed. Results Twenty-one patients (prevalence 3.3%) were diagnosed with isolated cleft MV using three-dimensional transesophageal echocardiography but not 2DE. The majority of these patients (n = 16) were noted to have anterior cleft MVs, with most located in the mid-A1 (n = 10) or mid-A3 (n = 5) scallops. Posterior clefts were less common (n = 5) and occurred at the site of the natural scallop indentations (three between P1 and P2 and two between P2 and P3). Among patients with either anterior or posterior MV cleft, there were no differences in left ventricular ejection fraction or three-dimensional MV geometry (annular distance, height, circumference, and area). There was a trend toward worse MR severity in patients with anterior cleft MV. Conclusions In patients with otherwise unexplained significant MR referred for transesophageal echocardiography, 3DE uncovered a considerably higher prevalence of isolated cleft MV than previously reported by 2DE, with the majority located in the anterior MV. Although the annular geometry was similar between patients with anterior and posterior cleft MVs, a trend toward more severe MR in anterior clefts may reflect underlying abnormalities in the embryologic development of the anterior MV leaflet. Evaluation of MV pathology is improved by 3DE, which should be used routinely in the setting significant MR.

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.

Background Three-dimensional (3D) echocardiography directly assesses right ventricular (RV) volumes without geometric assumptions, despite the complex shape of the right ventricle, and accordingly is more accurate and reproducible than the two-dimensional methodology, which is able to measure only surrogate parameters of RV function. Volumetric analysis has been hampered by frequent inability to clearly visualize RV endocardium, especially the RV free wall, in 3D echocardiographic images. The aim of this study was to test the hypothesis that RV contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis. Methods Thirty patients with a wide range of RV size and function and image quality underwent transthoracic 3D echocardiography with and without contrast enhancement and cardiovascular magnetic resonance imaging on the same day. RV end-diastolic and end-systolic volumes and ejection fraction were measured from contrast-enhanced and nonenhanced 3D echocardiographic images and compared with cardiovascular magnetic resonance reference values using linear regression and Bland-Altman analyses. Blinded repeated measurements were performed to assess measurement variability. Results RV contrast enhancement was feasible in all patients. RV volumes obtained both with and without contrast enhancement correlated highly with cardiovascular magnetic resonance (end-diastolic volume, r = 0.90 and r = 0.92; end-systolic volume, r = 0.92 and r = 0.94, respectively), but the correlation for ejection fraction was better with contrast ( r = 0.87 vs r = 0.70). Biases were smaller with contrast for all three parameters (end-diastolic volume, −16 ± 23 vs −36 ± 25 mL; end-systolic volume, −10 ± 16 vs −23 ± 18 mL; ejection fraction, −0.7 ± 5.5% vs −2.7 ± 8.1% of the mean measured values), reflecting improved accuracy. Also, measurement reproducibility was improved by contrast enhancement. Conclusions Contrast enhancement improves the visualization of RV endocardial borders, resulting in more accurate and reproducible 3D echocardiographic measurements of RV size and function. This approach may be particularly useful in patients with suboptimal image quality.

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.

International audience; 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 (r2 > 0.92) was found in all cases, with better results when using the SSM models comprising more than one frame of the cardiac cycle.

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.

Left atrial (LA) longitudinal strain is a novel parameter used for the evaluation of LA function, with demonstrated prognostic value in several cardiac diseases. However, the extent of load dependency of LA strain is not well known. The aim of this study was to evaluate the impact of acute changes in preload on LA strain, side by side with LA volume, in normal subjects.Twenty-five healthy volunteers (13 men; mean age, 31 ± 2 years) were prospectively enrolled, who underwent two-dimensional and three-dimensional echocardiographic imaging during acute stepwise reductions in preload using a tilt maneuver: baseline at 0°, followed by 40° and 80°. Left ventricular and LA size and function parameters were measured using standard methodology, and LA strain-time curves were obtained using speckle-tracking software (TomTec), resulting in reservoir, conduit, and contractile strain components. All parameters were compared among the three loading conditions using one-way analysis of variance for repeated measurements.Although there were no significant changes in blood pressure, heart rate increased significantly with tilt. As expected, LA volumes, left ventricular volumes, and left ventricular ejection fraction, as well as E wave, A wave, and e' significantly decreased with progressive inclination. In parallel, LA reservoir, conduit, and contractile strain values decreased with reduction in preload (reservoir: 42.9 ± 3.9% to 27.5 ± 3.8%, P .001; conduit: 29.3 ± 2.7% to 20.2 ± 5.0%, P .001; contractile: 13.6 ± 2.9% to 7.3 ± 3.5%, P .001). Paired post hoc analysis showed that all LA strain values were significantly different among all three tilt phases. Of note, percentage change in LA reservoir strain was significantly smaller than that in LA maximum volume.In normal subjects, LA strain is preload dependent but to a lesser degree than LA volume. This difference underscores the relative advantage of LA strain over maximum volume, when LA assessment is used as part of the diagnostic paradigm.

Preservation of native left ventricular (LV) function in patients supported with LV assist device (LVAD) may be beneficial to attain optimal hemodynamics and enhance potential recovery. Currently, LVAD speed optimization is based on hemodynamic parameters, without considering residual native LV function. We hypothesized that alternatively, LV rotational mechanics can be quantified by 3D echocardiography (3DE), and may help preserve native LV function while optimizing LVAD speed. The goal of this study was to test the feasibility of quantifying the effects of LVAD implantation on LV rotational mechanics and to determine whether conventional speed optimization maximally preserves native LV function. We studied 55 patients with LVADs, who underwent 3DE imaging and quantitative analysis of LV twist. Thirty patients were studied before and after LVAD implantation. The remaining 25 patients were studied during hemodynamic ramp studies. The pump speed at which LV twist was maximal was compared with the hemodynamics-based optimal speed. LV twist decreased following LVAD implantation from 4.2 ± 2.7 to 2.3 ± 1.9° (P

Aims Right ventricular (RV) remodelling involves changes in size, function, and shape. Although three-dimensional echocardiography (3DE) allows imaging of RV morphology, regional RV shape analysis has not been evaluated using 3DE. We developed a technique to quantify RV shape and tested its ability to differentiate normal from pressure overloaded right ventricles. Methods Transthoracic 3DE RV images were acquired in 54 subjects, including 39 patients with pulmonary artery hypertension (PAH) and 15 normal controls (NL). 3D RV surfaces were reconstructed (TomTec) at end-diastole and end-systole (ED, ES) and processed using custom software to calculate mean curvature of the inflow and outflow tracts (RVIT, RVOT), apex, and body (both divided into free wall and septum). Methods and Results Septal segments (apical and body) in NLs were characterized by concavity (curvature 0) in ES. In PAH, however, the septum remained convex, bulging into the left ventricle throughout the cardiac cycle. In keeping with the ‘bellows-like’ action of RV contraction in the NL group, the body free wall transitioned from a convex surface at ED to a more flattened surface at ES, while the apex free wall progressed from a less convex surface at ED to a more convex surface at ES. In contrast, in PAH, both RV free-wall segments (apical and body) remained equally convex throughout the cardiac cycle. Conclusions Curvature analysis using 3D echocardiography allows quantitative evaluation of RV remodelling, which could be used to track differential changes in regional RV shape, as a way to assess disease progression or regression.

This study hypothesized that left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS) derived from 3-dimensional echocardiographic (3DE) images would better predict mortality than those obtained by 2-dimensional echocardiographic (2DE) measurements, and that 3DE-based LV shape analysis may have added prognostic value.Previous studies have shown that both LVEF and GLS derived from 2DE images predict mortality. Recently, 3DE measurements of these parameters were found to be more accurate and reproducible because of independence of imaging plane and geometric assumptions. Also, 3DE analysis offers an opportunity to accurately quantify LV shape.We retrospectively studied 416 inpatients (60 ± 18 years of age) referred for transthoracic echocardiography between 2006 and 2010, who had good-quality 2DE and 3DE images were available. Mortality data through 2016 were collected. Both 2DE and 3DE images were analyzed to measure LVEF and GLS. Additionally, 3DE-derived LV endocardial surface information was analyzed to obtain global shape indices (sphericity and conicity) and regional curvature (anterior, septal, inferior, lateral walls). Cardiovascular (CV) mortality risks related to these indices were determined using Cox regression.Of the 416 patients, 208 (50%) died, including 114 (27%) CV-related deaths over a mean follow-up period of 5 ± 3 years. Cox regression revealed that age and body surface area, all 4 LV function indices (2D EF, 3D EF, 2D GLS, 3D GLS), and regional shape indices (septal and inferior wall curvatures) were independently associated with increased risk of CV mortality. GLS was the strongest prognosticator of CV mortality, superior to EF for both 2DE and 3DE analyses, and 2D EF was the weakest among the 4 functional indices. A 1% decrease in GLS magnitude was associated with an 11.3% increase in CV mortality risk.GLS predicts mortality better than EF by both 3DE and 2DE analysis, whereas 3D EF is a better predictor than 2D EF. Also, LV shape indices provide additional risk assessment.

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.

This study examined cardiac remodeling and functional changes induced by 5 days of head-down (−6°) bed rest (HDBR) and the effectiveness of short-arm centrifugation (SAC) in preventing them in males. Twelve healthy men (mean age: 33 ± 7) were enrolled in a crossover design study (BR-AG1, European Space Agency), including one sedentary (CTRL) and two daily SAC countermeasures (SAC1, 30 min continuously; SAC2, 30 min intermittently) groups. Measurements included plasma and blood volume and left ventricular (LV) and atrial (LA) dimensions by transthoracic echocardiography (2- and 3-dimensional) and Doppler inflows. Results showed that 5 days of HDBR had a major impact on both the geometry and cardiac function in males. LV mass and volume decreased by 16 and 14%, respectively; LA volume was reduced by 36%; Doppler flow and tissue Doppler velocities were reduced during early filling by 18 and 12%, respectively; and aortic flow velocity time integral was decreased by 18% with a 3% shortening of LV ejection time. These modifications were presumably due to decreased physiological loading and dehydration, resulting in reduced plasma and blood volume. All these changes were fully reversed 3 days after termination of HDBR. Moreover, SAC was not able to counteract these changes, either when applied continuously or intermittently.

Background Right ventricular (RV) strain is a potentially useful prognostic marker in patients with pulmonary arterial hypertension (PAH). However, published reports regarding the accuracy of two-dimensional echocardiography (2DE)-derived RV strain against an independent reference in this patient population are limited. The aims of this study were: (1) to study the relationship between 2DE RV longitudinal strain and cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (RVEF) in patients with PAH; (2) to compare 2DE-derived and CMR-derived RV longitudinal strain in these patients; and (3) to determine the reproducibility of these measurements. Methods Thirty patients with PAH underwent 2DE and CMR imaging within a 2-hour time period. 2DE RV longitudinal strain was measured from a focused RV apical four-chamber view using speckle tracking software. CMR RV longitudinal strain was measured from short-axis slices acquired using fast-strain-encoded sequence. Global peak systolic RV longitudinal strain was calculated for both 2DE and CMR. Results RV longitudinal strain using 2DE software correlated well with CMR-derived RVEF (R = 0.69, P = 0.0006). There was moderate agreement when comparing 2DE to CMR RV longitudinal strain (R = 0.74, P = 0.0002; bias −1%, limits of agreement −9 to 7%). Inter-observer variability and intra-observer variability for RV longitudinal strain were lower for 2DE than CMR. Conclusions RV longitudinal strain by 2DE provides a good alternative for CMR-derived RVEF in patients with PAH. The moderate agreement in strain measurements between 2DE and CMR suggests that further software improvements are needed before these measurements can be used interchangeably in clinical practice.

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.

with the advent of real-time 3-dimensional transesophageal echocardiography (3d tee), rapid creation of high-quality, true-to-life images of mitral valve anatomy and pathology has become possible in the vast majority of patients ([1][1]). In addition to common mitral valve lesions, such as

Aims Although recommended by current guidelines, adoption of three-dimensional echocardiographic (3DE) chamber quantification in clinical practice has lagged because of time-consuming analysis. We recently validated an automated algorithm that measures left atrial (LA) and left ventricular (LV) volumes and ejection fraction (EF). This study aimed to determine the accuracy and reproducibility of these measurements in a multicentre setting. Methods and results 180 patients underwent 3DE imaging (Philips) at six sites. Images were analysed using automated HeartModel (HM) software with endocardial border correction when necessary and by manual tracing. Measurements were performed by each site and by the Core Laboratory (CL) as the reference. Inter-technique comparisons included HM measurements by the sites against manual tracing by CL, and showed strong correlations (r-values: LVEDV: 0.97, LVESV: 0.97, LVEF: 0.88, LAV: 0.96), with the automated technique slightly underestimating LV volumes (biases: LVEDV: -14 ± 20 ml, LVESV: -6 ± 20 ml), LVEF (-2 ± 7%) and LAV (-9 ± 10 ml). Intra-technique comparisons included HM measurements by the sites against CL, with and without corrections. Corrections were unnecessary or minimal in most patients, and improved the measurements only modestly. Comparisons without corrections showed perfect agreement for all parameters. With corrections, correlations were better (r-values: LVEDV: 0.99, LVESV: 0.99, LVEF: 0.94, LAV: 0.99) and biases (LVEDV: -8 ± 12 ml, LVESV: -6 ± 12 ml, LVEF: 1 ± 5%, LAV: -10 ± 6 ml) smaller than in inter-technique comparison. All automated measurements with corrections were more reproducible than manual measurements. Conclusion Automated 3DE analysis of left-heart chambers is an accurate alternative to conventional manual methodology, which yields almost the same values across laboratories and is more reproducible. This technique may contribute towards full integration of 3DE quantification into clinical routine.

Objectives To determine the accuracy of calcium-containing rings measurements imaged by three-dimensional echocardiography (3DE), multi-slice CT (MSCT) and cardiac magnetic resonance (CMR) under ideal conditions against the true ring dimensions. To compare the accuracy of aortic annulus (AoA) measurements in ex vivo human hearts using 3DE, MSCT and CMR. To determine the accuracy of AoA measurements in an in vivo human model. Design 3DE, MSCT and CMR imaging were performed on 30 calcium-containing rings and 28 explanted human hearts. Additionally, 15 human subjects with clinical indication for MSCT underwent 3DE. Two experts in each modality measured the images. Main outcome measures Bias and intraclass correlation coefficient for accuracy of imaging measurements when compared with actual ring dimensions. Bias, intraclass correlation coefficient and variability were obtained: (1) when comparing explanted human heart AoA measurements from the two remaining imaging modalities with the most accurate one as determined from the ring measurements and (2) in in vivo human AoA measurements. Analysis was repeated on explanted heart subgroups divided by aortic valve Agatston score. Results Against the known ring dimensions, CMR had the highest accuracy and the lowest variability. MSCT measurements had high accuracy but wider variability and 3DE had the lowest accuracy with the largest variability. When 3DE and MSCT were compared with CMR, 3DE underestimated and MSCT overestimated AoA dimensions, but inter-measurement variability of 3DE and MSCT were similar. When divided by Agatston score, both 3DE and MSCT measurements were larger and showed greater variability with increasing calcium burden. The in vivo study showed that the correlation between 3DE and MSCT measurements was high; however, 3DE measurements were smaller than those measured with MSCT. Conclusions In the in vitro model, CMR measurements were the most accurate for assessing the actual dimensions suggesting that further investigations on its role in AoA measurement in TAVR are needed. However from the in vivo model, MSCT and 3DE are reasonable alternatives with the understanding that they can slightly overestimate and underestimate annular dimensions, respectively.

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 Accurate segmental mitral valve (MV) analysis is essential for surgical planning. Although real-time three-dimensional (3D) transesophageal echocardiography has improved the ability to visualize the MV, accurate localization of MV pathology from 3D transesophageal echocardiographic images still remains experience dependent. Three-dimensional parametric maps of the MV obtained from these images further simplify the visualization of MV anatomy. The aims of this study were to examine whether 3D parametric maps of the MV could improve the diagnostic accuracy in localizing pathology and to determine their usefulness for readers with different levels of training. Methods Five novice (American Society of Echocardiography [ASE] level 2), three intermediate-level (ASE level 3; 500 MV cases) readers interpreted MV segmental anatomy in 50 patients (30 with degenerative MV disease, 20 with normal MVs). All readers reviewed two-dimensional and 3D transesophageal echocardiographic and 3D parametric maps at sequential weekly sessions. The results were compared with surgical findings. Results Expert readers were the most accurate irrespective of image type. Novice readers were the least accurate and commonly misinterpreted P2 and P3 scallops. Their accuracy was highest when interpreting 3D parametric maps (from 87% with two-dimensional transesophageal echocardiography to 92%). Intermediate readers' accuracy fell between the other two groups irrespective of image type and showed no change with the use of parametric maps. Conclusions This is the first study to show that the interpretation of 3D parametric maps improves the accuracy of localization of MV pathology by novice readers. Therefore, parametric maps should be used routinely by less experienced readers during the assessment of degenerative MV disease.

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.

Background The aim of this study was to determine the feasibility and accuracy of a new real-time 3-dimensional (RT3D) matrix-array transesophageal echocardiographic probe for the determination of left atrial appendage (LAA) geometry. Methods Sixty-six consecutive patients (mean age, 53 ± 17 years) referred for 2-dimensional (2D) transesophageal echocardiography (TEE) underwent additional RT3D TEE. The feasibility of RT3D TEE for LAA geometry was studied in the first 37 patients, and 2D and RT3D transesophageal echocardiographic quantification of the LAA were compared in the subsequent 29 patients. The LAA orifice diameter and depth were measured using biplane 2D TEE, and LAA orifice area was calculated as an ellipse. LAA orifice area and depth were measured in 3D and correlated to 2D measurement and were also correlated to 64-slice cardiac computed tomography (CT) in 8 patients. Results All 66 patients underwent RT3D matrix-array TEE without complication. In the feasibility study, the LAA was well visualized in 95%. In the quantitation study, 2D TEE underestimated LAA orifice area compared with 3D imaging (3.1 ± 1.3 vs 4.2 ± 2.2 cm 2 ; r = 0.55). LAA depth by 2D and 3D imaging were well correlated (3.7 ± 0.7 vs 3.4 ± 0.7 cm; r = 0.77). LAA orifice area on CT was well correlated with area on 3D TEE ( r = 0.98) but not with area 2D TEE ( r = 0.13). Bland-Altman analysis demonstrated that 2D TEE systematically underestimated LAA orifice area compared with 3D TEE (mean bias, −1.0 cm 2 , with wide limits of agreement [−4.6 to 2.6 cm 2] . In the 8 patients who underwent both 3D TEE and CT, the mean bias was 0.15 cm 2 , with narrow limits of agreement (−0.50 to 0.20 cm 2 ). Conclusions RT3D TEE for the visualization and quantitative analysis of LAA orifice area is feasible and correlates well with 64-slice cardiac CT.

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 The strategy for mitral valve (MV) repair has recently focused on the restoration of the submitral apparatus. However, the relationship between geometric changes of the submitral apparatus and the mitral leaflets has not been systematically investigated. The aim of this study was to determine the relationships among chordal length (CL) and LV size and leaflet surface area (LSA) in normal subjects, patients with primary (degenerative) mitral regurgitation (PMR), and patients with functional (secondary) mitral regurgitation (FMR). Methods A total of 72 patients who underwent three-dimensional transesophageal echocardiography, including: 27 with PMR with isolated P2 flail leaflet, 25 with FMR with greater than mild mitral regurgitation, and 20 with normal mitral valves. LSA was quantified at midsystole from full-volume midesophageal views. CL was calculated by averaging the lengths of eight primary chords from transgastric full-volume data sets using multiplanar reconstruction. Results Both CL and LSA in the PMR group were significantly longer compared with the FMR and normal control groups. No difference in CL was noted between patients with FMR and normal subjects. In all three groups, CL and LSA did not correlate with LV systolic or diastolic dimensions. Although CL did not correlate with LSA in the FMR group, a moderate correlation ( R = 0.62) was observed in the PMR group. Conclusions In patients with FMR with greater than mild mitral regurgitation, the chords retain normal length, despite LSA and LV enlargement. In patients with PMR with flail P2 scallops, CL elongation of primary chords is associated with larger LSA but not with LV dimensions. This information may have implications for clinical strategies for mitral valve repair surgery, including the submitral approach and percutaneous procedures.

ObjectivesWe tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia.BackgroundThe RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers.MethodsElectrocardiographically triggered harmonic RT3DE datasets were acquired (Philips 7500) while infusion of Definity was initiated and reached a steady state. Protocol 1 was performed in nine isolated rabbit hearts and included three coronary flow levels. In protocol 2, changes in regional perfusion caused by partial left anterior descending artery occlusion were measured in five pigs. In protocol 3, adenosine-induced changes in perfusion were measured in eight normal volunteers. Myocardial video-intensity (MVI) was measured over time in three-dimensional (3D) slices to calculate peak contrast inflow rate (PCIR). In pigs, PCIR was measured on a regional basis and validated against microspheres.ResultsThe RT3DE imaging allowed selection of slices for perfusion analysis in rabbit hearts, pigs, and humans. Administration of contrast resulted in clearly visible and quantifiable changes in MVI. In rabbits, The PCIR progressively decreased with coronary flow (p < 0.0001). In pigs, coronary occlusion caused a 59 ± 26% decrease in PCIR exclusively in the left anterior descending artery territory (p < 0.05) in agreement with microspheres. In humans, adenosine increased PCIR to 198 ± 57% of baseline (p < 0.05).ConclusionsContrast-enhanced RT3DE imaging provides the basis for volumetric imaging and quantification of myocardial perfusion.

We recently developed a new approach for contrast echocardiographic quantification of myocardial perfusion, based on brief interruptions of contrast infusion, which was designed to overcome the limitations of existing techniques. In this study, our technique was initially validated in a series of animal experiments designed to detect regional perfusion variations in vivo. Subsequently, clinical feasibility of perfusion measurements was tested.Regional perfusion was measured transthoracically in 6 anesthetized pigs during baseline, partial left anterior descending coronary artery occlusion, and reperfusion, and validated with fluorescent microspheres. Adenosine-induced changes in perfusion were measured in 8 healthy volunteers. In both protocols, imaging was optimized during contrast infusion (Definity). Infusion was interrupted to allow contrast clearance and images were acquired during subsequent contrast inflow. Myocardial videointensity was measured over time and peak contrast inflow rate was calculated.In pigs, partial coronary occlusion resulted in a 47 +/- 23% decrease in peak contrast inflow rate in the left anterior descending coronary artery perfusion territory (P.05), which was reversed during reperfusion, without concomitant decrease in other perfusion territories. These changes were in agreement with microspheres. In human beings, adenosine increased peak contrast inflow rate to 278 +/- 123% of baseline (P.05).The interruption of contrast infusion technique is a sensitive tool for accurate quantification of myocardial perfusion, which may constitute an alternative to currently used techniques.

Aims Determination of left ventricular (LV) volumes and ejection fraction (EF) from two-dimensional echocardiographic (2DE) images is subjective, time-consuming, and relatively inaccurate because of foreshortened views and the use of geometric assumptions. Our aims were (1) to validate a new method for rapid, online measurement of LV volumes from real-time three-dimensional echocardiographic (RT3DE) data using cardiac magnetic resonance (CMR) as the reference and (2) to compare its accuracy and reproducibility with standard 2DE measurements. Methods and results CMR, 2DE, and RT3DE datasets were obtained in 50 patients. End-systolic and end-diastolic volumes (ESV and EDV) were calculated from the 2DE images using biplane method of disks. ES and ED RT3DE datasets were analysed using prototype software designed to automatically detect the endocardial surface using a deformable shell model and calculate ESV and EDV from voxel counts. 2DE and RT3DE-derived volumes were compared with CMR (linear regression, Bland–Altman analysis). In most patients, analysis of RT3DE data required

Background In the last decade, multiple studies depicted discrepancies between mitral valvular orifice area (MVA) measurements obtained with the pressure half-time (PHT) method and invasive methods during the immediate post-percutaneous mitral valvuloplasty (PMV) period. Our aim was to assess the accuracy of Real-Time 3D echo (RT3D) to measure the MVA in the immediate post-PMV period. The invasively determined MVA was used as the gold standard. Methods and results We studied 29 patients with rheumatic mitral stenosis from two centres (27 women; mean age 48.2±11.3 years), all of which had underwent PMV. MVA was calculated before and after PMV using the PHT method, 2D echo planimetry, RT3D echo planimetry and invasive determination (Gorlin's method). The RT3D MVA assessment showed a better agreement with the invasively derived MVA before and in the immediate post-PMV period (Bland-Altman analysis: Average difference between both methods and limits of agreement: 0.01 (−0.31 to 0.33) cm2 and −0.12 (−0.71 to 0.47) cm2) before and immediately after the PMV, respectively. Conclusions RT3D is a feasible and accurate technique for measuring MVA in patients with RMVS. It has the best agreement with the invasively determined MVA, particularly in the immediate post-PMV period.

Ventricular resynchronization with multisite pacing in heart failure patients results in acute improvement of myocardial performance, but the mechanism is unknown. Our goals were to determine whether multisite pacing results in acute improvement of myocardial performance in postoperative single-ventricle patients, and to elucidate the mechanism by assessing the synchronization of regional ventricular contraction during multisite pacing using real-time three-dimensional echocardiographic imaging.Multisite pacing studies were performed in 26 single-ventricle patients (mean age, 28 months; range, 7 days to 11 years) undergoing some form of single-ventricle palliation (stage I Norwood, 4; aortopulmonary shunt, 1; cavopulmonary shunt, 9; Fontan, 8; Fontan revision, 3; valve replacement, 1). Electrocardiogram, blood pressure, mixed-venous oxygen saturation, and three-dimensional echocardiograms (n = 10) were recorded at baseline and during multisite pacing. Data were analyzed to obtain regional volume-time curves for 16 three-dimensional segments of the systemic ventricle. An index of asynchrony was calculated at baseline and during pacing as the standard deviation of all segmental volume-time curves from onset to end of ejection.With multisite pacing performed at a median postoperative day 2 (range, 0 to 9), QRS duration decreased in 24 of 26 patients (93.9 +/- 17.5 versus 71.7 +/- 10.8 ms; p0.001); systolic blood pressure increased in 25 of 26 patients (86.3 +/- 20.0 versus 93.8 +/- 20.2 mm Hg; p0.001); cardiac index increased in 21 of 22 patients (3.2 +/- 0.8 versus 3.7 +/- 1.0 L x min(-1) x m(-2); p0.001); and the index of asynchrony improved in 8 of 10 patients (10.3 +/- 4.8 versus 6.0 +/- 1.4; p0.04).Multisite pacing improves cardiac performance after single-ventricle palliation. Real-time three-dimensional echocardiography demonstrated that multisite pacing improved the synchrony of ventricular contraction.

Background— Left ventricular (LV) mass is an important predictor of morbidity and mortality, especially in patients with systemic hypertension. However, the accuracy of 2D echocardiographic LV mass measurements is limited because acquiring anatomically correct apical views is often difficult. We tested the hypothesis that LV mass could be measured more accurately from real-time 3D (RT3D) data sets, which allow offline selection of nonforeshortened apical views, by comparing 2D and RT3D measurements against cardiac MR (CMR) measurements. Methods and Results— Echocardiographic imaging was performed (Philips 7500) in 21 patients referred for CMR imaging (1.5 T, GE). Apical 2- and 4-chamber views and RT3D data sets were acquired and analyzed by 2 independent observers. The RT3D data sets were used to select nonforeshortened apical 2- and 4-chamber views (3DQ-QLAB, Philips). In both 2D and RT3D images, LV long axis was measured; endocardial and epicardial boundaries were traced, and mass was calculated by use of the biplane method of disks. CMR LV mass values were obtained through standard techniques (MASS Analysis, GE). The RT3D data resulted in significantly larger LV long-axis dimensions and measurements of LV mass that correlated with CMR better ( r =0.90) than 2D ( r =0.79). The 2D technique underestimated LV mass (bias, 39%), whereas RT3D measurements showed only minimal bias (3%). The 95% limits of agreement were significantly wider for 2D (52%) than RT3D (28%). Additionally, the RT3D technique reduced the interobserver variability (37% to 7%) and intraobserver variability (19% to 8%). Conclusions— RT3D imaging provides the basis for accurate and reliable measurement of LV mass.

Background No technique exists for objective evaluation of left ventricular wall motion in contrast-enhanced images. We tested a new technique for quantification of regional fractional area change using contrast-enhanced power modulation imaging with color kinesis. Methods The feasibility of this technique for detecting acute ischemia was first tested in 11 pigs. Next, the accuracy for detecting resting wall-motion abnormalities was determined in 52 patients requiring contrast and compared with conventional interpretation of 2-dimensional images by inexperienced readers. Expert interpretation of 2-dimensional images served as the gold standard. Results In pigs, coronary occlusion resulted in reversible hypokinesis and reduced regional fractional area change. In patients with poor acoustic windows, this technique's accuracy for quantitative detection of resting wall-motion abnormalities was 86% compared with 81% for conventional interpretation by inexperienced readers ( P Conclusions Regional wall motion can be accurately assessed using color-encoded power modulation imaging for patients requiring contrast. This technique may prove a useful diagnostic aid to echocardiographers of varying levels of experience.

Objective The feasibility and accuracy of direct transthoracic 3-dimensional (3D) mitral valve area (MVA) measurements obtained using freehand scanning was investigated in patients with mitral stenosis. Methods A total of 30 patients (26 women, 4 men; aged 55 ± 13 years) underwent a 2-dimensional (2D) and Doppler study 1 hour before percutaneous balloon mitral valvuloplasty. Transthoracic freehand data were acquired using a magnetic receiver attached to a broadband transducer, gated to electrocardiography and respiration. Volumetric MVA measurements from the left ventricle and left atrium were obtained and compared with MVA measurements derived from 2D planimetry, pressure half-time, and proximal isovelocity surface area. Invasive Gorlin MVA measurements were the gold standard for comparison. Results In all, 29 patients (97%) had 3D data allowing MVA measurements. Direct 3D measurements from the left ventricle had the least bias (0.06 ± 0.19 cm 2 ) and tightest limits of agreement (−0.44 to 0.32) compared with left atrium measurements (0.17 ± 0.25 cm 2 and −0.67 to 0.33, respectively). The proximal isovelocity surface area method (bias: 0.09 ± 0.34 cm 2 ) was the most accurate of all 2D methods followed by pressure half-time (0.17 ± 0.36 cm 2 ) and planimetry (0.21 ± 0.29 cm 2 ). Conclusion Direct 3D MVA measurements from the left ventricle using transthoracic freehand scanning are more accurate than traditional 2D methods.

Background: Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scale renditions of the jets, which were difficult to differentiate from surrounding cardiac structures. Recently, a color-coded display of three-dimensional (3D) regurgitant flow has been developed. However, this display was unable to integrate cardiac anatomy, thereby losing spatial information, which made it difficult to determine the jet origin and its spatial trajectory. To overcome this limitation, an improved method of 3D color reconstruction of regurgitant jets obtained from color flow Doppler using a transesophageal approach was developed to allow the combined display of both color flow and gray scale information. Objectives: To demonstrate the feasibility of 3D reconstruction of regurgitant mitral flow jets using an improved method of color encoding digital data acquired by transesophageal echocardiography (TEE). Methods: We studied 46 patients undergoing a clinically indicated TEE study. All subjects had mitral regurgitation detected on a previous transthoracic study. Atrial fibrillation or poor image quality were not used as exclusion criteria. The 3D study was performed using a commercial ultrasound imaging system with a TEE probe (Sonos 5500, Agilent Technologies). A rotational mode of acquisition was used to collect two-dimensional (2D) color flow images at 3-degree intervals over 180 degrees. Images were processed off line using the Echo-View Software (TomTec Imaging Systems). Volume-rendered 3D color flow jets were displayed along with gray scale information of the adjacent cardiac structures. Results: Mitral regurgitant flow, displayed in left atrial and two longitudinal orientations, was successfully reconstructed in all patients. The time for acquisition, post-processing, and rendering ranged between 10 and 15 minutes. There were 28 centrally directed jets and 15 eccentric lesions. Eight patients in the study had periprosthetic mitral regurgitant flow. Conclusions: Three-dimensional imaging of mitral regurgitant jets is feasible in the majority of patients. This improved technique provides additional information to that obtained from the 2D examination. Particularly, in patients with paravalvular leaks 3D color flow Doppler provides information on the origin and the extent of the dehiscence, as well as insight into the jet direction. In addition, in patients with eccentric mitral regurgitation, this new modality overcomes the inherent limitations of 2D echo Doppler by depicting the full extent of the jet trajectory. (ECHOCARDIOGRAPHY, Volume 20, April 2003)

A robust and efficient approach to reconstruction of the descending thoracic aorta from contiguous 3-D transesophageal echocardiographic (TEE) images is proposed. An ad hoc image acquisition protocol was designed to acquire ordered and partially overlapped 3-D TEE data sets, followed by dedicated image processing to align and fuse all acquired data sets. Alignment strategy implemented pairwise rigid registration guided by a priori knowledge, and it was validated using artificially misaligned images. Image fusion was finally performed to enable visualization and analysis of extended field-of-view of the acquired aorta. The application of different fusion techniques was also investigated. The method was applied to a population of 17 consecutive patients. Qualitative and quantitative results supported the feasibility and accuracy of the proposed approach. In a clinical scenario, its application could allow the quantitative assessment of aortic plaque burden in the descending thoracic aorta from 3-D TEE images.

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.

OBJECTIVE—To assess the feasibility of measuring left atrial (LA) function with acoustic quantification (AQ) and then assess the effects of age and sex on LA reservoir, conduit, and booster pump function. PATIENTS AND SETTING—165 subjects without cardiovascular disease, 3-79 years old, were enrolled by six tertiary hospital centres. INTERVENTIONS—Continuous LA AQ area data were acquired and signal averaged to form composite waveforms which were analysed off-line. MAIN OUTCOME MEASURES—Parameters of LA performance according to age and sex. RESULTS—Signal averaged LA waveforms were sufficiently stable and detailed to allow automated analysis in all cases. An age related increase in LA area was noted. LA reservoir function did not vary with age or sex. All parameters of LA passive and active emptying revealed a significant age dependency. Overall, the passive emptying phase accounted for 66% of total LA emptying ranging from 76% in the youngest to 44% in the oldest decade. LA contraction accounted for 34% of atrial emptying in all subjects combined with the older subjects being more dependent on atrial booster pump function. When adjusted for atrial size, there were no sex related differences in LA function. CONCLUSIONS—LA reservoir, conduit, and booster pump function can be assessed with automated analysis of signal averaged LA area waveforms. As LA performance varies with age, establishment of normal values should enhance the evaluation of pathologic states in which LA function is important. Keywords: aging; atrium; echocardiography

The advantages of digital echocardiography studies include ease of retrieval, review, comparison, duplication, and quantitation as well as the potential for moving studies over networks. However, the large amounts of data associated with digital echocardiography studies have posed new problems. Reduction of the amount of data can be accomplished with image compression, in particular MPEG-1 (Moving Pictures Expert Group), which is designed for dynamic image sequences. However the effects of different levels of compression on the quality and diagnostic content of echocardiographic images need to be established. Digital sequences of single cardiac cycles were acquired in 40 consecutive patients, MPEG-1-compressed at different effective ratios (60:1, 80:1, 120:1, 200:1, 300:1, 370:1, 500:1), reviewed, and scored for endocardial visualization. The overall visualization scores and percentages of nonvisualized segments in the compressed images were not different from the uncompressed images up to a compression ratio of 200:1. Differential effects of compression were noted on a segmental basis and also varied with baseline image quality. The ability to correctly identify regional wall motion abnormalities did not decrease until compression ratios of 1:200 or higher were used. Digital echocardiography loops, MPEG-1-compressed at an effective ratio of 200:1, demonstrate no degradation in endocardial visualization quality or diagnostic content. Compression at this ratio has the potential to reduce the storage size of digital echocardiography studies to less than 1% of their current size.

Power Doppler is an ultrasound technique that color-encodes the change in amplitude of the ultrasound signal, which reflects changes in the position of scatterers between ultrasound pulses. Power Doppler can be used with echocardiographic contrast agents in a harmonic imaging mode to opacify a cardiac chamber. The opacification of a cardiac chamber can aid in visualizing the silhouette of intracardiac masses and displaying blood flow patterns. Four cases are presented that demonstrate the use of harmonic power Doppler to aid in the identification of a left ventricular apical thrombus, a left atrial thrombus, and a left ventricular pseudoaneurysm. (J Am Soc Echocardiogr 1999;12:871-5.)

OBJECTIVES To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patient’s data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segment’s response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography.

Objectives. We tested the feasibility of using analysis of color kinesis images to objectively assess global and regional left ventricular (LV) diastolic function in patients with dilated cardiomyopathy (DCM). In addition, the ability of this technique to track drug-induced changes on LV diastolic properties was studied. Background. Diastolic dysfunction contributes to symptomatology in patients with DCM. The assessment of LV diastolic function using conventional Doppler echocardiography is indirect and is confounded by multiple variables. Moreover, the noninvasive evaluation of regional diastolic properties is difficult. In contrast, color kinesis directly tracks and color-encodes regional diastolic endocardial motion. Methods. We studied 24 patients with DCM and mitral regurgitation (MR) and 24 age-matched normal subjects. Transmitral and pulmonary vein flow velocities were measured using pulsed Doppler echocardiography. Diastolic color kinesis images were used to calculate indexes of magnitude and timing of global and regional diastolic function. Diastolic asynchrony was evaluated in different subgroups of patients with DCM. The effects of drug infusions (nitroprusside and dobutamine) were also studied. Results. Color kinesis indexes of global diastolic function showed significant differences between patients with DCM and normal subjects. Compared with Doppler indexes, color kinesis was less confounded by MR and was capable of differentiating between drug-induced lusitropic and vasodilator effects. Diastolic asynchrony was increased in patients with DCM and severe MR. Conclusions. Quantitative analysis of global and regional LV diastolic function in patients with DCM using color kinesis is feasible.

OBJECTIVES: Peripartum cardiomyopathy is a rare complication of pregnancy. Thirty percent of patients with this disorder are reported to recover baseline ventricular function within 6 months of delivery, but the ability of these ventricles to respond to hemodynamic stress is unknown. The aim of this investigation was to quantitatively assess the contractile reserve of patients with a history of peripartum cardiomyopathy and recovered left ventricular function. STUDY DESIGN: Baseline left ventricular contractility was assessed by use of the load and heart rate–independent relationship between end-systolic stress and rate-corrected velocity of fiber shortening. Data were acquired from "recovered" patients (10.5 ± 11.6 months after delivery) and compared with data from matched nonpregnant controls with use of two-dimensionally targeted M-mode echocardiography and calibrated subclavian pulse tracings that were recorded over a wide range of afterloads (end-systolic stress) generated by methoxamine (1 mg/min) infusion. Contractile reserve was assessed by a dobutamine challenge (5 μg/kg/min) and quantified as the vertical deviation of the dobutamine end-systolic stress minus the corrected velocity of fiber shortening data point from the baseline contractility line. RESULTS: Patients with peripartum cardiomyopathy and matched controls had normal baseline heart rates, blood pressures, ventricular dimensions, and left ventricular function. Contractile reserve, however, was reduced in patients with recovered peripartum cardiomyopathy (0.30 ± 0.12 vs 0.17 ± 0.04 circ/sec, p CONCLUSIONS: Women with a history of peripartum cardiomyopathy who have regained normal resting left ventricular size and performance have decreased contractile reserve revealed by the use of a dobutamine challenge test. Ventricles of these women may respond suboptimally to hemodynamic stress in spite of evidence of recovery by routine echocardiographic evaluation. (Am J Obstet Gynecol 1997;176:189-95.)

Background Differentiating between mitral valve (MV) prolapse (MVP) and MV billowing (MVB) on two-dimensional echocardiography is challenging. The aim of this study was to test the hypothesis that color-coded models of maximal leaflet displacement from the annular plane into the atrium derived from three-dimensional transesophageal echocardiography would allow discrimination between these lesions. Methods Three-dimensional transesophageal echocardiographic imaging of the MV was performed in 50 patients with ( n = 38) and without ( n = 12) degenerative MV disease. Definitive diagnosis of MVP versus MVB was made using inspection of dynamic three-dimensional renderings and multiple two-dimensional cut planes extracted from three-dimensional data sets. This was used as a reference standard to test an alternative approach, wherein the color-coded parametric models were inspected for integrity of the coaptation line and location of the maximally displaced portion of the leaflet. Diagnostic interpretations of these models by two independent readers were compared with the reference standard. Results In all cases of MVP, the color-coded models depicted loss of integrity of the coaptation line and maximal leaflet displacement extending to the coaptation line. MVB was depicted by preserved leaflet apposition with maximal displacement away from the coaptation line. Interpretation of the 50 color-coded models by novice readers took 5 to 10 min and resulted in good agreement with the reference technique (κ = 0.81 and κ = 0.73 for the two readers). Conclusions Three-dimensional color-coded models provide a static display of MV leaflet displacement, allowing differentiation between MVP and MVB, without the need to inspect multiple planes and while taking into account the saddle shape of the mitral annulus.

Background Right ventricular (RV) volume and functional assessments are essential in the management of pulmonary arterial hypertension but are often difficult to perform. Three-dimensional (3D) echocardiography is limited by acoustic dropout of the RV free wall in dilated ventricles. The aim of this study was to test the hypothesis that knowledge-based reconstruction, a novel method for 3D modeling of RV endocardium from two-dimensional echocardiographic images, could provide accurate measurements of RV volumes and systolic function. Methods Twenty-seven patients with pulmonary arterial hypertension were prospectively recruited for same-day echocardiography and cardiovascular magnetic resonance (CMR), which was used as a reference standard. Two-dimensional transthoracic echocardiographic images were acquired with 3D spatial localization equipment to allow 3D reconstruction. Image analysis was performed with dedicated software to obtain end-diastolic volume (EDV) and end-systolic volume (ESV) and RV ejection fraction (EF). The method of disks was used to determine RV volumes on CMR. Results Echocardiographic RV volumes correlated well with CMR (EDV, R = 0.87; ESV, R = 0.88; EF, R = 0.75). For interobserver analyses, coefficients of variability were 7.8 ± 7.0% for EDV, 10.2 ± 8.0% for ESV, and 15.4 ± 13.8% for EF. For intraobserver analyses, coefficients of variability were 7.1 ± 5.1% for EDV, 8.3 ± 7.0% for ESV, and 10.9 ± 9.2% for EF. On Bland-Altman analyses, volumes obtained on transthoracic echocardiography (TTE) were slightly larger than those obtained by CMR (ΔEDV TTE-CMR , 5.8 ± 33.7 mL; ΔESV TTE-CMR , 3.5 ± 27.8 mL), whereas EFs tended to be slightly higher by CMR (ΔEF CMR-TTE , 0.5 ± 6.5%). Conclusions Knowledge-based reconstruction provides accurate and reproducible measurements of RV volumes in patients with pulmonary arterial hypertension. Larger studies are needed to confirm these results and to determine the practicality of this approach in daily practice and as an end point in clinical trials.

Background The aortic and mitral valves are anatomically linked through a fibrous continuity. The investigators hypothesized that severe aortic stenosis (AS) would alter this fibrous continuity, affecting both the mitral valve and left ventricular function, and that mitral valve function would be altered after aortic valve replacement (AVR). The aim of this study was to evaluate the impact of AS and its treatment with surgical AVR on the mitral valve. Methods Three-dimensional transesophageal echocardiography (using a Philips iE33 system) was performed on 49 patients: 20 controls with normal valves and left ventricular function, 20 with AS and normal left ventricular function studied before and after AVR, and nine with systolic heart failure and normal valves. Custom software tracked the aortic and mitral valves in three-dimensional space, allowing automated measurements of aortic and mitral annular (MA) morphology throughout the cardiac cycle. Results Patients with AS before AVR had reduced MA velocities. After AVR, aortic and MA areas were significantly smaller throughout the cardiac cycle compared with controls and pre-AVR values. MA displacement was reduced after AVR and in patients with systolic heart failure compared with those with AS and controls. Conclusions Dynamic MA function is changed with AS and after AVR through alterations in the aortic-mitral fibrous continuity. The prosthetic valve ring results in reduced aortic and MA areas, which could affect blood flow in and out of the left ventricle. These changes suggest that the design of future prosthetic aortic valves should be more flexible to preserve the function of the aortic-mitral fibrous continuity.

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.

BACKGROUND The Poiseuillian model of the arterial system currently applied in clinical physiology does not explain how arterial pressure is maintained during diastole after cessation of pulsatile aortic inflow. Arterial pressure-flow relations can be more accurately described by models that incorporate arterial viscoelastic properties such as arterial compliance. Continuous pressure and flow measurements are needed to evaluate these properties. Since the techniques used to date to acquire such data have been invasive, physiological models of the circulation that incorporate these properties have not been widely applied in the clinical setting. The purpose of this study was (1) to validate noninvasive methods for continuous measurement of central arterial pressure and flow and (2) to determine normal reference values for arterial compliance using physiological models of the circulation applied to the noninvasively acquired pressure and flow data. METHODS AND RESULTS Simultaneously acquired invasive and noninvasive aortic pressures (30 patients), flows (8 patients), and arterial mechanical properties (8 patients) were compared. Pressure was measured by high-fidelity catheter aortic micromanometer (invasive) and calibrated subclavian pulse tracing (noninvasive). Aortic inflow was determined from thermodilution-calibrated electromagnetic flow velocity data (invasive) and echo-Doppler data (noninvasive). Arterial compliance was determined for two- and three-element windkessel models of the circulation using the area method and an iterative procedure, respectively. Once validated, the noninvasive methodology was used to determine normal compliance values for a reference population of 70 subjects (age range, 20 to 81 years) with normal 24-hour ambulatory blood pressures and without Doppler-echocardiographic evidence for structural heart disease. The limits of agreement between invasive and noninvasive pressure data, compared at 10% intervals during ejection and nonejection, were narrow over a wide range of pressures, with no significant differences between methods. Invasive and noninvasive instantaneous aortic inflow values differed slightly but significantly at the start of ejection (P < .05), but during the latter 90% of ejection, values for the two methods were similar, with narrow limits of agreement. Total vascular resistance and arterial compliance values derived from invasive and noninvasive data were similar. Arterial compliance values for the normal population using the two-element model (C2E) ranged from 0.74 to 2.44 cm3/mm Hg (mean, 1.57 +/- 0.38 cm3/mm Hg), with a beat-to-beat variability of 5.2 +/- 3.9%. C2E decreased with increasing age (r = -.73, P < .001) and tended to be higher in men (1.67 +/- 0.41 cm3/mm Hg) than in women (1.51 +/- 0.35 cm3/mm Hg, P = .07). Compliance values for the three-element model (C3E) were predictably smaller than for the two-element model (mean, 1.23 +/- 0.30; range, 0.59 to 2.16 cm3/mm Hg, P < .001 versus C2E) but correlated with C2E values (r = .81, P < .001) and were also inversely related to age (r = -.56, P < .001). Ridge regression and principal component analyses both showed the compliance value to be a composite function whose variation could be best predicted by consideration of simultaneous values for five major hemodynamic determinants: heart rate, mean flow, mean aortic pressure, minimal diastolic pressure, and end-systolic pressure. Multivariate analysis revealed age and sex to be independent predictors of compliance (P < .01 for both). There were no differences in compliance between black and white subjects. CONCLUSIONS Noninvasive methods can be used to acquire the hemodynamic data necessary for clinical application of physiological models of the circulation that incorporate arterial viscoelastic properties such as arterial compliance. The strong inverse linear relation between model-based compliance estimates and age mandates incorporation of this demographic parameter in