Biniyam G Demissei1, Yong Fan2, Yiwen Qian1, Henry G Cheng1, Amanda M Smith1, Kelsey Shimamoto1, Natasha Vedage3, Hari K Narayan4, Marielle Scherrer-Crosbie1, Christos Davatzikos2, Bonnie Ky1,5,6. 1. Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Internal Medicine, Temple University Hospital, Philadelphia, PA, USA. 4. Department of Pediatrics, Division of Cardiology, Rady Children's Hospital San Diego, The University of California San Diego, San Diego, CA, USA. 5. Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 6. Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Abstract
AIMS: We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin. METHODS AND RESULTS: In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1-Q3) of 7 (2-24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value <50%. Median (Q1-Q3) baseline age was 48 (41-57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60-0.80) to 0.87 (95% CI 0.81-0.92), ΔAUC = 0.18 (95% CI 0.08-0.27) for the prediction of CTRCD. CONCLUSION: Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin. METHODS AND RESULTS: In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1-Q3) of 7 (2-24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value <50%. Median (Q1-Q3) baseline age was 48 (41-57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60-0.80) to 0.87 (95% CI 0.81-0.92), ΔAUC = 0.18 (95% CI 0.08-0.27) for the prediction of CTRCD. CONCLUSION: Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin. Published on behalf of the European Society of Cardiology. All rights reserved.
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