Valvular changes following anthracycline therapy: is it time to look beyond ejection fraction?

Abstract

Abstract Background Advancements in early detection and treatment of breast cancer have improved survival, but with the costs of side effects, with cardiotoxicity being the most significant one. Anthracycline (ANT) is the most recognized therapy leading to cardiotoxicity, mainly manifested as left ventricle (LV) dysfunction. While the changes in LV ejection fraction (LVEF) are well studied, little is known about the effect of ANT on valvular function. We aimed to evaluate the change in valvular function following ANT therapy in patients diagnosed with breast cancer. Methods The study population is part of the Israel Cardio-Oncology Registry (ICOR). All patients performed serial echocardiography; before (T1), during (T2), at the end (T3), and following (T4) ANT therapy, assessing valvular changes. Exclusion criteria included age below 18 and baseline LVEF <55%. Results The study included 141 female patients diagnosed with breast cancer and treated with ANT with a mean age of 51±12 years (Table 1). During a median follow-up of 255 [IQR 214–313] days, from T1 to T4, we observed a significant increase in the portion of patients developing new mitral regurgitation (MR) (3.5% to 18.7%, p<0.0001), with a trend for developing moderate and above MR (0.7% to 3.3%, p=0.13). While a statistically significant reduction in mean LVEF (60.2%±1.5 to 59.2%±2.7, p=0.0004) and median LV global longitudinal strain (LV GLS) (−21.6% [−20.0 to −23.0] to −20.0% [−19.1 to −21.1], p<0.0001) was observed (Figure 1), the values remain within the normal range with no significant clinical change. In a multivariate binary logistic regression model, age (OR 1.06, 95% CI: 1.01–1.11) and trastuzumab therapy (OR 5.59, 95% CI: 1.95–16.6) were strong independent predictors for MR development, while medical history was not. Conclusions MR development following ANT exposure is frequent, increasingly after the completion of ANT therapy. The parallel reduction in LV function might imply a functional mechanism. Larger trials are needed to evaluate the MR prognostic clinical role in cancer patients. Funding Acknowledgement Type of funding sources: None.