Effects of sacubitril/valsartan on left and right ventricular function during and after breast cancer therapy: a randomised placebo-controlled trial
M N Gynnild, A Mecinaj-Lilleaasen, T Wethal, V Vinje-Jakobsen, E O Jakobsen, S L Heck, J Geisler, S Larsen, A Rosner, H Dalen, T Omland, G Gulati, E HolteAbstract
Background
Sacubitril–valsartan may exert cardioprotective effects during anthracycline- and trastuzumab-based therapy in breast cancer; however, clinical evidence remains limited, and its impact on sensitive echocardiographic markers of left ventricular (LV) and right ventricular (RV) function has not been systematically evaluated in randomized settings.
Objectives
To characterize longitudinal changes in LV systolic and diastolic function and RV systolic function by echocardiography, and to evaluate the effects of sacubitril–valsartan versus placebo during and after breast cancer therapy.
Methods
In this predefined substudy of a randomized, placebo-controlled trial, 138 women receiving adjuvant anthracyclines (± trastuzumab) underwent comprehensive echocardiography at baseline, after completion of anthracycline therapy, and at 18 months. LV systolic (including global longitudinal strain and ejection fraction), LV diastolic, and RV systolic indices were analyzed in a blinded core laboratory. Longitudinal changes and between-group differences were assessed using mixed-effects regression models.
Results
Global longitudinal strain (GLS) remained stable in the sacubitril–valsartan group but deteriorated in the placebo group (between-group difference in change from baseline to 18 months −1.26%, 95% CI −2.19 to −0.33; p = 0.008). The between-group difference in GLS remained significant after adjustment for time-varying systolic blood pressure (−1.15%, 95% CI −2.09 to −0.20; p = 0.017). Sacubitril–valsartan was associated with more favorable RV free-wall strain (−2.82%, 95% CI −5.21 to −0.44), higher RV S′ velocity (+1.28 cm/s, 95% CI 0.43–2.13), and higher mitral e′ velocity (+0.83 cm/s, 95% CI 0.12–1.5). LV ejection fraction (LVEF) declined slightly and similarly in both groups (−0.31%, 95% CI −2.7 to 2.1) and no significant between-group differences were observed for conventional RV indices including tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). Changes in other diastolic indices were small and similar between groups. Categorical diastolic dysfunction remained infrequent throughout follow-up. Standard biplane grayscale and Doppler measurements were highly feasible (>90%), whereas feasibility was lower for three-dimensional LVEF (60–63%) and GLS (76–81%).
Conclusions
Sacubitril–valsartan was associated with more favorable trajectories of both left and right ventricular function assessed by sensitive echocardiographic measures, while conventional LVEF remained similar between groups. These findings suggest potential cardioprotective effects beyond LVEF preservation during breast cancer therapy.