Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes.

Deconvolution of BNP and NT-proBNP Immunoreactivities by Mass Spectrometry in Heart Failure and Sacubitril/Valsartan Treatment.

Background: Elevated BNP and the N-terminal fragment of the proBNP (NT-proBNP) are hallmarks of heart failure (HF). Generally, both biomarkers parallel each other. In patients receiving sacubitril/valsartan, BNP remained stable while NT-proBNP decreased.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

Background: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality.

Methods: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551).

Systemic Inflammation Evaluated by Interleukin-6 or C-Reactive Protein in Critically Ill Patients: Results From the FROG-ICU Study.

Background: The prognostic impact of high concentration of interleukin-6 (IL-6) or C-reactive protein (CRP), two routinely available markers of systemic inflammation in the general population of critically ill patients, remains unclear. In a large cohort of critically ill patients including septic and non-septic patients, we assessed the relationship between baseline IL-6 or CRP and mortality, organ dysfunction, and the need for organ support.

Methods: This was an ancillary analysis of the prospective French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study including patients with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following intensive care unit (ICU) admission.

proANP Metabolism Provides New Insights Into Sacubitril/Valsartan Mode of Action.

Background: Sacubitril/valsartan (S/V) treatment is beneficial in patients with heart failure with reduced ejection fraction (HFrEF), but its mode of action remains elusive, although it involves the increase in ANP (atrial natriuretic peptide).

Methods: Combining mass spectrometry and enzymatic assay in the plasma of 73 HFrEF patients treated with S/V and controls, we deciphered proANP processing that converts proANP into 4 vasoactive peptides.

Results: We found that proANP processing is sequential and involved meprin B, ECE (endothelin-converting enzyme) 1, and ANPEP (aminopeptidase N).

Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission.

Background: Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages.

Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol.

Aims: Our objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio-protective effect of metoprolol.

Methods And Results: Male C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg).

Protein S100B as a reliable tool for early prognostication after cardiac arrest.

Purpose: Early and reliable prognostication after cardiac arrest (CA) remains crucial. We hypothesized that protein-S100B (PS100B) could predict more accurately outcome in the early phase of CA compared with other current biomarkers.

Methods: This prospective single-center study included 330 adult comatose non-traumatic successfully resuscitated CA patients, treated with targeted temperature management but not extra-corporeal life support.

Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study.

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients.

Assessment of successful percutaneous mitral commissurotomy by MRproANP and sCD146.

Background: We studied the course of plasma concentrations of 4 cardiovascular biomarkers: natriuretic peptides (BNP, NT-proBNP; mid-regional (MR) pro-atrial NP); and soluble endothelial CD146 (sCD146), in patients with severe mitral valve stenosis undergoing percutaneous mitral commissurotomy (PMC) to identify potential markers of procedural success.

Methods: Biomarkers were tested in 40 patients the day before and the day after PMC. Success was defined as mitral valve area ≥ 1.

Vascular endothelial growth factor D is a biomarker of fluid overload in haemodialysis patients.

Background: Improved understanding and assessment of the complex physiology of volume regulation in haemodialysis (HD) patients are required to improve patient care and reduce mortality associated with fluid overload (FO).

Methods: We searched for FO-related biomarkers among 184 peptides associated with cardiovascular disease in a cohort of 30 HD patients. First, we assessed the direct impact of HD on the peptides of interest by comparing plasma concentrations before and after treatment.

Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics.

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.

Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.

Aims: Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to β-adrenergic receptor (β-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functional role in large mammals.

Adrecizumab, a non-neutralizing anti-adrenomedullin antibody, improves haemodynamics and attenuates myocardial oxidative stress in septic rats.

Background: Sepsis still represents a major health issue, with persistent high morbidity and mortality rates. Cardiovascular dysfunction occurs frequently during sepsis. Adrenomedullin has been identified as a key mediator in vascular tone regulation.

Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study.

Aim: This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug.

Methods And Results: We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment.

PKR modulates abnormal brain signaling in experimental obesity.

Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer's disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome ("metaflammasome") mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome.

Soluble CD146 and B-type natriuretic peptide dissect overhydration into functional components of prognostic relevance in haemodialysis patients.

Background: Accurate volume status evaluation and differentiation of cardiac and non-cardiac components of overhydration (OH) are fundaments of optimal haemodialysis (HD) management.

Methods: This study, by combining bioimpedance measurements, cardiovascular biomarkers and echocardiography, aimed at dissecting OH into its major functional components, and prospectively tested the association between cardiac and non-cardiac components of OH with mortality. In the first part, we validated soluble CD146 (sCD146) as a non-cardiac biomarker of systemic congestion in a cohort of 30 HD patients.

QSOX1, a novel actor of cardiac protection upon acute stress in mice.

QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion.

Sevoflurane for procedural sedation in critically ill patients: A pharmacokinetic comparative study between burn and non-burn patients.

Background: Sevoflurane has anti-inflammatory proprieties and short lasting effects making it of interest for procedural sedation in critically ill patients. We evaluated the pharmacokinetics of sevoflurane and metabolites in severely ill burn patients and controls. The secondary objective was to assess potential kidney injury.

The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin.

Aims: Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF.

Methods And Results: Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6.

Imbalanced Angiogenesis in Peripartum Cardiomyopathy - Diagnostic Value of Placenta Growth Factor.

Background: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.

Methods and results: Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65).