Biomarker-defined congestion profiles in very old adults with acute heart failure: beyond ejection fraction classification

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Acute heart failure (n=830). Intervention: High BNP and High CA125 (C4 phenotype) vs. Low BNP and Low CA125 (C1 phenotype). Primary outcome: All-cause mortality (HR 1.48, 95% CI 1.11-1.99, p=0.008).

Pau Llàcer; François Croset; Alberto Pérez Nieva; Jorge Campos; Marina García Melero; Carlos Perez; Marina Vergara; Paul Cevallos Castro; Juanes Oyuela Rodriguez; Cristina Fernández; María Pumares; Martín Fabregate; Beatriz Del Hoyo; Esteban Pérez Pisón; Luis Manzano

doi:10.1007/s41999-026-01505-y

May 25, 2026European Geriatric MedicineOpen Access

Biomarker-defined congestion profiles in very old adults with acute heart failure: beyond ejection fraction classification

View Full Paper

Ask AI

Bookmark

Share

Key result

Combined BNP and CA125 elevation in acute heart failure linked to ~48% higher mortality.

HR 1.48
95% CI 1.11-1.99
P=0.008
n=830

Figures

Why the study?

Congestion manifestation and prognostic relevance in very old adults with acute heart failure remain incompletely understood, and traditional LVEF classification may not capture its biological heterogeneity.

Do biomarker-defined congestion profiles using BNP and CA125 predict mortality and rehospitalization better than LVEF in very old adults with acute heart failure?

Key Points

To characterize congestion phenotypes defined by BNP and CA125 constellations in very old adults hospitalized with acute heart failure and evaluate their prognostic value compared with conventional LVEF categories.
Retrospective cohort study of 830 consecutive patients hospitalized with acute heart failure (median age 87 years, 65.6% women).
Congestion was assessed using clinical signs, echocardiography, point-of-care ultrasound, and circulating biomarkers (BNP and CA125).
Primary endpoints of all-cause mortality and heart failure rehospitalization were evaluated over a median follow-up of 310 days (IQR 62–543) using multivariable Cox regression models.
All-cause mortality reached 50.4% (418 deaths) overall; combined elevation of BNP and CA125 (C4: 59.3% mortality) independently predicted higher death risk compared with low levels of both (HR 1.48, 95% CI 1.11–1.99; p = 0.008).
Heart failure rehospitalization occurred in 36.3% of patients (301 events); isolated CA125 elevation (C3: 41.3% rehospitalization) was independently associated with increased readmission risk compared with low biomarker levels (HR 1.45, 95% CI 1.03–2.03; p = 0.031).

Study Design

Type

Cohort (n=830)

Multicenter

No

Structured PICO

Do biomarker-defined congestion profiles using BNP and CA125 predict mortality and rehospitalization better than LVEF in very old adults with acute heart failure?

P

Population

830 consecutive very old adults hospitalized with acute heart failure, median age 87 years, 65.6% women.

I

Intervention

Biomarker-defined congestion profiles (four subgroups defined by BNP and CA125 constellations)

C

Comparator

Comparison across the four biomarker-defined subgroups and conventional LVEF categories

O

Outcome

Heart failure rehospitalization and all-cause mortality over a median follow-up of 310 dayshard clinical

Main Result

Effect estimate: HR 1.48 (95% CI 1.11-1.99)

Absolute Event Rate: 59.3% vs 40.5%

p-value: p=0.008

In very old adults with acute heart failure, combined elevation of BNP and CA125 provides better prognostic discrimination for mortality and rehospitalization than conventional LVEF classification.

Limitations

Retrospective, single-center design may limit generalizability
Selected cohort of very old and multimorbid patients admitted to Internal Medicine may underrepresent patients with more severe systolic dysfunction
Congestion assessment was based on parameters measured at admission, without serial evaluation
Invasive hemodynamic measurements were not available
Biomarker-defined patient subgroups were based on median values and should be considered exploratory
Frailty was not formally assessed

Implication

May refine mortality risk stratification beyond LVEF in very old AHF; hypothesis-generating and requires prospective validation.

Abstract

Background Congestion is the main driver of worsening acute heart failure, yet its manifestation in very old adults and its relationship with prognosis remains incompletely understood. Traditional classification based on left ventricular ejection fraction (LVEF) may not adequately capture the biological heterogeneity of congestion in this population. We aimed to characterize patient subgroups defined by BNP and CA125 constellations, to characterize their clinical and echocardiographic features, and to evaluate their prognostic implications. As a secondary objective, we explored their relationship with conventional LVEF categories. Methods We conducted a retrospective cohort study including 830 consecutive patients hospitalized with acute heart failure. Congestion was assessed using clinical signs, echocardiography, biomarkers (BNP and CA125), and point-of-care ultrasound. Outcomes included heart failure rehospitalization and all-cause mortality over a median follow-up of 310 days (IQR 62–543). Multivariable Cox regression models were used. Results The median age was 87 years, and 65.6% were women. Four patient subgroups were defined by BNP and CA125 constellations, showing distinct clinical and echocardiographic profiles. Mortality increased progressively across phenotypes, with combined elevation of BNP and CA125 independently associated with higher risk of death (HR 1.48; p = 0.008). Isolated CA125 elevation was associated with increased rehospitalization risk (HR 1.45; p = 0.031). In contrast, LVEF categories showed limited prognostic discrimination. Conclusions In very old adults hospitalized with acute heart failure, combined elevation of BNP and CA125 was independently associated with increased mortality, while isolated CA125 elevation was associated with higher rehospitalization risk. LVEF was not independently associated with either outcome. These findings suggest that integrating BNP and CA125 may complement conventional LVEF classification for risk stratification in this population.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Llàcer et al. (2026) conducted a cohort in Acute heart failure (n=830). High BNP and High CA125 (C4 phenotype) vs. Low BNP and Low CA125 (C1 phenotype) was evaluated on All-cause mortality (HR 1.48, 95% CI 1.11-1.99, p=0.008). Combined elevation of BNP and CA125 in very old adults hospitalized with acute heart failure was independently associated with a higher risk of all-cause mortality (HR 1.48) compared to low levels of both biomarkers.

synapsesocial.com/papers/6a1422b132782f38666282ce https://doi.org/10.1007/s41999-026-01505-y

View Full Paper

Ask AI

Bookmark

Share

Biomarker-defined congestion profiles in very old adults with acute heart failure: beyond ejection fraction classification

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Biomarker-defined congestion profiles in very old adults with acute heart failure: beyond ejection fraction classification

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading