Sex differences in left atrial volumes, mechanics and stiffness in primary mitral regurgitation- a combined 2D and 3D echocardiographic study.

BACKGROUND: Mitral regurgitation (MR) causes left atrial (LA) enlargement and impaired reservoir function. We assessed whether changes in LA size, strain and stiffness in significant (moderate or greater) primary MR are sex-specific. METHODS AND RESULTS: In the 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study (3D-PRIME), 111 patients with primary MR were prospectively investigated with 2D and 3D echocardiography. MR was severe if the 3D regurgitant fraction was ≥50%. LA size was assessed by maximum, minimum and pre-A 3D volume (LAV), mechanics by peak reservoir (LASr) and contractile strain, and stiffness by the ratio: mitral peak E-wave divided by the annular e' velocity (E/e´)/LASr.Women were older, had higher heart rate, and lower body mass index and MR regurgitant volumes (p < 0.05). 3D LAV indexed for body surface area and LA contractile strain did not differ by sex, while LASr was lower (22.2% vs. 25.0%) and LA stiffness higher in women (0.56 vs. 0.44) (p < 0.05). In linear regression analysis, female sex was associated with higher LA stiffness independent of age, minimum LAV, left ventricular global longitudinal strain, diabetes and coronary artery disease (R2 0.56, all p < 0.05). In logistic regression analysis, women had a 4.0-fold (95% CI 1.2-13.1, p = 0.02) higher adjusted risk of increased LA stiffness than men. CONCLUSION: Women with significant primary MR have more impaired LA reservoir mechanics and increased LA stiffness compared to men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR.

Echocardiography Assessment of Rheumatic Heart Disease: Implications for Percutaneous Balloon Mitral Valvuloplasty.

Echocardiography is an important diagnostic imaging modality in recognizing rheumatic heart disease, a chronic sequelae of acute rheumatic fever. Left-sided heart valves, especially the mitral valve is typically affected, with stenosis or regurgitation as a consequence. Although assessment of valve area by 2D planimetry is the reference method for mitral stenosis severity, 3D planimetry provides more accurate measurement and diagnostic value. Careful selection of patients in terms of echocardiographic criteria is essential to ensure safety and success of the intervention and better long-term outcomes. Several echocardiographic scores based upon mitral valve mobility, thickening, calcification, and subvalvular thickening are developed to assess mitral valve anatomy and the feasibility of percutaneous mitral commissurotomy. 3D transesophageal echocardiography (TEE) provides detailed information of the mitral anatomy (commissural fusions, and subvalvular apparatus) before intervention. In addition, 3D TEE planimetry provides a more accurate measurement of the valve area compared with 2D echocardiography. Generally, huge annular calcification and lack of commissural fusion are unfavorable echocardiographic markers that increase the risk of complications and preclude the feasibility of percutaneous balloon mitral valvuloplasty. More contemporary prospective echocardiography research studies on patients with RHD from low- and middle-income countries are needed.

Impact of aortic valve stenosis on myocardial deformation in different left ventricular levels: A three-dimensional speckle tracking echocardiography study.

BACKGROUND: Global systolic left ventricular (LV) myocardial function progressively declines as degenerative aortic valve stenosis (AS) progresses. Whether this results in uniformly distributed deformation changes from base to apex has not been investigated. METHODS: Eighty-five AS patients underwent three-dimensional (3D) echocardiography in this cross-sectional study. Patients were grouped by peak jet velocity into mild (n = 32), moderate (n = 31), and severe (n = 22) AS. 3D speckle tracking derived strain, rotation, twist, and torsion were obtained to assess global LV function and myocardial function at the apical, mid, and basal levels. RESULTS: Global longitudinal strain (GLS) was lower in patients with severe AS (-16.1 ± 2.4% in mild, -15.5 ± 2.5% in moderate, and -13.5 ± 3.0% in severe AS [all p < .01]). Peak basal and mid longitudinal strain (LS), basal rotation and twist from apical to basal level followed the same pattern, while peak apical LS was higher in moderate AS compared to severe AS (all p < .05). In multivariate analyses, lower GLS was particularly associated with male sex, higher body mass index and peak aortic jet velocity, lower basal LS with higher filling pressure (E/e') and LV mass, lower mid LS with higher RWT and presence of AS symptoms, and lower apical LS with male sex and higher systolic blood pressure, respectively (all p < .05). CONCLUSION: Using 3D speckle tracking echocardiography reveals regional and global changes in LV mechanics in AS related to the severity of AS, LV remodeling and presence of cardiovascular risk factors.

In silico analysis provides insights for patient-specific annuloplasty in Barlow's disease.

Objective: To predict the required mitral annular area reduction in patients with Barlow's disease to obtain a predefined leaflet area index by a novel in silico modeling method. Methods: Three-dimensional echocardiography was used to create patient-specific mitral valve models of 8 patients diagnosed with Barlow's disease and bileaflet prolapse preoperatively. Six patients were also studied postoperatively in a finite element framework, to quantify the optimal coaptation area index. For the patient-specific finite element analyses, realistic papillary muscle and annular motion are incorporated, also for the in silico annuloplasty analyses. The annuloplasty ring size is reduced moderately until the optimal coaptation area index is achieved for each patient. Results: The mean mitral annular area at end-diastole was reduced by 58 ± 7% postoperatively (P < .001), resulting in a postoperative coaptation area index of 20 ± 5%. To achieve the same coaptation area index with moderate annular reductions and no leaflet resection the annular reduction was 31 ± 6% (P < .001). Conclusions: In silico analysis in selected patients diagnosed with Barlow's disease demonstrates that annuloplasty with only moderate annular reduction may be sufficient to achieve optimal coaptation as compared to conventional surgical procedures.

Mechanical behavior and collagen structure of degenerative mitral valve leaflets and a finite element model of primary mitral regurgitation.

Degenerative mitral valve disease is the main cause of primary mitral regurgitation with two phenotypes: fibroelastic deficiency (FED) often with localized myxomatous degeneration and diffuse myxomatous degeneration or Barlow's disease. Myxomatous degeneration disrupts the microstructure of the mitral valve leaflets, particularly the collagen fibers, which affects the mechanical behavior of the leaflets. The present study uses biaxial mechanical tests and second harmonic generation microscopy to examine the mechanical behavior of Barlow and FED tissue. Three tissue samples were harvested from a FED patient and one sample is from a Barlow patient. Then we use an appropriate constitutive model by excluding the collagen fibers under compression. Finally, we built an FE model based on the echocardiography of patients diagnosed with FED and Barlow and the characterized material model and collagen fiber orientation. The Barlow sample and the FED sample from the most affected segment showed different mechanical behavior and collagen structure compared to the other two FED samples. The FE model showed very good agreement with echocardiography with 2.02±1.8 mm and 1.05±0.79 mm point-to-mesh distance errors for Barlow and FED patients, respectively. It has also been shown that the exclusion of collagen fibers under compression provides versatility for the material model; it behaves stiff in the belly region, preventing excessive bulging, while it behaves very softly in the commissures to facilitate folding. STATEMENT OF SIGNIFICANCE: This study quantifies for the first time the collagen microstructure and mechanical behavior of degenerative mitral valve (DMV) leaflets. These data will then be used for the first disease-specific finite element (FE) model of DMV. While current surgical repair of DMV is based on surgical experience, FE modeling has the potential to support decision-making and make outcomes predictable. We adopt a constitutive model to exclude collagen fiber under compressions, an important consideration when modeling the mitral valve, where the leaflets are folded to ensure complete closure. The results of this study provide essential data for understanding the relationship between collagen microstructure and degenerative mitral valve mechanics.

Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Correlation between Murmurs and Echocardiographic Findings; From an Imaging Cardiologist Point of View.

A heart murmur in adults is a common reason for referral for echocardiography at most general cardiology clinics in Europe. A murmur may indicate either a mild age-related valvular calcification or regurgitation, or represent a significant heart valve disease requiring valvular intervention. Generally, the correlation between murmurs by auscultation and severity of heart valve disease by echocardiography is poor. Particularly, the severity and characterization of diastolic murmurs by auscultation may poorly correlate with echocardiographic findings. This narrative review aims to summarize the differential diagnoses of physiological and pathological murmurs, describes the current referral practice of murmur patients for echocardiography, and presents a single-center experience on the correlation of auscultation and echocardiographic findings with a particular focus on aortic and mitral valve diseases. A careful auscultation of the heart prior to the echocardiogram is mandatory and may help to predict the echocardiographic findings and their interpretation in view of the clinical information. The correlation between clinical examination, point of care ultrasound and standard echocardiography is a matter of continued exploration.

Finite element analysis of mitral valve annuloplasty in Barlow's disease.

Barlow's Disease affects the entire mitral valve apparatus causing mitral regurgitation. Standard annuloplasty procedures lead to an average of 55% annular area reduction of the end diastolic pre-operative annular area in Barlow's diseased valves. Following annular reduction, mitral valvuloplasty may be needed, usually with special focus on the posterior leaflet. An in silico pipeline to perform annuloplasty by utilizing the pre- and -postoperative 3D echocardiographic recordings was developed. Our objective was to test the hypothesis that annuloplasty ring sizes based on a percentage (10%-25%) decrease of the pre-operative annular area at end diastole can result in sufficient coaptation area for the selected Barlow's diseased patient. The patient specific mitral valve geometry and finite element model were created from echocardiography recordings. The post-operative echocardiography was used to obtain the artificial ring geometry and displacements, and the motion of the papillary muscles after surgery. These were used as boundary conditions in our annuloplasty finite element analyses. Then, the segmented annuloplasty ring was scaled up to represent a 10%, 20% and 25% reduction of the pre-operative end diastolic annular area and implanted to the end diastolic pre-operative finite element model. The pre-operative contact area decrease was shown to be dependent on the annular dilation at late systole. Constraining the mitral valve from dilating excessively can be sufficient to achieve proper coaptation throughout systole. The finite element analyses show that the selected Barlow's diseased patient may benefit from an annuloplasty ring with moderate annular reduction alone.

Mitral Annular Elasticity Determines Severity of Regurgitation in Barlow's Mitral Valve Disease.

OBJECTIVES: Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle. METHODS: Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model. RESULTS: Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm2, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm2/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01). CONCLUSION: The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.

Comparison of ultrasound vector flow imaging and CFD simulations with PIV measurements of flow in a left ventricular outflow trackt phantom - Implications for clinical use and in silico studies.

In this study we have compared two modalities for flow quantification from measurement data; ultrasound (US) and shadow particle image velocimetry (PIV), and a flow simulation model using computational fluid dynamics (CFD). For the comparison we have used an idealized Quasi-2D phantom of the human left ventricular outflow tract (LVOT). The PIV data will serve as a reference for the true flow field in our setup. Furthermore, the US vector flow imaging (VFI) data has been post processed with model-based regularization developed to both smooth noise and sharpen physical flow features. The US VFI flow reconstruction results in an underestimation of the flow velocity magnitude compared to PIV and CFD. The CFD results coincide very well with the PIV flow field maximum velocities and curl intensity, as well as with the detailed vortex structure, however, this correspondence is subject to exact boundary conditions.

Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue.

Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.

High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis.

AIMS: Upon high wall shear stress, high-molecular-weight (HMW) von Willebrand Factor (VWF) multimers are degraded, thus, HMW VWF multimer deficiency mirrors haemodynamics at the site of aortic stenosis (AS). The aim of the present study was to analyse the role of HMW VWF multimer ratio for subcategorization of classical low-flow, low-gradient (LF/LG) AS. METHODS AND RESULTS: Eighty-three patients with classical LF/LG AS were prospectively recruited and HMW VWF multimer pattern was analysed using a densitometric quantification of western blot bands. Patients were subclassified into true-severe (TS) and pseudo-severe (PS) classical LF/LG AS based on dobutamine stress echocardiography (DSE). Positive and negative predictive values (PPV/NPV) of HMW VWF multimer ratio for diagnosis of the TS subtype were calculated. HMW VWF multimer ratio in TS classical LF/LG AS was significantly decreased compared to PS classical LF/LG AS (0.86 ± 0.27 vs. 1.06 ± 0.09, P < 0.001). HMW VWF multimer deficiency occurred exclusively in the TS subtype with an optimal PPV of 1.000 and NPV of 0.379. HMW VWF multimer ratio showed a strong correlation with mean transvalvular pressure gradients during DSE (r = -0.616; P < 0.001). HMW VWF multimer ratio measured at baseline was higher compared to levels measured after DSE (0.87 ± 0.27 vs. 0.84 ± 0.31; P = 0.031) indicating DSE-induced increased proteolysis. CONCLUSION: HMW VWF multimer ratio represents a valuable biomarker for classical LF/LG AS subclassification and mirrors haemodynamics during DSE. HMW VWF multimer ratio identifies the TS subtype without the use of other imaging techniques.

Impact of pulmonary hypertension on outcome in patients with moderate or severe tricuspid regurgitation.

Objectives: The true prevalence and disease burden of moderate or severe (significant) tricuspid regurgitation (TR) in patients undergoing routine echocardiography remains unknown. Our aim was to explore the prevalence of significant TR and the impact of pulmonary hypertension (PH) on outcome in a less selected cohort of patients referred to echocardiography. Methods: From 12 791 echocardiograms performed between January and December 2010, a total of 209 (1.6%) patients (72±14 years, 56% men) were identified with significant TR; 123 (0.96%) with moderate and 86 (0.67%) with severe TR. Median follow-up time was 80 months (mean 70±33 months). Systolic pulmonary artery pressure was derived from peak velocity of tricuspid regurgitant jet plus the right atrial pressure and considered elevated if ≥40 mm Hg (PH). Results: During follow-up there were 123 (59%) deaths with no difference in mortality between moderate and severe TR (p=0.456). The death rates were 93 (67%) in patients with PH versus 30 (42%) without PH (p<0.001). PH was associated with lower event-free survival in moderate (log-rank, p<0.001), but not in severe TR (log-rank, p=0.133). In a multivariate Cox regression analysis adjusted for age, smoking, coronary artery disease, reduced right ventricle S', lower left ventricular ejection fraction at baseline, right atrium size and mitral valve replacement, PH remained a significant predictor of all-cause mortality (HR 2.22; 95% CI 1.41 to 3.47, p=0.001). Conclusions: Moderate or severe TR was found in 1.6% of patients attending for routine echocardiograms. PH identified a high-risk subset of patients with moderate TR but not with severe TR.

The effect of chordae tendineae on systolic flow.

When using Computational Fluid Dynamics to simulate ventricular blood flow in the heart, it has been common practice to neglect the effect of the sub-valvular apparatus and the trabeculae on the flow conditions. In this study, we analyze the effect of neglecting the chordae tendineae on the fluid flow and pressure drop. To test the assumption we use a previously developed dynamic 3D model of the left ventricle, aorta and valves that is based on 3D echocardiographic recordings. To this model we add the chordae tendineae as a sub-grid model. The previously developed 3D model for the left ventricle during systole is based on real-time three-dimensional echocardiography (RT3DE) recordings of a 30 years old female volunteer. The segmented ventricular wall does not include details of the aorta and the mitral valve, so these were reconstructed. The subgrid model for the flow across the chordae tendineae is based on the Actuator Line Method, which means that they are represented by drag coefficients. The analysis shows that the effect of the chordae tendineae on the pressure drop and work efficiency of the normal heart during systole is minor, and it seems that for simulating ventricular fluid flow and pressure drop during systole, one can follow the current practice and ignore the chordae. However, there can be local effects such as small vortices behind the chordae. Whether such effects are important for a particular application must be evaluated for the given case.

Validation of a Holographic Display for Quantification of Mitral Annular Dynamics by Three-Dimensional Echocardiography.

BACKGROUND: Three-dimensional (3D) echocardiography with multiplanar reconstruction (MPR) is used clinically to quantify the mitral annulus. MPR images are, however, presented on a two-dimensional screen, calling into question their accuracy. An alternative to MPR is an autostereoscopic holographic display that enables in-depth visualization of 3D echocardiographic data without the need for special glasses. The aim of this study was to validate an autostereoscopic display using sonomicrometry as a gold standard. METHODS: In 11 anesthetized open-chest pigs, sonomicrometric crystals were placed along the mitral annulus and near the left ventricular apex. High-fidelity catheters measured left atrial and ventricular pressures. Adjustments of pre- and afterload were done by constriction of the inferior vena cava and the ascending aorta, respectively. Three-dimensional epicardial echocardiography was obtained from an apical view and converted to the autostereoscopic display. A 3D virtual semitransparent annular surface (VSAS) was generated to measure commissure width (CW), septal-lateral length, area of the mitral annular surface, nonplanarity angle, and the annular height-to-commissure width ratio in mid-systole and late diastole. RESULTS: Mitral annular measurements from the 3D VSAS derived from the 3D echocardiographic images and autostereoscopic display correlated well with sonomicrometry over a range of loading conditions: CW length (r = 0.98, P < .00001), septal-lateral length (r = 0.98, P < .00001), annular surface area (r = 0.93, P < .001), nonplanarity angle (r = 0.87, P < .001), and annular height-to-commissure width ratio (r = 0.85, P < .01). The 3D VSAS showed better agreement with the sonomicrometric measurements compared with MPR. CONCLUSIONS: Mitral annular measurements using 3D VSAS correlate well with sonomicrometry over a range of loading conditions and may represent a powerful tool for noninvasive quantification of mitral annular dynamics.

Semiautomated biventricular segmentation in three-dimensional echocardiography by coupled deformable surfaces.

With the advancement of three-dimensional (3-D) real-time echocardiography in recent years, automatic creation of patient specific geometric models is becoming feasible and important in clinical decision making. However, the vast majority of echocardiographic segmentation methods presented in the literature focus on the left ventricle (LV) endocardial border, leaving segmentation of the right ventricle (RV) a largely unexplored problem, despite the increasing recognition of the RV's role in cardiovascular disease. We present a method for coupled segmentation of the endo- and epicardial borders of both the LV and RV in 3-D ultrasound images. To solve the segmentation problem, we propose an extension of a successful state-estimation segmentation framework with a geometrical representation of coupled surfaces, as well as the introduction of myocardial incompressibility to regularize the segmentation. The method was validated against manual measurements and segmentations in images of 16 patients. Mean absolute distances of [Formula: see text], [Formula: see text], and [Formula: see text] between the proposed and reference segmentations were observed for the LV endocardium, RV endocardium, and LV epicardium surfaces, respectively. The method was computationally efficient, with a computation time of [Formula: see text].