Contractile Adaptation of the Left Ventricle Post-myocardial Infarction: Predictions by Rodent-Specific Computational Modeling

Mendiola, Emilio A.; Neelakantan, Sunder; Xiang, Qian; Merchant, Samer; Li, Ké; Hsu, Edward W.; Dixon, Richard A. F.; Vanderslice, Peter; Avazmohammadi, Reza

doi:10.1007/s10439-022-03102-z

Cited by 10 publications

(11 citation statements)

References 56 publications

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“…The effect of passive remodeling on RV functional performance is also evidenced by a growing body of clinical and preclinical studies 9 , including ours [10][11][12][13] , suggesting that excessive stiffening of the RVFW correlates with worse outcomes in PH. However, it remains unclear as to when and how the stiffening becomes excessive and is considered maladaptive.…”

Section: Introductionmentioning

confidence: 85%

“…These specimens were mounted on slides and then imaged using the Olympus VS120 Virtual Slide Scanning System to obtain images at 20x magnification. The images were used to calculate the distribution of myofiber angles as a function of transmural depth using methods described in our previous work 22-24 . Briefly, the Beta distribution functions of myofiber angles were calculated at each depth level and stacked together to obtain the fiber distribution as a function of transmural depth.…”

Section: Methodsmentioning

confidence: 99%

“…BPMbeats per minute, RVSP -RV systolic pressure, RVEDP -RV end-diastolic pressure, TAPSEtricuspid annular plane systolic excursion, PAT -Pulmonary acceleration time, TV Etricuspid valve (TV) E wave velocity, TVA -TV A-wave velocity, RVFWT -RVFW thickness. work [22][23][24] . Briefly, the Beta distribution functions of myofiber angles were calculated at each depth level and stacked together to obtain the fiber distribution as a function of transmural depth.…”

Section: Histological Analysis To Determine the Fiber-level Alteratio...mentioning

confidence: 99%

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Right ventricular stiffening and anisotropy alterations in pulmonary hypertension: Mechanisms and relations to function

Neelakantan,

Vang,

Mehdi

et al. 2024

Preprint

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Aims: Pulmonary hypertension (PH) results in an increase in RV afterload, leading to RV dysfunction and failure. The mechanisms underlying maladaptive RV remodeling poorly understood. In this study, we investigate the multiscale and mechanistic nature of RVFW biomechanical remodeling and its correlations with RV function adaptations. Methods and Results: Mild and severe models of PH, consisting of hypoxia (Hx) in Sprague-Dawley (SD) rats (n=6 each WT and PH) and Sugen- hypoxia (SuHx) in Fischer (CDF) rats (n=6 each WT and PH), were developed. Organ-level function and tissue-level stiffness and microstructure were quantified through in-vivo and ex-vivo measures, respectively. Multiscale analysis was used to determine the association between fiber-level remodeling, tissue-level stiffening, and organ-level dysfunction. Multiple animal models provided a wide range of RVFW stiffening and anisotropy alterations in PH. Decreased RV-pulmonary artery (PA) coupling correlated strongly with stiffening but showed a weaker association with the loss of RVFW anisotropy. Machine learning classification identified the range of adaptive and maladaptive RVFW stiffening. Multiscale modeling revealed that a key mechanism differentiating severe from mild stiffening was increases in collagen fiber tautness. Myofiber orientation analysis indicated a shift away from the predominantly circumferential fibers observed in healthy RVFW specimens, leading to a significant loss of anisotropy of the tissue. Conclusion: Multiscale biomechanical analysis indicated that although hypertrophy and fibrosis occur in both mild and severe PH, certain fiber-level remodeling events, including reduced undulations in the newly deposited collagen fibers and significant reorientations of myofibers, contributed excessive biomechanical maladaptation of the RVFW leading to severe RV-PA uncoupling. Collagen fiber remodeling, combined with the loss of tissue anisotropy, can provide an improved understanding of the transition from adaptive to maladaptive remodeling.

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Section: Introductionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Histological Analysis To Determine the Fiber-level Alteratio...mentioning

confidence: 99%

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Right ventricular stiffening and anisotropy alterations in pulmonary hypertension: Mechanisms and relations to function

Neelakantan,

Vang,

Mehdi

et al. 2024

Preprint

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“…Indeed, transmural variations from a counter-clockwise twist at the sub-endocardial layers to clockwise epicardial twisting, predicted by T 3D , are expected in light of myocardial helicity ranging from positive to negative angles from the endocardial layers to the epicardium. 4,[18][19][20] In contrast, minimal changes in T 3D peaks were observed transmurally between subendocardial layers to the epicardium along all the slices post-MVR (Fig. 1b).…”

Section: Advantages Of T 3d In Characterizing Torsionmentioning

confidence: 99%

“…3 This torsion is often compromised due to structural remodeling of the LV in cardiac diseases. 4,5 Mitral valve prolapse (MVP) and subsequent mitral regurgitation are considered to be influenced by remodeling within the left ventricle (LV). Thus, it is crucial to identify high-fidelity kinematic markers that could surrogate cardiac regional remodeling and, through these markers, investigate potential reverse remodeling in the LV following mitral valve surgery.…”

Section: Introductionmentioning

confidence: 99%

Four-dimensional assessment of left ventricular torsion in mitral valve prolapse using CMR

Mukherjee,

Mendiola,

Neelakantan

et al. 2024

Medical Imaging 2024: Image Processing

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The heterogeneity in myofiber helicity across the cardiac wall causes twisting (torsion) in the left ventricle (LV) during contraction, which is a significant contributor to its pumping function. Although important progress has been made in identifying and studying a quantitative "global" metric for torsion, four-dimensional (4D) torsion characteristics in the LV remain underexplored. We propose an imaging-based framework that uses myocardial motion obtained from cine cardiac magnetic resonance (CMR) scans of the LV to calculate torsion. We performed our LV torsion analysis in a mitral valve prolapse (MVP) human patient (n=1) pre-and post-MV repair. Establishing a high-fidelity torsion measure in the LV offers a rigorous regional marker to investigate the potential reversal of cardiac remodeling post-surgical interventions, such as MV repair. After image acquisition, a non-rigid image registration algorithm was used to calculate 4D LV displacements. Twisting was evaluated through (i) an in-plane rotation-based approximation (referred to as T 2D ) and (ii) a three-dimensional formulation involving in-plane and through-plane strains (referred to as T 3D ). Comparing T 2D to T 3D , broad regions of positive (counter-clockwise) rotation, captured through T 3D , were unrepresented by T 2D despite a qualitative agreement between the two metrics in capturing the average regional torsion. Also, the presence of comprehensive transmural positive torsion at the apical section was opposed to negative epicardial torsion at the midsection. Such variations in torsional behavior, captured by T 3D , are expected due to transmural helicity in fiber orientation. Overall, the underlying effects of through-plane shear in characterizing LV torsion were evidenced, and the image registration framework offered a comprehensive tool to capture 4D myocardial torsion that can complement conventional LV global markers.

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A Micro-anatomical Model of the Infarcted Left Ventricle Border Zone to Study the Influence of Collagen Undulation

Mendiola

Wang

Leatherman

et al. 2023

Lecture Notes in Computer Science

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Contractile Adaptation of the Left Ventricle Post-myocardial Infarction: Predictions by Rodent-Specific Computational Modeling

Cited by 10 publications

References 56 publications

Right ventricular stiffening and anisotropy alterations in pulmonary hypertension: Mechanisms and relations to function

Right ventricular stiffening and anisotropy alterations in pulmonary hypertension: Mechanisms and relations to function

Four-dimensional assessment of left ventricular torsion in mitral valve prolapse using CMR

A Micro-anatomical Model of the Infarcted Left Ventricle Border Zone to Study the Influence of Collagen Undulation

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