Objective To investigate the correlation between serum levels of phosphoglycerate mutase family member 5(PGAM5)and YT521-B homology N6-methyladenosine RNA binding protein 2(YTHDF2)with ventricular remodeling and prognosis in patients with heart failure with preserved e-jection fraction(HFpEF).Methods A total of 175 HFpEF patients(HFpEF group)were selected as subjects,and 90 healthy volunteers undergoing physical examinations were chosen as the control group.The HFpEF patients were divided into adverse prognosis group(n=61)and favorable progno-sis group(n=114)based on their prognosis status.Serum PGAM5 and YTHDF2 levels were meas-ured using enzyme-linked immunosorbent assay.Ventricular remodeling indicators[left ventricular posterior wall thickness(LVPWT),left ventricular end-diastolic diameter(LVEDD),interventricular septal thickness at end-diastole(IVST)and left ventricular mass index(LVMI)]were assessed by transthoracic echocardiography.Pearson correlationanalysis was used to analyze the relationship be-tween serum PGAM5 and YTHDF2 levels and ventricular remodeling indicators.The relationships of serum PGAM5 and YTHDF2 levels with the prognosis of HFpEF patients,as well as predictive effi-cacy,were evaluated using multivariate unconditional logistic regression analysis and receiver oper-ating characteristic curve analysis,respectively.Results Levels of LVPWT,LVEDD,IVST,LVMI and YTHDF2 in the HFpEF group were significantly higher than those in the control group,while PGAM5 levels were significantly lower(P＜0.05).Serum PGAM5 levels in HFpEF patients showed negative correlations with LVPWT,LVEDD,IVST and LVMI,whereas YTHDF2 levels showed positive correlation(P＜0.05).The incidence of adverse prognosis among 175 HFpEF pa-tients was 34.86％(61/175).Significant differences were observed in age,New York Heart Asso-ciation(NYHA)heart function classification,N-terminal pro-B-type natriuretic peptide(NT-proBNP),LVPWT,LVEDD,IVST,LVMI,PGAM5 and YTHDF2 between the adverse prognosis group and favorable prognosis group.High levels of PGAM5 and YTHDF2 were independent protective and risk factors for adverse prognosis in HFpEF patients(P＜0.05).The area under the curve for predic-ting adverse prognosis in HFpEF patients using combined serum PGAM5 and YTHDF2 levels was 0.884,which was greater than the values obtained from individual predictions of 0.790 and 0.791(Z=3.722,3.373;P＜0.001).Conclusion Decreased serum PGAM5 levels and increased YTHDF2 levels are associated with worsening ventricular remodeling and poor prognosis in HFpEF patients.Combined measurement of serum PGAM5 and YTHDF2 levels shows high predictive effica-cy for the prognosis of HFpEF patients.