Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy

M Linschoten; A J Teske; A F Baas; A Vink; D Dooijes; H F Baars; F W Asselbergs

doi:10.1016/j.cardfail.2017.03.003

Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy

M Linschoten, A J Teske, A F Baas, A Vink, D Dooijes, H F Baars, F W Asselbergs

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.

Original language	English
Pages (from-to)	476-479
Number of pages	4
Journal	Journal of Cardiac Failure
Volume	23
Issue number	6
Early online date	2017
DOIs	https://doi.org/10.1016/j.cardfail.2017.03.003
Publication status	Published - Jun 2017

Keywords

Journal Article
heart failure
genetics
Cardiotoxicity
chemotherapy
Breast Neoplasms/diagnostic imaging
Cardiomyopathies/chemically induced
Humans
Middle Aged
Genetic Variation/genetics
Connectin/genetics
Fatal Outcome
Carcinoma, Ductal/diagnostic imaging
Adult
Antineoplastic Agents/adverse effects
Female

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10.1016/j.cardfail.2017.03.003

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title = "Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy",

abstract = "Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.",

keywords = "Journal Article, heart failure, genetics, Cardiotoxicity, chemotherapy, Breast Neoplasms/diagnostic imaging, Cardiomyopathies/chemically induced, Humans, Middle Aged, Genetic Variation/genetics, Connectin/genetics, Fatal Outcome, Carcinoma, Ductal/diagnostic imaging, Adult, Antineoplastic Agents/adverse effects, Female",

author = "M Linschoten and Teske, {A J} and Baas, {A F} and A Vink and D Dooijes and Baars, {H F} and Asselbergs, {F W}",

note = "Funding Information: Folkert W. Asselbergs is supported by a Dekker scholarship– Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Center BRC86A . The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation , CVON2015-12 eDETECT and CVON2014-40 DOSIS . Funding Information: Folkert W. Asselbergs is supported by a Dekker scholarship?Junior Staff Member 2014T001?Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Center BRC86A. The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

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language = "English",

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AU - Linschoten, M

AU - Teske, A J

AU - Baas, A F

AU - Vink, A

AU - Dooijes, D

AU - Baars, H F

AU - Asselbergs, F W

N1 - Funding Information: Folkert W. Asselbergs is supported by a Dekker scholarship– Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Center BRC86A . The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation , CVON2015-12 eDETECT and CVON2014-40 DOSIS . Funding Information: Folkert W. Asselbergs is supported by a Dekker scholarship?Junior Staff Member 2014T001?Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Center BRC86A. The authors acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. Publisher Copyright: © 2017 Elsevier Inc.

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N2 - Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.

AB - Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.

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KW - Humans

KW - Middle Aged

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KW - Antineoplastic Agents/adverse effects

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JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

IS - 6

ER -

Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy

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