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.

Left ventricular geometry predicts optimal response to percutaneous mitral repair via MitraClip: Integrated assessment by two- and three-dimensional echocardiography.

OBJECTIVES: To assess impact of left ventricular (LV) chamber remodeling on MitraClip (MClp) response. BACKGROUND: MitraClip is the sole percutaneous therapy approved for mitral regurgitation (MR) but response varies. LV dilation affects mitral coaptation; determinants of MClp response are uncertain. METHODS: LV and mitral geometry were quantified on pre- and post-procedure two-dimensional (2D) transthoracic echocardiography (TTE) and intra-procedural three-dimensional (3D) transesophageal echocardiography (TEE). Optimal MClp response was defined as ≤mild MR at early (1-6 month) follow-up. RESULTS: Sixty-seven degenerative MR patients underwent MClp: Whereas MR decreased ≥1 grade in 94%, 39% of patients had optimal response (≤mild MR). Responders had smaller pre-procedural LV end-diastolic volume (94 ± 24 vs. 109 ± 25 mL/m2 , p = 0.02), paralleling smaller annular diameter (3.1 ± 0.4 vs. 3.5 ± 0.5 cm, p = 0.002), and inter-papillary distance (2.2 ± 0.7 vs. 2.5 ± 0.6 cm, p = 0.04). 3D TEE-derived annular area correlated with 2D TTE (r = 0.59, p < 0.001) and was smaller among optimal responders (12.8 ± 2.1 cm2 vs. 16.8 ± 4.4 cm2 , p = 0.001). Both 2D and 3D mitral annular size yielded good diagnostic performance for optimal MClp response (AUC 0.73-0.84, p < 0.01). In multivariate analysis, sub-optimal MClp response was associated with LV end-diastolic diameter (OR 3.10 per-cm [1.26-7.62], p = 0.01) independent of LA size (1.10 per-cm2 [1.02-1.19], p = 0.01); substitution of mitral annular diameter for LV size yielded an independent association with MClp response (4.06 per-cm2 [1.03-15.96], p = 0.045). CONCLUSIONS: Among degenerative MR patients undergoing MClp, LV and mitral annular dilation augment risk for residual or recurrent MR, supporting the concept that MClp therapeutic response is linked to sub-valvular remodeling.

Transcatheter MitraClip repair alters mitral annular geometry - device induced annular remodeling on three-dimensional echocardiography predicts therapeutic response.

BACKGROUND: Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain. METHODS: The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE. RESULTS: Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p < 0.01). In multivariate analysis, sub-optimal MitraClip response was independently associated with larger pre-procedural mitral annular area on 3D TEE (OR 1.93 per cm2/m2 [CI 1.19-3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02-1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95-30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p < 0.001) as well as mitral tenting height, area, and volume (all p < 0.05): Magnitude of MitraClip induced reductions in mitral annular circumference on intra-procedural 3D TEE was greater among patients with, compared to those without, sub-optimal MitraClip response (>mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028). CONCLUSIONS: MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.

Echocardiography-quantified myocardial strain-a marker of global and regional infarct size that stratifies likelihood of left ventricular thrombus.

BACKGROUND: Myocardial strain provides a novel means of quantifying subtle alterations in contractile function; incremental utility post-MI is unknown. OBJECTIVES: To test longitudinal-quantified by postprocessing routine echo-for assessment of MI size measured by cardiac magnetic resonance (CMR) and conventional methods, and assess regional and global strain (GLS) as markers of LV thrombus. METHODS: The population comprised of patients with anterior ST-segment MI who underwent echo and CMR prospectively. Preexisting echoes were retrieved, re-analyzed for strain, and compared to conventional MI markers as well as CMR-evidenced MI, function, and thrombus. RESULTS: Seventy-four patients underwent echo and CMR 4 ± 1 weeks post-MI; 72% had abnormal GLS. CMR-quantified MI size was 2.5-fold larger and EF lower among patients with abnormal GLS, paralleling 2.6-3.1 fold differences in Q-wave size and CPK (all P ≤ .002). GLS correlated with CMR-quantified MI (r = .66), CPK (r = .52) and Q-wave area (r = .44; all P ≤ .001): Regional strain was lower in the base, mid, and apical LV among patients with CMR-defined transmural MI in each territory (P < .05) and correlated with cine-CMR regional EF (r = .53-.71; P < .001) and echo wall motion (r = .45-.71; P < .001). GLS and apical strain were ~2-fold lower among patients with LV thrombus (P ≤ .002): Apical strain yielded higher diagnostic performance for thrombus (AUC: 0.83 [0.72-0.93], P = .001) than wall motion (0.73 [0.58-0.88], P = .02), as did global strain (0.78 [0.65-0.90], P = .005) compared to LVEF (0.58 [0.45-0.72], P = .41). CONCLUSIONS: Echo-quantified longitudinal strain provides a marker of MI size and improves stratification for post-MI LV thrombus beyond conventional indices.

Neochord placement versus triangular resection in mitral valve repair: A finite element model.

BACKGROUND: Recurrent mitral regurgitation after mitral valve repair is common, occurring in nearly 50% of patients within 10 years of surgery. Durability of repair is partly related to stress distribution over the mitral leaflets. We hypothesized that repair with neochords (NCs) results in lower stress than leaflet resection (LR). MATERIALS AND METHODS: Magnetic resonance imaging and 3D echocardiography were performed before surgical repair of P2 prolapse in a single patient. A finite element model of the left ventricle and mitral valve was created previously, and the modeling program LS-DYNA was used to calculate leaflet stress for the following repairs: Triangular LR; LR with ring annuloplasty (LR + RA); One NC; Two NCs; and 2NC + RA. RESULTS: (1) NC placement resulted in stable posterior leaflet stress: Baseline versus 2 NC at end diastole (ED), 12.1 versus 12.0 kPa, at end systole (ES) 20.3 versus 21.7 kPa. (2) In contrast, LR increased posterior leaflet stress: Baseline versus LR at ED 12.1 versus 40.8 kPa, at ES 20.3 versus 46.1 kPa. (3) All repair types reduced anterior leaflet stress: Baseline versus 2 NC versus LR 34.2 versus 25.8 versus 20.6 kPa at ED and 80.8 versus 76.8 versus 67.8 kPa at ES. (4) The addition of RA reduced leaflet stress relative to repair without RA. CONCLUSIONS: Neochord repair restored normal leaflet coaptation without creating excessive leaflet stress, whereas leaflet resection more than doubled stress across the posterior leaflet. The excess stress created by leaflet resection was partially, but not completely, mitigated by ring annuloplasty.

Suture Forces for Closure of Transapical Transcatheter Aortic Valve Replacement: A Mathematical Model.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis in intermediate, high-risk, and inoperable patients. TAVR has multiple access routes, including transfemoral (TF), transapical (TA), direct aortic (DA), axillary, transcarotid, and transcaval. The most commonly applied algorithm is a TF-first approach, where only when patients are unsuitable for TF are alternatives such as TA considered. An infrequent - but dreaded - risk is left ventricular (LV) apical bleeding from tearing or rupture with the TA approach. With burgeoning transcatheter mitral technology that requires a TA approach, the study aim was to develop a mathematical model to determine suture forces for TA closure. METHODS: Preoperative cine-cardiac magnetic resonance imaging (MRI) was used to acquire three-dimensional (3D) LV geometry at end-systole and end-diastole. Endocardial and epicardial boundaries were manually contoured using MeVisLab, a surface reconstruction software. 3D surfaces of endocardium and epicardium were reconstructed, and surfaces at end-systole were used to create a 3D LV finite element (FE) mesh. TA access was mimicked by developing a 10-mm defect within the LV FE model. The LV apex was closed using a virtual suture technique in FE analysis with the application of two virtual sutures. After virtual closure, a FE analysis was performed of LV model diastolic filling and systolic contraction. RESULTS: Proof of concept was achieved to develop an LV transapical access site and perform FE analysis to achieve closure. The FE method of virtual suture technique successfully approximated the LV apical defect. The peak axial forces on virtual sutures at end-diastole and end-systole were 0.445N and 0.736N, respectively. CONCLUSIONS: A LV TA access model was mathematically developed that could be used to evaluate the suture tension of the TA closure process. Further development of this approach may be useful to risk-stratify patients in the future for LV apical tearing. Video 1: Cine cardiac magnetic resonance imaging of the left ventricle. Video 2: Slow motion animation of left ventricular baseline simulation. Video 3: Animation of the virtual suturing process.

Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone.

After myocardial infarction, a poorly contracting nonischemic border zone forms adjacent to the infarct. The cause of border zone dysfunction is unclear. The goal of this study was to determine the myofilament mechanisms involved in postinfarction border zone dysfunction. Two weeks after anteroapical infarction of sheep hearts, we studied in vitro isometric and isotonic contractions of demembranated myocardium from the infarct border zone and a zone remote from the infarct. Maximal force development (Fmax) of the border zone myocardium was reduced by 31 ± 2% versus the remote zone myocardium (n = 6/group, P < 0.0001). Decreased border zone Fmax was not due to a reduced content of contractile material, as assessed histologically, and from myosin content. Furthermore, decreased border zone Fmax did not involve altered cross-bridge kinetics, as assessed by muscle shortening velocity and force development kinetics. Decreased border zone Fmax was associated with decreased cross-bridge formation, as assessed from muscle stiffness in the absence of ATP where cross-bridge formation should be maximized (rigor stiffness was reduced 34 ± 6%, n = 5, P = 0.011 vs. the remote zone). Furthermore, the border zone myocardium had significantly reduced phosphorylation of myosin essential light chain (ELC; 41 ± 10%, n = 4, P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in the border zone myocardium, suggesting that doxycycline had a protective effect. In conclusion, myofilament dysfunction contributes to postinfarction border zone dysfunction, myofilament dysfunction involves impaired cross-bridge formation and decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be beneficial for limiting postinfarct border zone dysfunction.

Effect of mitral annuloplasty device shape and size on leaflet and myofiber stress following repair of posterior leaflet prolapse: a patient-specific finite element simulation.

BACKGROUND AND AIM OF THE STUDY: Mitral annuloplasty (MA) devices are available in different shapes and sizes, but the preferred shape and size are unclear. METHODS: A previously described and validated finite element (FE) model of the left ventricle (LV) with mitral valve (MV) based on magnetic resonance imaging and three-dimensional echocardiography images from a patient with posterior leaflet (PL; P2) prolapse was used in this study. FE models of MA devices with different shapes (flat partial, shallow saddle, pronounced saddle) and sizes (36-30) were created. Virtual leaflet resection + MA with each shape and size were simulated. Leaflet geometry, stresses in the leaflets and base of the LV, and forces in the chordae and MA sutures were calculated. RESULTS: All MA shapes increased the mitral coaptation length, reduced the elevated PL stress at end-diastole (ED) and end-systole (ES) that occurred after leaflet resection, and reduced anterior leaflet (AL) stress at ES. MA devices of all shapes and sizes modestly reduced myofiber stress at the LV base in ED and ES. In general, saddle-shaped devices had the greatest effect. CONCLUSION: All MA shapes increased coaptation length and reduced mitral leaflet stress and myofiber stress in the base of the LV. an additional reduction in MA size further increased coaptation length and reduced leaflet and myofiber stress. In general, saddle-shaped devices had the greatest effect.

Applications of computational modeling in cardiac surgery.

Although computational modeling is common in many areas of science and engineering, only recently have advances in experimental techniques and medical imaging allowed this tool to be applied in cardiac surgery. Despite its infancy in cardiac surgery, computational modeling has been useful in calculating the effects of clinical devices and surgical procedures. In this review, we present several examples that demonstrate the capabilities of computational cardiac modeling in cardiac surgery. Specifically, we demonstrate its ability to simulate surgery, predict myofiber stress and pump function, and quantify changes to regional myocardial material properties. In addition, issues that would need to be resolved in order for computational modeling to play a greater role in cardiac surgery are discussed.

Left ventricular pressure gating in ovine cardiac studies: a software-based method.

Cardiac imaging using magnetic resonance requires a gating signal in order to compensate for motion. Human patients are routinely scanned using an electrocardiogram (ECG) as a gating signal during imaging. However, we found that in sheep the ECG is not a reliable method for gating. We developed a software based method that allowed us to use the left ventricular pressure (LVP) as a reliable gating signal. By taking the time derivative of the LVP (dP/dt), we were able to start imaging at both end-diastole for systolic phase images, and end-systole for diastolic phase images. We also used MR tissue tagging to calculate 3D strain information during diastole. Using the LVP in combination with our digital circuit provided a reliable and time efficient method for ovine cardiac imaging. Unlike the ECG signal the left ventricular pressure was a clean signal and allowed for accurate, nondelay based triggering during systole and diastole.

Electromechanical feedback with reduced cellular connectivity alters electrical activity in an infarct injured left ventricle: a finite element model study.

Myocardial infarction (MI) significantly alters the structure and function of the heart. As abnormal strain may drive heart failure and the generation of arrhythmias, we used computational methods to simulate a left ventricle with an MI over the course of a heartbeat to investigate strains and their potential implications to electrophysiology. We created a fully coupled finite element model of myocardial electromechanics consisting of a cellular physiological model, a bidomain electrical diffusion solver, and a nonlinear mechanics solver. A geometric mesh built from magnetic resonance imaging (MRI) measurements of an ovine left ventricle suffering from a surgically induced anteroapical infarct was used in the model, cycled through the cardiac loop of inflation, isovolumic contraction, ejection, and isovolumic relaxation. Stretch-activated currents were added as a mechanism of mechanoelectric feedback. Elevated fiber and cross fiber strains were observed in the area immediately adjacent to the aneurysm throughout the cardiac cycle, with a more dramatic increase in cross fiber strain than fiber strain. Stretch-activated channels decreased action potential (AP) dispersion in the remote myocardium while increasing it in the border zone. Decreases in electrical connectivity dramatically increased the changes in AP dispersion. The role of cross fiber strain in MI-injured hearts should be investigated more closely, since results indicate that these are more highly elevated than fiber strain in the border of the infarct. Decreases in connectivity may play an important role in the development of altered electrophysiology in the high-stretch regions of the heart.

Growth and remodeling of the left ventricle: A case study of myocardial infarction and surgical ventricular restoration.

Cardiac growth and remodeling in the form of chamber dilation and wall thinning are typical hallmarks of infarct-induced heart failure. Over time, the infarct region stiffens, the remaining muscle takes over function, and the chamber weakens and dilates. Current therapies seek to attenuate these effects by removing the infarct region or by providing structural support to the ventricular wall. However, the underlying mechanisms of these therapies are unclear, and the results remain suboptimal. Here we show that myocardial infarction induces pronounced regional and transmural variations in cardiac form. We introduce a mechanistic growth model capable of predicting structural alterations in response to mechanical overload. Under a uniform loading, this model predicts non-uniform growth. Using this model, we simulate growth in a patient-specific left ventricle. We compare two cases, growth in an infarcted heart, pre-operative, and growth in the same heart, after the infarct was surgically excluded, post-operative. Our results suggest that removing the infarct and creating a left ventricle with homogeneous mechanical properties does not necessarily reduce the driving forces for growth and remodeling. These preliminary findings agree conceptually with clinical observations.

All Roads Lead to Rome: Diverse Etiologies of Tricuspid Regurgitation Create a Predictable Constellation of Right Ventricular Shape Changes.

Introduction: Myriad disorders cause right ventricular (RV) dilation and lead to tricuspid regurgitation (TR). Because the thin-walled, flexible RV is mechanically coupled to the pulmonary circulation and the left ventricular septum, it distorts with any disturbance in the cardiopulmonary system. TR, therefore, can result from pulmonary hypertension, left heart failure, or intrinsic RV dysfunction; but once it occurs, TR initiates a cycle of worsening RV volume overload, potentially progressing to right heart failure. Characteristic three-dimensional RV shape-changes from this process, and changes particular to individual TR causes, have not been defined in detail. Methods: Cardiac MRI was obtained in 6 healthy volunteers, 41 patients with ≥ moderate TR, and 31 control patients with cardiac disease without TR. The mean shape of each group was constructed using a three-dimensional statistical shape model via the particle-based shape modeling approach. Changes in shape were examined across pulmonary hypertension and congestive heart failure subgroups using principal component analysis (PCA). A logistic regression approach based on these PCA modes identified patients with TR using RV shape alone. Results: Mean RV shape in patients with TR exhibited free wall bulging, narrowing of the base, and blunting of the RV apex compared to controls (p < 0.05). Using four primary PCA modes, a logistic regression algorithm identified patients with TR correctly with 82% recall and 87% precision. In patients with pulmonary hypertension without TR, RV shape was narrower and more streamlined than in healthy volunteers. However, in RVs with TR and pulmonary hypertension, overall RV shape continued to demonstrate the free wall bulging characteristic of TR. In the subgroup of patients with congestive heart failure without TR, this intermediate state of RV muscular hypertrophy was not present. Conclusion: The multiple causes of TR examined in this study changed RV shape in similar ways. Logistic regression classification based on these shape changes reliably identified patients with TR regardless of etiology. Furthermore, pulmonary hypertension without TR had unique shape features, described here as the "well compensated" RV. These results suggest shape modeling as a promising tool for defining severity of RV disease and risk of decompensation, particularly in patients with pulmonary hypertension.

Imaging in Pulmonary Vascular Disease-Understanding Right Ventricle-Pulmonary Artery Coupling.

The right ventricle (RV) and pulmonary arterial (PA) tree are inextricably linked, continually transferring energy back and forth in a process known as RV-PA coupling. Healthy organisms maintain this relationship in optimal balance by modulating RV contractility, pulmonary vascular resistance, and compliance to sustain RV-PA coupling through life's many physiologic challenges. Early in states of adaptation to cardiovascular disease-for example, in diastolic heart failure-RV-PA coupling is maintained via a multitude of cellular and mechanical transformations. However, with disease progression, these compensatory mechanisms fail and become maladaptive, leading to the often-fatal state of "uncoupling." Noninvasive imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography, allow us deeper insight into the state of coupling for an individual patient, providing for prognostication and potential intervention before uncoupling occurs. In this review, we discuss the physiologic foundations of RV-PA coupling, elaborate on the imaging techniques to qualify and quantify it, and correlate these fundamental principles with clinical scenarios in health and disease. © 2022 American Physiological Society. Compr Physiol 12: 1-26, 2022.

Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure.

A novel method for quantifying in-vivo regional left ventricular myocardial contractility in the border zone of a myocardial infarction.

Homogeneous contractility is usually assigned to the remote region, border zone (BZ), and the infarct in existing infarcted left ventricle (LV) mathematical models. Within the LV, the contractile function is therefore discontinuous. Here, we hypothesize that the BZ may in fact define a smooth linear transition in contractility between the remote region and the infarct. To test this hypothesis, we developed a mathematical model of a sheep LV having an anteroapical infarct with linearly-varying BZ contractility. Using an existing optimization method (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," J. Biomech. Eng., 131(11), pp. 111001), we use that model to extract active material parameter T(max) and BZ width d(n) that "best" predict in-vivo systolic strain fields measured from tagged magnetic resonance images (MRI). We confirm our hypothesis by showing that our model, compared to one that has homogeneous contractility assigned in each region, reduces the mean square errors between the predicted and the measured strain fields. Because the peak fiber stress differs significantly (~15%) between these two models, our result suggests that future mathematical LV models, particularly those used to analyze myocardial infarction treatment, should account for a smooth linear transition in contractility within the BZ.

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.

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.

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.

Right Ventricular Shape Distortion in Tricuspid Regurgitation.

Tricuspid regurgitation (TR) is a failure in right-sided AV valve function which, if left untreated, leads to marked cardiac shape changes and heart failure. However, the specific right ventricular shape changes resulting from TR are unknown. The goal of this study is to characterize the RV shape changes of patients with severe TR. RVs were segmented from CINE MRI images. Using particle-based shape modeling (PSM), a dense set of homologous landmarks were placed with geometric consistency on the endocardial surface of each RV, via an entropy-based optimization of the information content of the shape model. Principal component analysis (PCA) identified the significant modes of shape variation across the population. These modes were used to create a patient-prediction model. 32 patients and 6 healthy controls were studied. The mean RV shape of TR patients demonstrated increased sphericity relative to controls, with the three most dominant modes of variation showing significant widening of the short axis of the heart, narrowing of the base at the RV outflow tract (RVOT), and blunting of the RV apex. By PCA, shape changes based on the first three modes of variation correctly identified patient vs. control hearts 86.5% of the time. The shape variation may further illuminate the mechanics of TR-induced RV failure and recovery, providing potential targets for therapies including novel devices and surgical interventions.