BACKGROUND: Sacubitril-valsartan (SV), an angiotensin receptor-neprilysin inhibitor, improves clinical outcomes in HFrEF patients through reverse remodeling; however, predictors of response remain uncertain. Left atrial strain (LAS) assessment may refine the definition and prediction of remodeling in this cohort. METHODS: In our hospital's heart failure registry, HFrEF patients prescribed SV were retrospectively identified. Correlations were assessed between LAS phases (reservoir [LASr], conduit [LAScd], and contractile [LASct]) and both left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV), using baseline values and therapy-associated changes (Δ). Multivariable linear regression was used to investigate associations between baseline LAS phases and subsequent ΔLVEF and ΔLVESV. RESULTS: Among 127 patients, SV therapy was associated with improvements in LVEF (+5.8 ± 12.8%; p < 0.001) and LVESV (-23.5 ± 53.5 mL; p < 0.001), as well as in left atrial and ventricular volumes. At baseline, LASr and LAScd correlated with both LVEF and LVESV, while only ΔLASr correlated with both ΔLVEF and ΔLVESV. On multivariable regression, baseline LASr, and LAScd were both associated with subsequent ΔLVEF (β per 5% increase: -1.69 [95% CI: -3.03 to -0.36] and -2.12 [95% CI: -4.12 to -0.13], respectively) and ΔLVESV (β per 5% increase: 11.01 [95% CI: 5.28 to 16.74], and 14.95 [95% CI: 6.39 to 23.51], respectively). When additionally adjusted for the baseline of the corresponding outcome measure, only LASr remained independently associated with ΔLVESV (β per 5% increase: 4.77 [95% CI: 0.01 to 9.53], p = 0.049). CONCLUSION: In HFrEF patients, LASr tracks SV-associated reverse remodeling and is independently associated with subsequent therapy-associated changes in LVESV.