Background: Cardiac power-to-left ventricular mass (power/mass) is an index reflecting the muscular hydraulic pump capability of the heart, and the E/e' ratio is a specific indicator for identifying increased left ventricular filling pressure. Limited data exist regarding the prognostic value of incorporating power/mass and E/e' ratio in heart failure with preserved ejection fraction (HFpEF). Materials and methods: In total, 475 patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with complete baseline echocardiography data were included in our analysis. Patients were categorized into four groups according to power/mass and E/e' ratio. The risk of outcomes was examined using Cox proportional hazards models and competing risk models. Results: Patients with low power/mass and high E/e' were more likely to be males (60.5%), with higher waist circumference, and had a higher prevalence of diabetes (52.1%), atrial fibrillation (50.4%), and lower estimated glomerular filtration rate (eGFR). Combined resting power/mass and E/e' have graded correlations with left ventricular (LV) dysfunction and clinical outcomes in patients with HFpEF. After multivariable adjustments, an integrative approach combining power/mass and E/e' remained to be a powerful prognostic predictor, with the highest HRs of clinical outcomes observed in patients with low power/mass and high E/e' (all-cause mortality: HR 3.45; 95% CI: 1.69- 7.05; P = 0.001; hospitalization for heart failure: HR 3.27; 95% CI: 1.60-6.67; P = 0.001; and primary endpoint: HR 3.07; 95% CI: 1.73-5.42; P < 0.001). Conclusion: In patients with HFpEF, an echo-derived integrated approach incorporating resting power/mass and E/e' ratio remained to be a powerfulprognosis predictor and may be useful to risk-stratify patients with this heterogeneous syndrome.