Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Breast Neoplasms
/ drug therapy
Cardiotoxicity
Diastole
Doxorubicin
/ adverse effects
Echocardiography, Doppler
Female
Humans
Longitudinal Studies
Middle Aged
Prospective Studies
Risk Assessment
Risk Factors
Stroke Volume
/ drug effects
Time Factors
Trastuzumab
/ adverse effects
Ventricular Dysfunction, Left
/ chemically induced
Ventricular Function, Left
/ drug effects
anthracyclines
cardio-oncology
cardiotoxicity
chemotherapy
diastolic dysfunction
trastuzumab
Journal
JACC. Cardiovascular imaging
ISSN: 1876-7591
Titre abrégé: JACC Cardiovasc Imaging
Pays: United States
ID NLM: 101467978
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
12
10
2018
revised:
20
06
2019
accepted:
08
07
2019
pubmed:
23
9
2019
medline:
8
10
2020
entrez:
23
9
2019
Statut:
ppublish
Résumé
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).
Sections du résumé
OBJECTIVES
This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.
BACKGROUND
Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.
METHODS
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%.
RESULTS
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).
CONCLUSIONS
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).
Identifiants
pubmed: 31542526
pii: S1936-878X(19)30729-6
doi: 10.1016/j.jcmg.2019.07.018
pmc: PMC7236624
mid: NIHMS1587628
pii:
doi:
Substances chimiques
Doxorubicin
80168379AG
Trastuzumab
P188ANX8CK
Banques de données
ClinicalTrials.gov
['NCT01173341']
Types de publication
Comparative Study
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
198-210Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL118018
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL141802
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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