cDPP3 and Outcomes in Acute Heart Failure: An Analysis of the STRONG-HF and CORTAHF Studies

Q: What are the key findings of this study?

In patients with acute heart failure, elevated baseline cDPP3 ≥ 40 ng/mL was not significantly associated with 180-day clinical outcomes.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Acute Heart Failure (n=1068). Intervention: Elevated baseline cDPP3 (≥40 ng/mL) vs. Baseline cDPP3 <40 ng/mL. Primary outcome: Composite of all-cause mortality or HF readmission through 180 days (STRONG-HF) (Not significantly associated with outcomes, p=0.57).

Q: What does this research mean for the field?

In patients with acute heart failure, elevated baseline circulating dipeptidyl peptidase 3 (cDPP3 ≥ 40 ng/mL) is not associated with adverse 180-day clinical outcomes or congestion relief. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

J Bruno; Christopher Edwards; Koji Takagi; F Azibani; B Davison; Gad Cotter; K Bourgeois; Oliver Hartmann; A P Ambrosy; A Mebazaa; Adrien Picod

doi:10.1093/eschf/xvag076

March 14, 2026ESC Heart FailureOpen Access

cDPP3 and Outcomes in Acute Heart Failure: An Analysis of the STRONG-HF and CORTAHF Studies

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Key result

Elevated baseline cDPP3 fails to predict 180-day clinical outcomes in acute heart failure.

Not significantly associated with outcomes
P=0.57
n=1,068

Figures

Graphical abstract published by ESC Heart Failure — Graphical abstract · Published by ESC Heart Failure · CC BY

Why the study?

Does elevated baseline cDPP3 (≥40 ng/mL) predict adverse clinical outcomes or correlate with congestion relief during GDMT optimization in patients with acute heart failure?

Key Points

To assess the clinical relevance, prognostic value, and longitudinal changes of circulating dipeptidyl peptidase 3 (cDPP3) in patients with acute heart failure undergoing medical therapy optimization.
Measured cDPP3 at baseline and follow-up (day 90 in STRONG-HF; day 30 in CORTAHF) and evaluated associations with 180-day and 90-day outcomes, respectively.
Evaluated longitudinal changes in cDPP3 during guideline-directed medical therapy (high-intensity vs. usual care in STRONG-HF) and assessed predictors of elevated baseline cDPP3 (≥40 ng/mL).
In STRONG-HF, 222 of 973 patients (23%) had baseline cDPP3 ≥ 40 ng/mL, but this elevation was not associated with 180-day clinical outcomes (P = .57).

Study Design

Type

Cohort (n=1,068)

Multicenter

Yes

Structured PICO

Does elevated baseline cDPP3 (≥40 ng/mL) predict adverse clinical outcomes or correlate with congestion relief during GDMT optimization in patients with acute heart failure?

P

Population

1,068 patients hospitalized for acute heart failure from the STRONG-HF (n=973) and CORTAHF (n=95) trials, evaluated for the prognostic significance of baseline cDPP3.

E

Exposure

Baseline circulating dipeptidyl peptidase 3 (cDPP3) concentration ≥ 40 ng/mL (prognostic threshold); and high-intensity care consisting of rapid up-titration of guideline-directed medical therapy (ACEi/ARB/ARNI, beta-blocker, MRA) for the trajectory analysis.

C

Comparator

Baseline cDPP3 < 40 ng/mL; and usual care for the trajectory analysis.

O

Outcome

Composite of all-cause mortality or heart failure readmission through 180 days (in STRONG-HF) and composite of death, worsening heart failure, or heart failure readmission through 90 days (in CORTAHF).composite

Main Result

Effect estimate: Not significantly associated with outcomes

p-value: p=0.57

In patients hospitalized for acute heart failure without overt shock, circulating DPP3 levels are only mildly elevated, are independently associated with MRA use and Black ethnicity, and do not serve as an independent predictor of 180-day adverse clinical outcomes.

Limitations

Pooled analysis combined data from two distinct clinical trials
CORTAHF cohort was too small to allow definitive conclusions
Heterogeneity in terms of HF aetiology and clinical severity
Detailed haemodynamic data were not available
Observational nature of this biomarker analysis limits causal inference
Potential ex vivo haemolysis falsely elevating cDPP3
Very low number of CORTAHF patients with cDPP3 ≥ 40 ng/mL, making those analyses primarily driven by STRONG-HF
Heterogeneity of heart failure aetiologies, trigger factors, disease stages, and haemodynamic profiles making interpretation challenging
Mid-term timeframe of analysis might miss transient early dynamics

Discussion

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Implication

Elevated cDPP3 lacks prognostic value in acute HF without shock; leaves open its role in cardiogenic shock or as a modifiable target.

Abstract

INTRODUCTION: Circulating dipeptidyl peptidase 3 (cDPP3) is implicated in cardiocirculatory failure and elevated concentrations predict poor outcomes in shock states. Its role in acute heart failure (AHF) is unexplored. We assessed the clinical relevance of cDPP3 in AHF. METHODS: Analyses were performed using two prospective AHF trials: STRONG-HF and CORTAHF. cDPP3 was measured at baseline and follow-up (day 90 in STRONG-HF; day 30 in CORTAHF). Associations with 180-day (STRONG-HF) and 90-day (CORTAHF) outcomes were evaluated according to baseline concentrations. Longitudinal changes during guideline-directed medical therapy (GDMT) optimization and predictors of elevated cDPP3 were analysed. RESULTS: In STRONG-HF, 222/973 patients (23%) had cDPP3 ≥ 40 ng/mL. These patients were younger (58 ± 15 vs. 65 ± 13 years, P < .0001), more frequently female (47.7% vs. 35.8%, P = .0013) and Black (42.8% vs. 14.4%, P < .0001), with lower NT-proBNP concentrations (P < .0001). Baseline cDPP3 ≥ 40 ng/mL was not associated with 180-day outcomes. Over 90 days, cDPP3 decreased by -15% with high-intensity care and -8% with usual care (P = .078). Changes in cDPP3 were not associated with NT-proBNP reduction (continuous P = .797; ≥30% responder P = .990). In pooled multivariable analysis, MRA use was independently associated with cDPP3 ≥ 40 ng/mL (OR 3.83; 95% CI 1.47-9.96; P = .006), whereas non-Black ethnicity was associated with lower odds (OR 0.43; 95% CI 0.29-0.64; P < .0001). CONCLUSION: In AHF, cDPP3 was mildly elevated and was not associated with clinical outcomes or congestion relief during GDMT optimization. Elevated cDPP3 identified a distinct clinical phenotype but did not confer adverse prognosis.

Cite This Study

Bruno et al. (2026) conducted a cohort in Acute Heart Failure (n=1,068). Elevated baseline cDPP3 (≥40 ng/mL) vs. Baseline cDPP3 <40 ng/mL was evaluated on Composite of all-cause mortality or HF readmission through 180 days (STRONG-HF) (Not significantly associated with outcomes, p=0.57). In patients with acute heart failure, elevated baseline cDPP3 ≥ 40 ng/mL was not significantly associated with 180-day clinical outcomes.

synapsesocial.com/papers/69ba424e4e9516ffd37a27ac https://doi.org/10.1093/eschf/xvag076

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cDPP3 and Outcomes in Acute Heart Failure: An Analysis of the STRONG-HF and CORTAHF Studies

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Abstract

Cite This Study

cDPP3 and Outcomes in Acute Heart Failure: An Analysis of the STRONG-HF and CORTAHF Studies

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Abstract

Cite This Study

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