Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy
This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction. Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on...
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| Veröffentlicht in: | JACC. Cardiovascular imaging 2020-01, Vol.13 (1), p.198-210 |
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| creator | Upshaw, Jenica N. Finkelman, Brian Hubbard, Rebecca A. Smith, Amanda M. Narayan, Hari K. Arndt, Linzi Domchek, Susan DeMichele, Angela Fox, Kevin Shah, Payal Clark, Amy Bradbury, Angela Matro, Jennifer Adusumalli, Srinath Carver, Joseph R. Ky, Bonnie |
| description | This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.
Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to |
| doi_str_mv | 10.1016/j.jcmg.2019.07.018 |
| format | Article |
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Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%.
Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e′ velocities, and increases in E/e′ (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (−2.1%; 95% confidence intervals [CI]: −3.1 to −1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e′ ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022).
A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341)
[Display omitted]</description><identifier>ISSN: 1936-878X</identifier><identifier>EISSN: 1876-7591</identifier><identifier>DOI: 10.1016/j.jcmg.2019.07.018</identifier><identifier>PMID: 31542526</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; anthracyclines ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Breast Neoplasms - drug therapy ; cardio-oncology ; Cardiotoxicity ; chemotherapy ; Diastole ; diastolic dysfunction ; Doxorubicin - adverse effects ; Echocardiography, Doppler ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stroke Volume - drug effects ; Time Factors ; trastuzumab ; Trastuzumab - adverse effects ; Ventricular Dysfunction, Left - chemically induced ; Ventricular Dysfunction, Left - diagnostic imaging ; Ventricular Dysfunction, Left - physiopathology ; Ventricular Function, Left - drug effects</subject><ispartof>JACC. Cardiovascular imaging, 2020-01, Vol.13 (1), p.198-210</ispartof><rights>2020 American College of Cardiology Foundation</rights><rights>Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-f225397ebc2887b554ba6b26eaeab07359ae8a79a75c3b8bee67791a9b7cab273</citedby><cites>FETCH-LOGICAL-c455t-f225397ebc2887b554ba6b26eaeab07359ae8a79a75c3b8bee67791a9b7cab273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jcmg.2019.07.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31542526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Upshaw, Jenica N.</creatorcontrib><creatorcontrib>Finkelman, Brian</creatorcontrib><creatorcontrib>Hubbard, Rebecca A.</creatorcontrib><creatorcontrib>Smith, Amanda M.</creatorcontrib><creatorcontrib>Narayan, Hari K.</creatorcontrib><creatorcontrib>Arndt, Linzi</creatorcontrib><creatorcontrib>Domchek, Susan</creatorcontrib><creatorcontrib>DeMichele, Angela</creatorcontrib><creatorcontrib>Fox, Kevin</creatorcontrib><creatorcontrib>Shah, Payal</creatorcontrib><creatorcontrib>Clark, Amy</creatorcontrib><creatorcontrib>Bradbury, Angela</creatorcontrib><creatorcontrib>Matro, Jennifer</creatorcontrib><creatorcontrib>Adusumalli, Srinath</creatorcontrib><creatorcontrib>Carver, Joseph R.</creatorcontrib><creatorcontrib>Ky, Bonnie</creatorcontrib><title>Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy</title><title>JACC. Cardiovascular imaging</title><addtitle>JACC Cardiovasc Imaging</addtitle><description>This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.
Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%.
Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e′ velocities, and increases in E/e′ (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (−2.1%; 95% confidence intervals [CI]: −3.1 to −1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e′ ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022).
A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341)
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Cardiovascular imaging</jtitle><addtitle>JACC Cardiovasc Imaging</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>13</volume><issue>1</issue><spage>198</spage><epage>210</epage><pages>198-210</pages><issn>1936-878X</issn><eissn>1876-7591</eissn><abstract>This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.
Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%.
Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e′ velocities, and increases in E/e′ (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (−2.1%; 95% confidence intervals [CI]: −3.1 to −1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e′ ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022).
A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341)
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| ispartof | JACC. Cardiovascular imaging, 2020-01, Vol.13 (1), p.198-210 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| subjects | Adult anthracyclines Antineoplastic Combined Chemotherapy Protocols - adverse effects Breast Neoplasms - drug therapy cardio-oncology Cardiotoxicity chemotherapy Diastole diastolic dysfunction Doxorubicin - adverse effects Echocardiography, Doppler Female Humans Longitudinal Studies Middle Aged Prospective Studies Risk Assessment Risk Factors Stroke Volume - drug effects Time Factors trastuzumab Trastuzumab - adverse effects Ventricular Dysfunction, Left - chemically induced Ventricular Dysfunction, Left - diagnostic imaging Ventricular Dysfunction, Left - physiopathology Ventricular Function, Left - drug effects |
| title | Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy |
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