Atrial natriuretic peptide at discharge as a predictive marker for early rehospitalization in patients with heart failure with preserved ejection fraction

Abstract Background Hospitalization indicates poor prognosis in heart failure (HF) and frequent admissions is associated with worse outcomes, irrespective of left ventricular ejection fraction (LVEF)(1). Approximately 30% of patients are readmitted within 30 days, and the hemodynamic instability phase may last up to 90 days post-discharge(2). Although natriuretic peptides, namely ANP and BNP, are widely studied diagnostic markers, their role in predicting early rehospitalization in HF with preserved ejection fraction (HFpEF) patients remains inconsistent. Recent studies suggest discharge-phase testing offers better prognostic value(3), but no study has focused specifically on biomarkers for early rehospitalization in HFpEF, a growing and critical patient group in ageing society. Methods A retrospective analysis was conducted on 147 HFpEF patients hospitalized for acute heart failure between January 2015 and October 2020. Patients without measurement of natriuretic peptides and patients with end-stage renal failure were excluded. The ANP and BNP levels were measured at admission and discharge. Rehospitalization events were analyzed using survival curves and landmark analyses to evaluate the prognostic impact of natriuretic peptides. Results Of the 147 patients, 47 (32.0%) were rehospitalized within one year, with 22 cases (15.0%) occurring in the first 90 days post-discharge. Kaplan-Meier analysis assessed ANP and BNP levels at admission and discharge for their association with heart failure (HF) readmission within 365 days in HFpEF patients. Admission levels of ANP and BNP showed no significant predictive value (Fig1A and B). However, patients with high discharge ANP (≥113 pg/mL) had significantly higher HF readmission rates (Fig1C; p = 0.028). While high discharge BNP (≥184 pg/mL) showed only a trend toward increased rehospitalization (Fig1D; p = 0.072), discharge biomarkers overall were more prognostic than admission levels. Further analysis focused on discharge ANP and BNP as predictors of early rehospitalization within 90 days. High discharge ANP (dis-ANP) levels were associated with significantly higher 90-day rehospitalization rates (Fig2A; p = 0.0053), while discharge BNP showed no statistically significant difference (Fig2B; p = 0.074). At 30 and 60 days, high dis-ANP showed trends or significant differences, with this pattern persisting beyond 31 days. Subgroup analysis revealed that dis-ANP’s prognostic value was stronger in patients without atrial fibrillation (AF) and in those with a lower left atrial volume index (LAVI), showing significantly fewer rehospitalizations at 90 and 365 days in these groups. Conclusions Discharge ANP level served as a strong predictor of early rehospitalization in HFpEF patients. These findings suggest that incorporating ANP measurements into post-discharge management may enhance risk stratification and facilitate targeted interventions to reduce early rehospitalization in patients with HFpEF.Figure 1 Figure 2