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Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure

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Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure. / Lewalle, Alexandre Rene Marie; Land, Sander; Merken, Jort; Raafs, Anne; Sepulveda, Pilar ; Heymans, Stephane; Kleinjans, Jos; Niederer, Steven Alexander.

In: Biophysical Journal, Vol. 117, No. 12, 17.12.2019, p. 2337-2348.

Research output: Contribution to journalArticle

Harvard

Lewalle, ARM, Land, S, Merken, J, Raafs, A, Sepulveda, P, Heymans, S, Kleinjans, J & Niederer, SA 2019, 'Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure', Biophysical Journal, vol. 117, no. 12, pp. 2337-2348. https://doi.org/10.1016/j.bpj.2019.07.033

APA

Lewalle, A. R. M., Land, S., Merken, J., Raafs, A., Sepulveda, P., Heymans, S., Kleinjans, J., & Niederer, S. A. (2019). Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure. Biophysical Journal, 117(12), 2337-2348. https://doi.org/10.1016/j.bpj.2019.07.033

Vancouver

Lewalle ARM, Land S, Merken J, Raafs A, Sepulveda P, Heymans S et al. Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure. Biophysical Journal. 2019 Dec 17;117(12):2337-2348. https://doi.org/10.1016/j.bpj.2019.07.033

Author

Lewalle, Alexandre Rene Marie ; Land, Sander ; Merken, Jort ; Raafs, Anne ; Sepulveda, Pilar ; Heymans, Stephane ; Kleinjans, Jos ; Niederer, Steven Alexander. / Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure. In: Biophysical Journal. 2019 ; Vol. 117, No. 12. pp. 2337-2348.

Bibtex Download

@article{f578dae3704049a2b78c6d29f4b3b0c2,
title = "Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure",
abstract = "Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage of HF, which allows few or no treatment options. Identifying the causes of compromised cardiac function in this patient group may improve early patient diagnosis and support treatment selection. To link doxorubicin-induced changes in cardiac cellular and tissue mechanical properties to overall cardiac function, we apply a multiscale biophysical biomechanics model of the heart to measure the plausibility of changes in model parameters representing the passive, active, or anatomical properties of the left ventricle for reproducing measured patient phenotypes. We create representative models of healthy controls (N = 10) and patients with HF induced by (N = 22) or unrelated to (N = 25) doxorubicin therapy. The model predicts that HF in the absence of doxorubicin is characterized by a 2- to 3-fold stiffness increase, decreased tension (0–20%), and ventricular dilation (of order 10–30%). HF due to doxorubicin was similar but showed stronger bias toward reduced active contraction (10–30%) and less dilation (0–20%). We find that changes in active, passive, and anatomical properties all play a role in doxorubicin-induced cardiotoxicity phenotypes. Differences in parameter changes between patient groups are consistent with doxorubicin cardiotoxicity having a greater dependence on reduced cellular contraction and less anatomical remodeling than HF not caused by doxorubicin.",
author = "Lewalle, {Alexandre Rene Marie} and Sander Land and Jort Merken and Anne Raafs and Pilar Sepulveda and Stephane Heymans and Jos Kleinjans and Niederer, {Steven Alexander}",
year = "2019",
month = dec,
day = "17",
doi = "10.1016/j.bpj.2019.07.033",
language = "English",
volume = "117",
pages = "2337--2348",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Elsevier BV",
number = "12",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure

AU - Lewalle, Alexandre Rene Marie

AU - Land, Sander

AU - Merken, Jort

AU - Raafs, Anne

AU - Sepulveda, Pilar

AU - Heymans, Stephane

AU - Kleinjans, Jos

AU - Niederer, Steven Alexander

PY - 2019/12/17

Y1 - 2019/12/17

N2 - Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage of HF, which allows few or no treatment options. Identifying the causes of compromised cardiac function in this patient group may improve early patient diagnosis and support treatment selection. To link doxorubicin-induced changes in cardiac cellular and tissue mechanical properties to overall cardiac function, we apply a multiscale biophysical biomechanics model of the heart to measure the plausibility of changes in model parameters representing the passive, active, or anatomical properties of the left ventricle for reproducing measured patient phenotypes. We create representative models of healthy controls (N = 10) and patients with HF induced by (N = 22) or unrelated to (N = 25) doxorubicin therapy. The model predicts that HF in the absence of doxorubicin is characterized by a 2- to 3-fold stiffness increase, decreased tension (0–20%), and ventricular dilation (of order 10–30%). HF due to doxorubicin was similar but showed stronger bias toward reduced active contraction (10–30%) and less dilation (0–20%). We find that changes in active, passive, and anatomical properties all play a role in doxorubicin-induced cardiotoxicity phenotypes. Differences in parameter changes between patient groups are consistent with doxorubicin cardiotoxicity having a greater dependence on reduced cellular contraction and less anatomical remodeling than HF not caused by doxorubicin.

AB - Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage of HF, which allows few or no treatment options. Identifying the causes of compromised cardiac function in this patient group may improve early patient diagnosis and support treatment selection. To link doxorubicin-induced changes in cardiac cellular and tissue mechanical properties to overall cardiac function, we apply a multiscale biophysical biomechanics model of the heart to measure the plausibility of changes in model parameters representing the passive, active, or anatomical properties of the left ventricle for reproducing measured patient phenotypes. We create representative models of healthy controls (N = 10) and patients with HF induced by (N = 22) or unrelated to (N = 25) doxorubicin therapy. The model predicts that HF in the absence of doxorubicin is characterized by a 2- to 3-fold stiffness increase, decreased tension (0–20%), and ventricular dilation (of order 10–30%). HF due to doxorubicin was similar but showed stronger bias toward reduced active contraction (10–30%) and less dilation (0–20%). We find that changes in active, passive, and anatomical properties all play a role in doxorubicin-induced cardiotoxicity phenotypes. Differences in parameter changes between patient groups are consistent with doxorubicin cardiotoxicity having a greater dependence on reduced cellular contraction and less anatomical remodeling than HF not caused by doxorubicin.

U2 - 10.1016/j.bpj.2019.07.033

DO - 10.1016/j.bpj.2019.07.033

M3 - Article

VL - 117

SP - 2337

EP - 2348

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 12

ER -

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