Prognostic value of early NT-proBNP changes in acute HF varies across LVEF spectrum

In a retrospective analysis, a greater early NT-proBNP reduction was associated with lower risks of all-cause mortality, CV death, and recurrent HF hospitalizations in patients with acute HF but not in those with LVEF ≥65%.

This summary is based on the publication of Núñez-Marín G, de la Espriella R, Llàcer P, et al. - Prognostic value of early changes in NT-proBNP across left ventricular ejection fraction status in acute heart failure. Eur J Heart Fail. 2026 Jan 21:xuag018 [Online ahead of print]. doi: 10.1093/ejhf/xuag018

Introduction and methods

Background

In patients with acute HF (AHF), greater NT-proBNP reductions are associated with improved outcomes across the LVEF spectrum although to a lesser extent in HFpEF [1-4]. In the HFpEF population, HF patients with supranormal LVEF (HFsnEF; typically defined as LVEF ≥65%) may represent a distinct pathophysiological subgroup [5-8].

Aim of the study

The study aim was to evaluate the prognostic value of early NT-proBNP changes in patients hospitalized for AHF, across LVEF categories.

Methods

In a retrospective analysis of an ongoing AHF registry conducted at 3 tertiary centers in Spain, 3276 consecutive patients hospitalized for AHF (both new-onset and decompensated chronic HF) in the period 2008–2021 were included. At baseline, 1190 patients (36.3%) had LVEF ≤40%, 436 (13.3%) had LVEF 41%–49%, 1031 (31.5%) had LVEF 50%–64%, and 619 (18.9%) had LVEF ≥65%. Plasma NT-proBNP levels were measured at admission and within 48–72 hours, at the discretion of the treating physician. Median follow-up time was 1.65 years (IQR: 0.40–2.66).

Outcomes

The primary endpoints were all-cause mortality, CV death, and recurrent hospitalization for HF.

Main results

• The cumulative incidence of all-cause mortality was lower in patients with an early decline in NT-proBNP levels from baseline to the second measurement of ≥30% (n=1058) than in those with NT-proBNP decline <30% (n=2218) (12.8 per 100 person-years; 95%CI: 11.6–14.1 vs. 20.0 per 100 person-years; 95%CI: 18.8–21.2; P<0.001).
• Similar patterns were observed for the rates of CV death and recurrent HF hospitalizations (both P<0.001).
• When the relative NT-proBNP change was analyzed as a continuous variable, after multivariable adjustment, a greater NT-proBNP decline showed a strong relationship with a lower risk of all-cause mortality in patients with LVEF ≤40% (P<0.001). This association weakened in patients with LVEF 41%–49% (P=0.014) and those with LVEF 50%–64% (P=0.003) and was nonsignificant in participants with LVEF ≥65% (P=0.382; P for interaction=0.022).
• Heterogenous associations were also found between the relative NT-proBNP change and CV death (P for interaction=0.031) and recurrent HF hospitalizations (P for interaction=0.002), ranging from strong associations in patients with LVEF ≤40% (both P<0.001) to nonsignificant associations in those with LVEF ≥65% (both P>0.05).
• Similar patterns for the relationships with the 3 outcomes were seen when the relative NT-proBNP change was analyzed as a dichotomous variable (≥30% vs. <30%).

Conclusion

This retrospective analysis of an observational Spanish multicenter cohort of patients hospitalized for AHF showed that a greater early NT-proBNP reduction was independently associated with lower risks of all-cause mortality, CV death, and recurrent HF hospitalizations, particularly in those with LVEF ≤40%. The prognostic association progressively attenuated with increasing LVEF and was no longer present in patients with HFsnEF (i.e., LVEF ≥65%).

The authors conclude: “Our findings caution against the uniform application of NT-proBNP dynamics for risk stratification across the entire spectrum of AHF. [...] By demonstrating differential risk-marker behavior at supranormal EF, these data both underscore the need to identify and validate alternative prognostic markers tailored to this subgroup and inform the ongoing debate on whether supranormal EF HF constitutes a specific entity within HFpEF.”

Find this article online at Eur J Heart Fail.

References

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