Image-Based Modelling of Cardiac Mechanics

The main objective of this study was to model the left ventricle (LV) based on 2D echocardiography imaging technique to assess the cardiac mechanics for group of patients affected by heart failure. A prospective study has been made at Ibn Al-Bitar center for cardiac surgery, for 13 patients with heart failure (HF), 9 patients were males (69%) and 4 females (31%). The mean age was 54±7 years. Those patients were supposed to undergo a CRT-D (Cardiac Resynchronization Therapy Defibrillator) implant as they didn’t respond to drug therapy. Before CRT-D implantation, 2D echocardiography was performed for all the patients, to model the left ventricle and to measure indices that were used to evaluate cardiac mechanics which are LV pressure, wall stresses, global longitudinal strain, and cardiac output. After 3-months of follow-up, 2D echocardiography was re-assessed and the left ventricular mechanics has been re-measured. Post CRT-D implantation, significant improvement in the cardiac mechanics was observed in 54% of the patients which were called responders (patients that respond to CRT-D device) and the other patients were called non-responders. It has been seen that, the circumferential wall stresses were decreased in responder’s group while increased or remain unchanged in non-responders. Global longitudinal strain for the responder’s group were increased while remain unchanged in the non-responders. So, patients were divided into responders and non-responders, based on improvement of the cardiac mechanics after 3-moths of follow up. It has been concluded that the modelling of the left ventricle based on images obtained from 2D echocardiography imaging techniques, was an important computational tool that was used to enhance understanding and support the evaluation, surgical guidance and treatment management of basic biophysics underlying cardiac mechanics.

Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loops Figure 2. Mean mid-LV strains

336 Right ventricular mechanics in patients affected by pulmonary valve stenosis, before and after percutaneous pulmonary angioplasty

Aims Pulmonary valve stenosis accounts for 6–9% of all congenital heart diseases. The main effect of this obstructive lesion is a rise in right ventricular pressure; this overload leads to multiple changes in shape, dimensions, and volume of the ventricle. The diagnosis is based on transthoracic echocardiography and invasive heart catheterization. Usually the stenosis is classified into mild, moderate, and severe based on pressure gradient between right ventricle and pulmonary artery and on the ratio between right ventricle and left ventricle systolic pressure. Percutaneous balloon valvuloplasty is the treatment of choice in severe pulmonary valve stenosis in patients of all ages; alternatively surgical valvotomy is an option in selected cases. The aim of this study is to evaluate the mechanical changes of the right ventricle in patients undergoing balloon pulmonary valvuloplasty using transthoracic and speckle-tracking echocardiography (STE). Furthermore, we sought to investigate the correlation between haemodynamic and echocardiographic parameters to better evaluate the degree of pulmonary valve stenosis before and after treatment. Methods and results Forty-three pediatric patients (19 males), mean age 3.2 ± 4.9 years with severe pulmonary valve stenosis and indication for percutaneous balloon valvuloplasty were recruited at the University Hospital of Padua. All patients underwent standard transthoracic echocardiography (TTE), STE with analysis of right ventricle global longitudinal strain (RVGLS) one day before and one day after the procedure. For each patient were collected invasive parameters during the interventional procedure before and after balloon valvuloplasty. After the procedure, there was an immediate statistically significant reduction of both peak-to-peak transpulmonary gradient (Dp post) and ratio between the systolic pressure of right and left ventricle (RV/LV ratio) with a drop of 29.3 ± 14.67 mmHg and 0.43 ± 0.03, respectively. Post-procedural echocardiography showed peak and mean transvalvar pressure gradient drop (50 ± 32.23 and 31 ± 17.97, respectively). The degree of pulmonary valve regurgitation was mild in 8% of patients before the procedure, following the intervention it reached 29% with a statistically significant increase (P = 0.007). However, the incidence of pulmonary valve moderate and severe regurgitation remained stable after the procedure. The analysis of right ventricular function and mechanics showed a significant improvement of Fractional Area Change (FAC) immediately after the procedure (40.11% vs. 44.42%, P = 0,01). On the other hand, right ventricular longitudinal systolic function parameters, TAPSE (P = 0.60) and longitudinal strain (P = 0.31), did not improve significantly after intervention. Finally, pre-procedural invasive RV/LV ratio showed good correlation to echocardiographic transvalvular peak and mean pressure gradient (R = 0.375, P = 0.019 and R = 0.40, P = 0.012, respectively), as well as with FAC (R = 0.31, P = 0.05), TAPSE (R = 0.62, P < 0.001), and RVGLS (R = 0.46, P = 0.01). Conclusions Percutaneous balloon pulmonary valvuloplasty represents an efficient and safe procedure to relieve severe pulmonary valve stenosis. Interestingly, the analysis of right ventricular mechanics on echocardiography demonstrated an immediate global systolic function improvement following afterload reduction. Conversely, longitudinal systolic function did not show improvement immediately after intervention, possibly due to the necessity of longer time to recover. Finally, invasive preprocedural RV/LV ratio demonstrated better correlation with echocardiographic evaluation of stenosis degree and right ventricular function compared to invasive peak-to-peak pressure gradient. Therefore, RV/LV ratio should be preferred for the assessment of pulmonary valve stenosis.

Impact of BMI z-score On Left Ventricular Mechanics in a Pediatric Population

Background: Adolescent weight disorders ranging from anorexia nervosa (AN) to obesity (OB) can impact the heart by causing opposite alterations in its morphology, suggesting a direct impact of BMI on the heart. Cardiac function is relatively preserved as assessed by standard ultrasound methods. However, few studies have used speckle-tracking echocardiography (STE), which can detect subtle alterations of left ventricular (LV) function by evaluating deformations. The aim of this study was to assess the link between BMI z-score of female adolescents and myocardial function. Methods: Ninety-one female adolescents comprising 26 AN patient (age 14.6 ± 1.9 y), 28 OB patients (age 13.2 ± 1.4 y), and 37 controls (age 14.0 ± 2.0 y) underwent STE to assess LV morphology and myocardial regional deformations. Findings: The BMI z-score of our population ranged from −4.6 to 5.2. LV morphological remodeling was significantly and positively correlated with BMI z-score (R² = 0.456, p < 0.0001 for LV mass). Global longitudinal strain (LS) and regional LS recorded at the mid and apical levels were significantly correlated with BMI z-score (R² = 0.196, p = 0.0001 and R² = 0.274, p < 0.0001 respectively for apical and medial LS). Circumferential strains and twisting mechanics were not correlated with BMI z-score. Fibrinogen and SBP were the main variables explaining the alteration of longitudinal strains. Conclusion: A impact of BMI z-score on LV mechanics was observed especially on medial and apical LS. Neither circumferential nor twisting mechanics were altered by BMI z-score in female adolescents.

Features of changes in left ventricular mechanics in patients with epicardial obesity

Currently, there is no single non-invasive marker that can directly assess left ventricular (LV) diastolic function. Untwist of LV contributes to diastolic suction and early filling. Speckle-tracking imaging can be used to diagnose diastolic dysfunction at the preclinical stage. Objective To study the features of changes in the parameters of LV mechanics and their relationship with the levels of serum markers of myocardial fibrosis in patients with epicardial obesity (EO). Materials and methods The study included 125 men with general obesity. All patients underwent transthoracic echocardiography (ECG) to assess the thickness of epicardial adipose tissue (tEAT) as equivalent to visceral obesity, as well as to diagnose diastolic dysfunction (DD) of left ventricle (LV). According to the results of ECG, the patients were divided into 2 groups: EO(+) with epicardial fat thickness (tEAT) ≥7 mm (n=78); EO(−) with (tEAT) &lt;7 mm (n=40). DD LV was detected in 7 patients, who were subsequently excluded from the analysis. Profibrotic markers in blood serum (MMP-3, collagen I, collagen III, TGF-β, VEGFA, PICP) were determined in all patients using enzyme immunoassay. Using speckle-tracking ECG, the mechanics of LV were studied (twist LV, peak twist ratio LV, time to peak twist of LV, peak untwist ratio LV, time to peak untwist of LV). The exclusion criteria were the presence of coronary pathology, arterial hypertension, and type 2 diabetes mellitus. Results In the group of patients with EO(+) statistically significant increase the level of all studied profibrotic markers was revealed. According to the results of speckle-tracking ECG in the EO(+) group an increase peak untwist ratio LV to −125.56 (−141.0; −117.0)deg/s (p=0.003) and an increase time to peak untwist of LV of 469.44 (509.0; 401.0) msec was determined in comparison with the EO(−) group (p=0.03). A weak statistically significant effect of tEAT on the peak untwist ratio LV in EO(+) group was revealed (r=0.28; p=0.03). In addition, there was a significant relationship between peak untwist ratio LV and markers of myocardial fibrosis MMP-3 (r=0.23; p=0.03) and collagen type III (r=0.25; p=0.04). Conclusion Thus, LV unwinding may be a new non-invasive marker of LV DD at the preclinical stage, since this parameter reflects the mechanical aspect of global diastolic function, especially the early phase of diastole. FUNDunding Acknowledgement Type of funding sources: None.

Global and regional right ventricular mechanics in repaired tetralogy of Fallot with chronic severe pulmonary regurgitation: a three-dimensional echocardiography study

Background Data about the right ventricular (RV) mechanics adaptation to volume overload in patients with repaired tetralogy of Fallot (rToF) are limited. Accordingly, we sought to assess the mechanics of the functional remodeling occurring in the RV of rToF with severe pulmonary regurgitation. Methods We used three-dimensional transthoracic echocardiography (3DTE) to obtain RV data sets from 33 rToF patients and 30 age- and sex- matched controls. A 3D mesh model of the RV was generated, and RV global and regional longitudinal (LS) and circumferential (CS) strain components, and the relative contribution of longitudinal (LEF), radial (REF) and anteroposterior (AEF) wall motion to global RV ejection fraction (RVEF) were computed using the ReVISION method. Results Corresponding to decreased global RVEF (45 ± 6% vs 55 ± 5%, p < 0.0001), rToF patients demonstrated lower absolute values of LEF (17 ± 4 vs 28 ± 4), REF (20 ± 5 vs 25 ± 4) and AEF (17 ± 5 vs 21 ± 4) than controls (p < 0.01). However, only the relative contribution of LEF to global RVEF (0.39 ± 0.09 vs 0.52 ± 0.05, p < 0.0001) was significantly decreased in rToF, whereas the contribution of REF (0.45 ± 0.08 vs 0.46 ± 0.04, p > 0.05) and AEF (0.38 ± 0.09 vs 0.39 ± 0.04, p > 0.05) to global RVEF was similar to controls. Accordingly, rToF patients showed lower 3D RV global LS (-16.94 ± 2.9 vs -23.22 ± 2.9, p < 0.0001) and CS (-19.79 ± 3.3 vs -22.81 ± 3.5, p < 0.01) than controls. However, looking at the regional RV deformation, the 3D CS was lower in rToF than in controls only in the basal RV free-wall segment (p < 0.01). 3D RV LS was reduced in all RV free-wall segments in rToF (p < 0.0001), but similar to controls in the septum (p > 0.05). Conclusions 3DTE allows a quantitative evaluation of the mechanics of global RVEF. In rToF with chronic volume overload, the relative contribution of the longitudinal shortening to global RVEF is affected more than either the radial or the anteroposterior components.

Causes of altered ventricular mechanics in hypertrophic cardiomyopathy: an in-silico study

Background Hypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or contrast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements. Methods We conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart models were evaluated globally and regionally. Results Hypertrophy of the LV affected the course of strain, strain rate, and wall thickening—the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduction of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA. Conclusions This study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of HCM.