Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity

BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological co...

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Authors: Galan-Arriola, Carlos, Lobo-Gonzalez, Manuel, Vilchez, Jean Paul, Lopez-Martin, Gonzalo J., Molina-Iracheta, Antonio, Pérez-Martínez, Claudia, Aguero, Jaume, Fernandez-Jimenez, Rodrigo, Martín-García, Ana, Oliver, Eduardo, Villena-Gutierrez, Rocio, Pizarro, Gonzalo, Sánchez, Pedro L, Fuster, Valentin, Sanchez-Gonzalez, Javier, Ibáñez, Borja
Format: article
Publication Date:2019
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8991
Online Access:http://hdl.handle.net/20.500.12105/8991
Access Level:Open access
Keyword:Animals
Antibiotics, Antineoplastic
Cardiotoxicity
Disease Models, Animal
Doxorubicin
Drug Administration Schedule
Male
Swine
Time Factors
Magnetic Resonance Imaging
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spelling Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced CardiotoxicityGalan-Arriola, CarlosLobo-Gonzalez, ManuelVilchez, Jean PaulLopez-Martin, Gonzalo J.Molina-Iracheta, AntonioPérez-Martínez, ClaudiaAguero, JaumeFernandez-Jimenez, RodrigoMartín-García, AnaOliver, EduardoVillena-Gutierrez, RocioPizarro, GonzaloSánchez, Pedro LFuster, ValentinSanchez-Gonzalez, JavierIbáñez, BorjaAnimalsAntibiotics, AntineoplasticCardiotoxicityDisease Models, AnimalDoxorubicinDrug Administration ScheduleMaleSwineTime FactorsMagnetic Resonance ImagingBACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.ElsevierMinisterio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Sociedad Española de CardiologíaFundación ProCNICUnión Europea. Comisión Europea20202020-01-2920192019-02-0120192019-02-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documenthttp://hdl.handle.net/20.500.12105/8991reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SEV-2015-0505 Not availableEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 707642open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/89912026-06-12T12:43:37Z
dc.title.none.fl_str_mv Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
title Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
spellingShingle Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
Galan-Arriola, Carlos
Animals
Antibiotics, Antineoplastic
Cardiotoxicity
Disease Models, Animal
Doxorubicin
Drug Administration Schedule
Male
Swine
Time Factors
Magnetic Resonance Imaging
title_short Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
title_full Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
title_fullStr Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
title_full_unstemmed Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
title_sort Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
dc.creator.none.fl_str_mv Galan-Arriola, Carlos
Lobo-Gonzalez, Manuel
Vilchez, Jean Paul
Lopez-Martin, Gonzalo J.
Molina-Iracheta, Antonio
Pérez-Martínez, Claudia
Aguero, Jaume
Fernandez-Jimenez, Rodrigo
Martín-García, Ana
Oliver, Eduardo
Villena-Gutierrez, Rocio
Pizarro, Gonzalo
Sánchez, Pedro L
Fuster, Valentin
Sanchez-Gonzalez, Javier
Ibáñez, Borja
author Galan-Arriola, Carlos
author_facet Galan-Arriola, Carlos
Lobo-Gonzalez, Manuel
Vilchez, Jean Paul
Lopez-Martin, Gonzalo J.
Molina-Iracheta, Antonio
Pérez-Martínez, Claudia
Aguero, Jaume
Fernandez-Jimenez, Rodrigo
Martín-García, Ana
Oliver, Eduardo
Villena-Gutierrez, Rocio
Pizarro, Gonzalo
Sánchez, Pedro L
Fuster, Valentin
Sanchez-Gonzalez, Javier
Ibáñez, Borja
author_role author
author2 Lobo-Gonzalez, Manuel
Vilchez, Jean Paul
Lopez-Martin, Gonzalo J.
Molina-Iracheta, Antonio
Pérez-Martínez, Claudia
Aguero, Jaume
Fernandez-Jimenez, Rodrigo
Martín-García, Ana
Oliver, Eduardo
Villena-Gutierrez, Rocio
Pizarro, Gonzalo
Sánchez, Pedro L
Fuster, Valentin
Sanchez-Gonzalez, Javier
Ibáñez, Borja
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Sociedad Española de Cardiología
Fundación ProCNIC
Unión Europea. Comisión Europea
dc.subject.none.fl_str_mv Animals
Antibiotics, Antineoplastic
Cardiotoxicity
Disease Models, Animal
Doxorubicin
Drug Administration Schedule
Male
Swine
Time Factors
Magnetic Resonance Imaging
topic Animals
Antibiotics, Antineoplastic
Cardiotoxicity
Disease Models, Animal
Doxorubicin
Drug Administration Schedule
Male
Swine
Time Factors
Magnetic Resonance Imaging
description BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-02-01
2019
2019-02-01
2020
2020-01-29
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/8991
url http://hdl.handle.net/20.500.12105/8991
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES SEV-2015-0505 Not available
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 707642
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406523403272192
score 15,812429

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