Risk Stratification of Stage B Heart Failure with BNP Levels of 35–100 pg/mL: Development of the PHASE Index from the CHART-2 Study

Abstract Background B-type natriuretic peptide (BNP) levels of 35–100 pg/mL, common in preclinical heart failure (HF), are associated with heterogeneous prognosis and are influenced by age and renal function. We aimed to characterize risk heterogeneity in preclinical HF patients with BNP levels of 35–100 pg/mL, and to develop a practical risk stratification model. Methods Data from the Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) Study, a prospective multicenter cohort with long-term follow-up, were analyzed. Among patients with Stage B HF (n = 4,074; age 67.6 ± 12.0 years), the predictability of BNP for 10-year HF-related events was evaluated across strata of age and estimated glomerular filtration rate (eGFR). In patients with BNP levels of 35–100 pg/mL, a composite risk score—the Pre-Heart Failure Assessment and Screening Evaluation (PHASE) Index—was developed using classification and regression tree analysis and multivariable Cox proportional hazards modeling. Results BNP discrimination varied significantly by age and eGFR (p < 0.05), indicating that a single BNP threshold is insufficient for risk stratification in preclinical HF. The PHASE Index, incorporating age, BNP, eGFR, left ventricular ejection fraction, body mass index, and hypertension, stratified patients with BNP levels of 35–100 pg/mL into four categories and demonstrated superior discrimination compared with BNP alone (c-index 0.723 vs. 0.587, p < 0.05). Conclusions Patients with preclinical HF and BNP levels of 35–100 pg/mL exhibit substantial risk heterogeneity. The PHASE Index improves identification of high-risk individuals and provides a pragmatic tool for risk stratification beyond the conventional BNP threshold.