Diastolic Geometry Research Articles

Left atrial geometry in an ovine ischemic mitral regurgitation model: implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism

BackgroundTranscatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms.MethodsA group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI).ResultsSix animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI.ConclusionsSystolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.

Quantitative flow ratio-guided surgical intervention in symptomatic myocardial bridging.

Patients with myocardial bridging (MB) are associated with adverse cardiovascular events, but a decision to perform surgical intervention, especially for patients with systolic intermediate stenosis, is a difficult clinical issue. Fractional flow reserve (FFR) represents a novel method for the functional evaluation of coronary stenosis, but the relationship between FFR and MB remains controversial because of the cyclic dynamic stenosis of MB. Quantitative flow ratio (QFR) is a novel index allowing fast assessment of FFR from a diagnostic coronary angiography. This study aimed to investigate the relationship between QFR and MB patients and to further develop a prediction model of QFR-guided surgical intervention for these patients. Forty-five symptomatic lone MB patients who had undergone coronary angiography were consecutively enrolled in this study. MB was located in the middle of left anterior descending artery with intermediate stenosis during systole. The patients were retrospectively divided into a medical therapy group or a surgical therapy group. Systolic geometry based QFR (SG-QFR) and diastolic geometry based QFR (DG-QFR) were calculated based on three-dimensional quantitative coronary angiography and patient-specific flow velocity. Subsequently, time-averaged QFR (TA-QFR) is defined as the average of SG-QFR and DG-QFR. Receiver operating characteristic curve analysis revealed that TA-QFR (AUC = 0.91; 95% CI: 0.79-0.98) was found to be the best pre-operative index for surgical intervention to MB, when compared with DG-QFR (AUC = 0.69; 95% CI: 0.53-0.82; difference: 0.22; 95% CI: 0.04-0.41; p = 0.02) and SG-QFR (AUC = 0.87; 95% CI: 0.74-0.95; difference: 0.04; 95% CI: 0.00-0.08; p = 0.03). TA-QFR improved the performance of functional evaluation in MB patients with intermediate stenosis during systole and is useful for guiding surgical intervention.

Abstract 16830: Functional Stenosis After Undersizing Mitral Annuloplasty is Governed by Pre-Operative Mitral Valve Opening Geometry

Introduction: Surgical repair of functional mitral regurgitation (FMR) with undersizing mitral annuloplasty (UMA) is a common practice. Though excessive annular downsizing can improve coaptation, it raises the risk of functional mitral stenosis (FMS). Predicting if certain patients can develop FMS after UMA, can help with surgical planning and inform the safe levels of downsizing. In this study, we sought to investigate that the pre-operative diastolic geometry of the mitral valve can predict the risk of developing FMS with UMA. Methods: Pig mitral valves (n=8) were excised and mounted into a left heart simulator with steady diastolic flow only [ Fig1A ]. Three leaflet tethering patterns were mimicked in this model: annular dilation (AD), AD + asymmetric tethering (Asym) and AD + symmetric tethering (Sym) [ Fig1B ]. Under each condition, the annulus was downsized to different levels by an adjustable UMA [ Fig1C ]. Millar pressure catheter and Echocardiography were used to measure MV pressure gradient and diastolic configuration under various conditions. Results: Under each tethering geometry (AD, AD + Asym and AD + Sym respectively), pressure gradient gradually increases as the downsizing level increases. Also, at each specific level of downsizing, pressure gradient increases as the subannular tethering increases. Similarly, at each specific level of downsizing, EOA decreases as the subannular tethering increases. Under each tethering geometry, EOA also decreases as the downsizing level increases [ Fig1D ]. In addition, it is demonstrated that at different flow rates, both pressure gradient and EOA correlates with anterior diastolic angle, which is impacted mainly by preoperative subannular tethering [ Fig1E ]. Conclusions: In FMR, the hemodynamic outcome of MV after UMA depends on both the extent of annular downsizing and preoperative leaflet tethering geometry, both of which should be taken into account when deciding the optimal surgical intervention.

Undersized Mitral Annuloplasty Increases Strain in the Proximal Lateral Left Ventricular Wall

Recurrence of mitral regurgitation (MR) after undersized mitral annuloplasty (MA) for ischemic MR is as high as 60%, with the recurrence rate likely due to continued dilation of the left ventricle (LV). To better understand the causes of recurrent MR, we studied the effect of undersized MA on strain in the LV wall. We hypothesize that the acute change in ventricular shape induced by MA will cause increased strain in regions nearest the mitral valve. Finite element models were previously reported, based on cardiac magnetic resonance images of 5 sheep with mild to moderate ischemic MR. A 24-mm saddle-shaped rigid annuloplasty ring was modeled and used to simulate virtual MA. Longitudinal and myofiber strains were calculated at end-diastole and end-systole, with preoperative early diastolic geometry as the reference state. The undersized MA significantly increased longitudinal strain at end-diastole in the lateral LV wall. The effect was greatest in the proximal-lateral endocardial surface, where longitudinal strain after MA was approximately triple the preoperative strain (11.17% ± 2.15% vs 3.45% ± 0.92%, p= 0.0057). In contrast, postoperative end-diastolic fiber strain decreased in this same region (2.53% ± 2.14% vs 7.72% ± 1.79%, p= 0.0060). There were no significant changes in either strain type at end-systole. Undersized MA increased longitudinal strain in the proximal lateral LV wall at end-diastole. This procedure-related strain at the proximal-lateral LV wall may foster continued LV enlargement and subsequent recurrence of mitral regurgitation.

High-resolution subject-specific mitral valve imaging and modeling: experimental and computational methods.

The diversity of mitral valve (MV) geometries and multitude of surgical options for correction of MV diseases necessitates the use of computational modeling. Numerical simulations of the MV would allow surgeons and engineers to evaluate repairs, devices, procedures, and concepts before performing them and before moving on to more costly testing modalities. Constructing, tuning, and validating these models rely upon extensive in vitro characterization of valve structure, function, and response to change due to diseases. Micro-computed tomography ([Formula: see text]CT) allows for unmatched spatial resolution for soft tissue imaging. However, it is still technically challenging to obtain an accurate geometry of the diastolic MV. We discuss here the development of a novel technique for treating MV specimens with glutaraldehyde fixative in order to minimize geometric distortions in preparation for [Formula: see text]CT scanning. The technique provides a resulting MV geometry which is significantly more detailed in chordal structure, accurate in leaflet shape, and closer to its physiological diastolic geometry. In this paper, computational fluid-structure interaction (FSI) simulations are used to show the importance of more detailed subject-specific MV geometry with 3D chordal structure to simulate a proper closure validated against [Formula: see text]CT images of the closed valve. Two computational models, before and after use of the aforementioned technique, are used to simulate closure of the MV.

Role of Mitral Annulus Diastolic Geometry on Intraventricular Filling Dynamics

The mitral valve (MV) is a bileaflet valve positioned between the left atrium and ventricle of the heart. The annulus of the MV has been observed to undergo geometric changes during the cardiac cycle, transforming from a saddle D-shape during systole to a flat (and less eccentric) D-shape during diastole. Prosthetic MV devices, including heart valves and annuloplasty rings, are designed based on these two configurations, with the circular design of some prosthetic heart valves (PHVs) being an approximation of the less eccentric, flat D-shape. Characterizing the effects of these geometrical variations on the filling efficiency of the left ventricle (LV) is required to understand why the flat D-shaped annulus is observed in the native MV during diastole in addition to optimizing the design of prosthetic devices. We hypothesize that the D-shaped annulus reduces energy loss during ventricular filling. An experimental left heart simulator (LHS) consisting of a flexible-walled LV physical model was used to characterize the filling efficiency of the two mitral annular geometries. The strength of the dominant vortical structure formed and the energy dissipation rate (EDR) of the measured fields, during the diastolic period of the cardiac cycle, were used as metrics to quantify the filling efficiency. Our results indicated that the O-shaped annulus generates a stronger (25% relative to the D-shaped annulus) vortical structure than that of the D-shaped annulus. It was also found that the O-shaped annulus resulted in higher EDR values throughout the diastolic period of the cardiac cycle. The results support the hypothesis that a D-shaped mitral annulus reduces dissipative energy losses in ventricular filling during diastole and in turn suggests that a symmetric stent design does not provide lower filling efficiency than an equivalent asymmetric design.

Importance of initial stress for abdominal aortic aneurysm wall motion: Dynamic MRI validated finite element analysis

Currently the transverse diameter is the primary decision criterion to assess rupture risk in patients with an abdominal aortic aneurysm (AAA). To obtain a measure for more patient-specific risk assessment, aneurysm wall stress, calculated using finite element analysis (FEA), has been evaluated in literature. In many cases, initial stress, present in the AAA wall during image acquisition, is not taken into account. In the current study the effect of initial stress incorporation (ISI) is determined by directly comparing wall displacements extracted from FEA and dynamic MRI.Ten patients with an aneurysm diameter >5.5cm were scanned with cardiac triggered MRI. Semi-automatic segmentation of the AAA was performed on the diastolic phase. The segmented in-slice contours were propagated through the remaining cardiac phases using an active contour model as to track wall displacements on MRI. Consequently, FEA with and without ISI (no-ISI) was performed using the diastolic geometry with simultaneously measured intra-aneurysm pressure values as boundary condition. Contours extracted from FEA were compared with MRI contours at corresponding cardiac phases by distance and relative area differences.The wall displacements from FEA with ISI show significant better correspondence with wall motion from MRI data in comparison with the no-ISI FEA (deviation in wall displacement 1.7% vs. 12.4%; p<0.001). Based on these results it can be concluded that incorporation of initial stress significantly improves wall displacement accuracy of FEA and therefore it should be incorporated in future analyses.

The study on the change of left ventricular geometry shape and left ventricular regional function in mitral insufficiency (MI)

Objective To evaluate the left ventricle geometry shape and left heart regional function in mitral insufficiency (MI) by quantitative tissue velocity imaging (QTVI) and the left ventricle systolic and diastolic geometry spbericity index. Methods Thirty normal subjects and 62 MI patients underwent QTVI and color Doppler imaging (CDFI) were enrolled in this study in order to measure the left ven-tricular geometry shape and left ventrieular regional function along LV apical long-axis view. Off-line LV regional velocity images along LV apical long-axis view were synchronously obtained. Peak tissue velocities of LV regional muscular tissue during systole(Vs),systolic acceler-ation(a), early diastole(Ve), LA contraction(Va)were synchronously measured as the index of left ventricular regional systolic and dias-tolic function. The left ventricle geometry shape index were reflected from the systolic and diastolic geometry sphericity index (SIs and Sid) and the left ventrieular ejection fraction (LVEF) and the peak D and peak a (PVd/PVa) of pulmonary veins flowing spectrum reflected the global left ventricular function index. The Vs, Ve, Va, a, PVd/PVd ratio, LVEF, SIs, SId were recorded and their correlation between normal subjects and patients with MI were compared. Result Vs, Ve,Va,a,PVd/ PVa ratio,SIs,SId in patients with MI were significantly re-duced. There was positive relation between Sis and a(r=0.602)and Ve/Va and SId(r=0.635). Conclusion There was negative rela-tion between regional cardiac function and LV spberieity, the higher cardiac function was accompanied with the lower SI. Key words: Ultrasonography, doppler; Heart ventricles/AH; Mitral valve insufficiency/US; Ventricular function, left

Whole heart modeling: from validation of animal experiments to the reconstruction of the human magnetocardiogram

Our interest in heart modeling is on one hand strongly motivated by the desire to compare cardiac simulation results with data obtained from magnetocardiogram (MCG) measurements of human beings and animals in various setups. On the other hand, we have started to integrate imaging data at various levels in our modeling approach. In the first part, we report in detail on simulations of anatomically realistic models for animal ventricles using the modified Beeler-Reuter ionic model and compare these with experimental data. Simulations of a rabbit heart were carried out and compared with experiments in Langendorff perfusion. The time evolution of the spatial profiles of the extracellular potential on the surface of the rabbit heart was correctly reproduced. The effects of ajmaline (Na-channel blockage) and palmitoleic acid (decrease of intracellular conductivity) were included subsequently in the model. In addition, pacing simulations of the ventricles have been performed using different frequencies. Occurrence of action potential duration alternans was found for frequencies greater than 230 bpm. Fibrillation occurred for frequencies greater than 260 bpm. Finally, the influence of geometry change during the human heart beat on MCG signals was investigated. We computed the MCG using the ten Tusscher ionic model for 2-dimensional cuts through the ventricles recorded by magnetic resonance imaging during systole resp. diastole and found a much shorter QRS for the diastolic geometry. Furthermore, the dynamic geometry of the heart was recorded and translated into a moving finite element mesh used in 3-dimensional simulations of the heart.

Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method

Patient-specific wall stress simulations on abdominal aortic aneurysms may provide a better criterion for surgical intervention than the currently used maximum transverse diameter. In these simulations, it is common practice to compute the peak wall stress by applying the full systolic pressure directly on the aneurysm geometry as it appears in medical images. Since this approach does not account for the fact that the measured geometry is already experiencing a substantial load, it may lead to an incorrect systolic aneurysm shape. We have developed an approach to compute the wall stress on the true diastolic geometry at a given pressure with a backward incremental method. The method has been evaluated with a neo-Hookean material law for several simple test problems. The results show that the method can predict an unloaded configuration if the loaded geometry and the load applied are known. The effect of incorporating the initial diastolic stress has been assessed by using three patient-specific geometries acquired with cardiac triggered MR. The comparison shows that the commonly used approach leads to an unrealistically smooth systolic geometry and therefore provides an underestimation for the peak wall stress. Our backward incremental modelling approach overcomes these issues and provides a more plausible estimate for the systolic aneurysm volume and a significantly different estimate for the peak wall stress. When the approach is applied with a more complex material law which has been proposed specifically for abdominal aortic aneurysm similar effects are observed and the same conclusion can be drawn.

The relationship between diastolic function of the left ventricle and QT dispersion in patients with myocardial infarction

Lack of synchronicity concerns not only the electrical but also the mechanical function of the left ventricle and causes impaired ventricular filling. To our knowledge a direct association between electrical dispersion and impairment of left ventricular filling has not been reported. The study group comprised 71 patients with myocardial infarction. Echocardiographic Doppler studies and QT dispersion measurements from standard 12-lead electrocardiograms were performed during the second week of hospitalization. The study population was divided into high, intermediate and low QT dispersion groups. Differences in the left ventricular filling parameters between high and low QT dispersion groups were assessed. Patients with high QT dispersion had larger end-diastolic volume (134±31 vs. 107±19 ml; P=0.049) and tended to have shorter E-wave deceleration time (155±18 vs. 175±20 ms; P=0.056) compared with patients with low QT dispersion. There was a negative correlation between E-wave deceleration time and QT dispersion ( r=–0.248; P=0.05). We conclude that greater dispersion of repolarization is accompanied by changes in the left ventricular diastolic geometry and more ‘restrictive’ filling. The hypothesis that left ventricular filling abnormalities are caused by increased electrical dispersion deserves further study, especially under controlled, experimental conditions.

An androgenic steroid decreases left ventricular compliance in rats

The effect of chronic administration of an androgenic steroid on left ventricular (LV) compliance and contractility was studied in rats. Rats received a biweekly intramuscular injection of nandrolone decanoate (5 mg/kg; steroid group) or the vehicle (control group) for 3 mo. Cardiac performance was measured in anesthetized open-chest ventilated rats. LV compliance was determined from the slope of the LV end-diastolic pressure (LVEDP) vs. LV end-diastolic (LVED) strain relation measured in the long and short axes of the LV. LV regional myocardial compliance was determined from the slope of the LVED stress vs. LVED strain relation (myocardial elastic stiffness constant). Cardiac contractility was determined from the slope of the LV end-systolic (LVES) pressure vs. LVES strain relation. Systolic performance was also assessed from the slope of the pressure-length area (PL area) or stroke work vs. LVED strain and LVEDP relations. Nandrolone decanoate decreased body weight, heart weight, and plasma testosterone concentrations but increased the heart weight-to-body weight ratio. Nandrolone decanoate decreased LV compliance (slope of LVEDP vs. LVED strain relation in long and short axes; steroid vs. control, P < 0.01). This occurred as a result of an increased regional myocardial stiffness (myocardial elastic stiffness constant; steroid vs. control, P < 0.01), which resulted in a reduced cardiac systolic performance (PL area vs. LVEDP, slope of steroid vs. control group, P < 0.005). Diastolic geometry (LV wall thickness-to-radius ratio) and cardiac contractility were unchanged with steroid administration. In conclusion, chronic administration of the androgenic steroid nandrolone decanoate decreases LV myocardial compliance and thus overall cardiac performance without altering contractility in rats.

Doppler echocardiographic demonstration of the differential effects of right ventricular pressure and volume overload on left ventricular geometry and filling

To compare the effects of isolated right ventricular pressure and volume overload on left ventricular diastolic geometry and filling, 11 patients with primary pulmonary hypertension, 11 patients with severe tricuspid regurgitation due to tricuspid valve resection and 11 normal subjects were studied with use of Doppler echocardiography techniques. Right ventricular systolic overload in primary pulmonary hypertension resulted in substantial leftword ventricular septal shift that was most marked at end-systole and early diastole and decreased substantially by end-diastole. Right ventricular diastolic overload after tricuspid valve resection resulted in maximal leftward ventricular septal shift at end-diastole sparing end-systole and early diastole. The early diastolic distortion of left ventricular geometry associated with right ventricular pressure overload resulted in prolongation of isovolumetric relaxation of the left ventricle (129 ± 39 ms) and a reduction in early diastolic finding compared with values in normal subjects.Late diastolic distortion of left ventricular geometry associated with right ventricular volume overload had no influence on the duration of left ventricular isovolumetric relaxatoon (52 ± 32 ms) but caused a reduction in the atrial systolic contribution to late distolic filling of the left ventricle compared with values in normal sujects. In patients with right ventricular pressure overload, 52 ± 16% of left ventricular filling occurred in early diastole compared with 78 ± 11% in patients with right ventricular volume overload (p < 0.001). The differential effects of systolic and diastolic right ventricular overload on the pattern of left ventricular filling appear to bt related to the timing of leftward ventricular septal displacement.

Left ventricular geometry during intermittent positive pressure ventilation in dogs

We have analyzed how regional left ventricular (LV) performance may contribute to global LV performance during a single intermittent positive pressure ventilation (IPPV) respiratory cycle using chronically instrumented dogs with endocardial piezoelectric crystals in the three orthogonal axes, anterior-posterior (AP), septal-lateral freewall (SL), and long axis (LA) dimensions (D). Right ventricular (RV) SLD and aortic flow were also measured. Changes in LV geometry were evaluated during IPPV at two respiratory rates (10 and 20 breaths/min) and during inferior vena caval (IVC) occlusion since a change in systemic venous return is a major component of an IPPV inspiration. During an IPPV inspiration the RV SL end-diastolic D decreased, while the LV AP end-diastolic D increased ( P < .01) and LV SL end diastolic D decreased ( P < .001). LV end-diastolic and end-systolic volumes tended to increase during early inspiration and then diminished to an early expiratory minimum ( P < .05) associated with early expiratory minimum stroke volumes and measured aortic flows ( P < .02). In contrast, during IVC occlusion, the LV SL end-diastolic D initially increased while the AP end-diastolic D was falling. Thus, entirely different changes in LV end diastolic geometry result from IVC occlusion and lung inflation. These studies suggest a common factor of cardiac compression by the lung during inspiration altering diastolic intraventricular distribution of the LV preload and raise the question of whether respiratory-induced changes in LV geometry may independently modulate LV systolic pump function.

Diastolic geometry and sarcomere lengths in the chronically dilated canine left ventricle.

In 10 dogs left ventricular geometry and ultrastructure were examined 3 to 12 weeks after chronic ventricular dilatation was induced by means of a large arteriovenous shunt. Following cardiac catheterization, the hearts were arrested and fixed in diastole at the left ventricular end-diastolic pressures (LVEDP) which existed in the beating heart. Transmural LVEDP were increased in all animals (avg. 27 mm Hg). The diastolic pressure-volume relationship was shifted to the right, the average end-diastolic volume of the chronically dilated ventricles (avg. 103 ml) being larger than that of previously studied acutely dilated ventricles (avg. 72 ml, P &lt;.01), but calculated diastolic wall stress values were not different. Sarcomere lengths in the chronically dilated hearts averaged 2.19±.02 µ ( SE ) (range 2.11 to 2.27), a value near the apex of the sarcomere length-tension curve, but not significantly different from sarcomere lengths in acutely dilated ventricles. Slippage between myofibrils, reflected by a loss of normal alignment of the Z lines, appeared to be one mechanism underlying this adaptation. The findings indicate that sarcomeres in the canine left ventricular wall are remarkably resistant to chronic as well as to acute overstretch. They further imply that little or no Frank-Starling reserve mechanism was available in these ventricles and raise the possibility that a descending limb of the heart's performance as a pump need not reflect a descending limb at the sarcomere level.