Background: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognized that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterization. We therefore aimed to analyze the available aggregate evidence for ANT related diastolic dysfunction.

Methods: Studies reporting on diastolic function before and after ANT in breast cancer patients without cardiac disease were included. We evaluated echocardiographic parameters derived from pulsed wave Doppler interrogation of the mitral valve inflow (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e’) and E/e’ ratio).

Results: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT (difference in means (DM) 0.14, 95% CI [0.06 – 0.22], p < 0.001) (Figure 1), while EDT was not influenced in the course of cancer therapy (DM -5.71, 95% CI [-13,17 – 1.74], p = 0.133). Mean tissue Doppler velocity of the mitral ring e’ and the LV filling pressures analysed through E/e’ ratio showed no significant change after ANT (DM 1.26, 95% CI [0.002 – 2.52], p = 0.050) (Figure 2), and (DM -0.25, 95% CI [-0.65 – 0.14)], p = 0.212, respectively) (Figure 3). A modest reduction in LVEF and global longitudinal strain (GLS) was observed at the end of ANT therapy (DM 3.77, 95%CI [1.68 – 5.86], p < 0.001) and (DM - 2.16%, 95%CI [-3.38 – -0.94]) respectively. Patients receiving ANT doses over 400 mg/m² doxorubicin or epirubicin equivalent showed a significant change in E/A and e’ after ANT.

Conclusion: ANT had a modest early impact on E/A ratio, without changing EDT, e’, or  E/e’ in patients with breast cancer without cardiac disease. Randomized studies on larger populations, using new parameters e.g. left atrial function parameter, strain parameter, and multimodality imaging are required in order to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity. 

Figure 1. Overall and individual study estimates of the difference in means (DM) for E/A ratio before and after anthracycline-based chemotherapy

Square boxes denote DM for each study, parallelogram boxes denote the overall DM, and horizontal lines represent 95% confidence intervals. E/A = mitral E-wave filling velocity/mitral A-wave filling velocity.

Figure 2. Overall and individual study estimates of difference in means (DM) for the e’ mean velocity of the mitral ring before and after anthracycline-based chemotherapy

Square boxes denote DM for each study, parallelogram boxes denote the overall DM, and horizontal lines represent 95% confidence intervals.

Figure 3. Overall and individual study estimates of difference in means (DM) for the E/e’ ratio before and after anthracycline-based chemotherapy

Square boxes denote DM for each study, parallelogram boxes denote the overall DM, and horizontal lines represent 95% confidence intervals.