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Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer

BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult...

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Autores principales: Kotwinski, Paul, Smith, Gillian, Cooper, Jackie, Sanders, Julie, Ma, Louise, Teis, Albert, Kotwinski, David, Mythen, Michael, Pennell, Dudley J., Jones, Alison, Montgomery, Hugh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135038/
https://www.ncbi.nlm.nih.gov/pubmed/27911951
http://dx.doi.org/10.1371/journal.pone.0165262
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author Kotwinski, Paul
Smith, Gillian
Cooper, Jackie
Sanders, Julie
Ma, Louise
Teis, Albert
Kotwinski, David
Mythen, Michael
Pennell, Dudley J.
Jones, Alison
Montgomery, Hugh
author_facet Kotwinski, Paul
Smith, Gillian
Cooper, Jackie
Sanders, Julie
Ma, Louise
Teis, Albert
Kotwinski, David
Mythen, Michael
Pennell, Dudley J.
Jones, Alison
Montgomery, Hugh
author_sort Kotwinski, Paul
collection PubMed
description BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. METHODS: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. RESULTS: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0–26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300–450] mg/m(2)); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17–2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73–17.61]), body surface area (OR 2.08 [1.36–3.20] per standard deviation (0.16m(2)) increase), and Trastuzumab therapy (OR 3.35 [1.18–9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70–0.86]. CONCLUSIONS: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure–indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.
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spelling pubmed-51350382016-12-21 Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer Kotwinski, Paul Smith, Gillian Cooper, Jackie Sanders, Julie Ma, Louise Teis, Albert Kotwinski, David Mythen, Michael Pennell, Dudley J. Jones, Alison Montgomery, Hugh PLoS One Research Article BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. METHODS: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. RESULTS: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0–26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300–450] mg/m(2)); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17–2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73–17.61]), body surface area (OR 2.08 [1.36–3.20] per standard deviation (0.16m(2)) increase), and Trastuzumab therapy (OR 3.35 [1.18–9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70–0.86]. CONCLUSIONS: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure–indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area. Public Library of Science 2016-12-02 /pmc/articles/PMC5135038/ /pubmed/27911951 http://dx.doi.org/10.1371/journal.pone.0165262 Text en © 2016 Kotwinski et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kotwinski, Paul
Smith, Gillian
Cooper, Jackie
Sanders, Julie
Ma, Louise
Teis, Albert
Kotwinski, David
Mythen, Michael
Pennell, Dudley J.
Jones, Alison
Montgomery, Hugh
Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title_full Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title_fullStr Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title_full_unstemmed Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title_short Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer
title_sort body surface area and baseline blood pressure predict subclinical anthracycline cardiotoxicity in women treated for early breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135038/
https://www.ncbi.nlm.nih.gov/pubmed/27911951
http://dx.doi.org/10.1371/journal.pone.0165262
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