Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy

Alis Bonsignore; Thomas H Marwick; Scott C Adams; Babitha Thampinathan; Emily Somerset; Eitan Amir; Mike Walker; Husam Abdel-Qadir; C Anne Koch; Heather J Ross; Anna Woo; Bernd J Wintersperger; Mark J Haykowsky; Paaladinesh Thavendiranathan

doi:10.1016/j.jaccao.2021.08.010

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy

JACC CardioOncol. 2021 Nov 16;3(5):678-691. doi: 10.1016/j.jaccao.2021.08.010. eCollection 2021 Dec.

Authors

Alis Bonsignore¹, Thomas H Marwick², Scott C Adams^{1

3}, Babitha Thampinathan³, Emily Somerset⁴, Eitan Amir⁵, Mike Walker⁶, Husam Abdel-Qadir^{3

7}, C Anne Koch⁸, Heather J Ross³, Anna Woo⁶, Bernd J Wintersperger⁹, Mark J Haykowsky¹⁰, Paaladinesh Thavendiranathan^{3

9}

Affiliations

¹ Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada.
² Baker Heart and Diabetes Institute, Melbourne, Victoria, and Menzies Research Institute, Hobart, Tasmania, Australia.
³ Ted Rogers Program in Cardiotoxicity Prevention, Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁴ Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Medical Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
⁶ Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁷ Women's College Hospital, University of Toronto, Toronto, Ontario, Canada.
⁸ Radiation Medicine Program, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
⁹ Joint Department of Medical Imaging, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
¹⁰ University of Alberta, Faculty of Nursing, College of Health Science, Edmonton, Alberta, Canada.

Abstract

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 (VO₂peak) (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 VO₂peak using a cycle ergometer. Regression models were used to examine the association between VO₂peak and clinical, imaging, and cardiac biomarkers individually and in combination.

Results: Among 147 patients (age 52.2 ± 9.3 years), the mean VO₂peak was 19.1 ± 5.0 mL O₂·kg^-1·min^-1 (84.2% ± 18.7% of predicted); 44% had a VO₂peak below threshold for functional independence (<18 mL O₂·kg^-1·min^-1). In multivariable analysis, absolute global longitudinal strain (GLS) (β = 0.58; P = 0.007), age per 10 years (β: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (β = -0.45; P = 0.038) were associated with VO₂peak. GLS added incremental value in explaining the variability in VO₂peak. 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 VO₂peak.

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.

Keywords: BNP, B-type natriuretic peptide; CORE, cardio-oncology rehabilitation; CPET, cardiopulmonary exercise test; CRF, cardiorespiratory fitness; CTRCD, cancer therapy–related cardiac dysfunction; GLS, global longitudinal strain; LV, left ventricle/ventricular; LVEF, left ventricular ejection fraction; LVMi, left ventricular mass index; VO2peak, peak oxygen consumption; anthracyclines; cardiopulmonary exercise testing; echocardiography; exercise training; global longitudinal strain; hsTnI, high-sensitivity troponin I; trastuzumab.