Breast Cancer Research and Treatment

, Volume 143, Issue 3, pp 531–539 | Cite as

Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy

  • Michel G. Khouri
  • Whitney E. Hornsby
  • Niels Risum
  • Eric J. Velazquez
  • Samantha Thomas
  • Amy Lane
  • Jessica M. Scott
  • Graeme J. Koelwyn
  • James E. Herndon
  • John R. Mackey
  • Pamela S. Douglas
  • Lee W. JonesEmail author


Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise “stress” is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to −17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (−16.1 ± 0.9 vs. −20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min−1 m−2 mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0.001). Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients.


Adjuvant therapy Breast cancer Cardiotoxicity Echocardiography Stress testing 



Analysis of covariance


Body surface area


Coronary artery disease


Cardiac magnetic resonance


Cardiopulmonary exercise test




End-diastolic volume


Estrogen receptor


End-systolic volume


Global longitudinal strain


Human epidermal growth factor receptor


Heart failure


Lower limit of normal


Left ventricle/ventricular


Left ventricular contractile reserve


Left ventricular ejection fraction


Multi-gated acquisition scan


Stroke volume


2-Dimensional echocardiography


2-Dimensional speckle-tracking echocardiography


3-Dimensional echocardiography


Peak oxygen consumption


Wall motion scoring index


Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

Experiments performed in this study comply with the current laws of the United States.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Michel G. Khouri
    • 1
  • Whitney E. Hornsby
    • 1
  • Niels Risum
    • 2
  • Eric J. Velazquez
    • 1
  • Samantha Thomas
    • 1
  • Amy Lane
    • 1
  • Jessica M. Scott
    • 3
  • Graeme J. Koelwyn
    • 4
  • James E. Herndon
    • 1
  • John R. Mackey
    • 5
  • Pamela S. Douglas
    • 1
  • Lee W. Jones
    • 1
    Email author
  1. 1.Duke Cancer InstituteDuke University Medical CenterDurhamUSA
  2. 2.The Heart CenterRigshospitaletCopenhagenDenmark
  3. 3.NASA Johnson Space CenterHoustonUSA
  4. 4.School of Health and Exercise SciencesUniversity of British ColumbiaKelownaCanada
  5. 5.Cross Cancer InstituteEdmontonCanada

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