Hari K Narayan1, Benjamin French2, Abigail M Khan3, Theodore Plappert3, David Hyman3, Akinyemi Bajulaiye3, Susan Domchek4, Angela DeMichele5, Amy Clark4, Jennifer Matro4, Angela Bradbury4, Kevin Fox4, Joseph R Carver6, Bonnie Ky7. 1. Department of Pediatrics, Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Medicine, Division of Cardiology, The University of Pennsylvania, Philadelphia, Pennsylvania. 4. Department of Medicine, Division of Oncology, The University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, The University of Pennsylvania, Philadelphia, Pennsylvania. 5. Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania; Department of Medicine, Division of Oncology, The University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, The University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Medicine, Division of Cardiology, The University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, The University of Pennsylvania, Philadelphia, Pennsylvania. 7. Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania; Department of Medicine, Division of Cardiology, The University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, The University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: bonnie.ky@uphs.upenn.edu.
Abstract
OBJECTIVES: This study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD). BACKGROUND: Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity. METHODS: We performed a prospective, longitudinal cohort study of breast cancer participants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (effective arterial elastance [Ea]/end-systolic elastance [Eessb]) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver-operating characteristic curves were used to evaluate the predictive ability of these measures. RESULTS: In total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (interquartile range: 0.9 to 2.4 years), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Eessb, circumferential strain, and circumferential strain rate were associated with 21% to 38% increased odds of CTRCD (p < 0.001). Changes in longitudinal strain (p = 0.037), radial strain (p = 0.015), and radial strain rate (p = 0.006) were also associated with CTRCD. Ea/Eessb (area under the curve: 0.703; 95% confidence interval: 0.583 to 0.807) and circumferential strain (area under the curve: 0.655; 95% confidence interval: 0.517 to 0.767) demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results. CONCLUSIONS: Over an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy.
OBJECTIVES: This study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD). BACKGROUND:Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity. METHODS: We performed a prospective, longitudinal cohort study of breast cancerparticipants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (effective arterial elastance [Ea]/end-systolic elastance [Eessb]) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver-operating characteristic curves were used to evaluate the predictive ability of these measures. RESULTS: In total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (interquartile range: 0.9 to 2.4 years), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Eessb, circumferential strain, and circumferential strain rate were associated with 21% to 38% increased odds of CTRCD (p < 0.001). Changes in longitudinal strain (p = 0.037), radial strain (p = 0.015), and radial strain rate (p = 0.006) were also associated with CTRCD. Ea/Eessb (area under the curve: 0.703; 95% confidence interval: 0.583 to 0.807) and circumferential strain (area under the curve: 0.655; 95% confidence interval: 0.517 to 0.767) demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results. CONCLUSIONS: Over an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy.
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