Clinical Scorecard: Levels of Circulating Dipeptidyl Peptidase 3, an Inhibitor of Angiotensin-(1–7), in Acute Heart Failure: Findings from the PUSH-AHF Study
At a Glance
Category | Detail |
|---|
Condition | Acute heart failure |
Key Mechanisms | Dipeptidyl peptidase 3 (DPP3) degrades bioactive peptides, including angiotensin II and angiotensin-(1–7). Its potential contribution to impaired diuretic response remains under investigation. |
Target Population | Adults with new-onset or decompensated acute heart failure |
Care Setting | Hospitalized patients enrolled in a single-center, pragmatic, open-label, randomized controlled trial |
Key Highlights
This PUSH-AHF biomarker substudy included 287 patients with available baseline circulating DPP3 (cDPP3) measurements.
Median baseline cDPP3 was 39 ng/mL (interquartile range, 26–62 ng/mL). Concentrations decreased by 17% within 24 hours and subsequently stabilized.
Both the lowest and highest cDPP3 quartiles were associated with lower estimated glomerular filtration rate and higher urea and N-terminal pro–B-type natriuretic peptide concentrations.
Higher baseline cDPP3 was associated with lower 24-hour natriuresis under standard care. This association was not observed with natriuresis-guided therapy, although the treatment-by-cDPP3 interaction was not significant.
cDPP3 did not significantly modify treatment effects on all-cause death or heart failure hospitalization within 180 days.
Guideline-Based Recommendations
Diagnosis
Management
Monitoring & Follow-up
Risks
Hemolysis can increase measured cDPP3 concentrations and potentially affect biomarker classification.
Associations with decongestive response do not establish causality or demonstrate that elevated cDPP3 independently predicts worse long-term outcomes in this population.
Patient & Prescribing Data
PUSH-AHF enrolled 310 adults with acute heart failure; 287 were included in this biomarker substudy. Their mean age was 73 years, and 43% were women. Patients received either natriuresis-guided diuretic therapy or standard care.
The analysis does not establish that selecting treatment according to cDPP3 concentrations improves survival or reduces heart failure hospitalization.
Clinical Best Practices
Interpret cDPP3 findings as exploratory rather than as established guidance for individualized treatment.
Distinguish improvements in early sodium excretion and urine output from effects on mortality and hospitalization.
Consider missing measurements, potential hemolysis effects, and the limited power to detect treatment interactions when interpreting the results.
Related Resources & Content
Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial — Ter Maaten JM, Beldhuis IE, Van der Meer P, Krikken JA, Postmus D, Coster JE, et al — Nature Medicine — 2023.
Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial — Ter Maaten JM, Beldhuis IE, Van der Meer P, Krikken JA, Coster JE, Nieuwland W, et al — European Journal of Heart Failure — 2022.
Dipeptidyl peptidase 3, a marker of the antagonist pathway of the renin–angiotensin–aldosterone system in patients with heart failure — Boorsma EM, Ter Maaten JM, Damman K, Van Veldhuisen DJ, Dickstein K, Anker SD, et al — European Journal of Heart Failure — 2021.
Circulating dipeptidyl peptidase 3 modulates systemic and renal hemodynamics through cleavage of angiotensin peptides — Picod A, Placier S, Genest M, Callebert J, Julian N, Zalc M, et al — Hypertension — 2024.
Novel methods for the quantification of dipeptidyl peptidase 3 (DPP3) concentration and activity in human blood samples — Rehfeld L, Funk E, Jha S, Macheroux P, Melander O, Bergmann A — The Journal of Applied Laboratory Medicine — 2019.
