Prevalence and Prognostic Value of Updated Pre-HF Staging Definitions

Background Heart failure (HF) guidelines redefined Stage B HF to include elevated cardiac biomarkers alongside echocardiographic abnormalities. Whether this improves identification and prognostication beyond the former echo-only definition is unknown. Methods Participants without HF or CVD were pooled from four community-based cohorts (ARIC, CRIC, FHS Offspring, FHS Third Generation). Stage B Former was defined as echo abnormalities alone, Stage B Updated as echo and/or biomarker abnormalities, and Stage B Updated further subclassified as Biomarker Only, Echo Only, or Biomarker+Echo. Cox models assessed HF risk for Stage B vs Stage A under each definition and across Stage B updated subtypes. Incremental value over PREVENT-HF was assessed by NRI/IDI. Optimal NT-proBNP thresholds for predicting HF risk were stratified by echo abnormality status. Results Among 11,426 participants (56% women, mean 60y), 8,413 (73.6%) were Stage B Updated vs 6,659 (58.3%) Stage B Former , with 15.4% newly classified by biomarkers alone. Risk of incident HF associated with Stage B versus Stage A HF was higher using the updated (aHR[95%CI], 3.02[2.12–4.31]) versus former definition (1.67[1.36–2.06]). Among Stage B updated subtypes, Stage B Biomarker Only (3.11[2.07–4.66]) and Stage B Biomarker+Echo (5.12 [3.54–7.41]) carried elevated risk of incident HF, but Stage B Echo Only did not (1.31 [0.86–1.99]). When added to PREVENT-HF, the updated definition improved reclassification (NRI, 0.099[0.040–0.152]) and discrimination slope (IDI, 0.009[0.006–0.012]); the former provided a smaller gain in discrimination slope (IDI, 0.003[0.000–0.007]) without improving reclassification (NRI, 0.020[−0.050 to 0.088]). Optimal NT-proBNP thresholds were lower without than with echo abnormalities (80.3 vs 166.3 pg/mL), and risk above each threshold was elevated in both strata (5.70[3.00–10.83] and 4.84[3.75–6.24]). Conclusions Incorporating biomarkers into HF staging identifies a substantial at-risk subgroup missed by echo alone, supporting biomarker inclusion in Stage B HF criteria.