The Role of Diastolic Stress Echo and Myocardial Work in Early Detection of Cardiac Dysfunction in Women with Breast Cancer Undergoing Chemotherapy

<b>Background</b>: Anthracycline-based chemotherapy, while highly effective for breast cancer, poses a significant risk for chemotherapy-related cardiac dysfunction (CTRCD), mainly determined by left ventricular ejection fraction (LVEF) reduction. Objectives: We aimed to evaluate the diagnostic utility of speckle tracking analysis (STA) and Diastolic Stress Test Echocardiography (DSTE) for the early detection of cardiac dysfunction either CTRCD or heart failure with preserved ejection fraction (HFpEF) in women undergoing chemotherapy for breast cancer and developed exertional dyspnea and/or fatigue during follow-up. <b>Methods</b>: In this prospective case-control study, 133 women receiving anthracycline-based chemotherapy (with or without anti-HER2 therapy) (chemotherapy group-CTG) and 65 age-matched healthy women as the control group (CG) underwent resting echocardiographic assessment, including LVEF, global longitudinal strain (GLS), myocardial work indices, biomarkers assay (NT-proBNP, troponin, galectin-3) and DSTE at baseline. That assessment was repeated after 12 months in CTG. <b>Results</b>: In this prospective case-control study, 133 women receiving anthracycline-based chemotherapy (with or without anti-HER2 therapy) were included. Based on the presence of CTRCD, they were further subdivided into a CTRCD subgroup (<i>n</i> = 37) and a CTRCD-free subgroup (<i>n</i> = 88). At the end of this study, CTG showed worse values of LVEF, GLS, myocardial work indices than baseline and CG (<i>p</i> < 0.05). Subgroup comparison (CTRCD vs. CTRCD-free) showed significant impairment in LVEF (53.60% vs. 62.60%, <i>p</i> < 0.001), GLS (-16.68% vs. -20.31%, <i>p</i> < 0.001), DSTE-derived tricuspid regurgitation maximum velocity (TRVmax) (3.05 vs. 2.31 m/s, <i>p</i> < 0.001) and elevated biomarkers (NT-proBNP: 200.06 vs. 61.49 pg/mL; troponin: 12.42 vs. 3.95 ng/L, <i>p</i> < 0.001) in the former subgroup. Regression analysis identified GLS, NT-proBNP, troponin, and TRVmax as independent predictors of CTRCD. Notably, a subgroup of CTRCD-free patients (<i>n</i> = 16) showed a high probability for HFpEF based on the HFA-PEFF score, with elevated GLS, NT-proBNP and DSTE-derived TRVmax compared to the rest of CTRCD-free patients and the CG (<i>p</i> < 0.001). <b>Conclusions:</b> STA and DSTE significantly outperform conventional LVEF in detecting subclinical cardiac dysfunction among women with breast cancer receiving chemotherapy. The combination of novel echocardiographic techniques and biomarkers may enable the detection of early CTRCD, including the under-estimated presence of HFpEF among breast cancer women with HF symptoms.