Key result
Elevated baseline cDPP3 in acute heart failure is not associated with 180-day outcomes or congestion relief.
Why the study?
Circulating dipeptidyl peptidase 3 (cDPP3) predicts poor outcomes in shock states, but its clinical relevance in acute heart failure remains unexplored.
Does elevated baseline cDPP3 predict adverse clinical outcomes or congestion relief in patients with acute heart failure?
Does elevated baseline cDPP3 predict adverse clinical outcomes or congestion relief in patients with acute heart failure?
In acute heart failure, elevated cDPP3 identifies a distinct clinical phenotype (younger, more frequently female and Black) but is not associated with adverse clinical outcomes or congestion relief during GDMT optimization.
Should not guide risk stratification in acute HF; leaves open relevance of its distinct demographic phenotype on GDMT.
Aims 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 Analysis 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 < 0.0001), more frequently female (47.7% vs. 35.8%, p = 0.0013) and Black (42.8% vs. 14.4%, p < 0.0001), with lower NT-proBNP concentrations (p<0.0001). 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=0.078). Changes in cDPP3 were not associated with NT-proBNP reduction (continuous p=0.797; ≥30% responder p=0.990). In pooled multivariable analysis, MRA use was independently associated with cDPP3 ≥40 ng/mL (OR 3.83; 95% CI 1.47-9.96; p = 0.006), whereas non-Black ethnicity was associated with lower odds (OR 0.43; 95% CI 0.29-0.64; p < 0.0001).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.
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Bruno et al. (2026) studied this question. Elevated baseline cDPP3 (≥40 ng/mL, present in 23% of patients) in acute heart failure was not associated with 180-day clinical outcomes or congestion relief.
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