ObjectiveTo investigate the effects of sacubitril/valsartan on myocardial energy metabolism and the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) mRNA in elderly patients with congestive heart failure (CHF) complicated by rapid atrial fibrillation (AF).MethodsA total of 150 elderly patients with CHF admitted to Xingtai Central Hospital from August 2022 to January 2024 were selected and randomly divided into a control group and an observation group. Patients who did not meet the inclusion and exclusion criteria were excluded. Eventually, 145 patients were included, including 71 in the control group and 74 in the observation group. The control group received conventional treatment, while the observation group was treated with additional sacubitril/valsartan. The following parameters were compared between the two groups: clinical efficacy, cardiac function parameters[ left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF)], myocardial injury markers[ creatine kinase-MB(CK-MB), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)], heart rate variability (HRV) indexes [standard deviation of NN intervals (SDNN), standard deviation of average NN intervals (SDANN), percentage of successive NN intervals differing by more than 50 ms (pNN50), and root mean square of successive differences (RMSSD)], myocardial energy metabolism markers [phosphocreatine to adenosine triphosphate (PCr/ATP) ratio, inorganic phosphate to phosphocreatine (Pi/PCr) ratio, and Pi/ATP ratio], mRNA expression levels of TLR4 and NF-κB, and adverse events.ResultsThe total effective rate in the observation group was significantly higher than that in the control group (χ²=7.097, P < 0.01). After treatment, the observation group showed significant reduction in LVEDD and LVESD, and increase in LVEF (t=3.070, 3.903, 5.831; P < 0.05). Compared to the control group, CK-MB, cTnI, NT-proBNP in the observation group were significantly lower (t=2.475, 4.005, 16.011; P < 0.05), while SDNN, SDANN, PNN50, RMSSD were higher (t=14.236, 6.835, 8.243, 3.292; P < 0.05). Compared to the control group, Pi/PCr and Pi/ATP were lower in the observation group, while PCr/ATP were higher (t=2.601, 5.015, 3.593; P < 0.05). The mRNA expressions of TLR4 and NF-κB in the observation group were lower than the control group (t=15.267, 10.855; P < 0.05). No statistically significant difference in adverse events was observed between the two groups (χ²=0.445, P > 0.05).ConclusionSacubitril/valsartan improves cardiac function and myocardial energy metabolism in elderly patients with CHF and rapid AF, while inhibiting TLR4 and NF-κB expressions, demonstrating a favorable safety profile.