Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy.
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.
Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
M
M
Linschoten
Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
A J
AJ
Teske
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
A F
AF
Baas
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
A
A
Vink
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
D
D
Dooijes
Department of Cardiology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, The Netherlands.
H F
HF
Baars
Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, London, United Kingdom. Electronic address: f.w.asselbergs@umcutrecht.nl.
F W
FW
Asselbergs
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D044584:Carcinoma, Ductal / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000235:genetics*; D064211:Connectin / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged
D000970:Antineoplastic Agents; D064211:Connectin; C577285:TTN protein, human
Cardiotoxicity; chemotherapy; genetics; heart failure