Changes in Myocardial Microstructure and Mechanics With Progressive Left Ventricular Pressure Overload

Torres, William M.; Barlow, Shayne C.; Moore, Amber; Freeburg, Lisa; Hoenes, Abigail; Doviak, Heather; Zile, Michael R.; Shazly, Tarek; Spinale, Francis G.

doi:10.1016/j.jacbts.2020.02.007

Cited by 17 publications

(18 citation statements)

References 87 publications

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“…In a recent study using an animal model of HFpEF induced by LV pressure overload, the septum seemed to suffer more profoundly from circumferential diastolic myocardial stiffness than other myocardial segments. 37 We observed that oxygenation and abnormalities along with circumferential systolic and diastolic dysfunction were most prevalent in the septum (Figure 4), possibly representing earlier stages of the remodeling process.…”

Section: Myocardial Oxygenation In Relation To Ventricular Geometry A...mentioning

confidence: 81%

“…In a porcine HFpEF model, collagen content increased but also fiber angle orientation changed during the disease process between longitudinal and circumferential orientations, which was associated with a rise in chamber stiffness. 37 Of note, both, circumferential and longitudinal orientation are of prognostic value in heart failure. 10 Moreover, such collagen deposition may lead to increasing microvascular dysfunction, which may further entertain the pathophysiologic spiral of HFpEF.…”

Section: Discussionmentioning

confidence: 99%

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Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction

Fischer

Guensch

Jung

et al. 2022

Circ: Heart Failure

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Background: The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR). Methods: In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)–CMR of the myocardial oxygenation response to a vasoactive breathing maneuver. Results: Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P <0.001). This was correlated with septal wall thickness (r=−0.54, P =0.003), edema (myocardial T2; β=−0.26% oxygenation-sensitive/ms [95% CI, −0.49 to −0.03], P =0.029), and reduced diastolic strain rate (β=1.50% oxygenation-sensitive/s -1 [95% CI, 0.06–2.90], P =0.042). Conclusions: In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive–CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.

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Section: Myocardial Oxygenation In Relation To Ventricular Geometry A...mentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction

Fischer

Guensch

Jung

et al. 2022

Circ: Heart Failure

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“…Global tissue stiffness has been examined using finite element (FE) modeling by comparing the mechanical properties of an HFpEF cardiac ventricle to a healthy heart of a different subject (Sack et al, 2018). Torres et al (2020) have recently investigated LV stiffening in response to progressive pressure overload. A predictor variable for LV stiffness was derived from computed stress magnitudes in the circumferential and longitudinal directions.…”

Section: Introductionmentioning

confidence: 99%

Material property alterations for phenotypes of heart failure with preserved ejection fraction: A numerical study of subject-specific porcine models

Weissmann

Charles

Richards

et al. 2022

Front. Bioeng. Biotechnol.

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A substantial proportion of heart failure patients have a preserved left ventricular (LV) ejection fraction (HFpEF). This condition carries a high burden of morbidity and mortality and has limited therapeutic options. left ventricular pressure overload leads to an increase in myocardial collagen content, causing left ventricular stiffening that contributes to the development of heart failure patients have a preserved left ventricular ejection fraction. Although several heart failure patients have a preserved left ventricular ejection fraction models have been developed in recent years to aid the investigation of mechanical alterations, none has investigated different phenotypes of the disease and evaluated the alterations in material properties. In this study, two similar healthy swine were subjected to progressive and prolonged pressure overload to induce diastolic heart failure characteristics, providing a preclinical model of heart failure patients have a preserved left ventricular ejection fraction. Cardiac magnetic resonance imaging (cMRI) scans and intracardiac pressures were recorded before and after induction. In both healthy and disease states, a corresponding finite element (FE) cardiac model was developed via mesh morphing of the Living Heart Porcine model. The material properties were derived by calibrating to its passive and active behavior. The change in the passive behavior was predominantly isotropic when comparing the geometries before and after induction. Myocardial thickening allowed for a steady transition in the passive properties while maintaining tissue incompressibility. This study highlights the importance of hypertrophy as an initial compensatory response and might also pave the way for assessing disease severity.

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“…Volume overload models, associated with eccentric hypertrophy, have been generated by either cutting the chordae tendineae to induce mitral regurgitation ( Sahli Costabal et al, 2019 ; Li et al, 2020 ) or by implanting a pacemaker to repeatedly introduce premature ventricular contraction (PVC) ( Torrado et al, 2021 ). Pressure overload models, which are usually linked to concentric hypertrophy, have been created by aortic banding ( Olver et al, 2019 ; Torres et al, 2020 ), diet modification ( Holzem et al, 2015 ; Olver et al, 2019 ), or genetic modification ( LeGrice et al, 2012 ; Wilson et al, 2017 ). On the other hand, exercised-induced hypertrophic models have also been created in both small and large animals by swim training, wheel running, or treadmill running ( Wang et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

“…Most of these in vivo studies evaluate the effects of growth on the cardiac function (e.g., ejection fraction, cardiac output, hemodynamics) as well as morphological changes of the left ventricular (LV) (e.g., relative wall thickness). A few studies have used histology, acquired either ex vivo at the end of the study or through invasive biopsy, to quantify the level of cardiomyocyte growth ( Olver et al, 2019 ; Sahli Costabal et al, 2019 ; Li et al, 2020 ) or the changes in collagen fiber orientation ( Torres et al, 2020 ). Due to the limitations associated with ex vivo analysis and the added complexity and risks of in vivo biopsies, there is a profound paucity of data on the microstructural changes of the myocardium during LV growth and remodeling.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Exercise-Induced Myocardium Growth Using Finite Element Modeling and Bayesian Optimization

et al. 2021

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Cardiomyocyte growth can occur in both physiological (exercised-induced) and pathological (e.g., volume overload and pressure overload) conditions leading to left ventricular (LV) hypertrophy. Studies using animal models and histology have demonstrated the growth and remodeling process at the organ level and tissue–cellular level, respectively. However, the driving factors of growth and the mechanistic link between organ, tissue, and cellular growth remains poorly understood. Computational models have the potential to bridge this gap by using constitutive models that describe the growth and remodeling process of the myocardium coupled with finite element (FE) analysis to model the biomechanics of the heart at the organ level. Using subject-specific imaging data of the LV geometry at two different time points, an FE model can be created with the inverse method to characterize the growth parameters of each subject. In this study, we developed a framework that takes in vivo cardiac magnetic resonance (CMR) imaging data of exercised porcine model and uses FE and Bayesian optimization to characterize myocardium growth in the transverse and longitudinal directions. The efficacy of this framework was demonstrated by successfully predicting growth parameters of 18 synthetic LV targeted masks which were generated from three LV porcine geometries. The framework was further used to characterize growth parameters in 4 swine subjects that had been exercised. The study suggested that exercise-induced growth in swine is prone to longitudinal cardiomyocyte growth (58.0 ± 19.6% after 6 weeks and 79.3 ± 15.6% after 12 weeks) compared to transverse growth (4.0 ± 8.0% after 6 weeks and 7.8 ± 9.4% after 12 weeks). This framework can be used to characterize myocardial growth in different phenotypes of LV hypertrophy and can be incorporated with other growth constitutive models to study different hypothetical growth mechanisms.

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Changes in Myocardial Microstructure and Mechanics With Progressive Left Ventricular Pressure Overload

Cited by 17 publications

References 87 publications

Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction

Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction

Material property alterations for phenotypes of heart failure with preserved ejection fraction: A numerical study of subject-specific porcine models

Characterization of Exercise-Induced Myocardium Growth Using Finite Element Modeling and Bayesian Optimization

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