Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure

BACKGROUND Natriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested. OBJECTIVES The authors compared plasma concentrations and relative strength of associations of A- and B -type NPs with cardiac structure/function and clinical outcomes in HF. METHODS Midregional pro-atrial natriuretic peptide (MR-proANP), B -type natriuretic peptide (BNP), and N -terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all -cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission. RESULTS Among 1,278 patients (age 60.1 +/- 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% +/- 14%), median concentrations of MR-proANP were 990 pg/mL (Q1 -Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1 -Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1 -Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MRproANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/ NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MRproANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all -cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05). CONCLUSIONS MR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B -peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall. (J Am Coll Cardiol HF 2024;12:461-474) (c) 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.