Similar predictive value of six-minute walking distance and B-type natriuretic peptide in heart failure with reduced to mid-range ejection fraction

The prognostic insights of heart failure (HF) with mid-range (40-49%) ejection fraction (HFmrEF) are not fully elucidated. We investigated whether the six-minutes walking test (6MWT) and brain natriuretic peptide (BNP) are predictive of outcome across the spectrum of LV systolic dysfunction and whether the HFmrEF cut-off impacts the risk stratification abilities of these tests. We studied 538 outpatients, aged 70±12 years, 28% females, with stable chronic HF and EF<50%, 349 with HFmrEF and 189 with HFrEF. End-points were all-cause and cardiac death. HFrEF patients were more often male, with ischemic etiology, severe symptoms, higher BNP levels, and cardiac mortality than HFmrEF subjects. During 32 (15-46) months follow-up, 123 (23%) patients died, 95 (18%) for cardiac causes. Cut-offs of 125 pg/ml for BNP and 360 meters for 6MWT distance were associated with lower all-cause (10% vs 38%, p<0.001 and 10% vs 26%, p<0.001, respectively) and cardiac mortality (6% vs 36%, p<0.001 and 8% vs 23%, p<0.001, respectively). BNP (HR 2.144, 95%CI, 1.403-3.276) and 6MWT walked distance (HR 1.923, 95%CI, 1.195-3.096) independently predicted outcome, after adjustment for age, gender, obesity, kidney dysfunction, ischemic etiology, NYHA class, unlike the 40% LVEF threshold. Model discrimination and survival differences were significant across LVEF strata. Higher BNP levels and shorter walked distance combined identified patients (26% overall) at particularly poor prognosis in both phenotype groups. Despite differences between HFmrEF and HFrEF patients in clinical and biomarker profile, BNP levels and 6MWT walked distance retain prognostic value over the entire spectrum of LV systolic dysfunction.