Circulating dipeptidyl peptidase 3 levels in acute heart failure: insights from the PUSH-AHF trial
S Legtenberg, I E Beldhuis, L E E C Zonneveld, A A Voors, K Damman, J M Ter MaatenAbstract
Background
Angiotensin-(1-7) lowers blood pressure by promoting vasodilation and opposing Angiotensin II in the vasculature, kidneys, and brain, while DPP3 limits these effects by inactivating Ang-(1-7). While the role of DPP3 has been studied in chronic heart failure (HF), data in acute HF are limited. This study aimed to evaluate DPP3 levels and the association with clinical profiles and outcomes in patients with acute HF.
Method
We analyzed patients enrolled in the PUSH-AHF, a single center, randomized trial of natriuresis-guided diuretic therapy versus standard of care (SOC) in acute HF. DPP3 levels were measured at baseline, 24 hours, 48 hours, 72 hours and discharge. We assessed associations between DPP3 levels and clinical characteristics, 24-hour natriuresis, and the combined endpoint of 180-day all-cause mortality or HF hospitalization. Additionally, we evaluated whether diuretic treatment strategy modified these associations.
Results
At baseline, DPP3 was available in 287 patients (mean age 73±12, 43% female) with a median concentration of 39 (26-62) ng/mL. DPP3 levels decreased significantly within the first 24 hours of hospitalization and stabilized thereafter. Patients in the lowest and highest quartiles of DPP3 levels had lower eGFR, higher urea, and NT-proBNP levels (all p<0.03) compared to those in the intermediate quartiles. Natriuresis-guided therapy resulted in greater natriuresis and diuresis at 24 hours in the higher DPP3 quartiles compared to SOC, with only the association with diuresis persisting at 48 hours; no significant treatment–DPP3 interactions were observed. DPP3 levels did not modify the treatment effect on the overall neutral combined endpoint.
Conclusion
Higher circulating DPP3 concentrations are associated with impaired kidney function and reduced diuretic response in acute HF. Natriuresis-guided therapy improved diuretic response, especially in patients with high baseline DPP3. These findings support further investigation of DPP3 as a potential biomarker for diuretic responsiveness in acute HF.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.