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Aims: Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated., Methods and Results: We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care., Conclusions: Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Heart failure is the most common cardiovascular complication during pregnancy and the postpartum period. It is associated with increased risk of maternal morbidity and mortality as well as potentially life-threatening foetal pathology. Management of heart failure in pregnancy requires expert knowledge of cardiovascular disease as well as obstetrics which underscores the importance of multidisciplinary cardio-obstetrics teams in order to optimize diagnosis, treatment and outcome. This includes counselling of women at risk before and during the course of pregnancy in order to strengthen the relationship between medical specialists and patients, as well as to allow patient-centred delivery of care and improve quality of life., (© 2024 European Society of Cardiology.)

Aims: Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice., Methods and Results: cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling., Conclusion: Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Aims: Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of cardiovascular mediators. Its administration has been shown to be associated with impaired cardiac contraction and kidney haemodynamics while its inhibition restored cardiac contraction in a pre-clinical model of severe heart failure in mice. Circulating DPP3 (cDPP3) was found to be elevated in shock. The present study aims to assess the association between cDPP3 and worsening haemodynamics, namely refractory shock, in a cohort of cardiogenic shock (CS)., Methods and Results: This is an ancillary study of OptimaCC, a prospective, double-blind, multicentre, randomized study assessing efficacy and safety of catecholamines in 57 patients with CS after acute myocardial infarction. cDPP3 was measured in plasma at inclusion, 24 h, 48 h, and 72 h, and haemodynamic and biological parameters were recorded at inclusion. cDPP3 values were higher in refractory CS than non-refractory CS at inclusion (median [interquartile range]; 76.1 [37.9-238.7] ng/mL vs. 32.8 [23.9-47.6] ng/mL, P = 0.014), at 24 h (P < 0.001) and up to 48 h (P = 0.027). Furthermore, cDPP3 at inclusion discriminated CS patients who did develop refractory shock vs. non-refractory with an area under the curve of 0.73 (95% confidence interval [CI] 0.55-0.92). The high cDPP3 group (cDPP3 ≥59.1 ng/mL) at inclusion had a higher Simplified Acute Physiology Score II (SAPS II), lower cardiac index and lower estimated glomerular filtration rate. More importantly, in CS patients with high cDPP3 at inclusion, those who rapidly decreased cDPP3 at 24 h exhibited a striking reduction in the occurrence of refractory shock and death., Conclusion: In CS patients, cDPP3 gives an early prediction of outcome, including development of refractory status and/or survival., Clinical Trial Registration: clinicaltrials.gov Identifier NCT01367743., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)