Abstract
Growth and Remodelling (G&R) processes are typical responses to changes in the heart’s loading conditions. The most frequent types of growth in the left ventricle (LV) are thought to involve growth parallel to (eccentric) or perpendicular to (concentric) the fiber direction. However, hypertrophic cardiomyopathy (HCM), a genetic mutation of the sarcomeric proteins, exhibits heterogeneous patterns of growth and fiber disarray despite the absence of clear changes in loading conditions. Previous studies have predicted cardiac growth due to increased overload in the heart [7, 12, 23] as well as modelled inverse G&R post-treatment [1, 14]. Since observed growth patterns in HCM are more complex than standard models of hypertrophy in the heart, fewer studies focus on the geometric changes in this pathological case. By adapting established kinematic growth tensors for the standard types of hypertrophy in an isotropic and orthotropic material model, the paper aims to identify different factors which contribute to the heterogeneous growth patterns observed in HCM. Consequently, it was possible to distinguish that fiber disarray alone does not appear to induce the typical phenotypes of HCM. Instead, it appears that an underlying trigger for growth in HCM might be a consequence of factors stimulating isotropic growth (e.g., inflammation). Additionally, morphological changes in the septal region resulted in higher amounts of incompatibility, evidenced by increased residual stresses in the grown region.
Keywords
- Growth and Remodelling
- Hypertrophic cardiomyopathy
- Computational modelling
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References
Arumugam, J., Mojumder, J., Kassab, G., Lee, L.C.: Model of anisotropic reverse cardiac growth in mechanical dyssynchrony. Sci. Rep. 9(1), 1–12 (2019)
Bayer, J.D., Blake, R.C., Plank, G., Trayanova, N.A.: A novel rule-based algorithm for assigning myocardial fiber orientation to computational heart models. Ann. Biomed. Eng. 40(10), 2243–2254 (2012)
Davies, M.J., McKenna, W.J.: Hypertrophic cardiomyopathy–pathology and pathogenesis. Histopathology 26(6), 493–500 (1995)
Del Bianco, F., Franzone, P.C., Scacchi, S., Fassina, L.: Electromechanical effects of concentric hypertrophy on the left ventricle: a simulation study. Comput. Biol. Med. 99, 236–256 (2018)
Doste, R., et al.: A rule-based method to model myocardial fiber orientation in cardiac biventricular geometries with outflow tracts. Int. J. Numer. Meth. Biomed. Eng. 35(4), e3185 (2019)
Fang, L., Ellims, A.H., Beale, A.L., Taylor, A.J., Murphy, A., Dart, A.M.: Systemic inflammation is associated with myocardial fibrosis, diastolic dysfunction, and cardiac hypertrophy in patients with hypertrophic cardiomyopathy. Am. J. Transl. Res. 9(11), 5063–5073 (2017)
Göktepe, S., Abilez, O.J., Parker, K.K., Kuhl, E.: A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. J. Theor. Biol. 265(3), 433–442 (2010)
Goodbrake, C., Goriely, A., Yavari, A.: The mathematical foundations of anelasticity: Existence of smooth global intermediate configurations. Proc. R. Soc. A 477(2245), 20200462 (2021)
Hadjicharalambous, M., Lee, J., Smith, N.P., Nordsletten, D.A.: A displacement-based finite element formulation for incompressible and nearly-incompressible cardiac mechanics. Comput. Method. Appl. M. 274, 213–236 (2014)
Holzapfel, G.A., Ogden, R.W.: Constitutive modelling of passive myocardium: a structurally based framework for material characterization. Philos. Trans. A Math. Phys. Eng. Sci. 367(1902), 3445–3475 (2009)
Humphrey, J.D., Rajagopal, K.R.: A constrained mixture model for growth and remodeling of soft tissues. Math. Mod. Meth. Appl. Sci. 12(3), 407–430 (2002)
Kerckhoffs, R.C., Omens, J.H., McCulloch, A.D.: A single strain-based growth law predicts concentric and eccentric cardiac growth during pressure and volume overload. Mech. Res. Commun. 42, 40–50 (2012)
Klues, H.G., Schiffers, A., Maron, B.J.: Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J. Am. Coll. 26(7), 1699–1708 (1995)
Lee, L.C., Genet, M., Acevedo-Bolton, G., Ordovas, K., Guccione, J.M., Kuhl, E.: A computational model that predicts reverse growth in response to mechanical unloading. Biomech. Model. Mechanobiol. 14(2), 217–229 (2014). https://doi.org/10.1007/s10237-014-0598-0
Lee, J., et al.: Multiphysics computational modeling in CHeart. SIAM J. Comput. 38(3), C150–C178 (2016)
Liew, A.C., Vassiliou, V.S., Cooper, R., Raphael, C.E.: Hypertrophic cardiomyopathy–past, present and future. Clin. Med. 6(12), 118 (2017)
Marian, A.J., Braunwald, E.: Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ. Res. 121(7), 749–770 (2017)
Maron, B.J., Roberts, W.C.: Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 59(4), 689–706 (1979)
Maron, B.J., Epstein, S.E.: Hypertrophic cardiomyopathy: a discussion of nomenclature. Amer. J. Cardiol. 43(6), 1242–1244 (1979)
Maron, B.J.: Hypertrophic cardiomyopathy: a systematic review. JAMA 287(10), 1308–1320 (2002)
MATLAB. 9.9.0.1524771 (R2020b). Natick, Massachusetts: The MathWorks Inc. (2020)
Mauger, C., et al.: An iterative diffeomorphic algorithm for registration of subdivision surfaces: application to congenital heart disease. Ann. Int. Conf. IEEE Eng. Med. Biol. Soc. 2018, 596–599 (2018)
Peirlinck, M., et al.: Using machine learning to characterize heart failure across the scales. Biomech. Model. Mechanobiol. 18(6), 1987–2001 (2019). https://doi.org/10.1007/s10237-019-01190-w
Rodriguez, E.K., Hoger, A., McCulloch, A.: Stress-dependent finite growth in soft elastic tissues. J. Biomech. 27(4), 455–467 (1994)
Semsarian, C., Ingles, J., Maron, M.S., Maron, B.J.: New perspectives on the prevalence of hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 65(12), 1249–1254 (2015)
Teare, D.: Asymmetrical hypertrophy of the heart in young adults. Brit. Heart J. 20(1), 1–8 (1958)
Witzenburg, C.M., Holmes, J.W.: A comparison of phenomenologic growth laws for myocardial hypertrophy. J. Elast. 129(1), 257–281 (2017)
Wolf, C.M., et al.: Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia. P. Natl. Acad. Sci. USA 102(50), 18123–18128 (2005)
Acknowledgements
Authors would like to acknowledge funding from Engineering and Physical Sciences Research Council (EP/R003866/1). This work was also supported by the Wellcome ESPRC Centre for Medical Engineering at King’s College London (WT203148/Z/16/Z) and the British Heart Foundation (TG/17/3/33406).
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Hager, S.P., Zhang, W., Miller, R.M., Lee, J., Nordsletten, D.A. (2021). An Exploratory Assessment of Focused Septal Growth in Hypertrophic Cardiomyopathy. In: Ennis, D.B., Perotti, L.E., Wang, V.Y. (eds) Functional Imaging and Modeling of the Heart. FIMH 2021. Lecture Notes in Computer Science(), vol 12738. Springer, Cham. https://doi.org/10.1007/978-3-030-78710-3_32
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