Assessment of Echocardiography and Biomarkers for the Extended Prediction of Cardiotoxicity in Patients Treated With Anthracyclines, Taxanes, and Trastuzumab

Abstract

Background Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Methods and Results Eighty-one women with newly diagnosed human epidermal growth factor receptor 2–positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro–B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%–43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%–14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro–B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. Conclusions In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Assessment of LVEF alone by either method appears insensitive to detect subclinical changes and predict subsequent cardiotoxicity. Decreases in myocardial deformation (strain) precede changes in LVEF and have been consistently predictive of cardiac dysfunction from trastuzumab 82, 83. The American Society of Echocardiography recommends global longitudinal strain measured by speckle tracking echocardiography as the modality of choice for detection of subclinical myocardial changes and risk prediction 17.…”

“…Additionally, optimal timing and frequency of measurement as well as the ideal cutoff have not yet been determined. An integrated approach using strain imaging and high‐sensitivity troponin may provide incremental value in predicting subsequent cardiac dysfunction, but needs further investigation 83. The recently published guidelines from the American Society of Clinical Oncology gives a moderate strength of recommendation for routine use of biomarkers and echocardiographic‐derived strain imaging for surveillance of cardiotoxicity, citing intermediate quality of evidence 53.…”

“…The recently published guidelines from the American Society of Clinical Oncology gives a moderate strength of recommendation for routine use of biomarkers and echocardiographic‐derived strain imaging for surveillance of cardiotoxicity, citing intermediate quality of evidence 53. Baseline N‐terminal pro–B‐type natriuretic peptide, a marker of hemodynamic stress, high‐sensitivity C‐reactive protein and growth differentiation factor‐15, markers of inflammation and oxidative stress, placental growth factor, a marker of angiogenesis, galectin‐3, a marker of fibrosis, soluble fms‐like tyrosine kinase receptor‐1, and others, have not shown significant association with future cardiac dysfunction 83, 85. Increases in N‐terminal pro–B‐type natriuretic peptide over time appear to correlate with changes in cardiac function; however, no thresholds have been established 87…”

Cardiac Imaging: Multimodality Advances and Surveillance Strategies in Detection of Cardiotoxicity

“…In a multicenter study comparing echocardiographic parameters in patients with HF, global longitudinal strain (GLS) assessment, a parameter evaluating longitudinal aspect of myocardial contraction using deformation imaging, appeared to have a higher and more reliable prognostic value than LVEF for the prediction of cardiac events and cardiac deaths [20]. 2D speckle tracking strain has already been evaluated in studies for a total of more than 700 patients concomitantly to the administration of cardiotoxic anticancer agents, with encouraging results concerning its capability to diagnose subclinical LV dysfunction of subsequent clinical relevance [21][22][23][24][25][26][27]. Based on these data, serial strain measurements are suggested during anticancer treatment [11••].…”

“…High-sensitive troponins assays may have a greater interest for the detection of subclinical myocardial damage. Sawaya et al recently demonstrated that highsensitive Tn-I assays in combination with echocardiography strain imaging increase the accuracy of early detection and prediction of CTRCD in breast cancer patients treated with anthracyclines and trastuzumab [22,24]. The ASE/EACVI consensus document recommends serial Tn-I levels be drawn with a chemotherapy regimen potentially associated with type I or type II toxicities or in case of their sequential administration [11••].…”