The assessment of congestion in patients with advanced heart failure: the role of mid-regional pro-adrenomedullin
G Reijans, L Fazzini, O Zucchetti, G Togni, L Guida, G Costandache, R Adobati, S D' Isa, L Di Odoardo, E Sciatti, M Gori, C Saiaci, S Valaperta, M Senni, E D' EliaAbstract
Background
Systemic congestion is a key feature of heart failure and is associated with hepatorenal dysfunction, recurrent hospitalizations, poorer prognosis, and reduced quality of life. Venous Excess Ultrasound (VExUS) has emerged as a reliable tool for the assessment of systemic congestion through evaluation of portal, hepatic, and renal venous flow patterns. Mid-regional pro-adrenomedullin (MR-proADM), a biomarker involved in vascular tone regulation and endothelial permeability, may reflect congestion due to its association with vascular leakage.
Purpose
To investigate whether, in patients with advanced HF (AdvHF) receiving levosimendan infusions as the last available pharmacological option, changes in MR-proADM from baseline (T0) to follow-up within 48 hours after end of infusion (T1), correlate with the change in VExUS score. Secondly, we explored the effect of levosimendan on congestion-related biomarkers and their relationship with MR-proADM.
Methods
This observational, prospective study included 14 patients with AdvHF enrolled between September and December 2025. MR-proADM was measured using a commercially available sandwich immunoassay. NT-proBNP, BNP, troponin I, sST2 and CA125 were also measured. Systemic congestion was evaluated using the VExUS score. Associations between MR-proADM, VExUS, as well as between MR-proADM and other congestion biomarkers, were analysed using Spearman’s rank correlation coefficient.
Results
MR-proADM increased from 1.01 nmol/L at T0 to 1.08 nmol/L at T1 (p = 0.12), corresponding to a median change of 0.06 nmol/L. VExUS scores showed no significant change (p = 0.16). No significant association was observed between changes in MR-proADM and changes in VExUS score (Spearman’s ρ = -0.46, p = 0.10). At baseline, MR-proADM showed a significant correlation with CA125 (ρ = 0.69, p = 0.01), which persisted at follow-up. At T1, MR-proADM was also significantly correlated with troponin I (ρ = 0.57, p = 0.04). Natriuretic peptides decreased from T0 to T1, whereas troponin I, ST2 and CA125 increased (Figure 1).
Conclusion
In this cohort of AdvHF patients treated with levosimendan, changes in MR-proADM increased slightly following infusion, while natriuretic peptides decreased, possibly reflecting differing underlying pathophysiological mechanisms. Although no significant association was observed between changes in MR-proADM and changes in VExUS score, the consistent association between MR-proADM and CA125 suggests a potential role for MR-proADM as a marker of extravascular congestion, rather than intravascular volume status. Larger studies in populations with more dynamic congestion profiles are needed to further elucidate the clinical utility of MR-proADM in AdvHF.Median normalized changes in biomarkersFor image description, please refer to the figure legend and surrounding text.