Residual native left ventricular function optimization using quantitative 3D echocardiographic assessment of rotational mechanics in patients with left ventricular assist devices.

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 < 0.01), reflecting the constricting effects on native function. With lower pump speeds, no significant changes were noted in LV twist, which peaked at a higher speed. In 11/25 (44%) patients, the conventional hemodynamic/2DE methodology and 3DE assessment of maximal residual function did not indicate the same optimal conditions, suggesting that a higher pump speed would have better preserved native function. In conclusion, quantitative 3DE analysis of LV rotational mechanics provides information, which together with hemodynamics may help select optimal pump speed, while maximally preserving native LV function.

Segmentation of the left ventricular endocardium from magnetic resonance images by using different statistical shape models.

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.

Right ventricular strain in pulmonary arterial hypertension: a 2D echocardiography and cardiac magnetic resonance study.

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.

Evaluation of myocardial deformation in patients with sickle cell disease and preserved ejection fraction using three-dimensional speckle tracking echocardiography.

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.

Assessment of right ventricular function using echocardiographic speckle tracking of the tricuspid annular motion: comparison with cardiac magnetic resonance.

BACKGROUND: Assessment of right ventricular (RV) function is difficult due to the complex shape of this chamber. Tricuspid annular plane systolic excursion (TAPSE) measured with M-mode echocardiography is frequently used as an index of RV function. However, its accuracy may be limited by ultrasound beam misalignment. We hypothesized that two-dimensional (2D) speckle tracking echocardiography (STE) could provide more accurate estimates of RV function. Accordingly, STE was used to quantify tricuspid annular displacement (TAD), from which RV longitudinal shortening fraction (LSF) was calculated. These STE derived indices were compared side-by-side with M-mode TAPSE measurements against cardiac magnetic resonance (CMR) derived RV ejection fraction (EF). METHODS: Echocardiography (Philips iE33, four-chamber view) and CMR (Siemens, 1.5 T) were performed on the same day in 63 patients with a wide range of RV EF (23-70% by CMR). TAPSE was measured using M-mode echocardiography. TAD and RV LSF were obtained using STE analysis (QLAB CMQ, Philips). TAPSE, TAD and RV LSF values were compared with RV EF obtained from CMR short axis stacks. RESULTS: STE analysis required <15 seconds and was able to track tricuspid annular motion in all patients as verified visually. Correlation between RV EF and TAD (0.61 free-wall, 0.65 septal) was similar to that with M-mode TAPSE (0.63). However, STE-derived RV LSF showed a higher correlation with CMR EF (r = 0.78). CONCLUSION: RV LSF measurement by STE is fast and easy to obtain and provides more accurate evaluation of RV EF than the traditional M-mode TAPSE technique, when compared to CMR reference. (Echocardiography 2012;29:19-24).

Noninvasive quantification of left ventricular elastance and ventricular-arterial coupling using three-dimensional echocardiography and arterial tonometry.

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.

A three-dimensional insight into the complexity of flow convergence in mitral regurgitation: adjunctive benefit of anatomic regurgitant orifice area.

Mitral effective regurgitant orifice area (EROA) using the flow convergence (FC) method is used to quantify the severity of mitral regurgitation (MR). However, it is challenging and prone to interobserver variability in complex valvular pathology. We hypothesized that real-time three-dimensional (3D) transesophageal echocardiography (RT3D TEE) derived anatomic regurgitant orifice area (AROA) can be a reasonable adjunct, irrespective of valvular geometry. Our goals were to 1) to determine the regurgitant orifice morphology and distance suitable for FC measurement using 3D computational flow dynamics and finite element analysis (FEA), and (2) to measure AROA from RT3D TEE and compare it with 2D FC derived EROA measurements. We studied 61 patients. EROA was calculated from 2D TEE images using the 2D-FC technique, and AROA was obtained from zoomed RT3DE TEE acquisitions using prototype software. 3D computational fluid dynamics by FEA were applied to 3D TEE images to determine the effects of mitral valve (MV) orifice geometry on FC pattern. 3D FEA analysis revealed that a central regurgitant orifice is suitable for FC measurements at an optimal distance from the orifice but complex MV orifice resulting in eccentric jets yielded nonaxisymmetric isovelocity contours close to the orifice where the assumptions underlying FC are problematic. EROA and AROA measurements correlated well (r = 0.81) with a nonsignificant bias. However, in patients with eccentric MR, the bias was larger than in central MR. Intermeasurement variability was higher for the 2D FC technique than for RT3DE-based measurements. With its superior reproducibility, 3D analysis of the AROA is a useful alternative to quantify MR when 2D FC measurements are challenging.

Quantification of left ventricular volumes using three-dimensional echocardiographic speckle tracking: comparison with MRI.

AIMS: Although the utility of two-dimensional (2D) speckle tracking echocardiography (STE) to quantify left ventricular (LV) volume has been demonstrated, this methodology is limited by foreshortened views, geometric modelling, and the assumption that speckles can be tracked from frame to frame, despite their out of plane motion. To circumvent these limitations, a three-dimensional (3D) speckle tracking algorithm was recently developed. Our goal was to evaluate the accuracy of the new 3D-STE side by side with 2D-STE using cardiac magnetic resonance (CMR) as a reference. METHODS AND RESULTS: Apical two- and four-chamber views (A2C and A4C) and real-time 3D datasets (Toshiba Artida 4D System) obtained in 43 patients with a wide range of LV size and function were analysed to measure LV end-systolic and end-diastolic volumes (ESV and EDV) using 2D and 3D-STE techniques. Short-axis CMR images (Siemens 1.5T scanner) acquired on the same day were analysed to obtain ESV and EDV reference values using the method of disks approximation. Reproducibility of both STE techniques was assessed using repeated measurements. While 2D-STE correlated well with CMR (r: 0.72-0.88), it underestimated LV volumes with relatively large biases (10-30 mL) and wide limits of agreement (SD: 36-51 mL), with A2C-derived measurements being worse than A4C values. The 3D-STE measurements showed higher correlation with CMR (0.87-0.92), and importantly smaller biases (1-16 mL) and narrower limits of agreement (SD: 28-37 mL). In addition, 3D-STE showed lower inter- and intra-observer variability (11-14% and 12-13%), than 2D-STE (16-17% and 12-16%, respectively). CONCLUSION: This is the first study to validate the new 3D-STE technique for LV volume measurements and demonstrate its superior accuracy and reproducibility over previously used 2D-STE technique.

Refining Severe Tricuspid Regurgitation Definition by Echocardiography with a New Outcomes-Based "Massive" Grade.

BACKGROUND: Current echocardiographic guidelines recommend that tricuspid regurgitation (TR) severity be graded in 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 three-dimensional images) and validation (n = 162) cohorts. The VC was measured in both the right ventricular (RV) inflow and apical four-chamber views and averaged. For the study cohort, tricuspid annular, RV end-diastolic (basal, mid, long axis) dimensions, tricuspid leaflet tenting height and area, RV free-wall longitudinal strain, and RV volumes were measured from two- and three-dimensional data sets. 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. Tricuspid annular and RV size were larger in the massive group (P < .05), while there were no significant differences in demographics between the TR groups. Importantly, in the independent validation cohort, the above VC cutoff also correlated with increased mortality in the massive group (log-rank P < .05). CONCLUSIONS: Among patients traditionally defined as having severe TR, a subset exists with massive TR, resulting in greater adverse RV remodeling and increased mortality. These patients may derive the greatest benefit from emerging percutaneous therapies.

Three-dimensional echocardiography investigation of the mechanisms of tricuspid annular dilatation.

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 < 0.01), RV EDV (r = 0.58; p < 0.01), RV end-diastolic long and short axes (r = 0.53, 0.42; both p < 0.01), TR degree (r = 0.40; p < 0.01) and sPAP (r = 0.32; p < 0.01). Multivariate analysis revealed that RA ESV was the only parameter independently associated with TA area (p < 0.05, r = 0.85). In conclusion, RA volume plays an important role in TA dilatation even in patients with normal SR. Understanding of annular remodeling mechanisms could aid in identifying patients at higher risk for TA dilatation, especially those scheduled for mitral valve surgery.

Echocardiographic evaluation of the effects of sacubitril-valsartan on vascular properties in heart failure patients.

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 cm2dyne-110-3, 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 cm2dyne-110-3 (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.

Feasibility of real-time three-dimensional transoesophageal echocardiography for guidance of percutaneous atrial septal defect closure.

AIMS: Intracardiac echocardiography (ICE) and two-dimensional transoesophageal echocardiography (2D TEE) are used in most centres for guiding transcatheter atrial septal defect (ASD) closure. ASDs have complex shapes that are not well characterized with 2D imaging. Real-time 3D TEE (RT3D TEE) provides en-face visualization of the ASD, allowing precise assessment of ASD dimensions. Accordingly, our aims were (i) to determine the feasibility of RT3D TEE to guide ASD closure and (ii) to compare ASD and balloon dimensions (BDs) using RT3D TEE vs. ICE and 2D TEE. METHODS AND RESULTS: Thirteen patients with ostium secundum ASD underwent transcatheter ASD closure. 2D TEE, RT3D TEE, and ICE images were acquired sequentially. RT3D TEE was feasible in all patients. Comparing RT3D TEE and 2D imaging, the mean difference in long-axis dimension was +0.5 mm (P= NS for both), and -1.4 mm in short-axis (2D TEE, P < 0.05; ICE, P = 0.06). BD was greater with 3D TEE vs. ICE (+0.9 mm). CONCLUSION: RT3D TEE can be used to guide transcatheter ASD closure with the advantages of lower cost than ICE, and ability to visualize en-face views of the ASD. ASD and BD as measured by RT3D TEE differ when compared with 2D imaging.

Age and body surface area dependency of mitral valve and papillary apparatus parameters: assessment by real-time three-dimensional echocardiography.

AIMS: Real-time three-dimensional echocardiography (RT3DE) has been used to quantify mitral valve (MV) annular size and leaflet tenting parameters in small numbers of patients with different pathologies. We sought to establish normal values for RT3DE mitral annular, tenting, and papillary muscle parameters over a wide age range and to study their age and body surface area (BSA) dependency. METHODS AND RESULTS: Transthoracic wide-angled RT3DE images of the MV were acquired in 120 subjects (52 females, 68 males, age: 37+/-20 years) with normal left ventricular (LV) function, no risk factors, and less than or equal to mild mitral regurgitation. Custom software (RealView) was used to trace the MV annulus, leaflets, and the papillary apparatus in mid-systole in 18 sequential cut planes obtained from the 3D data sets. Mitral valve annular area and height as well as tenting parameters (maximum and mean tenting height and mid-systolic tenting volume) were obtained and correlated with age and BSA. Wide inter-subject variability was noted in all parameters. Despite this variability, parameters directly affected by LV size were found to be BSA-dependent: MV annular area showed highest correlation with BSA (r=0.78), followed by inter-papillary distance (r=0.58) and postero-medial (PM) and antero-lateral (AL) papillary muscle annular distance (r=0.57 and r=0.46, respectively). Age did not correlate with either annular or tenting parameters, but showed moderate negative correlation with inter-papillary muscle angle (r= -0.52) and mild negative correlation with inter-papillary distance (r= -0.32), both normalized by BSA. CONCLUSIONS: Real-time three-dimensional echocardiography-derived MV annular, tenting, and papillary muscle parameters vary widely in normal subjects. When used clinically, normal values of parameters that are age- and/or BSA-dependent need to be adjusted accordingly.

3D echocardiographic global longitudinal strain can identify patients with mildly-to-moderately reduced ejection fraction at higher cardiovascular risk.

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.

Echocardiographic Assessment of the Tricuspid Annulus: The Effects of the Third Dimension and Measurement Methodology.

BACKGROUND: Evaluation of the tricuspid annulus is crucial for the decision making at the time of left heart surgery. Current recommendations for tricuspid valve repair are based on two-dimensional (2D) transthoracic echocardiography (TTE), despite the known underestimation compared with three-dimensional (3D) echocardiography. However, little is known about the differences in 3D tricuspid annular (TA) sizing using TTE versus transesophageal echocardiography (TEE). The aims of this study were to (1) compare 2D and 3D TA measurements performed with both TTE and TEE and (2) compare two 3D methods for TA measurements: multiplanar reconstruction (MPR) and dedicated software (DS) designed to take into account TA nonplanarity. METHODS: Seventy patients underwent 2D and 3D TTE and TEE. Two-dimensional images were used to measure TA diameter from apical four-chamber, right ventricular-focused (TTE), and midesophageal four-chamber (TEE) views. Three-dimensional full-volume data sets were analyzed using both MPR and DS, to obtain major and minor axes, perimeter, and area. Intertechnique agreement was assessed using Bland-Altman analysis. RESULTS: Measurements on 2D TTE and TEE, which were view dependent, underestimated TA major dimensions in all views compared with 3D values, irrespective of the 3D method. MPR and DS measurements were significantly different, with DS resulting in larger values for all parameters, irrespective of approach. No differences were found between 3D TTE and 3D TEE for both MPR and DS. CONCLUSIONS: Our findings highlight the need for methodology that respects the 3D geometry of the tricuspid annulus, including its nonplanarity, which cannot be accurately assessed from 2D images and is not equally taken into account by different 3D measurement methodologies. Accordingly, a 3D cutoff value for TA enlargement needs to be established and is likely to be larger than the guideline-recommended 2D-based 40-mm cutoff. Importantly, noninvasive 3D TTE can be used instead of 3D TEE because TA measurements are not different.

Machine Learning-Based Three-Dimensional Echocardiographic Quantification of Right Ventricular Size and Function: Validation Against Cardiac Magnetic Resonance.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 variation <7% and intraclass correlations ≥0.95 for all measurements. CONCLUSIONS: 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.

Diagnosis of Isolated Cleft Mitral Valve Using Three-Dimensional Echocardiography.

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.

Feasibility of Left Ventricular Global Longitudinal Strain Measurements from Contrast-Enhanced Echocardiographic Images.

BACKGROUND: Although left ventricular global longitudinal strain (GLS) is an index of systolic function recommended by the guidelines, poor image quality may hamper strain measurements. While contrast agents are commonly used to improve endocardial visualization, no commercial speckle-tracking software is able to measure strain in contrast-enhanced images. This study aimed to test the accuracy of speckle-tracking software when applied to contrast-enhanced images in patients with suboptimal image quality. METHODS: We studied patients with a wide range of GLS values who underwent transthoracic echocardiography. Protocol 1 included 44 patients whose images justified use of contrast but still allowed noncontrast speckle-tracking echocardiography (STE), which was judged as accurate and used as a reference. Protocol 2 included 20 patients with poor image quality that precluded noncontrast STE; cardiac magnetic resonance- (CMR-) derived strain was used as the reference instead. Half the manufacturer recommended dose of a commercial contrast agent (Definity/Optison/Lumason) was used to provide partial contrast enhancement. Higher than normal mechanical indices (0.6-0.7) and lowest frequency range for maximal penetration settings were used for imaging. GLS was measured (Epsilon) with and without contrast-enhanced images and by CMR-derived feature tracking (TomTec). Comparisons included linear regression and Bland-Altman analyses. RESULTS: The contrast STE analysis failed in 4/64 patients (6%). Manual corrections were needed to optimize tracking with contrast in all patients. GLS measurements were in good agreement between contrast and noncontrast images (r = 0.85; mean GLS in the contrast images, -12.9% ± 4.7%; bias, 0.34% ± 2.4%). Good agreement was also noted between contrast STE- and CMR-derived strain (r = 0.83; mean, GLS -13.5% ± 4.0%; bias, 0.72% ± 2.5%). CONCLUSIONS: We found that GLS measurements from contrast-enhanced images are feasible and accurate in most patients, even in those with poor image quality that precludes strain measurements without contrast enhancement.

Activin A and Late Postpartum Cardiac Dysfunction Among Women With Hypertensive Disorders of Pregnancy.

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.

Load Dependency of Left Atrial Strain in Normal Subjects.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.