Transcatheter heart valve interventions: where are we? Where are we going?

Transcatheter heart valve interventions have transformed the outcomes of patients with valvular heart disease (VHD) who are unfavourable candidates for surgery. Technological advances have allowed extension of these interventions to younger or lower risk patients and those with other forms of VHD and may in the future permit earlier treatment of VHD in less symptomatic patients or those with moderate disease. The balance of risks and benefits is likely to differ between lower and higher risk patients, and more evidence is needed to evaluate the net benefit of transcatheter technology in these groups. As academic researchers, clinicians, industry, and patient stakeholders collaborate to research these broader indications for transcatheter valve interventions, it is essential to address (i) device durability and deliverability, (ii) specific anatomical needs (e.g. bicuspid aortic valves, aortic regurgitation, mitral and tricuspid valve disease), (iii) operator training, and (iv) the reinforced importance of the multidisciplinary Heart Team.

An image fusion tool for echo-guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis.

BACKGROUND: The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic-derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. METHODS: An image fusion tool for echo-guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient-specific LV function in fluoroscopy. A set of coronary venography-derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time-to-peak values from echocardiography speckle-tracking radial strain traces were color-coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo-defined target segments, and CRT response. RESULTS: Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo-suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. CONCLUSIONS: The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery.

Automatic alignment of standard views for transesophageal echocardiographic images.

Purpose: 3D transesophageal echocardiography (TEE) has become an important modality for pre- and peri-operative imaging of valvular heart disease. TEE can give excellent visualization of valve morphology in 3D rendering. As a convention, 3D TEE images are reformatted in three standard views. We describe a method for automatic calculation of parameters needed to define the standard views from 3D TEE images using no manual input. Approach: An algorithm was designed to find the center of the mitral valve and the left ventricular outflow tract (OT). These parameters defined the three-chamber view. The problem was modeled as a state estimation problem in which a 3D model was deformed based on shape priors and edge detection using a Kalman filter. This algorithm is capable of running in real time after initialization. Results: The algorithm was validated by comparing the automatic alignments of 106 TEE images against manually placed landmarks. The median error for determining the mitral valve center was 7.1 mm, and the median error for determining the left ventricular OT orientation was 13.5 deg. Conclusion: The algorithm is an accurate tool for automating the process of finding standard views for TEE images of the mitral valve.

Assessment of subendocardial vs. subepicardial left ventricular rotation and twist using two-dimensional speckle tracking echocardiography: comparison with tagged cardiac magnetic resonance.

AIMS: The aim of this article is to evaluate the accuracy and reproducibility of two-dimensional speckle tracking echocardiography (2D-STE) for the estimation of left ventricular (LV) twist, using tagged cardiac magnetic resonance (cMR) as the reference standard, and to assess how much 2D-STE rotational parameters are affected by the level at which measurements are made within the LV. METHODS AND RESULTS: Forty-three patients with various heart diseases and 10 healthy volunteers underwent cMR and 2D-STE on the same day. With both methods, basal and apical time-rotation curves were generated at endocardial, midwall, and epicardial levels. By using the most apical cMR short-axis cross-section as a comparator, apical rotation was significantly underestimated by 2D-STE. When 2D-STE and cMR short-axis cross-sections were matched for their internal dimensions, measurements of endocardial, midwall, and epicardial twists no longer differ between cMR and 2D-STE (12.6 +/- 5.9 vs. 12.5 +/- 5.7 degrees , 10.5 +/- 4.6 vs. 9.7 +/- 4.1 degrees , and 8.9 +/- 4.0 vs. 8.4 +/- 3.7 degrees , respectively, all P = ns). CONCLUSION: Compared with tagged cMR, 2D-STE underestimates apical rotation and LV twist. This is related to the inability of 2D-STE to image the real LV apex in most of the patients. However, when 2D-STE and cMR data are compared at similar acquisition levels, both techniques provide similar values.

Mitral Annulus Segmentation Using Deep Learning in 3-D Transesophageal Echocardiography.

3D Transesophageal Echocardiography is an excellent tool for evaluating the mitral valve and is also well suited for guiding cardiac interventions. We introduce a fully automatic method for mitral annulus segmentation in 3D Transesophageal Echocardiography, which requires no manual input. One hundred eleven multi-frame 3D transesophageal echocardiography recordings were split into training, validation, and test sets. Each 3D recording was decomposed into a set of 2D planes, exploiting the symmetry around the centerline of the left ventricle. A deep 2D convolutional neural network was trained to predict the mitral annulus coordinates, and the predictions from neighboring planes were regularized by enforcing continuity around the annulus. Applying the final model and post-processing to the test set data gave a mean error of 2.0 mm - with a standard deviation of 1.9 mm. Fully automatic segmentation of the mitral annulus can alleviate the need for manual interaction in the quantification of an array of mitral annular parameters and has the potential to eliminate inter-observer variability.

Adaptive Color Gain for Vena Contracta Quantification in Valvular Regurgitation.

Severe valvular regurgitation can lead to pulmonary hypertension, atrial fibrillation and heart failure. Vena contracta width is used to estimate the severity of the regurgitation. Parameters affecting visualization of color Doppler have a significant impact on the measurement. We propose a data-driven method for automated adjustment of color gain based on the peak power of the color Doppler signal in the vicinity of the vena contracta. A linear regression model trained on the peak power was used to predict the orifice diameter. According to our study, the color gain should be set to about 6 dB above where color Doppler data completely disappears from the image. Based on our method, orifices with reference diameters of 4, 6.5 and 8.5 mm were estimated with relative diameter errors within 18%, 12% and 14%, respectively.

Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis.

AIMS: This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. METHODS AND RESULTS: The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean ± 1.96 SD) of 0.5 ± 5.7 mL for LA minimum volume and -1.6 ± 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. CONCLUSION: The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

Spatiotemporal registration of multiple three-dimensional echocardiographic recordings for enhanced field of view imaging.

The use of three-dimensional (3-D) echocardiography is limited by signal dropouts and narrow field of view. Data compounding is proposed as a solution to overcome these limitations by combining multiple 3-D recordings to form a wide field of view. The first step of the solution requires registration between the recordings both in the spatial and temporal dimension for dynamic organs such as the heart. Accurate registration between the individual echo recordings is crucial for the quality of compounded volumes. A temporal registration method based on a piecewise one-dimensional cubic B-spline in combination with multiscale iterative Farnebäck optic flow method for spatial registration was described. The temporal registration method was validated on in vivo data sets with annotated timing of mitral valve opening. The spatial registration method was validated using in vivo data and compared to registration with Procrustes analysis using manual contouring as a benchmark. The spatial accuracy was assessed in terms of mean of absolute distance and Hausdorff distance between the left ventricular contours. The results showed that the temporal registration accuracy is in the range of half the time resolution of the echo recordings and the achieved spatial accuracy of the proposed method is comparable to manual registration.

Automated Segmentation of the Right Ventricle in 3D Echocardiography: A Kalman Filter State Estimation Approach.

As the right ventricle's (RV) role in cardiovascular diseases is being more widely recognized, interest in RV imaging, function and quantification is growing. However, there are currently few RV quantification methods for 3D echocardiography presented in the literature or commercially available. In this paper we propose an automated RV segmentation method for 3D echocardiographic images. We represent the RV geometry by a Doo-Sabin subdivision surface with deformation modes derived from a training set of manual segmentations. The segmentation is then represented as a state estimation problem and solved with an extended Kalman filter by combining the RV geometry with a motion model and edge detection. Validation was performed by comparing surface-surface distances, volumes and ejection fractions in 17 patients with aortic insufficiency between the proposed method, magnetic resonance imaging (MRI), and a manual echocardiographic reference. The algorithm was efficient with a mean computation time of 2.0 s. The mean absolute distances between the proposed and manual segmentations were 3.6 ± 0.7 mm. Good agreements of end diastolic volume, end systolic volume and ejection fraction with respect to MRI ( -26±24 mL , -16±26 mL and 0 ± 10%, respectively) and a manual echocardiographic reference (7 ± 30 mL, 13 ± 17 mL and -5±7% , respectively) were observed.

Parametric ultrasound and fluoroscopy image fusion for guidance of left ventricle lead placement in cardiac resynchronization therapy.

Recent studies show that the response rate to cardiac resynchronization therapy (CRT) could be improved if the left ventricle (LV) is paced at the site of the latest mechanical activation, but away from the myocardial scar. A prototype system for CRT lead placement guidance that combines LV functional information from ultrasound with live x-ray fluoroscopy was developed. Two mean anatomical models, each containing LV epi-, LV endo- and right ventricle endocardial surfaces, were computed from a database of 33 heart failure patients as a substitute for a patient-specific model. The sphericity index was used to divide the observed population into two groups. The distance between the mean and the patient-specific models was determined using a signed distance field metric (reported in mm). The average error values for LV epicardium were [Formula: see text] and for LV endocardium were [Formula: see text]. The validity of using average LV models for a CRT procedure was tested by simulating coronary vein selection in a group of 15 CRT candidates. The probability of selecting the same coronary branch, when basing the selection on the average model compared to a patient-specific model, was estimated to be [Formula: see text]. This was found to be clinically acceptable.

Enhancing bull sexual behavior using estrus-specific molecules identified in cow urine.

Deficiencies in bull mating behavior have implications for bovine artificial insemination activities. The aim of this study was to identify the compounds present in fluids emitted by cows during estrus, which could enhance bull libido. Chemical analysis of urine samples from cows led to the characterization of molecules varying specifically at the preestrous and estrous stages. The synthetic counterpart molecules (1,2-dichloroethylene, squalene, coumarin, 2-butanone, oleic acid) were used to investigate the biological effects on male sexual behavior and sperm production. When presented to males, 2-butanone and oleic acid synthetic molecules significantly lowered mounting reaction time and ejaculation time (-33% and 21% after 2-butanone inhalation, respectively, P < 0.05). The "squalene +1,2-dichloroethylene" combination induced a 9% increase of sperm quantity (P < 0.05). This study suggests that the identified estrous-specific molecules could be part of the chemical signals involved in male and female mating behavior and may be used for a wide range of applications. The identification of these molecules may have implications for the cattle breeding industry.

Angiographic right and left ventricular function in arrhythmogenic right ventricular dysplasia.

We prospectively documented right ventricular (RV) and left ventricular (LV) volumes and ejection fractions in a large series of patients with arrhythmogenic RV dysplasia/cardiomyopathy (ARVD/C). Eighty-five patients with ARVD/C and 11 controls underwent 2 successive orthogonal right and left monoplane x-ray-digitized cineangiographies. Volumes were calculated using the hemielliptical RV and ellipsoidal LV models. All controls and 58 of 85 patients (ARVD/C-I) had a RV ejection fraction > or =35% and 27 patients had a RV ejection fraction <35% (ARVD/C-II). Tricuspid annulus plane systolic excursion (TAPSE) was lower in ARVD/C-II than in ARVD/C-I patients (6 +/- 3 vs 14 +/- 3 mm) and controls (16 +/- 2 mm) (each p <0.001). In patients with ARVD/C, TAPSE was positively related to RV ejection fraction (r = 0.79) and to crista supraventricularis shortening (r = 0.81) (each p <0.001). Sensitivity and specificity of TAPSE <12 mm in identifying patients with RV ejection fraction <35% were 96% and 78%, respectively. LV ejection fraction was > or =50% in 68 patients, 40% to 49% in 10, and <40% in 7. Diffuse RV outflow tract aneurysm was observed in 9 patients, all belonging to ARVD/C-II, and this sign identified patients with LV ejection fraction <40% with 86% sensitivity and 96% specificity. In conclusion, 68% of ARVD/C patients had normal RV ejection fraction and RV volumes, and 80% of ARVD/C patients had normal LV ejection fraction. Decreased TAPSE <12 mm and a diffuse RV outflow tract aneurysm were sensitive and specific indicators of RV ejection fraction <35% and LV ejection fraction <40%, respectively.

Efficient model-based quantification of left ventricular function in 3-D echocardiography.

Quantitative functional analysis of the left ventricle plays a very important role in the diagnosis of heart diseases. While in standard two-dimensional echocardiography this quantification is limited to rather crude volume estimation, three-dimensional (3-D) echocardiography not only significantly improves its accuracy but also makes it possible to derive valuable additional information, like various wall-motion measurements. In this paper, we present a new efficient method for the functional evaluation of the left ventricle from 3-D echographic sequences. It comprises a segmentation step that is based on the integration of 3-D deformable surfaces and a four-dimensional statistical heart motion model. The segmentation results in an accurate 3-D + time left ventricle discrete representation. Functional descriptors like local wall-motion indexes are automatically derived from this representation. The method has been successfully tested both on electrocardiography-gated and real-time 3-D data. It has proven to be fast, accurate, and robust.

Bull semen in vitro fertility after cryopreservation using egg yolk LDL: a comparison with Optidyl, a commercial egg yolk extender.

Low-density lipoproteins (LDL) have been previously isolated and identified as the cryoprotective fraction of yolk. The effect of LDL on sperm motility after freezing-thawing has been reported, but no study has been made to assess the effect of LDL on bull semen fertility. The aim of this study was to evaluate the fertility of bull semen cryopreserved in the presence of LDL. Motility of semen cryopreserved in LDL was analyzed and compared to semen cryopreserved with Optidyl, a commercial extender containing egg yolk. To evaluate the fertilizing ability of semen, we used in vitro fertilization test, whereas acrosome and plasma membrane integrity were also evaluated. The percentage of motile spermatozoa was two fold higher after freezing in LDL than in Optidyl 54.4% versus 30.2% (P < 0.05). The cleavage rate was significantly higher after fertilization with semen frozen in LDL than with Optidyl 63.0% versus 54.8% (P < 0.05). No significant difference was observed on the blastocyst rate after in vitro culture. Integrity of the acrosome and the plasma membrane were maintained in both extenders. In conclusion, LDL preserve bull semen quality and fertilizing ability, allowing also better semen motility, after the freeze-thaw process.

Semi-automatic landmark detection in digital X-ray images of the spine.

Quantitative diagnosis of 3D scoliotic deformities depends on a number of dedicated measurements. Existing methods rely on the manual determination of a series of anatomical landmarks in X-ray images. We have developed an automatic method to alleviate the burden of this tedious task. Our method looks for a compromise between local image information and global prior constraints and finds the most probable points using dynamic programming optimization. Remaining errors can be quickly corrected by effective user interaction. The first results are promising.

3D reconstruction and analysis of the vertebral body line.

Quantitative analysis of 3D spinal deformities includes measurements related to individual vertebrae and measurements related to the overall shape of the spine. For the latter aspect, we propose to build a 3D model of the line that connects all vertebrae centres. We present two methods that allow reconstructing this vertebral body line in a quick and easy way. Various new descriptors of the spinal shape can be automatically computed. A study is under way to assess their clinical relevance and reliability.

Accuracy of measuring mitral annular velocity by 2D speckle tracking imaging.

BACKGROUND: Recent developments in 2D speckle tracking imaging allow not only measurements of regional myocardial strain, but also velocities of the mitral annulus. The aim of this study was to determine the accuracy of speckle tracking derived mitral annulus velocity compared with conventional pulsed wave Doppler measurements. METHODS: 2D speckle tracking was acquired from the apical 4-chamber view (QLab, Speckle SQ, Philips, Andover, MA) in 169 subjects. While using texture tracking, two small regions of interest (ROIs) were placed in the septal (IVS) and lateral corners (LAT) of the mitral annulus. The software automatically tracked the ROIs frame-by-frame, yielding regional mean velocity curves of the mitral annulus throughout the cardiac cycle (synthetic pulsed wave Doppler; SPW). From these curves, peak systolic, early- and late-diastolic velocities of the mitral annulus (S'-SPW, E'-SPW, and A'-SPW) were measured. Peak systolic, early- and late-diastolic velocity in the mitral annulus (S', E', and A') by conventional pulsed wave tissue Doppler tracing were also obtained. RESULTS: Adequate ROI tracking was observed in 150/169 subjects in IVS and 139/169 subjects in LAT of the mitral annulus. All annular velocities derived from SPW were significantly lower than corresponding velocities obtained from conventional method in both IVS and LAT regions of the mitral annulus. However, significant correlation between S' (E', A')-SPW and S' (E', A') was observed. In particular, a good correlation between E'-SPW and E' was noted in both IVS (r=0.89, P<0.001) and LAT (r=0.85, P<0.001) regions of the mitral annulus. If we defined E/E'-SPW in IVS>26 for predicting E/E' in IVS>15, sensitivity, specificity, and accuracy were 83%, 97%, and 94%, respectively. E/E'-SPW in LAT>13 had a 94% sensitivity, 92% specificity, and 93% accuracy for predicting E/E' in LAT>10. CONCLUSIONS: The values of annular velocities by SPW were significantly lower compared to those assessed by traditional tissue velocities. However, new cut-off values of E/E'-SPW for predicting elevated LV filling pressure highly correlated with traditional parameters. 2D speckle tracking imaging provides another strategy for evaluating LV filling pressures.

Measurement of left ventricular mass by real-time three-dimensional echocardiography: validation against magnetic resonance and comparison with two-dimensional and m-mode measurements.

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

Integrating functional and anatomical information to facilitate cardiac resynchronization therapy.

Multiple imaging modalities are required in patients receiving cardiac resynchronization therapy. We have developed a strategy to integrate echocardiographic and angiographic information to facilitate left ventricle (LV) lead position. Full three-dimensional LV-volumes (3DLVV) and dyssynchrony maps were acquired before and after resynchronization. At the time of device implantation, 3D-rotational coronary venous angiography was performed. 3D-models of the veins were then integrated with the pre- and post-3DLVV. In the case displayed, prior to implantation, the lateral wall was delayed compared to the septum. The LV lead was positioned into the vein over the most delayed region, resulting in improved LV synchrony.

Review of myocardial motion estimation methods from optical flow tracking on ultrasound data.

Quantitative analysis of cardiac motion is of great clinical interest in assessment of ventricular function. Ultrasound imaging, especially matrix transducers acquiring real-time three dimensional data, provide valuable information, from which quantitative measures of cardiac function can be extracted via optical flow computation. Such analysis requires tracking of the image brightness patterns with underlying assumptions of visual persistency. We present a review of myocardial motion analysis on cardiac ultrasound, based on optical-flow computation, with phantom and clinical evaluations for segmental wall assessment and motion features quantification.