Early detection of anthracycline‐ and trastuzumab‐induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters

Abstract

AimsTo evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and resultsSeventy-two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high-sensitivity cardiac troponin T, NT-proBNP, global longitudinal strain (GLS), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High-sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT-proBNP augmented after each anthracycline cycle (mean pre-cycle levels of 72 ± 68 pg/mL and post-cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post-anthracycline treatment and the decline in GLS was more pronounced (À17.6% vs. À21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02-1.24), odds ratio = 0.66 (0.44-0.92), P < 0.05] at 1 month post-anthracycline treatment. Neither high-sensitivity troponin T nor NT-proBNP was capable of predicting subsequent cardiotoxicity. Conclusions One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab-induced cardiotoxicity.

Usefulness of Global Longitudinal Strain-Guided Management in Preventing Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor-Induced Myocardial Damage

“…It was concluded that 3 months after anthracycline initiation was the optimal time to detect a decline in GLS. 12 In the present study, we reported that 89.5% of overall GLS-CTRCD was detected up to the sixth course of trastuzumab. GLS-CTRCD was detected in 21.1% and 73.7% of all patients after the first and third courses of trastuzumab, indicating that trastuzumab-associated GLS-CTRCD is frequently observed in the early phase of treatment.…”

“…Díaz-Antón et al conducted a study on the optimal timing of echocardiography to detect GLS-CTRCD. 12 That study included patients with breast cancer who were treated with anthracycline and/or trastuzumab, and echocardiography tests were performed more frequently than in many other studies. Echocardiography was performed before starting chemotherapy, between the second and third courses of anthracycline, and 1, 3, 6, and 12 months after the end of anthracycline treatment.…”

The Value of Troponin as a Biomarker of Chemotherapy-Induced Cardiotoxicity

“…A recent study that evaluated 80 patients with breast cancer treated with AC showed that the value of hs-cTnT increased gradually during AC therapy, and that it reached a maximum peak after 1 month, with similar patterns observed in patients with and without cardiotoxicity. In addition, a linear dependence of cTnT with age was observed, but it was not correlated with the level of toxicity [ 38 ].…”

Considerations of Subgroup Classification When Analyzing Risk of Developing Cardiometabolic Risk Factors in Patients With Breast Cancer

“…Chemotherapy causes not only renal and neurological toxicity but also premature ovarian failure, inflammation and cognitive decline, and cardiotoxicity after anthracycline-based regimen or targeted therapy with trastuzumab. 4…”