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Clinical, echocardiographic, and biomarker associations with impaired cardiorespiratory fitness early after HER2-targeted breast cancer therapy


Bonsignore, A and Marwick, TH and Adams, SC and Thampinathan, B and Somerset, E and Amir, E and Walker, M and Abdel-Qadir, H and Koch, CA and Ross, HJ and Woo, A and Wintersperger, BJ and Haykowsky, MJ and Thavendiranathan, P, Clinical, echocardiographic, and biomarker associations with impaired cardiorespiratory fitness early after HER2-targeted breast cancer therapy, Jacc: Cardiooncology, 3, (5) pp. 678-691. ISSN 2666-0873 (2021) [Refereed Article]

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Copyright Statement

2021 by The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, (

DOI: doi:10.1016/j.jaccao.2021.08.010


BACKGROUND Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible.

OBJECTIVES The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO(2)peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk.

METHODS Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 + 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO(2)peak using a cycle ergometer. Regression models were used to examine the association between VO(2)peak and clinical, imaging, and cardiac biomarkers individually and in combination.

RESULTS Among 147 patients (age 52.2 +/- 9.3 years), the mean VO(2)peak was 19.1 +/- 5.0 mL O-2 center dot kg(-1).min(-1) (84.2% +/- 18.7% of predicted); 44% had a VO(2)peak below threshold for functional independence (<18 mL O-2 center dot kg(-1).min(-1)). In multivariable analysis, absolute global longitudinal strain (GLS) (beta = 0.58; P = 0.007), age per 10 years (beta: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (beta = -0.45; P = 0.038) were associated with VO(2)peak. GLS added incremental value in explaining the variability in VO(2)peak. The combination of age >= 50 years, E/e' >= 7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS >= 18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO(2)peak.

CONCLUSIONS Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Item Details

Item Type:Refereed Article
Keywords:anthracyclines, cardiopulmonary exercise testing, echocardiography, exercise training, global longitudinal strain, trastuzumab
Research Division:Health Sciences
Research Group:Epidemiology
Research Field:Epidemiology not elsewhere classified
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Preventive medicine
UTAS Author:Marwick, TH (Professor Tom Marwick)
ID Code:152665
Year Published:2021
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-08-23
Last Modified:2022-09-08
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