Background <p>Patients with concomitant atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) face significant morbidity and limited therapeutic options. This retrospective cohort study evaluated the effects of dapagliflozin combined with sacubitril/valsartan on cardiac electrophysiological and myocardial motion parameters in this population.</p> Methods <p>Data from 292 patients treated between January 2022 and December 2024 were analyzed. Patients received either sacubitril/valsartan alone (SVC Group, <i>n</i> = 154) or combined with dapagliflozin (D + SVC Group, <i>n</i> = 138). At baseline and at 6 months, cardiac structure/function, electrophysiology, biomarkers, and functional capacity were assessed, in addition to the evaluation of clinical events and safety.</p> Results <p>Baseline characteristics were comparable between groups. After 6 months, the D + SVC Group demonstrated significantly greater improvements in left atrial volume index (LAVI, <i>p</i> &lt; 0.001), left ventricular ejection fraction (LVEF, <i>p</i> = 0.004), left ventricular mass index (LVMI, <i>p</i> = 0.011), left atrial diameter (LAD, <i>p</i> = 0.009), E/e′ ratio (<i>p</i> &lt; 0.001), heart rate variability indices (<i>p</i> &lt; 0.05), P-wave duration (PWD, <i>p</i> = 0.008), P-wave dispersion (PD, <i>p</i> = 0.002), P-terminal force in V1 (PTFV1, <i>p</i> &lt; 0.001), NT-proBNP (<i>p</i> &lt; 0.001), NLR (<i>p</i> &lt; 0.001), hs-CRP levels (<i>p</i> &lt; 0.001), 6-minute walk distance (<i>p</i> = 0.002), and Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 scores (<i>p</i> &lt; 0.001) than the SVC Group. The D + SVC group exhibited reduced rates of HF rehospitalization (<i>p</i> = 0.026) and cardiovascular death (<i>p</i> = 0.030), along with a greater reduction in AF burden (<i>p</i> &lt; 0.001).</p> Conclusion <p>These findings suggest that adding dapagliflozin to sacubitril/valsartan may provide additional benefits for these patients.</p>