Multi-scale modeling of excitation-contraction coupling in the normal and failing heart

Kerckhoffs, Roy; Campbell, Stuart G.; Flaim, Sarah N.; Howard, Elliot J.; Sierra-Aguado, Jazmin; Mulligan, Lawrence J.; McCulloch, Andrew D.

doi:10.1109/iembs.2009.5332708

Cited by 9 publications

(11 citation statements)

References 7 publications

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“…Increasingly complex "multiscale models" are being used to further understanding of complex interacting processes, such as excitation contraction coupling and mechanical function, 13,14 and the role of myocardial stretch in arrhythmia in the context of commotio cordis. 28 This numeric model predicted wall stress based purely on LA anatomy by assuming the LA to be a linear elastic shell.…”

Section: Cardiac Modeling and Wall Stressmentioning

confidence: 99%

“…11,12 Greater understanding of how atrial remodeling supports AF may allow refinement of substrate modification and improve outcomes. Computer modeling has been used to better understand complex processes such as excitation contraction coupling and mechanical function 13,14 and may help understand how stretch is distributed in the walls of the left atrium (LA) and how this affects atrial remodeling.…”

Section: Clinical Perspective On P 360mentioning

confidence: 99%

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Left Atrial Wall Stress Distribution and Its Relationship to Electrophysiologic Remodeling in Persistent Atrial Fibrillation

Hunter

Liu²,

Lu³

et al. 2012

Circ: Arrhythmia and Electrophysiology

103

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Background-Atrial stretch causes remodeling that predisposes to atrial fibrillation. We tested the hypothesis that peaks in left atrial (LA) wall stress are associated with focal remodeling. Methods and Results-Nineteen patients underwent LA mapping before catheter ablation for persistent atrial fibrillation.Finite Element Analysis was used to predict wall stress distribution based on LA geometry from CT. The relationship was assessed between wall stress and (1) electrogram voltage and (2) complex fractionated atrial electrograms (CFAE), using CFAE mean (the mean interval between deflections). Wall stress varied widely within atria and between subjects (median, 36 kPa; interquartile range, 26 -51 kP). Peaks in wall stress (Ն90th percentile) were common at the pulmonary vein (PV) ostia (93%), the appendage ridge (100%), the high posterior wall (84%), and the anterior wall and septal regions (42-84%). Electrogram voltage showed an inverse relationship across quartiles for wall stress (19% difference across quartiles, Pϭ0.016). There was no effect on CFAE mean across quartiles of wall stress. Receiver operating characteristic analysis showed high wall stress was associated with low voltage (ie, Ͻ0.5 mV) and electrical scar (ie, Ͻ0.05 mV; both PϽ0.0001) and with absence of CFAE (ie, CFAE mean Ͻ120 ms; PϽ0.0001). However, peaks in wall stress and CFAE were found at 88% of PV ostia. Conclusions-Peaks in wall stress were associated with areas of low voltage, suggestive of focal remodeling. Although peaks in wall stress were not associated with LA CFAE, the PV ostia may respond differently. (Circ Arrhythm Electrophysiol. 2012;5:351-360.)

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Section: Cardiac Modeling and Wall Stressmentioning

confidence: 99%

Section: Clinical Perspective On P 360mentioning

confidence: 99%

Left Atrial Wall Stress Distribution and Its Relationship to Electrophysiologic Remodeling in Persistent Atrial Fibrillation

Hunter

Liu²,

Lu³

et al. 2012

Circ: Arrhythmia and Electrophysiology

103

View full text Add to dashboard Cite

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“…The material model used in this study is similar to that proposed by Guccione et al [49], [50] and utilized by Kerckoff [23], [41], [51], [52] and others [45], [53]–[55] where the fiber is an exponential function of the fiber strain. The primary difference is that the cross fiber stiffness terms are expressed in the Guccione model as an exponential while in the Weiss model they are represented as a linear function of the trace of the deviatoric deformation gradient [26], [27].…”

Section: Discussionmentioning

confidence: 99%

Incorporation of a Left Ventricle Finite Element Model Defining Infarction Into the XCAT Imaging Phantom

Veress

Segars

Tsui

et al. 2011

IEEE Trans. Med. Imaging

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The 4D extended cardiac-torso (XCAT) phantom was developed to provide a realistic and flexible model of the human anatomy and cardiac and respiratory motions for use in medical imaging research. A prior limitation to the phantom was that it did not accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). We overcame this limitation in a previous study by combining the phantom with a finite-element (FE) mechanical model of the left ventricle (LV) capable of more realistically simulating regional defects caused by ischemia. In the present work, we extend this model giving it the ability to accurately simulate motion abnormalities caused by myocardial infarction (MI), a far more complex situation in terms of altered mechanics compared with the modeling of acute ischemia. The FE model geometry is based on high resolution CT images of a normal male subject. An anterior region was defined as infarcted and the material properties and fiber distribution were altered, according to the bio-physiological properties of two types of infarction, i.e., fibrous and remodeled infarction (30% thinner wall than fibrous case). Compared with the original, surface-based 4D beating heart model of the XCAT, where regional abnormalities are modeled by simply scaling down the motion in those regions, the FE model was found to provide a more accurate representation of the abnormal motion of the LV due to the effects of fibrous infarction as well as depicting the motion of remodeled infarction. In particular, the FE models allow for the accurate depiction of dyskinetic motion. The average circumferential strain results were found to be consistent with measured dyskinetic experimental results. Combined with the 4D XCAT phantom, the FE model can be used to produce realistic multimodality sets of imaging data from a variety of patients in which the normal or abnormal cardiac function is accurately represented.

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“…It should also be noted that a common cause of death in post-MI patients is the development of arrhythmias due to the conduction abnormalities introduced by the scar tissue. This facet of the disease process is beyond the scope of the current model and would require a conduction/mechanical model in order to evaluate such as those developed by Kerckhoffs et al [12,13,42,43].…”

Section: Discussionmentioning

confidence: 99%

The Direct Incorporation of Perfusion Defect Information to Define Ischemia and Infarction in a Finite Element Model of the Left Ventricle

Veress

Fung

Lee

et al. 2015

Journal of Biomechanical Engineering

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This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59 ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54 ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R 2 ¼ 0.99).

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Multi-scale modeling of excitation-contraction coupling in the normal and failing heart

Abstract: Here we describe new computational models of cardiac electromechanics starting from the cellular scale and building to the tissue, organ and system scales. We summarize application to human genetic diseases (LQT1 and LQT3) and to modeling of congestive heart failure.

Cited by 9 publications

References 7 publications

Left Atrial Wall Stress Distribution and Its Relationship to Electrophysiologic Remodeling in Persistent Atrial Fibrillation

Left Atrial Wall Stress Distribution and Its Relationship to Electrophysiologic Remodeling in Persistent Atrial Fibrillation

Incorporation of a Left Ventricle Finite Element Model Defining Infarction Into the XCAT Imaging Phantom

The Direct Incorporation of Perfusion Defect Information to Define Ischemia and Infarction in a Finite Element Model of the Left Ventricle

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