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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

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Abstract

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.

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Fig. 1
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Abbreviations

ANCOVA:

Analysis of covariance

BSA:

Body surface area

CAD:

Coronary artery disease

CMR:

Cardiac magnetic resonance

CPET:

Cardiopulmonary exercise test

DOX:

Doxorubicin

EDV:

End-diastolic volume

ER:

Estrogen receptor

ESV:

End-systolic volume

GLS:

Global longitudinal strain

HER:

Human epidermal growth factor receptor

HF:

Heart failure

LLN:

Lower limit of normal

LV:

Left ventricle/ventricular

LVCR:

Left ventricular contractile reserve

LVEF:

Left ventricular ejection fraction

MUGA:

Multi-gated acquisition scan

SV:

Stroke volume

2DE:

2-Dimensional echocardiography

2D-STE:

2-Dimensional speckle-tracking echocardiography

3DE:

3-Dimensional echocardiography

VO2peak :

Peak oxygen consumption

WMSI:

Wall motion scoring index

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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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Authors and Affiliations

  1. Duke Cancer Institute, Duke University Medical Center, Box 3085, Durham, NC, 27710, USA

    Michel G. Khouri, Whitney E. Hornsby, Eric J. Velazquez, Samantha Thomas, Amy Lane, James E. Herndon, Pamela S. Douglas & Lee W. Jones

  2. The Heart Center, Rigshospitalet, Copenhagen, Denmark

    Niels Risum

  3. NASA Johnson Space Center, Houston, TX, USA

    Jessica M. Scott

  4. School of Health and Exercise Sciences, University of British Columbia, Kelowna, BC, Canada

    Graeme J. Koelwyn

  5. Cross Cancer Institute, Edmonton, AB, Canada

    John R. Mackey

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  1. Michel G. Khouri
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  6. Amy Lane
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Correspondence to Lee W. Jones.

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Khouri, M.G., Hornsby, W.E., Risum, N. et al. 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. Breast Cancer Res Treat 143, 531–539 (2014). https://doi.org/10.1007/s10549-013-2818-1

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