Evolution of natural myocardial shear wave behavior in young hearts: determinant factors and reproducibility analysis.

BACKGROUND: Myocardial diastolic function assessment in children by conventional echocardiography is challenging. Recent high frame rate (HFR) echocardiography facilitates the assessment of myocardial stiffness (MS) -a key factor of diastolic function- by measuring the propagation velocities of myocardial shear waves (SWs). However, normal values of natural SWs in children are currently lacking. OBJECTIVES: To explore the behavior of natural SW among children and adolescents, their reproducibility, and the factors affecting SW velocities from childhood into adulthood. METHODS: 106 healthy children (2-18 years) and 62 adults (19-80 years) were recruited. HFR images were acquired using a modified commercial scanner. An anatomical M-mode was drawn along the ventricular septum, and propagation velocities of natural SWs after mitral valve closure (MVC) were measured in the tissue acceleration coded M-mode display. RESULTS: Throughout life, SW velocities after MVC exhibited pronounced age dependency (r= 0.73; P<0.001). Among the pediatric population, SW velocities correlated significantly with measures of cardiac geometry (septal thickness and left ventricular end-diastolic dimension), local hemodynamics (systolic blood pressure), as well as with echocardiographic parameters of systolic and diastolic function (global longitudinal strain (GLS), mitral E/e', isovolumetric relaxation time and mitral deceleration time) (P <0.001). In a multivariate analysis including all these factors, the predictors of SW velocities were age, mitral E/e', and GLS (r= 0.81). CONCLUSIONS: Natural myocardial SW velocities in children can be detected and measured. SW velocities showed significant dependence on age and diastolic function. Natural SWs could be a promising additive tool for assessment of diastolic function among children.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Ultrasound Shear Wave Elastography in Cardiology.

The advent of high-frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart's thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Continuous shear wave measurements for dynamic cardiac stiffness evaluation in pigs.

Ultrasound-based shear wave elastography is a promising technique to non-invasively assess the dynamic stiffness variations of the heart. The technique is based on tracking the propagation of acoustically induced shear waves in the myocardium of which the propagation speed is linked to tissue stiffness. This measurement is repeated multiple times across the cardiac cycle to assess the natural variations in wave propagation speed. The interpretation of these measurements remains however complex, as factors such as loading and contractility affect wave propagation. We therefore applied transthoracic shear wave elastography in 13 pigs to investigate the dependencies of wave speed on pressure-volume derived indices of loading, myocardial stiffness, and contractility, while altering loading and inducing myocardial ischemia/reperfusion injury. Our results show that diastolic wave speed correlates to a pressure-volume derived index of operational myocardial stiffness (R = 0.75, p < 0.001), suggesting that both loading and intrinsic properties can affect diastolic wave speed. Additionally, the wave speed ratio, i.e. the ratio of systolic and diastolic speed, correlates to a pressure-volume derived index of contractility, i.e. preload-recruitable stroke work (R = 0.67, p < 0.001). Measuring wave speed ratio might thus provide a non-invasive index of contractility during ischemia/reperfusion injury.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Transmural Wave Speed Gradient May Distinguish Intrinsic Myocardial Stiffening From Preload-Induced Changes in Operational Stiffness in Shear Wave Elastography.

BACKGROUND: Shear wave elastography (SWE) is a promising technique to non-invasively assess myocardial stiffness based on the propagation speed of mechanical waves. However, a high wave propagation speed can either be attributed to an elevated intrinsic myocardial stiffness or to a preload-induced increase in operational stiffness. OBJECTIVE: Our objective was to find a way to discriminate intrinsic myocardial stiffening from stiffening caused by an increased pressure in SWE. METHODS: We used the finite element method to study the shear wave propagation patterns when stiffness and/or pressure is elevated, compared to normal stiffness and pressure. Numerical findings were verified in a few human subjects. RESULTS: The transmural wave speed gradient was able to distinguish changes in intrinsic stiffness from those induced by differing hemodynamic load (a speed of ±3.2 m/s in parasternal short-axis (PSAX) view was associated with a wave speed gradient of -0.17 ± 0.15 m/s/mm when pressure was elevated compared to 0.04 ± 0.05 m/s/mm when stiffness was elevated). The gradient however decreased when stiffness increased (decrease with a factor 3 in PSAX when stiffness doubled at 20 mmHg). The human data analysis confirmed the presence of a wave speed gradient in a patient with elevated ventricular pressure. CONCLUSION: Cardiac SWE modeling is a useful tool to gain additional insights into the complex wave physics and to guide post-processing. The transmural differences in wave speed may help to distinguish loading-induced stiffening from intrinsic stiffness changes. SIGNIFICANCE: The transmural wave speed gradient has potential as a new diagnostic parameter for future clinical studies.

Right ventricular strain related to pulmonary artery pressure predicts clinical outcome in patients with pulmonary arterial hypertension.

AIMS: In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters. METHODS AND RESULTS: Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%. CONCLUSION: RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker.

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops.

BACKGROUND: Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties. OBJECTIVES: This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method. METHODS: In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury. RESULTS: Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant ß (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001). CONCLUSIONS: Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

Comparing Myocardial Shear Wave Propagation Velocity Estimation Methods Based on Tissue Displacement, Velocity and Acceleration Data.

Shear wave elastography (SWE) is a promising technique used to assess cardiac function through the evaluation of cardiac stiffness non-invasively. However, in the literature, SWE varies in terms of tissue motion data (displacement, velocity or acceleration); method used to characterize mechanical wave propagation (time domain [TD] vs. frequency domain [FD]); and the metric reported (wave speed [WS], shear or Young's modulus). This variety of reported methodologies complicates comparison of reported findings and sheds doubt on which methodology better approximates the true myocardial properties. We therefore conducted a simulation study to investigate the accuracy of various SWE data analysis approaches while varying cardiac geometry and stiffness. Lower WS values were obtained by the TD method compared with the FD method. Acceleration-based WS estimates in the TD were systematically larger than those based on velocity (∼10% difference). These observations were confirmed by TD analysis of 32 in vivo SWE mechanical wave measurements. In vivo data quality is typically too low for accurate FD analysis. Therefore, our study suggests using acceleration-based TD analysis for in vivo SWE to minimize underestimation of the true WS and, thus, to maximize the sensitivity of SWE to detect stiffness changes resulting from pathology.

High-Frame-Rate Speckle Tracking for Echocardiographic Stress Testing.

Stress echocardiography helps to diagnose cardiac diseases that cannot easily be detected or do not even manifest at rest. In clinical practice, assessment of the stress test is usually performed visually and, therefore, in a qualitative and subjective way. Although speckle tracking echocardiography (STE) has been proposed for the quantification of function during stress, its time resolution is inadequate at high heart rates. Recently, high-frame-rate (HFR) imaging approaches have been proposed together with dedicated STE algorithms capable of handling small interframe displacements. The aim of this study was to determine if HFR STE is effective in assessing strain and strain rate parameters during echocardiographic stress testing. Specifically, stress echocardiography, at four different workload intensities, was performed in 25 healthy volunteers. At each stress level, HFR images from the apical four-chamber view were recorded using the ULA-OP 256 experimental scanner. Then, the myocardium was tracked with HFR STE, and strain and strain rate biomarkers were extracted to further analyze systolic and diastolic (early and late) peaks, as well as a short-lived isovolumic relaxation peak during stress testing. The global systolic strain response was monophasic, revealing a significant (p < 0.001) increase at low stress but then reaching a plateau. In contrast, all strain rate indices linearly increased (p < 0.001) with increasing stress level. These findings are in line with those reported using tissue Doppler imaging and, thus, indicate that HFR STE can be a useful tool in assessing cardiac function during stress echocardiography.

Inter-vendor variability in strain measurements depends on software rather than image characteristics.

Despite standardization efforts, vendors still use specific proprietary software algorithms for echocardiographic strain measurements, which result in high inter-vendor variability. Using vendor-independent software could be one solution. Little is known, however, how vendor specific image characteristics can influence tracking results of such software. We therefore investigated the reproducibility, accuracy, and scar detection ability of strain measurements on images from different vendors by using a vendor-independent software. A vendor-independent software (TomTec Image Arena) was used to analyse datasets of 63 patients which were obtained on machines from four different ultrasound machine vendors (GE, Philips, Siemens, Toshiba). We measured the tracking feasibility, inter-vendor bias, the relative test-re-test variability and scar discrimination ability of strain measurements. Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition. Tracking feasibility on vendor datasets were significantly different (p < 0.001). Variability of global longitudinal strain (GLS) measurements was similar among the vendors whereas variability of segmental longitudinal strain (SLS) showed modest difference. Relative test-re-test variability of GLS and SLS showed no relevant differences. No significant difference in scar detection capability was observed. Average GLS and SLS values were similar among vendors. Reproducibility of GLS measurements showed no difference among vendors and was in acceptable range. SLS reproducibility was high but similar for all vendors. No relevant difference was found for identifying regional dysfunction. Tracking feasibility showed a substantial difference among images from different vendors. Our findings demonstrate that tracking results depend mainly on the software used and show little influence from vendor specific image characteristics.

In Vivo Comparison of Multiline Transmission and Diverging Wave Imaging for High-Frame-Rate Speckle-Tracking Echocardiography.

High-frame-rate (HFR) speckle-tracking echocardiography (STE) assesses myocardial function by quantifying motion and deformation at high temporal resolution. Among the proposed HFR techniques, multiline transmission (MLT) and diverging wave (DW) imaging have been used in this context both being characterized by specific advantages and disadvantages. Therefore, in this article, we directly contrast both approaches in an in vivo setting while operating at the same frame rate (FR). First, images were recorded at baseline (resting condition) from healthy volunteers and patients. Next, additional acquisitions during stress echocardiography were performed on volunteers. Each scan was contoured and processed by a previously proposed 2-D HFR STE algorithm based on cross correlation. Then, strain curves and their end-systolic (ES) values were extracted for all myocardial segments for further statistical analysis. The baseline acquisitions did not reveal differences in estimated strain between the acquisition modes ( ); myocardial segments ( ); or an interaction between imaging mode and depth ( ). Similarly, during stress testing, no difference ( p = 0.7 ) was observed for the two scan sequences, stress levels or an interaction sequence-stress level ( p = 0.94 ). Overall, our findings show that MLT and DW compoundings give comparable HFR STE strain values and that the choice for using one method or the other may thus rather be based on other factors, for example, system requirements or computational cost.

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

OBJECTIVES: The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients. BACKGROUND: After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole. METHODS: A total of 52 HTx recipients who underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping. RESULTS: SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values. CONCLUSIONS: End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.

A Novel 2-D Speckle Tracking Method for High-Frame-Rate Echocardiography.

Speckle tracking echocardiography (STE) is a clinical tool to noninvasively assess regional myocardial function through the quantification of regional motion and deformation. Even if the time resolution of STE can be improved by high-frame-rate (HFR) imaging, dedicated HFR STE algorithms have to be developed to detect very small interframe motions. Therefore, in this article, we propose a novel 2-D STE method, purposely developed for HFR echocardiography. The 2-D motion estimator consists of a two-step algorithm based on the 1-D cross correlations to separately estimate the axial and lateral displacements. The method was first optimized and validated on simulated data giving an accuracy of ~3.3% and ~10.5% for the axial and lateral estimates, respectively. Then, it was preliminarily tested in vivo on ten healthy volunteers showing its clinical applicability and feasibility. Moreover, the extracted clinical markers were in the same range as those reported in the literature. Also, the estimated peak global longitudinal strain was compared with that measured with a clinical scanner showing good correlation and negligible differences (-20.94% versus -20.31%, p -value = 0.44). In conclusion, a novel algorithm for STE was developed: the radio frequency (RF) signals were preferred for the axial motion estimation, while envelope data were preferred for the lateral motion. Furthermore, using 2-D kernels, even for 1-D cross correlation, makes the method less sensitive to noise.

Acute redistribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling.

AIMS: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling. METHODS AND RESULTS: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001). CONCLUSION: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT.