Quinapril treatment curtails decline of global longitudinal strain and mechanical function in hypertensive rats.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as an early imaging biomarker of cardiac mechanical dysfunction. OBJECTIVE: To assess the impact of angiotensin-converting enzyme (ACE) inhibitor treatment of hypertensive heart disease on LV GLS and mechanical function. METHODS: The spontaneously hypertensive rat (SHR) model of hypertensive heart disease ( n  = 38) was studied. A subset of SHRs received quinapril (TSHR, n  = 16) from 3 months (mo). Wistar Kyoto rats (WKY, n  = 13) were used as controls. Tagged cardiac MRI was performed using a 4.7 T Varian preclinical scanner. RESULTS: The SHRs had significantly lower LV ejection fraction (EF) than the WKYs at 3 mo (53.0 ±â€Š1.7% vs. 69.6 ±â€Š2.1%, P  < 0.05), 14 mo (57.0 ±â€Š2.5% vs. 74.4 ±â€Š2.9%, P  < 0.05) and 24 mo (50.1 ±â€Š2.4% vs. 67.0 ±â€Š2.0%, P  < 0.01). At 24 mo, ACE inhibitor treatment was associated with significantly greater LV EF in TSHRs compared to untreated SHRs (64.2 ±â€Š3.4% vs. 50.1 ±â€Š2.4%, P  < 0.01). Peak GLS magnitude was significantly lower in SHRs compared with WKYs at 14 months (7.5% ±â€Š0.4% vs. 9.9 ±â€Š0.8%, P  < 0.05). At 24 months, Peak GLS magnitude was significantly lower in SHRs compared with both WKYs (6.5 ±â€Š0.4% vs. 9.7 ±â€Š1.0%, P  < 0.01) and TSHRs (6.5 ±â€Š0.4% vs. 9.6 ±â€Š0.6%, P  < 0.05). CONCLUSIONS: ACE inhibitor treatment curtails the decline in global longitudinal strain in hypertensive rats, with the treatment group exhibiting significantly greater LV EF and GLS magnitude at 24 mo compared with untreated SHRs.

Correcting bias in cardiac geometries derived from multimodal images using spatiotemporal mapping.

Cardiovascular imaging studies provide a multitude of structural and functional data to better understand disease mechanisms. While pooling data across studies enables more powerful and broader applications, performing quantitative comparisons across datasets with varying acquisition or analysis methods is problematic due to inherent measurement biases specific to each protocol. We show how dynamic time warping and partial least squares regression can be applied to effectively map between left ventricular geometries derived from different imaging modalities and analysis protocols to account for such differences. To demonstrate this method, paired real-time 3D echocardiography (3DE) and cardiac magnetic resonance (CMR) sequences from 138 subjects were used to construct a mapping function between the two modalities to correct for biases in left ventricular clinical cardiac indices, as well as regional shape. Leave-one-out cross-validation revealed a significant reduction in mean bias, narrower limits of agreement, and higher intraclass correlation coefficients for all functional indices between CMR and 3DE geometries after spatiotemporal mapping. Meanwhile, average root mean squared errors between surface coordinates of 3DE and CMR geometries across the cardiac cycle decreased from 7 ± 1 to 4 ± 1 mm for the total study population. Our generalised method for mapping between time-varying cardiac geometries obtained using different acquisition and analysis protocols enables the pooling of data between modalities and the potential for smaller studies to leverage large population databases for quantitative comparisons.

TRF2 rescues telomere attrition and prolongs cell survival in Duchenne muscular dystrophy cardiomyocytes derived from human iPSCs.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Heart failure, driven by cardiomyocyte death, fibrosis, and the development of dilated cardiomyopathy, is the leading cause of death in DMD patients. Current treatments decrease the mechanical load on the heart but do not address the root cause of dilated cardiomyopathy: cardiomyocyte death. Previously, we showed that telomere shortening is a hallmark of DMD cardiomyocytes. Here, we test whether prevention of telomere attrition is possible in cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPSC-CMs) and if preventing telomere shortening impacts cardiomyocyte function. We observe reduced cell size, nuclear size, and sarcomere density in DMD iPSC-CMs compared with healthy isogenic controls. We find that expression of just one telomere-binding protein, telomeric repeat-binding factor 2 (TRF2), a core component of the shelterin complex, prevents telomere attrition and rescues deficiencies in cell size as well as sarcomere density. We employ a bioengineered platform to micropattern cardiomyocytes for calcium imaging and perform Southern blots of telomere restriction fragments, the gold standard for telomere length assessments. Importantly, preservation of telomere lengths in DMD cardiomyocytes improves their viability. These data provide evidence that preventing telomere attrition ameliorates deficits in cell morphology, activation of the DNA damage response, and premature cell death, suggesting that TRF2 is a key player in DMD-associated cardiac failure.

MITEA: A dataset for machine learning segmentation of the left ventricle in 3D echocardiography using subject-specific labels from cardiac magnetic resonance imaging.

Segmentation of the left ventricle (LV) in echocardiography is an important task for the quantification of volume and mass in heart disease. Continuing advances in echocardiography have extended imaging capabilities into the 3D domain, subsequently overcoming the geometric assumptions associated with conventional 2D acquisitions. Nevertheless, the analysis of 3D echocardiography (3DE) poses several challenges associated with limited spatial resolution, poor contrast-to-noise ratio, complex noise characteristics, and image anisotropy. To develop automated methods for 3DE analysis, a sufficiently large, labeled dataset is typically required. However, ground truth segmentations have historically been difficult to obtain due to the high inter-observer variability associated with manual analysis. We address this lack of expert consensus by registering labels derived from higher-resolution subject-specific cardiac magnetic resonance (CMR) images, producing 536 annotated 3DE images from 143 human subjects (10 of which were excluded). This heterogeneous population consists of healthy controls and patients with cardiac disease, across a range of demographics. To demonstrate the utility of such a dataset, a state-of-the-art, self-configuring deep learning network for semantic segmentation was employed for automated 3DE analysis. Using the proposed dataset for training, the network produced measurement biases of -9 ± 16 ml, -1 ± 10 ml, -2 ± 5 %, and 5 ± 23 g, for end-diastolic volume, end-systolic volume, ejection fraction, and mass, respectively, outperforming an expert human observer in terms of accuracy as well as scan-rescan reproducibility. As part of the Cardiac Atlas Project, we present here a large, publicly available 3DE dataset with ground truth labels that leverage the higher resolution and contrast of CMR, to provide a new benchmark for automated 3DE analysis. Such an approach not only reduces the effect of observer-specific bias present in manual 3DE annotations, but also enables the development of analysis techniques which exhibit better agreement with CMR compared to conventional methods. This represents an important step for enabling more efficient and accurate diagnostic and prognostic information to be obtained from echocardiography.

Systematic Comparison of Left Ventricular Geometry Between 3D-Echocardiography and Cardiac Magnetic Resonance Imaging.

Aims: Left ventricular (LV) volumes estimated using three-dimensional echocardiography (3D-echo) have been reported to be smaller than those measured using cardiac magnetic resonance (CMR) imaging, but the underlying causes are not well-understood. We investigated differences in regional LV anatomy derived from these modalities and related subsequent findings to image characteristics. Methods and Results: Seventy participants (18 patients and 52 healthy participants) were imaged with 3D-echo and CMR (<1 h apart). Three-dimensional left ventricular models were constructed at end-diastole (ED) and end-systole (ES) from both modalities using previously validated software, enabling the fusion of CMR with 3D-echo by rigid registration. Regional differences were evaluated as mean surface distances for each of the 17 American Heart Association segments, and by comparing contours superimposed on images from each modality. In comparison to CMR-derived models, 3D-echo models underestimated LV end-diastolic volume (EDV) by -16 ± 22, -1 ± 25, and -18 ± 24 ml across three independent analysis methods. Average surface distance errors were largest in the basal-anterolateral segment (11-15 mm) and smallest in the mid-inferoseptal segment (6 mm). Larger errors were associated with signal dropout in anterior regions and the appearance of trabeculae at the lateral wall. Conclusions: Fusion of CMR and 3D-echo provides insight into the causes of volume underestimation by 3D-echo. Systematic signal dropout and differences in appearances of trabeculae lead to discrepancies in the delineation of LV geometry at anterior and lateral regions. A better understanding of error sources across modalities may improve correlation of clinical indices between 3D-echo and CMR.

A finite element model of the cardiac ventricles with coupled circulation: Biventricular mesh generation with hexahedral elements, airbags and a functional mockup interface to the circulation.

INTRODUCTION: Finite element (FE) mechanics models of the heart are becoming more sophisticated. However, there is lack of consensus about optimal element type and coupling of FE models to the circulation. We describe biventricular (left (LV) and right (RV) ventricles) FE mechanics model creation using hexahedral elements, airbags and a functional mockup interface (FMI) to lumped-parameter models of the circulation. METHODS: Cardiac MRI (CMR) was performed in two healthy volunteers and a single patient with ischemic heart disease (IHD). CMR images were segmented and surfaced, meshing with hexahedral elements was performed with a "thin butterfly with septum" topology. LV and RV inflow and outflow airbags were coupled to lumped-parameter circulation models with an FMI interface. Pulmonary constriction (PAC) and vena cava occlusion (VCO) were simulated and end-systolic pressure-volume relations (ESPVR) were calculated. RESULTS: Mesh construction was prompt with representative contouring and mesh adjustment requiring 32 and 26 min Respectively. The numbers of elements ranged from 4104 to 5184 with a representative Jacobian of 1.0026 ± 0.4531. Agreement between CMR-based surfaces and mesh was excellent with root-mean-squared error of 0.589 ± 0.321 mm. The LV ESPVR slope was 3.37 ± 0.09 in volunteers but 2.74 in the IHD patient. The effect of PAC and VCO on LV ESPVR was consistent with ventricular interaction (p = 0.0286). CONCLUSION: Successful co-simulation using a biventricular FE mechanics model with hexahedral elements, airbags and an FMI interface to lumped-parameter model of the circulation was demonstrated. Future studies will include comparison of element type and study of cardiovascular pathologies and device therapies.

A kinematic model-based analysis framework for 3D Cine-DENSE-validation with an axially compressed gel phantom and application in sheep before and after antero-apical myocardial infarction.

PURPOSE: Myocardial strain is increasingly used to assess left ventricular (LV) function. Incorporation of LV deformation into finite element (FE) modeling environment with subsequent strain calculation will allow analysis to reach its full potential. We describe a new kinematic model-based analysis framework (KMAF) to calculate strain from 3D cine-DENSE (displacement encoding with stimulated echoes) MRI. METHODS: Cine-DENSE allows measurement of 3D myocardial displacement with high spatial accuracy. The KMAF framework uses cine cardiovascular magnetic resonance (CMR) to facilitate cine-DENSE segmentation, interpolates cine-DENSE displacement, and kinematically deforms an FE model to calculate strain. This framework was validated in an axially compressed gel phantom and applied in 10 healthy sheep and 5 sheep after myocardial infarction (MI). RESULTS: Excellent Bland-Altman agreement of peak circumferential (Ecc ) and longitudinal (Ell ) strain (mean difference = 0.021 ± 0.04 and -0.006 ± 0.03, respectively), was found between KMAF estimates and idealized FE simulation. Err had a mean difference of -0.014 but larger variation (±0.12). Cine-DENSE estimated end-systolic (ES) Ecc , Ell and Err exhibited significant spatial variation for healthy sheep. Displacement magnitude was reduced on average by 27%, 42%, and 56% after MI in the remote, adjacent and MI regions, respectively. CONCLUSIONS: The KMAF framework allows accurate calculation of 3D LV Ecc and Ell from cine-DENSE.

Finite-element based optimization of left ventricular passive stiffness in normal volunteers and patients after myocardial infarction: Utility of an inverse deformation gradient calculation of regional diastolic strain.

INTRODUCTION: Left ventricular (LV) diastolic dysfunction (DD) is common after myocardial infarction (MI). Whereas current clinical assessment of DD relies on indirect markers including LV filling, finite element (FE) -based computational modeling directly measures regional diastolic stiffness. We hypothesized that an inverse deformation gradient (DG) method calculation of diastolic strain (IDGDS) allows the FE model-based calculation of regional diastolic stiffness (material parameters; MP) in post-MI patients with DD. METHODS: Cardiac magnetic resonance (CMR) with tags (CSPAMM) and late gadolinium enhancement (LGE) was performed in 10 patients with post-MI DD and 10 healthy volunteers. The 3-dimensional (3D) LV DG from end-diastole (ED) to early diastolic filling (EDF; DGED→EDF) was calculated from CSPAMM. Diastolic strain was calculated from DGEDF→ED by inverting the DGED→EDF. FE models were created with MI and non-MI (remote; RM) regions determined by LGE. Guccione MPs C, and exponential fiber, bf, and transverse, bt , terms were optimized with IDGDS strain. RESULTS: 3D circumferential and longitudinal diastolic strain (Ecc;Ell) calculated using IDGDS in CSPAMM obtained in volunteers and MI patients were [Formula: see text]  = 0.27 ± 0.01, [Formula: see text]  = 0.24 ± 0.03 and [Formula: see text]  = 0.21 ± 0.02, and [Formula: see text]  = 0.15 ± 0.02, respectively. MPs in the volunteer group were CH = 0.013 [0.001, 0.235] kPa, [Formula: see text]  = 20.280 ± 4.994, and [Formula: see text]  = 7.460 ± 2.171 and CRM = 0.0105 [0.010, 0.011] kPa, [Formula: see text]  = 50.786 ± 13.511 (p = 0.0846), and [Formula: see text]  = 17.355 ± 2.743 (p = 0.0208) in the remote myocardium of post-MI patients. CONCLUSION: Diastolic strain, calculated from CSPAMM with IDGDS, enables calculation of FE model-based regional diastolic material parameters. Transverse stiffness of the remote myocardium, , may be a valuable new metric for determination of DD in patients after MI.

Left ventricular geometry during unloading and the end-systolic pressure volume relationship: Measurement with a modified real-time MRI-based method in normal sheep.

The left ventricular (LV) end-systolic (ES) pressure volume relationship (ESPVR) is the cornerstone of systolic LV function analysis. We describe a 2D real-time (RT) MRI-based method (RTPVR) with separate software tools for 1) semi-automatic level set-based shape prior method (LSSPM) of the LV, 2) generation of synchronized pressure area loops and 3) calculation of the ESPVR. We used the RTPVR method to measure ventricular geometry, ES pressure area relationship (ESPAR) and ESPVR during vena cava occlusion (VCO) in normal sheep. 14 adult sheep were anesthetized and underwent measurement of LV systolic function. Ten of the 14 sheep underwent RTMRI and eight of the 14 underwent measurement with conductance catheter; 4 had both RTMRI and conductance measurements. 2D cross sectional RTMRI were performed at apex, mid-ventricle and base levels during separate VCOs. The Dice similarity coefficient was used to compare LSSPM and manual image segmentation and thus determine LSSPM accuracy. LV cross-sectional area, major and minor axis length, axis ratio, major axis orientation angle and ESPAR were measured at each LV level. ESPVR was calculated with a trapezoidal rule. The Dice similarity coefficient between LSSPM and manual segmentation by two readers was 87.31±2.51% and 88.13±3.43%. All cross sections became more elliptical during VCO. The major axis orientation shifted during VCO but remained in the septo-lateral direction. LV chamber obliteration at the apical level occurred during VCO in 7 of 10 sheep that underwent RTMRI. ESPAR was non-linear at all levels. Finally, ESPVR was non-linear because of apical collapse. ESPVR measured by conductance catheter (EES,Index = 2.23±0.66 mmHg/ml/m2) and RT (EES,Index = 2.31±0.31 mmHg/ml/m2) was not significantly different. LSSPM segmentation of 2D RT MRI images is accurate and allows calculation of LV geometry, ESPAR and ESPVR during VCO. In the future, RTPVR will facilitate determination of regional systolic material parameters underlying ESPVR.

A Novel MRI-Based Finite Element Modeling Method for Calculation of Myocardial Ischemia Effect in Patients With Functional Mitral Regurgitation.

BACKGROUND: Functional Mitral Regurgitation (FMR) associated with coronary artery disease affects nearly 3 million patients in the United States. Both myocardial infarction (MI) and ischemia contribute to FMR development but uncertainty as to which patients will respond to revascularization (REVASC) of ischemia alone prevents rational decision making about FMR therapy. The aim of this study was to create patient-specific cardiac MRI (CMR) informed finite element (FE) models of the left ventricle (LV), calculate regional LV systolic contractility and then use optimized systolic material properties to simulate the effect of revascularization (virtual REVASC). METHODS: We describe a novel FE method able to predict the effect of myocardial ischemia on regional LV function. CMR was obtained in five patients with multi-vessel coronary disease and FMR before and 3 months after percutaneous REVASC and a single healthy volunteer. Patient-specific FE models were created and divided into 17 sectors where the systolic contractility parameter, T m a x of each sector was a function of regional stress perfusion (SP-CMR) and myocardial infarction (LGE-CMR) scores. Sector-specific circumferential and longitudinal end-systolic strain and LV volume from CSPAMM were used in a formal optimization to determine the sector based myocardial contractility, T m a x and ischemia effect, α. Virtual REVASC was simulated by setting α to zero. RESULTS: The FE optimization successfully converged with good agreement between calculated and experimental end-systolic strain and LV volumes. Specifically, the optimized T max for the healthy myocardium for five patients and the volunteer was 495.1, 336.8, 173.5, 227.9, 401.4, and 218.9 kPa. The optimized α was found to be 1.0, 0.44, and 0.08 for Patients 1, 2, and 3, and 0 for Patients 4 and 5. The calculated average of radial strain for Patients 1, 2, and 3 at baseline and after virtual REVASC was 0.23 and 0.25, respectively. CONCLUSION: We developed a novel computational method able to predict the effect of myocardial ischemia in patients with FMR. This method can be used to predict the effect of ischemia on the regional myocardium and promises to facilitate better understanding of FMR response to REVASC.

Efficient estimation of load-free left ventricular geometry and passive myocardial properties using principal component analysis.

Models of cardiac mechanics require a well-defined reference geometry from which deformations and hence myocardial strain and stress can be calculated. In the in vivo beating heart, the load-free (LF) geometry generally cannot be measured directly, since, in many cases, there is no stage at which the lumen pressures and contractile state are all zero. Therefore, there is a need for an efficient method to estimate the LF geometry, which is essential for an accurate mechanical simulation of left ventricular (LV) mechanics, and for estimations of passive and contractile constitutive parameters of the heart muscle. In this paper, we present a novel method for estimating both the LF geometry and the passive stiffness of the myocardium. A linear combination of principal components from a population of diastolic displacements is used to construct the LF geometry. For each estimate of the LF geometry and tissue stiffness, LV inflation is simulated, and the model predictions are compared with surface data at multiple stages during passive diastolic filling. The feasibility of this method was demonstrated using synthetically deformation data that were generated using LV models derived from clinical magnetic resonance image data, and the identifiability of the LF geometry and passive stiffness parameters were analysed using Hessian metrics. Applications of this method to clinical data would improve the accuracy of constitutive parameter estimation and allow a better simulation of LV wall strains and stresses.

Mechanical effects of MitraClip on leaflet stress and myocardial strain in functional mitral regurgitation - A finite element modeling study.

PURPOSE: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). METHODS: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. RESULTS: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). CONCLUSIONS: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement.

Microstructurally Motivated Constitutive Modeling of Heart Failure Mechanics.

Heart failure (HF) is one of the leading causes of death worldwide. HF is associated with substantial microstructural remodeling, which is linked to changes in left ventricular geometry and impaired cardiac function. The role of myocardial remodeling in altering the mechanics of failing hearts remains unclear. Structurally based constitutive modeling provides an approach to improve understanding of the relationship between biomechanical function and tissue organization in cardiac muscle during HF. In this study, we used cardiac magnetic resonance imaging and extended-volume confocal microscopy to quantify the remodeling of left ventricular geometry and myocardial microstructure of healthy and spontaneously hypertensive rat hearts at the ages of 12 and 24 months. Passive cardiac mechanical function was characterized using left ventricular pressure-volume compliance measurements. We have developed a, to our knowledge, new structurally based biomechanical constitutive equation built on parameters quantified directly from collagen distributions observed in confocal images of the myocardium. Three-dimensional left ventricular finite element models were constructed from subject-specific in vivo magnetic resonance imaging data. The structurally based constitutive equation was integrated into geometrically subject-specific finite element models of the hearts and used to investigate the underlying mechanisms of ventricular dysfunction during HF. Using a single pair of material parameters for all hearts, we were able to produce compliance curves that reproduced all of the experimental compliance measurements. The value of this study is not limited to reproducing the mechanical behavior of healthy and diseased hearts, but it also provides important insights into the structure-function relationship of diseased myocardium that will help pave the way toward more effective treatments for HF.

A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Subpopulations with Distinct Function and Drug Response Profiles.

The diversity of cardiac lineages contributes to the heterogeneity of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). Here, we report the generation of a hiPSC TBX5Clover2 and NKX2-5TagRFP double reporter to delineate cardiac lineages and isolate lineage-specific subpopulations. Molecular analyses reveal that four different subpopulations can be isolated based on the differential expression of TBX5 and NKX2-5, TBX5+NKX2-5+, TBX5+NKX2-5-, TBX5-NKX2-5+, and TBX5-NKX2-5-, mimicking the first heart field, epicardial, second heart field, and endothelial lineages, respectively. Genetic and functional characterization indicates that each subpopulation differentiates into specific cardiac cells. We further identify CORIN as a cell-surface marker for isolating the TBX5+NKX2-5+ subpopulation and demonstrate the use of lineage-specific CMs for precise drug testing. We anticipate that this tool will facilitate the investigation of cardiac lineage specification and isolation of specific cardiac subpopulations for drug screening, tissue engineering, and disease modeling.

Left Ventricular Diastolic Myocardial Stiffness and End-Diastolic Myofibre Stress in Human Heart Failure Using Personalised Biomechanical Analysis.

Understanding the aetiology of heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction requires knowledge of biomechanical factors such as diastolic myocardial stiffness and stress. Cine CMR images and intra-ventricular pressure recordings were acquired in 8 HFrEF, 11 HFpEF and 5 control subjects. Diastolic myocardial stiffness was estimated using biomechanical models and found to be greater in HFrEF (6.4 ± 1.2 kPa) than HFpEF (2.7 ± 0.6 kPa, p < 0.05) and also greater than control (1.2 ± 0.4 kPa, p < 0.005). End-diastolic mid-ventricular myofibre stress derived from the personalised biomechanics model was higher in HFrEF (2.9 ± 0.3 kPa) than control (0.9 ± 0.3 kPa, p < 0.01). Chamber stiffness, measured from the slope of the diastolic pressure-volume relationship, is determined by the intrinsic tissue properties as well as the size and shape of the heart, and was unable to distinguish between any of the three groups (p > 0.05). Personalised biomechanical analysis may provide more specific information about myocardial mechanical behaviour than global chamber indices, which are confounded by variations in ventricular geometry.

Increased cardiac work provides a link between systemic hypertension and heart failure.

The spontaneously hypertensive rat (SHR) is an established model of human hypertensive heart disease transitioning into heart failure. The study of the progression to heart failure in these animals has been limited by the lack of longitudinal data. We used MRI to quantify left ventricular mass, volume, and cardiac work in SHRs at age 3 to 21 month and compared these indices to data from Wistar-Kyoto (WKY) controls. SHR had lower ejection fraction compared with WKY at all ages, but there was no difference in cardiac output at any age. At 21 month the SHR had significantly elevated stroke work (51 ± 3 mL.mmHg SHR vs. 24 ± 2 mL.mmHg WKY; n = 8, 4; P < 0.001) and cardiac minute work (14.2 ± 1.2 L.mmHg/min SHR vs. 6.2 ± 0.8 L.mmHg/min WKY; n = 8, 4; P < 0.001) compared to control, in addition to significantly larger left ventricular mass to body mass ratio (3.61 ± 0.15 mg/g SHR vs. 2.11 ± 0.008 mg/g WKY; n = 8, 6; P < 0.001). SHRs showed impaired systolic function, but developed hypertrophy to compensate and successfully maintained cardiac output. However, this was associated with an increase in cardiac work at age 21 month, which has previously demonstrated fibrosis and cell death. The interplay between these factors may be the mechanism for progression to failure in this animal model.

Image-Based Investigation of Human in Vivo Myofibre Strain.

Cardiac myofibre deformation is an important determinant of the mechanical function of the heart. Quantification of myofibre strain relies on 3D measurements of ventricular wall motion interpreted with respect to the tissue microstructure. In this study, we estimated in vivo myofibre strain using 3D structural and functional atlases of the human heart. A finite element modelling framework was developed to incorporate myofibre orientations of the left ventricle (LV) extracted from 7 explanted normal human hearts imaged ex vivo with diffusion tensor magnetic resonance imaging (DTMRI) and kinematic measurements from 7 normal volunteers imaged in vivo with tagged MRI. Myofibre strain was extracted from the DTMRI and 3D strain from the tagged MRI. We investigated: i) the spatio-temporal variation of myofibre strain throughout the cardiac cycle; ii) the sensitivity of myofibre strain estimates to the variation in myofibre angle between individuals; and iii) the sensitivity of myofibre strain estimates to variations in wall motion between individuals. Our analysis results indicate that end systolic (ES) myofibre strain is approximately homogeneous throughout the entire LV, irrespective of the inter-individual variation in myofibre orientation. Additionally, inter-subject variability in myofibre orientations has greater effect on the variabilities in myofibre strain estimates than the ventricular wall motions. This study provided the first quantitative evidence of homogeneity of ES myofibre strain using minimally-invasive medical images of the human heart and demonstrated that image-based modelling framework can provide detailed insight to the mechanical behaviour of the myofibres, which may be used as a biomarker for cardiac diseases that affect cardiac mechanics.

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.