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1. The impact of transoesophageal echocardiography in elderly patients with infective endocarditis

Author: N’cho-Mottoh, Marie-Paule B, Erpelding, Marie-Line, Roubaud Baudron, Claire, Delahaye, François, Fraisse, Thibaut, Dijos, Marina, Ennezat, Pierre Vladimir, Fluttaz, Arnaud, Richard, Benjamin, Beaufort, Corinne, Nazeyrollas, Pierre, Brasselet, Camille, Pineau, Olivier, Tattevin, Pierre, Curlier, Elodie, Iung, Bernard, Forestier, Emmanuel, Selton-Suty, Christine, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Bordeaux [Bordeaux], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Alès-Cévennes (CHAC), CHU Grenoble, Centre Hospitalier Métropole Savoie [Chambéry], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHRU Nancy], and The initial research project ELDERL-IE, from which these data were analysed, was supported by a grant of the 'Fondation Coeur et Recherche' (France) in 2013.
Subjects: Elderly, Transoesophageal echocardiography, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, General Medicine, Infective endocarditis, Cardiology and Cardiovascular Medicine, Geriatric assessment
Abstract: International audience; BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.
Published: 2023

2. Associations of childhood adiposity with adult intima–media thickness and inflammation: a 20-year longitudinal population-based cohort

Author: Fujikawa, Tomona, Kobayashi, Masatake, Wagner, Sandra, Duarte, Kevin, Scherdel, Pauline, Heude, Barbara, Dupont, Vincent, Bozec, Erwan, Bresso, Emmanuel, Zannad, Faiez, Rossignol, Patrick, Girerd, Nicolas, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre Hospitalier Universitaire de Reims (CHU Reims), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project, European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), and European Project: ERA-CVD/0001/2016,MINOTAUR
Subjects: inflammation, Physiology, [SDV]Life Sciences [q-bio], childhood adiposity, Internal Medicine, biomarkers, Cardiology and Cardiovascular Medicine, carotid intima–media thickness
Abstract: International audience; Background: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking.Methods: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores.Results: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity.Conclusion: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.
Published: 2022

3. Dyskalemia in people at increased risk for heart failure

Author: Luca Monzo, João Pedro Ferreira, John G.F. Cleland, Pierpaolo Pellicori, Beatrice Mariottoni, Job A.J. Verdonschot, Mark R. Hazebroek, Tim J. Collier, Joe J. Cuthbert, Burkert Pieske, Frank Edelmann, Johannes Petutschnigg, Javed Khan, Fozia Z. Ahmed, Nicolas Girerd, Erwan Bozec, Javier Díez, Arantxa González, Andrew L. Clark, Franco Cosmi, Jan A. Staessen, Stephane Heymans, Patrick Rossignol, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universidade do Porto = University of Porto, University of Glasgow, Department of Cardiology, Cortona Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], London School of Hygiene and Tropical Medicine (LSHTM), Castle Hill Hospital, University of Hull [United Kingdom], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Manchester University NHS Foundation Trust (MFT), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Department of Cardiovascular Sciences [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The Netherlands Heart Institute, European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)
Subjects: Hyperkalaemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, heart failure prevention, hyperkalaemia, hypokalaemia, steroidal mineralocorticoid receptor antagonist, Heart failure prevention, Cardiology and Cardiovascular Medicine, Hypokalaemia, Steroidal mineralocorticoid receptor antagonist, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: AIMS: In people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia. METHODS AND RESULTS: The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at 5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration
Published: 2022

4. Performance of Early Capillary Refill Time Measurement on Outcomes in Cardiogenic Shock: An Observational, Prospective Multicentric Study

Author: Hamid Merdji, Anais Curtiaud, Antoine Aheto, Antoine Studer, Veli-Pekka Harjola, Alexandra Monnier, Kevin Duarte, Nicolas Girerd, Marion Kibler, Hafid Ait-Oufella, Julie Helms, Alexandre Mebazaa, Bruno Levy, Antoine Kimmoun, Ferhat Meziani, BOZEC, Erwan, Service de Médecine Intensive et Réanimation [Strasbourg], CHU Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Hospital [Finland] (HUS), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis (Réseau CRICS-TRIGGERSEP)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Microcirculation, Shock, Cardiogenic, Hemodynamics, Humans, Stroke Volume, Prospective Studies, Critical Care and Intensive Care Medicine, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Retrospective Studies
Abstract: International audience; Background: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock.Methods: All consecutive patients admitted in ICU for cardiogenic shock of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction and cardiac index) and peripheral tissue perfusion signs such as capillary refill time on the index fingertip, mottling and Pv-aCO2 (the difference between partial pressure of CO2 in venous blood and arterial blood) were recorded at inclusion (H0), H6, H12, H24 and H48. The composite primary endpoint was the association between 90-day mortality or the need for venoarterial-ECMO support.Results: 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time-points in non survivors or patients needing venoarterial-ECMO support. In univariate analysis, capillary refill time > 3 sec at inclusion was associated with 90-day all-cause mortality or venoarterial-ECMO support (Hazard Ratio of 12.38; 95% CI 2.91 to 52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93.Conclusion: In patients admitted in ICU for cardiogenic shock, our preliminary data suggest that a prolonged capillary refill time > 3 sec was associated with an early prediction of 90-day mortality or the need for venoarterial-ECMO support
Published: 2022

5. Spironolactone effect on cardiac structure and function of patients with heart failure and preserved ejection fraction: a pooled analysis of three randomized trials

Author: João Pedro Ferreira, John G. Cleland, Nicolas Girerd, Erwan Bozec, Patrick Rossignol, Pierpaolo Pellicori, Franco Cosmi, Beatrice Mariottoni, Scott D. Solomon, Bertram Pitt, Marc A. Pfeffer, Amil M. Shah, Johannes Petutschnigg, Burkert Pieske, Frank Edelmann, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, University of Glasgow, Cortona Hospital, Brigham and Women's Hospital [Boston], University of Michigan [Ann Arbor], University of Michigan System, Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and European Project: 305507
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiology and Cardiovascular Medicine
Abstract: International audience; Aims: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF.Methods and results: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF. Analysis of covariance was used to test the effect of spironolactone on echocardiographic changes. A total of 984 patients were included in this analysis: 452 (45.9%) from HOMAGE, 398 (40.4%) from Aldo-DHF, and 134 (13.6%) from TOPCAT. The pooled-cohort patient's median age was 71 (66-77) years and 39% were women. Median LAVi was 29 (24-35) ml/m2 , LVMi 100 (84-118) g/m2 , IVS thickness 12 (10-13) mm, E/e' ratio 11 (9-13), and LVEF 64 (59-69)%. Spironolactone reduced LAVi by -1.1 (-2.0 to -0.1) ml/m2 (p = 0.03); LVMi by -3.6 (-6.4 to -0.8) g/m2 (p = 0.01); IVS thickness by -0.2 (-0.3 to -0.1) mm (p = 0.01); E/e' ratio by -1.3 (-2.4 to -0.2) (p = 0.02); and increased LVEF by 1.7 (0.8-2.6)% (p < 0.01). No treatment-by-study heterogeneity was found except for E/e' ratio with a larger effect in Aldo-DHF and TOPCAT (interaction p < 0.01).Conclusions: Spironolactone improved cardiac structure and function of patients with HFpEF.
Published: 2022

6. Effects of Gender and Age on Self-reported Odor Imagery Ability

Author: Luca Fantin, Chloé Pinzano, Cécile Rumeau, Gabriela Hossu, Hadrien Ceyte, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Olfactory experience, Cellular and Molecular Neuroscience, Age, Odor imagery, Gender, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Olfaction, Sensory Systems
Abstract: International audience; Introduction Odor imagery is known to be more difficult than any other modality of sensory imagery. Consequently, wide between-individuals variability can be found in odor imagery ability. Several studies have shown a positive relationship between olfactory performance and odor imagery ability. In the light of factors known to influence smelling ability, this study therefore investigated the effects of two factors - gender and age - known to influence smelling ability, on self-declared odor imagery ability in normosmic individuals. Methods Seven hundred and nine French participants were asked to complete the web version of the French Vividness of Olfactory Imagery Questionnaire (fVOIQ). General linear models were used to determine the contributions of gender and age to odor imagery vividness scores. Moreover, scores were compared between age intervals ranging from 18-30 years old to 60 + years old. Results Our findings reveal that at any age, men and women have the same odor imagery ability. Odor imagery ability in self-declared normosmic individuals improves with age until 50-60 years old, and beyond this point the often-reported age-related olfactory decay does not alter it. Conclusions These findings suggest a high contribution of daily olfactory experience to the development of this cognitive function, and a relationship with olfactory performance that appears less linear than hypothesized.
Published: 2022

7. How can we optimise health technology assessment and reimbursement decisions to accelerate access to new cardiovascular medicines?

Author: Martin R. Cowie, Biykem Bozkurt, Javed Butler, Andrew Briggs, Maria Kubin, Adrian Jonas, Amanda I. Adler, Bray Patrick-Lake, Faiez Zannad, Royal Brompton Hospital, King‘s College London, Baylor College of Medicine (BCM), Baylor University, University of Mississippi Medical Center (UMMC), London School of Hygiene and Tropical Medicine (LSHTM), Department of Integrated Evidence Generation, Bayer AG, National Institute for Health and Care Excellence [Manchester, UK] (NICE), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Department of Strategic Partnerships, Evidation Health, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CVCT meetings are supported by unrestricted educational grants with no allocation for speakers’ fees., and BOZEC, Erwan
Subjects: Technology Assessment, Biomedical, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Quality of Life, Humans, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Regulatory approvals of, and subsequent access to, innovative cardiovascular medications have declined. How much of this decline relates to the final step of gaining reimbursement for new treatments is unknown. Payers and health technology assessment (HTA) bodies look beyond efficacy and safety to assess whether a new drug improves patient outcomes, quality of life, or satisfaction at a cost that is affordable compared to existing treatments. HTA bodies work within a limited healthcare budget, and this is one of the reasons why only half of newly approved drugs are accepted for reimbursement, or receive restricted or "optimised" recommendations from HTA bodies. All stakeholders have the common goal of facilitating access to safe, effective, and affordable treatments to appropriate patients. An important strategy to expedite this is providing optimal data. This is demonstrably facilitated by early (and ongoing) discussions between all stakeholders. Many countries have formal programmes to provide collaborative regulatory and HTA advice to developers. Other strategies include aligning regulatory and HTA processes, increasing use of real-world evidence, formally defining the decision-making process, and educating stakeholders on the criteria for positive decision making. Industry should focus on developing treatments for unmet medical needs, seek early engagement with HTA and regulatory bodies, improve methodologies for optimal price setting, develop internal systems to collaborate with national and international stakeholders, and conduct post-approval studies. Patient involvement in all stages of development, including HTA, is critical to capture the lived experience and priorities of those whose lives will be impacted by new treatment approvals.
Published: 2022

8. Albiglutide in patients with type 2 diabetes and heart failure: a post‐hoc analysis from Harmony Outcomes

Author: João Pedro Ferreira, Abhinav Sharma, Francisco Vasques‐Nóvoa, António Angélico‐Gonçalves, Ana Rita Leite, Marta Borges‐Canha, Davide Carvalho, Milton Packer, Faiez Zannad, Adelino Leite‐Moreira, João Sérgio Neves, BOZEC, Erwan, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular R&D Centre-UnIC@RISE, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, DREAM-CV Lab, McGill University = Université McGill [Montréal, Canada], McGill University Health Center [Montreal] (MUHC), Hospital de São João [Porto], Baylor University Medical Center, Baylor College of Medecine, Imperial College London, and This study was supported by national funds through FCT Fundação para a Ciência e Tecnologia, I.P., under the scope of the Cardiovascular R&D Center - UnIC (UIDB/00051/2020 and UIDP/00051/2020).
Subjects: Heart Failure, Diabetes Mellitus, Type 2, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiovascular Diseases, Humans, Hypoglycemic Agents, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Aim: Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). However, some studies suggest that their effects in patients with heart failure (HF) may be attenuated. We aimed to explore the effects of the GLP1-RA albiglutide on HF outcomes in patients with and without HF history enrolled in the Harmony Outcomes trial.Methods and results: Harmony Outcomes enrolled patients with T2D and cardiovascular disease randomized to either albiglutide or placebo over a median follow-up of 1.6 years. A total of 9462 patients were included, of whom 1922 (20%) had HF history. Patients with HF had more cardiovascular comorbidities, poorer renal function, and had a three to four-fold higher risk of HF events compared to patients without HF. Compared to placebo, the effect of albiglutide on the composite of cardiovascular death or HF hospitalization was more pronounced among patients without HF (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.95) than in patients with HF (HR 1.06, 95% CI 0.79-1.43) (interaction p = 0.062). A similar pattern was observed for HF hospitalizations (interaction p = 0.025). The effect of albiglutide on cardiovascular death, sudden death or 'pump failure' death, and all-cause mortality was also attenuated among patients with HF history, but without significant interaction (p > 0.1). The benefit of albiglutide to reduce atherosclerotic events was consistent regardless of HF history.Conclusions: In patients with T2D and cardiovascular disease, albiglutide appeared to have no effect in reducing HF-related events among patients with HF history. These findings, placed in the context of other trials, suggest that GLP1-RA may not improve HF outcomes in patients with HF.
Published: 2022

9. Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation

Author: Baudry, Guillaume, Coutance, Guillaume, Dorent, Richard, Bauer, Fabrice, Blanchart, Katrien, Boignard, Aude, Chabanne, Céline, Delmas, Clément, d'Ostrevy, Nicolas, Epailly, Eric, Gariboldi, Vlad, Gaudard, Philippe, Goéminne, Céline, Grosjean, Sandrine, Guihaire, Julien, Guillemain, Romain, Mattei, Mathieu, Nubret, Karine, Pattier, Sabine, Vermes, Emmanuelle, Sebbag, Laurent, Duarte, Kévin, Girerd, Nicolas, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), chirurgie cardio-vasculaire, CHU Clermont-Ferrand, Service de Chirurgie Cardio-Vasculaire, CHU Strasbourg-Nouvel Hôpital Civil, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], CHU Lille, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Université Victor Segalen - Bordeaux 2, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), the Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second ‘Investissements d'Avenir’ programme (reference: ANR-15-RHUS-0004), the French PIA project ‘Lorraine Université d'Excellence’ (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), and ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016)
Subjects: Advanced heart failure, Cardiorenal syndrome, [SDV]Life Sciences [q-bio], Congestion, Diuretic, Heart transplant
Abstract: International audience; Aims The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). Conclusions A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.
Published: 2023

10. Cardiac device-related infective endocarditis need for lead extraction whatever the device according to the ESC EORP EURO-ENDO registry

Author: Donal, Erwan, Tribouilloy, Christophe, Sadeghpour, Anita, Laroche, Cécile, Tude Rodrigues, Ana Clara, Pereira Nunes, Maria Do Carmo, Kang, Duk-Hyun, Hernadez-Meneses, Marta, Kobalava, Zhanna, de Bonis, Michele, Dworakowski, Rafal, Ivanovic, Branislava, Holicka, Maria, Kitai, Takeshi, Cruz, Ines, Huttin, Olivier, Colonna, Paolo, Lancellotti, Patrizio, Habib, Gilbert, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Centre Hospitalier Universitaire de Liège (CHU-Liège)
Subjects: Pacemaker, Implantable defibrillator, Infective endocarditis, Prognosis, Cardiac device, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, staphylococci
Abstract: International audience; Aims Cardiac device–related infective endocarditis (CDRIE) is a severe complication of cardiac device (CD) implantation and is usually treated by antibiotic therapy and percutaneous device extraction. Few studies report the management and prognosis of CDRIE in real life. In particular, the rate of device extraction in clinical practice and the management of patients with left heart infective endocarditis (LHIE) and an apparently non-infected CD (LHIE+CDRIE−) are not well described. Methods and results We sought to study in EURO-ENDO, the characteristics, prognosis, and management of 483 patients with a CD included in the European Society of Cardiology EurObservational Research Programme EURO-ENDO registry. Three populations were compared: 280 isolated CDRIE (66.7 ± 14.3 years), 157 patients with LHIE and an apparently non-infected CD (LHIE+CDRIE−) (71.1 ± 13.6), and 46 patients with both LHIE and CDRIE (LHIE+CDRIE+) (70.2 ± 10.1). Echocardiography was not always transoesophageal echography (TOE); it was transthoracic echography (TTE) for isolated CDRIE in 88.4% (TOE = 67.6%), for LHIE+CDRIE− TTE = 93.0% (TOE = 58.6%), and for CDRIE+LHIE+ TTE = 87.0% (TOE = 63.0%). Nuclear imaging was performed in 135 patients (positive for 75.6%). In-hospital mortality was lower in isolated CDRIE 13.2% vs. 22.3% and 30.4% for LHIE+CDRIE− and LHIE+CDRIE+ (P = 0004). Device extraction was performed in 62.1% patients with isolated CDRIE, 10.2% of LHIE+CDRIE− patients, and 45.7% of CDRIE+LHIE+ patients. Device extraction was associated with a better prognosis [hazard ratio 0.59 (0.40–0.87), P = 0.0068] even in the LHIE+CDRIE− group (P = 0.047). Conclusion Prognosis of endocarditis in patients with a CD remains poor, particularly in the presence of an associated LHIE. Although recommended by guidelines, device extraction is not always performed. Device removal was associated with better prognosis, even in the LHIE+CDRIE− group.
Published: 2023

11. Prognostic value of respiratory compliance course on mortality in COVID-19 patients with vv-ECMO

Author: Valentin, Simon, Amalric, Mathieu, Granier, Guillaume, Pequignot, Benjamin, Guervilly, Christophe, Duarte, Kevin, Girerd, Nicolas, Levy, Bruno, Dunand, Paul, Koszutski, Matthieu, Roze, Hadrien, Kimmoun, Antoine, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: Respiratory distress syndrome, [SDV]Life Sciences [q-bio], COVID-19, ECMO, Compliance
Abstract: International audience; Abstract Background COVID-19-associated acute respiratory distress syndrome (ARDS) supported by veno-venous extra-corporal membrane oxygenation (vv-ECMO) results in a high in-hospital mortality rate of more than 35%. However, after cannulation, no prognostic factor has been described to guide the management of these patients. The objective was to assess the association between static respiratory compliance over the first 10 days post-vv-ECMO implantation on 180-day mortality. Results In this multicentric retrospective study in three ECMO referral centers, all patients with COVID-19-associated ARDS supported by vv-ECMO were included from 03/01/2020 to 12/31/2021. Patients were ventilated with ultra-protective settings targeting a driving pressure lower than 15 cmH 2 O. 122 patients were included. Median age was 59 IQR (52–64), 83 (68%) were male, with a median body mass index of 33 (28–37) kg/m 2 . Delay between first symptoms to vv-ECMO implantation was 16 (10–21) days. Six-month death was 48%. Over the first ten days, compliance increased in 180 day survivors [from 18 (12–25) to 20 (15–27) mL/cmH 2 O] compared to non-survivors [from 12 (9–20) to 10 (8–14) mL/cmH 2 O, p interaction
Published: 2023

12. Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial

Author: Zuily, Stéphane, Lefèvre, Benjamin, Sanchez, Olivier, Empis de Vendin, Ombeline, de Ciancio, Guillaume, Arlet, Jean-Benoît, Khider, Lina, Terriat, Béatrice, Greigert, Hélène, Robert, Céline, Louis, Guillaume, Trinh-Duc, Albert, Rispal, Patrick, Accassat, Sandrine, Thiery, Guillaume, Montani, David, Azarian, Réza, Meneveau, Nicolas, Soudet, Simon, Le Mao, Raphaël, Maurier, François, Le Moing, Vincent, Quéré, Isabelle, Yelnik, Cécile, Lefebvre, Nicolas, Martinot, Martin, Delrue, Maxime, Benhamou, Ygal, Parent, Florence, Roy, Pierre-Marie, Presles, Emilie, Goehringer, François, Mismetti, Patrick, Bertoletti, Laurent, Rossignol, Patrick, Couturaud, Francis, Wahl, Denis, Thilly, Nathalie, Laporte, Silvy, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), F-Crin Innovte [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHR de Metz-Thionville, Centre Hospitalier Agen-Nérac, Hôpital Bicêtre, Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Department of Cardiology, University Hospital Jean Minjoz, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), UNEOS, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lapeyronie [Montpellier] (CHU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lille, CHU Lille, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpitaux Civils de Colmar, Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA), CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université Jean Monnet - Saint-Étienne (UJM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service de Chirurgie Vasculaire [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Princesse Grace, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole., and COVI-DOSE investigators: Stéphane Zuily, Francis Couturaud, François Goehringer, Silvy Laporte, Patrick Mismetti, Emilie Presles, Patrick Rossignol, Nathalie Thilly, Denis Wahl, Thomas Lecompte, Emmanuel Oger, Marie-Antoinette Sevestre, Florence Parent, Ygal Benhamou, Pierre-Marie Roy, Tristan Gigante, Morgane Gilg, Pierre-Luc Maclot, Bénédicte Rossignol, Jonathan Udot, Hélène Bouteille, Andréa Buchmuller, Céline Peurière, El Mehdi Siaghy, Valérie Bouaziz, Charlotte Daguin, Benjamin Grosjean, Véronique Saunier, Laurence Verger, Madlyne Jacquot, Nadine Petitpain, Martin Charly, Laurent Tordella, Emilie Presles, Guillaume Baronnet, Elisabeth Baux, Athanase Benetos, Jean-Baptiste Blanvillain, Marie Conrad, Guilhem Courte, Aurélie Cravoisy-Popovic, Virginie Dufrost, Sébastien Gibot, Philippe Guerci, Laure Joly, Antoine Kimmoun, Matthieu Koszutski, Alexandrine Larue, Bruno Levy, Marie-Reine Losser, Mathieu Mattei, Lionel Nace, Emmanuel Novy, Pierre Perez, Jean-Pierre Pertek, Camille Rigaux, Alexis Sauvage, Evelyne Schvoerer, Carine Thivilier, Lev Volkov, Piotr Zieminski, Manil Benlounes, Charles Cheng, Jean-Baptiste de Fréminville, Grégoire Détriché, Emmanuel Flammarion, Guillaume Goudot, Amer Hamdan, Raphaël Hindré, Corina Manoli, Emmanuel Messas, Adrien Michon, Tristan Mirault, Jean Pastré, Marie-Aude Penet, Benjamin Planquette, Geoffroy Volle, Rémy Hamdan, Aline Laubriet-Jazayeri, Vincent Petit, Lionel Piroth, Jean Pierre Quenot, Mélissa Saccu, Damien Barraud, Zoé Cavalli, Rostane Gaci, Mathilde Andreu, Laurent Bertoletti, Andréa Buchmuller, Elodie De Magalhaes, Sophie Bulifon, Athénaïs Boucly, Nathan Ebstein, Marc Humbert, Xavier Jaïs, Mitja Jevnikar, Laurent Savale, Andrei Horia Seferian, Charlotte Colin, Timothée Ganem, Mehdi Roumila, Romain Chopard, Matthieu Besutti, Basile Mouhat, Claire Andrejak, Stéphane Dupas, Gaëlle Le Roy, Santhi Samy-Modeliar, Anne Coste, Alexandre Fauche, David Goetghebeur, Christophe Gut-Gobert, Clément Hoffmann, Baptiste Hourmant, Cécile L'hévéder, Emmanuelle Lemoigne, Olivier Nepveu, Raphaël Paret, Gaël Picart, Saïd Azerkan, Chadia Boudaa, Julien Campagne, Peter Eszto, Benoît Godbert, Jean-François Guichard, Marion Heschung, Antoine Legoff, Jacques Mariot, Pascale Martin, Magalie Mercy, Julie Perrin, Stéphane Raymond, Nathalie Vernier, Pierre Fesler, Pierrick Henneton, Cédric Mercuzot, Nathalie Pansu, Lucas Perez, Loïc Andre, Edgar Bakhache, Marie-Charlotte Chopin, Marie Gilbert, Marc Lambert, Mohammad Ryadh Pokeerbux, François Danion, Yves Hansmann, Estelle Rougier, Yvon Ruch, Dominique Stéphan, Axel Ursenbach, Isabelle Connerade, Simon Gravier, Damien Kayser, Jean-Marc Michel, Mahsa Mohseni, Waël Younes, Ruxandra Burlacu, Amanda Lopes, Stéphane Mouly, Kladoum Nassarmadji, Damien Sène, Virginie Siguret, Alain Stepanian, Cédric Annweiler, Antoine Brangier, Vincent Dubee, Samir Henni, Jeanne Hersant, Jocelyne Loison, Léa Kern, Jean-Baptiste Laine, Claire Neveux-Brecheteau, Lucia Perez, Ruben Benainous, Bénédicte Giroux-Leprieur, Marilucy Lopez-Sublet, Saïda Khaled-Jousselin, Yohann Bernard, Amélie Amiot, Jessica Breistroff, Emilie Detry, Kadidiatou Diallo, Agnès Didier, Nathalie Dumont, Julie Egensperger, Aurélie Emmerich, Nelly François, Fanny Gallo, Valérie George, Quentin Gérome, Aurélie Gutehrle, Laure Lehman, Séverine Petit, Vanessa Piard, Maximilien Saint-Gilles, Olivier Terenzi, Amélie Marquette, Hélène Mortelette, Mathilde Audry, Amélie Cransac, Marine Maillard, Anaïs Boyer, Floriana Gallo, Arielle Urbing, Imane Zahaf, Alexandra Byczko, Amina Chaalal, Georgette Berlier, Corinne Bernabe, Souad Bezzeghoud, Caroline Chaudier, Carole Chauvet, Marina Davier, Carine Labruyere, Estelle Perrin, Michaël Pierre, Claire-Annissa Chekirine, Florence Voivret, Ramdane Meftali, Ouaffa Sabri, Anaïs Beulaygue, Julie Gall, Laure Girard, Soumia Haddaoui, Scheherazade Rami, Auriane Couderc, Aude Le Breton, Marie-Line Perruche, Cindy Claudon, Ludivine Roussel, Aude Barnier, Tiphaine Blanchard, Bénédicte Le Gall, Mélanie Pelouin, Anne-Sophie Veillon, Quam Aquereburu, Charlène Delaygue, Zahoua Ait Idir, Jérémy Drugeon, Déborah Dubrulle, Rabah Tezkratt, Anne-Sophie Frantz, Julie Drouaine, Jacqueline Dubois, Magali Eyriey, Elina Haerrel, Mélinda Beaudenon, Mialy Guenet, Thibaud Lecerf, Stéphanie Marechal-Girault, Sami Rehaiem, Romain Simon, Florence Dangeul-Potier, Morgane Goulvent, Souha Fliss, Fadhila Messani, Béatrice Mizejewski, Brigitte Mugnier, Valérie Opderbeck, Brigitte Risse
Subjects: Anticoagulation, Heparin, [SDV]Life Sciences [q-bio], COVID-19, Venous thromboembolism
Abstract: International audience; Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707).Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034).Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens.
Published: 2023

13. Effects of steroidal mineralocorticoid receptor antagonists on acute and chronic estimated glomerular filtration rate slopes in patients with chronic heart failure

Author: Vaduganathan, Muthiah, Ferreira, João Pedro, Rossignol, Patrick, Neuen, Brendon, Claggett, Brian L., Pfeffer, Marc A., McMurray, John J.V., Pitt, Bertram, Zannad, Faiez, Solomon, Scott D., BOZEC, Erwan, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Universidade do Porto = University of Porto, Centre Hospitalier Princesse Grace, University of New South Wales [Sydney] (UNSW), The George Institute for Global Health [Sydney] (GIGH), The University of Sydney, University of Glasgow, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], and University of Michigan System-University of Michigan System
Subjects: Heart Failure, Stroke Volume, Outcomes, Spironolactone, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trials, Kidney function, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mineralocorticoids, Humans, Cardiology and Cardiovascular Medicine, Glomerular Filtration Rate, Mineralocorticoid Receptor Antagonists
Abstract: Steroidal mineralocorticoid receptor antagonists (MRAs) form a cornerstone of the management of heart failure (HF), but little is known about the long-term effects of MRA therapy on kidney function. We evaluated acute and chronic estimated glomerular function (eGFR) slopes in the two largest completed trials testing steroidal MRAs in chronic HF.We conducted parallel post hoc eGFR slope analyses in two multinational, double-blind randomized, placebo-controlled trials of steroidal MRAs in chronic HF with reduced ejection fraction (EMPHASIS-HF) and preserved ejection fraction (TOPCAT Americas region). GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Annual slopes of eGFR were assessed by generalized random coefficient models. Least square mean differences in eGFR slopes between steroidal MRA and placebo arms were assessed. Median follow-up was 1.8 years (EMPHASIS-HF) and 3.3 years (TOPCAT Americas). From baseline to month 4-6 ('acute eGFR slope'), compared to placebo, MRA treatment led to an acute decline in eGFR of -2.4 ml/min/1.73 msup2/sup(95% confidence interval [CI] -3.4 to -1.4; p lt; 0.001) and -2.0 ml/min/1.73 msup2/sup(95% CI -3.0 to -1.8; p lt; 0.001) in EMPHASIS-HF and TOPCAT Americas, respectively. From month 4-6 to end of study, there was no difference in 'chronic eGFR slope' between MRA and placebo arms (-0.3 ml/min/1.73 msup2/sup/year [95% CI -1.3 to 0.7; p = 0.53] and 0.1 ml/min/1.73 msup2/sup/year [95% CI -1.4 to 1.7; p = 0.86]) in EMPHASIS-HF and TOPCAT Americas, respectively.Steroidal MRAs result in acute declines in eGFR but do not modify long-term kidney disease trajectories in chronic HF with reduced or preserved ejection fraction.EMPHASIS-HF (ClinicalTrials.gov NCT00232180) and TOPCAT (ClinicalTrials.gov NCT00094302).
Published: 2022

14. Clinical impact of changes in mitral regurgitation severity after medical therapy optimization in heart failure

Author: Matteo Pagnesi, Marianna Adamo, Iziah E. Sama, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Riccardo M. Inciardi, Chim C. Lang, Carlo M. Lombardi, Leong L. Ng, Piotr Ponikowski, Nilesh J. Samani, Faiez Zannad, Dirk J. van Veldhuisen, Adriaan A. Voors, Marco Metra, Università degli Studi di Brescia = University of Brescia (UniBs), University Medical Center Groningen [Groningen] (UMCG), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Robertson Centre for Biostatistics & Clinical Trials Unit, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Bergen (UiB), Stavanger University Hospital, National and Kapodistrian University of Athens (NKUA), University of Dundee, University Hospitals Leicester, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Department of Heart Diseases, Wroclaw Medical University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), The BIOSTAT-CHF project was funded by a grant from the European Commission (FP7-242209-BIOSTAT-CHF, EudraCT 2010-020808-29), European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), European Project, BOZEC, Erwan, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, EudraCT 2010–020808–29 - INCOMING, and Cardiovascular Centre (CVC)
Subjects: GRMT, Heart failure, Hospitalization, Mitral regurgitation, Mortality, Valvular heart disease, Angiotensin-Converting Enzyme Inhibitors, DIAGNOSIS, Angiotensin Receptor Antagonists, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PROGNOSTIC-SIGNIFICANCE, Humans, ESC GUIDELINES, Retrospective Studies, OUTCOMES, Infant, Mitral Valve Insufficiency, Stroke Volume, General Medicine, ASSOCIATION, CARE, R1, DYSFUNCTION, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Cardiology and Cardiovascular Medicine
Abstract: Background Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF). Methods A retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Results Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57–2.63; p p Conclusions Among patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome. Graphical abstract
Published: 2022

15. Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation

Author: Guillaume Baudry, Guillaume Coutance, Richard Dorent, Fabrice Bauer, Katrien Blanchart, Aude Boignard, Céline Chabanne, Clément Delmas, Nicolas D'Ostrevy, Eric Epailly, Vlad Gariboldi, Philippe Gaudard, Céline Goéminne, Sandrine Grosjean, Julien Guihaire, Romain Guillemain, Mathieu Mattei, Karine Nubret, Sabine Pattier, Matteo Pozzi, Patrick Rossignol, Emmanuelle Vermes, Laurent Sebbag, Nicolas Girerd, Elisabeth Hugon‐Vallet, Marie‐France Seronde, Pauline Fournier, Caroline Augier, Hospices Civils de Lyon (HCL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), French National Research Agency. Grant Numbers: ANR-16-ECVD-0002-02, ANR-15-CE14–0032-01, ANR-15-IDEX-04-LUE, ANR-15-RHUS-0004, ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), and ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015)
Subjects: Heart Failure, Waiting Lists, Advanced heart failure, [SDV]Life Sciences [q-bio], Prognosis, Cardiovascular diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Humans, Heart Transplantation, Heart transplant, Forrester's classification, Cardiology and Cardiovascular Medicine, Cardiac oedema
Abstract: International audience; Aims: The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist.Methods and results: All non-inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P = 0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P = 0.001 in 'cold-wet'.Conclusions: Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.
Published: 2022

16. Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial

Author: Wolfram Doehner, Stefan D Anker, Javed Butler, Faiez Zannad, Gerasimos Filippatos, João Pedro Ferreira, Afshin Salsali, Carolyn Kaempfer, Martina Brueckmann, Stuart J Pocock, James L Januzzi, Milton Packer, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), University of Mississippi Medical Center (UMMC), Baylor College of Medecine, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), University of Athens, Attikon Hospital, Cardiovascular R&D Centre-UnIC@RISE, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Rutgers University [Camden], Rutgers University System (Rutgers), mainanalytics GmbH, Sulzbach, Boehringer Ingelheim International GmbH, Medizinische Fakultät Mannheim, London School of Hygiene and Tropical Medicine (LSHTM), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Imperial College London, This study was funded by Boehringer Ingelheim and Eli Lilly. Graphical assistance was provided by 7.4 Ltd and was funded by Boehringer Ingelheim, and BOZEC, Erwan
Subjects: Heart Failure, Male, Sodium, Empagliflozin, Hyperuricemia, Heart failure with reduced ejection fraction, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Uric Acid, Hospitalization, Metabolism, Glucose, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes Mellitus, Type 2, Glucosides, Humans, Female, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine, Sodium-Glucose Transporter 2 Inhibitors, Outcome
Abstract: Background The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA. Methods The association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality was investigated in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricaemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) and in subgroups of patients of tertiles of SUA. Results Hyperuricaemia was prevalent in 53% of patients with no sex differences. Elevated SUA (highest tertile, mean SUA 9.38 ± 1.49 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.64 (95% confidence interval, CI 1.28–2.10); cardiovascular mortality, HR 1.98 (95% CI 1.35–2.91); all-cause mortality, HR 1.8 (95% CI 1.29–2.49), all P Conclusion Hyperuricaemia is common in HF and is an independent predictor of advanced disease severity and increased mortality. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricaemia. The benefit of empagliflozin on the primary outcome was observed independently of SUA.
Published: 2022

17. Baroreflex activation therapy with the <scp>Barostim</scp> ™ device in patients with heart failure with reduced ejection fraction: a patient level meta‐analysis of randomized controlled trials

Author: Andrew J.S. Coats, William T. Abraham, Michael R. Zile, Joann A. Lindenfeld, Fred A. Weaver, Marat Fudim, Johann Bauersachs, Sue Duval, Elizabeth Galle, Faiez Zannad, BOZEC, Erwan, University of Warwick [Coventry], Ohio State University [Columbus] (OSU), Medical University of South Carolina [Charleston] (MUSC), VA Medical Center, Vanderbilt University [Nashville], Keck School of Medicine [Los Angeles], University of Southern California (USC), Duke University [Durham], Duke Clinical Research Institute, Duke University, Hannover Medical School [Hannover] (MHH), University of Minnesota Medical School, University of Minnesota System, CVRx, Inc., Minneapolis, Minnesota, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], and French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT )
Subjects: Heart Failure, Electric Stimulation Therapy, Stroke Volume, Baroreflex, QP, Peptide Fragments, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Meta-analysis, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Natriuretic Peptide, Brain, Randomized controlled trials, Quality of Life, Autonomic nervous system, Humans, Cardiology and Cardiovascular Medicine, RC, Randomized Controlled Trials as Topic
Abstract: International audience; Aims: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFrEF.Methods and results: An individual patient data (IPD) meta-analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline-directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6-month changes in 6-min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT-proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of -13 points (95% CI -17, -10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT-proBNP
Published: 2022

18. Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled

Author: João Pedro Ferreira, Faiez Zannad, Javed Butler, Gerasimos Filipattos, Ivana Ritter, Elke Schüler, Bettina J Kraus, Stuart J Pocock, Stefan D Anker, Milton Packer, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens School of Medicine, Boehringer Ingelheim International GmbH, mainanalytics GmbH, Department of Internal Medicine I, University Hospital Würzburg, Comprehensive Heart Failure Centre, University and University Hospital of Würzburg, London School of Hygiene and Tropical Medicine (LSHTM), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Baylor College of Medecine, Imperial College London, and The EMPEROR-Reduced and Preserved trials were funded by Boehringer Ingelheim and Eli Lilly and Company (EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977 and EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).
Subjects: Heart Failure, Aminobutyrates, Biphenyl Compounds, Empagliflozin, Hypokalemia, Stroke Volume, Ventricular Function, Left, Hyperkalaemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucosides, Potassium, Humans, Hyperkalemia, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine
Abstract: Aims Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen heart failure prognosis. Some studies suggested that sodium-glucose cotransporter 2 inhibitors reduce hyperkalaemia, an effect that may have important clinical implications. This analysis evaluates the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF. Methods and results EMPEROR-Pooled (i.e. EMPEROR-Reduced and EMPEROR-Preserved combined) included 9583 patients with available serum potassium levels at baseline (98.6% of the total EMPEROR-Pooled population, n = 9718). Hyperkalaemia was identified by investigators’ reports of adverse events, and by a laboratory serum potassium value above 5.5 mmol/L and 6.0 mmol/L. The main outcome was a composite of investigator-reported hyperkalaemia or initiation of potassium binders. Patients with high potassium at baseline were more frequently diagnosed with diabetes and ischaemic HF aetiology and had lower left ventricular ejection fraction and estimated glomerular filtration rate but were more frequently treated with sacubitril/valsartan or mineralocorticoid receptor antagonists. Empagliflozin (compared with placebo) reduced the composite of investigator-reported hyperkalaemia or initiation of potassium binders [6.5% vs. 7.7%, hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.95, P = 0.01]. Empagliflozin reduced hyperkalaemia rates regardless of the definition used (serum potassium >5.5 mmol/l: 8.6% vs. 9.9%, HR 0.85, 95% CI 0.74–0.97, P = 0.017; serum potassium >6.0 mmol/l: 1.9% vs. 2.9%, HR 0.62, 95% CI 0.48–0.81, P Conclusions Empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.
Published: 2022

19. SGLT2i for evidence based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA

Author: Mark, Patrick, Sarafidis, Pantelis, Ekart, Robert, Ferro, Charles, Balafa, Olga, Fernandez-Fernandez, Beatriz, Herrington, William, Rossignol, Patrick, del Vecchio, Lucia, Valdivielso, José M., Mallamaci, Francesca, Ortiz, Alberto, Nistor, Ionut, Cozzolino, Mario, University of Glasgow, Aristotle University of Thessaloniki, Hippokration Hospital, University medical centre Maribor (UKC Maribor), University Hospitals Birmingham [Birmingham, Royaume-Uni], University of Birmingham [Birmingham], University Hospital of Ioannina, Universidad Autónoma de Madrid (UAM), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Nuffield Department of Population Health [Oxford], University of Oxford, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpital Princesse Grace [Monaco], ASST Lecco, University of Lleida-IRBLLEIDA-PCiTA, Vascular and Renal Translational Research Group and UDETMA, IRBLleida, CNR-IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hpertension Unit, Reggio Calabria, Reggio Calabria c/o Ospedali Riuniti, University of Medicine and Pharmacy 'Grigore T.Popa' Iasi (UMF lasi), Università degli Studi di Milano = University of Milan (UNIMI), AO/BFF research is supported by FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, PI21/00251, PI20/00744, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, Sociedad Madrileña de Nefrología (SOMANE), FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) funded by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia(MRR) and SPACKDc PMP21/00109, FEDER funds., European Project, and European Project: RD21/0005/000
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Chronic kidney disease (CKD) is a major public health issue affecting an estimated 850 million people globally. The leading causes of CKD is diabetes and hypertension, which together account for more than 50% of patients with end-stage kidney disease. Progressive CKD leads to the requirement for kidney replacement therapy with transplantation or dialysis. In addition, CKD, is a risk factor for premature cardiovascular disease, particularly from structural heart disease and heart failure (HF). Until 2015, the mainstay of treatment to slow progression of both diabetic and many non-diabetic kidney diseases was blood pressure control and renin-angiotensin system inhibition; however, neither angiotensin converting enzyme inhibitors (ACEIs) nor angiotensin receptor blockers (ARBs) reduced cardiovascular events and mortality in major trials in CKD. The emergence of cardiovascular and renal benefits observed with sodium-glucose cotransporter-2 inhibitors (SGLT2i) from clinical trials of their use as antihyperglycaemic agents has led to a revolution in cardiorenal protection for patients with diabetes. Subsequent clinical trials, notably DAPA-HF, EMPEROR, CREDENCE, DAPA-CKD and EMPA-KIDNEY have demonstrated their benefits in reducing risk of HF and progression to kidney failure in patients with HF and/or CKD. The cardiorenal benefits - on a relative scale - appear similar in patients with or without diabetes. Specialty societies’ guidelines are continually adapting as trial data emerges to support increasingly wide use of SGLT2i. This consensus paper from EURECA-m and ERBP highlights the latest evidence and summarises the guidelines for use of SGLT2i for cardiorenal protection focusing on benefits observed relevant to people with CKD.
Published: 2023

20. Version francaise des recommandations de la declaration d'Ottawa sur la conception et la conduite ethique d'essais randomises en clusters, dans le contexte legislatif francais

Author: A. Bourmaud, A. Fianu, C. Kervan, A. Verga-Gérard, I. Fournel, A. Dumas, J. Mancini, F. Alla, A. Omorou, B. Giraudeau, Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Sud Saint Pierre [Ile de la Réunion], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut des sciences de la santé publique [Marseille] (ISSPAM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Ethics, Informed Consent, Epidemiology, Cluster randomized trial, Public Health, Environmental and Occupational Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; INTRODUCTION: There is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement". METHOD: . The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group. RESULTS: . This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples. CONCLUSION: Without interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.; INTRODUCTION : Il existe une littérature croissante sur les défis éthiques soulevés par les essais randomisés en clusters (ou en grappes). Cette spécificité n'est pas prise en compte dans les textes réglementaires qui régissent la recherche, ce qui est source de difficultés pour les chercheurs utilisant ces schémas expérimentaux. La Déclaration d'Ottawa (Weijer et al. 2012) vise à fournir des conseils détaillés sur l’éthique de la conception, de la conduite et de l’évaluation des essais en clusters. Elle a pour objectif d'aider l'ensemble des acteurs de la recherche (parties prenantes et décideurs) à prendre des décisions éclairées en termes d’éthique relative à la particularité de ces schémas expérimentaux. Il semble que cette déclaration internationale ne soit pas assez accessible auprès de l'ensemble des acteurs français de la recherche en santé. L'objectif de cet article est de proposer à ces professionnels une traduction française de l’« Ottawa Statement », contextualisée et illustrée. METHODE : Le groupe de travail « Design complexe » du réseau RECaP (Recherche en épidémiologie clinique et en santé publique) a réalisé ce travail. Une première version a été discutée par les auteurs au travers de plusieurs réunions. Elle a été complétée par des explications contextuelles et par des exemples d’études françaises actuellement menées par les auteurs. La dernière version a été obtenue par consensus et validée par le groupe. RESULTATS : Ce travail présente les 15 recommandations regroupées en sept grandes questions : quelle justification pour le design en clusters ? Comment soumettre à un comité d’éthique ? Comment identifier les participants à la recherche ? Quand et comment obtenir un consentement éclairé ? Qui sont les personnes référentes ? Comment évaluer les bénéfices et les risques ? Comment protéger les personnes vulnérables ? Chacune de ces recommandations porte spécifiquement sur les essais en clusters. Ces recommandations sont expliquées et détaillées au travers d'exemples. CONCLUSION : Ce travail permet de fournir un cadre pour la mise en place, la conduite et l’évaluation éthique des essais randomisés en clusters en France. Sans ingérence dans les lois actuelles françaises. Dans le contexte actuel, il est indispensable que l'ensemble des groupes concernés puissent appuyer leurs décisions sur des recommandations en accord avec les principes élémentaires de l’éthique de la recherche en santé.
Published: 2023

21. Machine Learning–Based Phenogrouping in Mitral Valve Prolapse Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events

Author: Olivier Huttin, Nicolas Girerd, Antoine Jobbe-Duval, Anne-Laure Constant Dit Beaufils, Thomas Senage, Laura Filippetti, Caroline Cueff, Kevin Duarte, Antoine Fraix, Nicolas Piriou, Damien Mandry, Nathalie Pace, Solena Le Scouarnec, Romain Capoulade, Matthieu Echivard, Jean Marc Sellal, Marie Marrec, Marine Beaumont, Gabriella Hossu, Jean-Noel Trochu, Nicolas Sadoul, Pierre-Yves Marie, Charles Guenancia, Jean-Jacques Schott, Jean-Christian Roussel, Jean-Michel Serfaty, Christine Selton-Suty, Thierry Le Tourneau, Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - équipe Thorax - CHU Nantes (CIC - thorax), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondation Cœur et Recherche (TLT, 2013, Paris, France), French Ministry of Health 'PHRC-I 2012' (TLT, API12/N/019, Paris, France). T Le Tourneau was supported by an INSERM Translational Research Grant (2012-2016, Paris, France). The STAMP study (OH, CSS) was supported by a grant from the French Ministry of Health (APJ 2015, n°: 2016-A00954-47). Pr Girerd is supported by the French National Research Agency Fighting Heart Failure (ANR-15-RHU-0004), by the French PIA project Lorraine Université d’Excellence GEENAGE (ANR-15-IDEX-04-LUE) programs, and the Contrat de Plan Etat Région Lorraine and FEDER IT2MP, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), and European Project
Subjects: [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Abstract: International audience; Background: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment.Objectives: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis.Methods: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429 patients, 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes.Results: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain 42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles.Conclusions: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse; NCT03884426 and Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP]; NCT02879825).
Published: 2023

22. Birth weight and subclinical cardiovascular and renal damage in a population-based study (the STANISLAS cohort study)

Author: Marilucy Lopez-Sublet, Thomas Merkling, Nicolas Girerd, Constance Xhaard, Adrien Flahault, Erwan Bozec, Celine Leroy, Tomona Fujikawa, Allan Arthur Vaag, Alexandre Mebazaa, Caroline Michaela Kistorp, Barbara Heude, Jean Marc Boivin, Faiez Zannad, Sandra Wagner, Patrick Rossignol, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Steno Diabetes Center, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], University of Copenhagen = Københavns Universitet (UCPH), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Princesse Grace [Monaco], The studies mentioned were sponsored by the Nancy CHRU. They were supported by the Programme Hospitalier de Recherche Clinique (PHRC), by a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' programme (reference: ANR-15-RHU-0004), and Contrat de Plan Etat Région Lorraine and FEDER, La Région Lorraine, and la Fondation de Recherche en Hypertension artérielle, and by the EU FP6 program Ingenius Hypercare., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and European Project
Subjects: Physiology, [SDV]Life Sciences [q-bio], Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract: International audience; Objective: Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort.Methods: This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399 parents/629 children) initiated in 1993-1995, with a fourth examination conducted in 2011-2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima-media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation.Results: Mean (±SD) birth weight was 3.3 ± 0.6 kg. Heritability was moderate (42-44%). At the fourth visit, individuals were 37 years old (32.0-57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45-0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3 kg having a higher LVMI. A positive association (β 95% CI 5.09 (1.8-8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD.Conclusion: In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers.
Published: 2023

23. A machine learning derived echocardiographic algorithm identifies people at risk of heart failure with distinct cardiac structure, function, and response to spironolactone: findings from the HOMAGE trial

Author: Kobayashi, Masatake, Huttin, Olivier, Ferreira, João Pedro, Duarte, Kevin, González, Arantxa, Heymans, Stephane, Verdonschot, Job A.J., Rocca, Hans‐peter Brunner‐la, Pellicori, Pierpaolo, Clark, Andrew, Petutschnigg, Johannes, Edelmann, Frank, Cleland, John, Rossignol, Patrick, Zannad, Faiez, Girerd, Nicolas, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Institute of Health Carlos III, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Glasgow, University of Hull [United Kingdom], Castle Hill Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013)
Subjects: collagen, spironolactone, [SDV]Life Sciences [q-bio], biomarkers, Heart failure, Heart failure echocardiogram collagen spironolactone biomarkers, echocardiogram
Abstract: International audience; Background: An echocardiographic algorithm derived by machine learning (e'VM) characterizes preclinical individuals with different cardiac structure and function, biomarkers, and long-term risk of heart failure (HF). Our aim was the external validation of the e'VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone.Methods: The HOMAGE (Heart OMics in Aging) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e'VM algorithm was applied to 416 participants (mean age 74±7years, 25% women) with available echocardiographic variables (i.e., e' mean, left ventricular [LV] end-diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e'VM phenotypes.Results: A majority (>80%) had either "diastolic changes (D)", or "diastolic changes with structural remodeling (D/S)" phenotype. D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p0.10; Pinteraction
Published: 2023

24. Overcoming barriers in the design and implementation of clinical trials for acute kidney injury: a report from the 2020 Kidney Disease Clinical Trialists meeting

Author: Daniel Lazzareschi, Ravindra L Mehta, Laura M Dember, Juliane Bernholz, Alparslan Turan, Amit Sharma, Sachin Kheterpal, Chirag R Parikh, Omar Ali, Ivonne H Schulman, Abigail Ryan, Jean Feng, Noah Simon, Romain Pirracchio, Patrick Rossignol, Matthieu Legrand, BOZEC, Erwan, University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [San Diego] (UC San Diego), Perelman School of Medicine, University of Pennsylvania, AM-Pharma, Case Western Reserve University [Cleveland], Cleveland Clinic, Bayer Pharmaceuticals, University of Michigan [Ann Arbor], University of Michigan System, Johns Hopkins University School of Medicine [Baltimore], Verpora Ltd, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Division of Chronic Care Management, Centers for Medicare & Medicaid Services, University of Washington [Seattle], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], and French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT )
Subjects: pragmatic trial, Kidney Disease, Clinical Trials and Supportive Activities, Clinical Sciences, Renal and urogenital, Review, urologic and male genital diseases, AKI, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical Research, Humans, Transplantation, urogenital system, biomarkers, clinical trial, Acute Kidney Injury, Urology & Nephrology, Prognosis, female genital diseases and pregnancy complications, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, machine learning, Good Health and Well Being, Nephrology, outcome, epidemiology, Patient Safety
Abstract: Acute kidney injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease (CKD) and cardiovascular events. Randomized-controlled trials (RCTs) in this domain are notoriously challenging and many clinical studies in AKI have yielded inconclusive findings. Underlying this conundrum is the inherent heterogeneity of AKI in its etiology, presentation and course. AKI is best understood as a syndrome and identification of AKI subphenotypes is needed to elucidate the disease's myriad etiologies and to tailor effective prevention and treatment strategies. Conventional RCTs are logistically cumbersome and often feature highly selected patient populations that limit external generalizability and thus alternative trial designs should be considered when appropriate. In this narrative review of recent developments in AKI trials based on the Kidney Disease Clinical Trialists (KDCT) 2020 meeting, we discuss barriers to and strategies for improved design and implementation of clinical trials for AKI patients, including predictive and prognostic enrichment techniques, the use of pragmatic trials and adaptive trials.
Published: 2023

25. Optimisation of treatments for heart failure with reduced ejection fraction in routine practice: a position statement from a panel of experts

Author: Girerd, Nicolas, Leclercq, Christophe, Hanon, Olivier, Bayés-Genís, Antoni, Januzzi, James, Damy, Thibaut, Lequeux, Benoit, Meune, Christophe, Sabouret, Pierre, Roubille, François, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpitaux Universitaires Paris Centre, Université Paris Cité (UPCité), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Baim Institute for Clinical Research Boston MA, CHU Henri Mondor [Créteil], Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Titration, Cardiovascular diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Practice guidelines treatment algorithm, Heart failure, Treatment optimization, [SDV.IB]Life Sciences [q-bio]/Bioengineering, General Medicine
Abstract: International audience; Major international practice guidelines recommend the use of a combination of 4 medication classes in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) but do not specify how these treatments should be introduced and up-titrated. Consequently, many patients with HFrEF do not receive an optimized treatment regimen. This review proposes a pragmatic algorithm for treatment optimization designed to be easily applied in routine practice. The first goal is to ensure that all 4 recommended medication classes are initiated as early as possible to establish effective therapy, even at a low dose. This is considered preferable to starting fewer medications at a maximum dose. The second goal is to ensure that the intervals between the introduction of different medications and between different titration steps are as short as possible to ensure patient safety. Specific proposals are made for older patients (> 75 years) who are frail, and for those with cardiac rhythm disorders. Application of this algorithm should allow an optimal treatment protocol to be achieved within 2-months in most patients, which should the treatment goal in HFrEF.
Published: 2023

26. Anti‐spike <scp>IgG</scp> antibody kinetics following the second and third doses of <scp>BNT162b2</scp> vaccine in nursing home residents

Author: Helene Jeulin, Carlos Labat, Kevin Duarte, Simon Toupance, Gregoire Nadin, Denis Craus, Ioannis Georgiopoulos, Isabelle Gantois, François Goehringer, Athanase Benetos, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine, CNRS, LCPME, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de la Recherche Scientifique (CNRS), Maison Médicale, Rosières-aux-Salines, Université de Lorraine, CHRU-Nancy Brabois, Department of Clinical Geriatrics, Université de Lorraine, CHRU-Nancy Brabois, Department of Infectious and Tropical Diseases, and ANR-15-IDEX-0004
Subjects: Aged, 80 and over, Vaccines, SARS-CoV-2, viruses, COVID-19, nursing homes, Antibodies, Viral, vaccination, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Immunoglobulin G, Humans, RNA, Messenger, Geriatrics and Gerontology, BNT162 Vaccine
Abstract: International audience; Background: Duration of post-vaccination protection against COVID-19 in nursing home (NH) residents is a critical issue. The objective of this study was to estimate the duration of the IgG(S) response to the mRNA BNT162b2 vaccine in NH residents with (COV-Yes) or without (COV-No) history of SARS-CoV-2 infection.Methods: A 574 COV-Yes and COV-No NH residents were included in 2 cohorts: Main (n = 115, median age 87 years) or Confirmatory (n = 459, median age 89 years). IgG(S) quantification was carried out at three different time points following the BNT162b2 vaccine: three (1st) and seven (2nd) months after the 2nd dose, and 1 month after the 3rd dose (3rd quantification) in the Main cohort, and twice (2nd and 3rd) in the Confirmatory cohort. The seroneutralization capacity according to COVID-19 history was also measured in a subgroup of patients.Results: Neutralization capacity was strongly correlated with IgG(S) levels (R2 :76%) without any difference between COV-Yes and COV-No groups for the same levels of IgG(S). After the 2nd dose, duration of the assumed robust protection (IgG(S) >264 BAU/ml) was two-fold higher in the COV-Yes vs. COV-No group: 12.60 (10.69-14.44) versus 5.76 (3.91-8.64) months, with this advantage mainly due to the higher IgG(S) titers after the 2nd dose and secondary to a slower decay over time. After the 3rd dose, duration of robust protection was estimated at 11.87 (9.88-14.87) (COV-Yes) and 8.95 (6.85-11.04) (COV-No) months. These results were similar in both cohorts.Conclusions and relevance: In old subjects living in NH, history of SARS-CoV-2 infection provides a clear advantage in the magnitude and duration of high IgG(S) titers following the 2nd dose. Importantly, the 3rd dose induces a much more pronounced IgG(S) response than the 2nd dose in COV-No subjects, the effect of which should be able to ensure a prolonged protection against severe forms of COVID-19 in these subjects.
Published: 2022

27. A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19

Author: Abhinav Sharma, Malik Elharram, Jonathan Afilalo, Alexandria Flannery, Marc Afilalo, Chris Tselios, Jiayi Ni, Justin A. Ezekowitz, Matthew P. Cheng, Andrew P. Ambrosy, Faiez Zannad, James M. Brophy, Nadia Giannetti, Amal Bessissow, Nadine Kronfli, Ariane Marelli, Haya Aziz, Mohammad Alqahtani, Mona Aflaki, Morgan Craig, Renato D. Lopes, João Pedro Ferreira, McGill University Health Center [Montreal] (MUHC), Jewish General Hospital, University of Alberta, Kaiser Permanente, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Duke University [Durham], The RAAS-COVID-19 Randomized Controlled Trial was funded by the McGill Interdisciplinary Initiative in Infection and Immunity (MI4) and the Division of Cardiology at McGill University., and BOZEC, Erwan
Subjects: Adult, Heart Failure, COVID-19, Angiotensin-Converting Enzyme Inhibitors, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Renin-Angiotensin System, Angiotensin Receptor Antagonists, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Natriuretic Peptide, Brain, Humans, Female, Cardiology and Cardiovascular Medicine, Aldosterone, Antihypertensive Agents, Aged
Abstract: International audience; Background: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. Methods: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-totreat principle. Results: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); p= 0.60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06 to 2.62]; p=0.027); RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs.-27.5%; p= 0.024) and the incidence of acute heart failure (33% vs. 4.2%, p=0.016). Conclusion: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased BNP levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
Published: 2022

28. Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization

Author: Henry, Albert, Gordillo-Maranon, Maria, Finan, Chris, Schmidt, Amand F., Ferreira, Joao Pedro, Karra, Ravi, Sundström, Johan, Lind, Lars, Ärnlöv, Johan, Zannad, Faiez, Mälarstig, Anders, Hingorani, Aroon D., Lumbers, R. Thomas, University College of London [London] (UCL), University Medical Center [Utrecht], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Duke University Medical Center, Uppsala Universitet [Uppsala], University of New South Wales [Sydney] (UNSW), Karolinska Institutet [Stockholm], Dalarna University, Pfizer, This work is supported by the University College London (UCL) Hospitals National Institute for Health Research (NIHR) Biomedical Research Centre, the British Heart Foundation (BHF) Research Accelerator Award (AA/18/6/34223), and UK Research and Innovation / NIHR funded Multimorbidity Mechanism and Therapeutics Research Collaborative (MR/V033867/1). A. H. (FS/18/65/34186) and M.G. (FS/17/70/33482) acknowledge support by the BHF Cardiovascular Biomedicine PhD studentship. A.D.H. is an NIHR Senior Investigator. A.F.S is supported by BHF grant PG/18/503383, and acknowledges support by grant R01 LM010098 from the National Institutes of Health (USA). R.K. acknowledges support by the Walker-Inman Endowment, the Mandel Foundation, and by grant R03 HL144812-01. L.L. is supported by a grant from the Swedish Heart-Lung Foundation. J.Ä. is supported by grants from Swedish Research Council (2019-01015 and 2020-00243), the Swedish Heart-Lung Foundation (20180343 and 20210357). R.T.L. is supported by a UK Research and Innovation Rutherford Fellowship hosted by Health Data Research UK (MR/S003754/1) and BigData@Heart Consortium funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No. 116074. C.F., A.F.S., and R.T.L. acknowledge additional support from UCL Hospitals NIHR Biomedical Research Centre., and BOZEC, Erwan
Subjects: Heart Failure, Proteomics, Kardiologi, Mendelian randomization analysis, heart failure, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adrenomedullin, proteomics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Humans, Cardiac and Cardiovascular Systems, drug target prediction, Cardiology and Cardiovascular Medicine, Genome-Wide Association Study
Abstract: Background: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. Methods: We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis -protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis. Results: Forty-four of ninety proteins were positively associated with risk of incident HF ( P –4 ). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1. Conclusions: We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.
Published: 2022

29. Health Literacy throughout adolescence: Invariance and validity study of three measurement scales in the general population

Author: Virginie Ringa, Laurent Rigal, Francis Guillemin, Christine Hassler, Alexandra Rouquette, Stephan Van den Broucke, Cécile Allaire, Sylvie Azogui-Levy, Julien Mancini, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Catholique de Louvain = Catholic University of Louvain (UCL), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Laboratoire Educations et Pratiques de Santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, AP-HP. Université Paris Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire éducations et promotion de la santé (LEPS), Université Paris Cité – UFR Odontologie [Santé] (UPCité UFR Odontologie), Université Paris Cité (UPCité), HAL UVSQ, Équipe, UFR Odontologie [Santé] - Université Paris Cité (UFR Odontologie UPCité), Université Paris Cité – UFR Odontologie [Santé] (UPC UFR Odontologie), Université Paris Cité (UPC), Hôpital Bicêtre, Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), and UCL - SSH/IPSY - Psychological Sciences Research Institute
Subjects: HLSAC, Adolescent, Psychometrics, [SDV]Life Sciences [q-bio], HAS-A, Population, 030209 endocrinology & metabolism, Health literacy, psychometric properties, Developmental psychology, HLS-EU-Q16, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Humans, Measurement invariance, 030212 general & internal medicine, Child, education, Statistical hypothesis testing, education.field_of_study, 4. Education, Reproducibility of Results, General Medicine, Confirmatory factor analysis, Adolescence, [SDV] Life Sciences [q-bio], Psychometric properties, Health promotion, Convergent validity, Scale (social sciences), adolescence, Factor Analysis, Statistical, Psychology, health literacy
Abstract: International audience; Objective: To simultaneously investigate the psychometric properties of three recently developed health literacy measurement scales throughout adolescence in the general population. Methods: French versions of the Health Literacy for School-Aged Children (HLSAC, unidimensional) scale, the Health Literacy Assessment Scale for Adolescents (HAS-A, multidimensional) and the 16-item European Health Literacy Survey questionnaire (HLS-EU-Q16, unidimensional) were completed by 1 444 adolescents in 8th, 9th, 11th grade in general school and 11-12th grade in vocational school. Psychometric properties were studied using confirmatory factor analysis, McDonald's omega coefficient and hypothesis testing. Results: Structural validity was acceptable (HLS-EU-Q16) to good (HAS-A and HLSAC), no measurement invariance issue was found and internal consistency was acceptable for the three scales (0.68-0.84). Convergent validity was low (Pearson correlation coefficients < 0.5) and the only scale for which results were in agreement with a priori hypotheses was the HLSAC. Conclusions: Our results were supportive of the use of HLSAC to assess health literacy during adolescence but the HAS-A, with a slightly better structural validity, can also be promoted due to its three measured dimensions. Practice implications: The use of these scales in practice will help to focus on health literacy, a critical factor for prevention and health promotion in adolescence.
Published: 2022

30. Recommandations pour la mise en place d’études multicentriques avec IRM

Author: Irène Troprès, Elise Bannier, Marie Chupin, Emmanuelle Le Bars, Jean-Luc Anton, Gabriela Hossu, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), IRMaGe (IRMaGe), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), CATI Multicenter Neuroimaging Platform (CATI), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département de Radiologie [CHU de Rennes], Université de Rennes (UR), and Bannier, Elise
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, 030226 pharmacology & pharmacy, Clinical research, 030218 nuclear medicine & medical imaging, Recherche clinique, 03 medical and health sciences, 0302 clinical medicine, Multicentrique, Political science, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Multicenter, Humanities, MRI, IRM
Abstract: MRI is becoming increasingly important in clinical research studies, both in terms of inclusion criteria and endpoints. Markers based on MRI acquisitions are now regularly considered as primary endpoints. Especially in multicentre studies, the management of MRI acquisitions has to take into account the heterogeneity of MRI systems in terms of manufacturers, magnetic fields, coils and software versions. This is due to the number of important parameters that can be specified and optimised to obtain MR images, the variability between the solutions proposed by the manufacturers and the regular technical innovations. The aim of this article is to detail the steps and the people to involve in order to carry out an MRI study. Based on the experience and expertise of the members of the Réseau d’entraide multicentrique en IRM (REMI), we propose detailed recommendations to the French-speaking community, in order to better take into account the specificities of MRI at all stages of the study and to participate in improving the quality of MRI research. These recommendations also take into account the specificities of MRI research platforms and clinical imaging services, as well as regulatory constraints., L’IRM prend une place de plus en plus grande dans les études de recherche clinique, que ce soit au niveau des critères d’inclusion ou des critères d’évaluation. Des marqueurs basés sur l’exploitation des acquisitions IRM sont désormais considérés régulièrement comme critères principaux d’évaluation. Dans le cadre d’études multicentriques en particulier, la gestion des acquisitions IRM doit considérer l’hétérogénéité des systèmes IRM en termes de constructeurs, de champs magnétiques, d’antennes de réception et de versions logicielles. Cela s’explique par le nombre de paramètres importants qu’il est possible de spécifier pour obtenir une acquisition IRM, la variabilité entre les solutions proposées par les constructeurs et les innovations techniques régulières. L’objectif du présent article est de détailler les spécificités à prendre en compte et les personnes à impliquer pour réaliser une étude en IRM quel que soit l’organe concerné par l’imagerie. En s’appuyant sur l’expérience et l’expertise des membres du Réseau d’entraide multicentrique en IRM (REMI), nous proposons à la communauté francophone des recommandations détaillées, afin de mieux prendre en compte les spécificités de l’IRM à toutes les étapes de l’étude et de participer à l’amélioration de la qualité de la recherche en IRM. Ces recommandations prennent également en compte les spécificités des plateformes de recherche en IRM et des services d’imagerie clinique, ainsi que les contraintes réglementaires.
Published: 2022

31. Fenofibrate and Heart Failure Outcomes in Patients With Type 2 Diabetes: Analysis From ACCORD

Author: João Pedro Ferreira, Francisco Vasques-Nóvoa, Diana Ferrão, Francisca Saraiva, Inês Falcão-Pires, João Sérgio Neves, Abhinav Sharma, Patrick Rossignol, Faiez Zannad, Adelino Leite-Moreira, BOZEC, Erwan, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Centro Hospitalar Universitário de São João [Porto], McGill University Health Center [Montreal] (MUHC), and This study was supported by national funds through FCT Fundação para a Ciência e Tecnologia, I.P., under the scope of the Cardiovascular R&D Center – UnIC (UIDB/00051/2020 and UIDP/00051/2020).
Subjects: Heart Failure, Male, Advanced and Specialized Nursing, Simvastatin, Endocrinology, Diabetes and Metabolism, Middle Aged, Lipids, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucose, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes Mellitus, Type 2, Fenofibrate, Cardiovascular Diseases, Internal Medicine, Humans, Female, Hypolipidemic Agents
Abstract: OBJECTIVE Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid). RESEARCH DESIGN AND METHODS We used Cox regression analysis with background glucose-lowering strategy as the stratification variable. The median follow-up was 4.7 years. RESULTS A total of 5,518 patients were included. Median age was 62 years, and 31% were women. Prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95% CI 0.68–1.00 (P = 0.048). The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy, HR 0.64, 95% CI 0.48–0.85, and not among patients receiving intensive glucose-lowering strategy, HR 1.02, 95% CI 0.79–1.33 (Pinteraction = 0.017). A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline. CONCLUSIONS In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.
Published: 2022

32. Reconsidering the ejection fraction centric view of pharmacologic treatment for heart failure

Author: João Pedro Ferreira, Milton Packer, Javed Butler, Faiez Zannad, BOZEC, Erwan, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Imperial College London, University of Texas Southwestern Medical Center [Dallas], and University of Mississippi Medical Center (UMMC)
Subjects: Heart Failure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Stroke Volume, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience
Published: 2022

33. L’alliance thérapeutique est associée à l’adhésion au traitement chez les enfants atteints d’arthrite juvénile idiopathique

Author: Valérie Devauchelle-Pensec, Anaïs Arbault, Elisabeth Solau-Gervais, Irène Lemelle, L. Sparsa, Agnès Duquesne, Tu-Anh Tran, Anne Lohse, Camille Alleyrat, Francis Guillemin, Pascal Pillet, Linda Rossi, Laurence Goumy, Claire Ballot, Héloïse Reumaux, Centre Hospitalier de Belfort (Service de Rhumatologie), CH Belfort-Montbéliard, Service d'Onco-Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nancy, hôpital des Enfants [CHU Bordeaux], Pédiatrie hospices civils de Lyon, hôpital Femme-Mère-Enfant, Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique, CHU Nîmes, France, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service de Pédiatrie Générale [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Rhumatologie Pédiatrique, Centre Universitaire de Lille, Pediatric Rheumatology [Le Kremlin-Bicêtre], Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre] (CeRéMAIA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS
Abstract: Objectifs L’alliance therapeutique (AT) se definit comme l’engagement mutuel entre le soignant et le patient au cours du processus therapeutique. L’adhesion therapeutique est un enjeu majeur dans la prise en charge de l’arthrite juvenile idiopathique (AJI) et repose sur la forte capacite de l’enfant a suivre les traitements. Cette etude avait pour objectif d’evaluer l’association entre l’AT et l’adhesion therapeutique chez des patients atteints d’AJI. Methodes Etude observationnelle, transversale, multicentrique. Des enfants atteints d’AJI, âges de 8 a 16 ans ont ete inclus. Les enfants, leurs parents et les medecins ont complete le Helping Alliance Questionnaire (HAq-CP) pour mesurer l’AT. L’observance aux traitements a ete mesuree a l’aide du Child/Parent Adherence Report Questionnaire (CARQ & PARQ). Les donnees demographiques, les caracteristiques de la maladie, les traitements en cours et l’environnement social ont ete recueillis. La relation univariee entre l’AT et l’adhesion a ete mesuree a l’aide du coefficient de correlation de Pearson. L’analyse multivariee a utilise un modele de regression lineaire multiple. Resultats 119 patients ont ete inclus : 68,9 % de filles, l’âge moyen (ET) etait de 12,4 (2,9) ans, avec une duree de la maladie de 73,1 (48,2) mois. L’AJI etait en remission (52 %), de faible activite (32 %) et active (16 %). Les scores de l’AT etaient eleves (≥ 80/100) chez les enfants, les parents et les medecins. Le HAQ-CP a montre une forte correlation avec le CARQ (r = 0,31 ; p Conclusion L’AT exerce une forte influence sur l’adhesion therapeutique et pourrait jouer un role majeur dans l’efficacite du traitement.
Published: 2022

34. The Association of Smoking with Hospitalization and Mortality Differs According to Sex in Patients with Heart Failure Following Myocardial Infarction

Author: Trygve S, Hall, Stein, Ørn, Faiez, Zannad, Patrick, Rossignol, Kevin, Duarte, Scott D, Solomon, Dan, Atar, Stefan, Agewall, Kenneth, Dickstein, Nicolas, Girerd, BOZEC, Erwan, Oslo University Hospital [Oslo], Stavanger University Hospital, University of Stavanger, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), University of Oslo (UiO), University of Bergen (UiB), and The present work was carried out by researchers from Oslo University Hospital, INSERM - CIC1433 and U1116, CHU Nancy, Université de Lorraine, F-CRIN INI-CRCT Network, University Hospital of Nancy, Brigham and Women’s Hospital, Stavanger University Hospital, University of Bergen, and University of Oslo. No external funding was received
Subjects: Heart Failure, Male, Smoking, Myocardial Infarction, General Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Hospitalization, Cardiovascular diseases, Age, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Humans, Sex, Female, Mortality, Clinical Investigation Smoking, Aged
Abstract: International audience; Background: Smoking has been associated with higher morbidity and mortality following myocardial infarction (MI), but reports of the impact on morbidity and mortality for females and elderly patients experiencing MI complicated with left ventricular dysfunction or overt heart failure are limited. Methods: In an individual patient data meta-analysis of high-risk MI patients, the association of smoking with hospitalizations and death were investigated. Weighted Cox proportional hazard modelling were used to study the risks of smoking on adjudicated endpoints among different sex and age categories. Results: 28,735 patients from the CAPRICORN, EPHESUS, OPTIMAAL and VALIANT trials were assessed. After weighting, smokers (N=18,148) were unfrequently women (29.2%) and a minority were above ≥80 years (9.8%). Smoking was significantly more associated with all-cause hospitalizations in women (hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.16-1.32) than in men (HR=1.10; CI 1.05-1.16) resulting in a significant interaction between smoking and sex (p=0.005). Smoking was predictive of all-cause mortality homogenously across age categories (p for interaction=0.25) and sex (p for interaction=0.58). Conclusions: The influence of smoking on morbidity differed according to sex following high-risk MI. The deleterious impact of smoking on hospitalization appeared particularly potent in women, which should further reinforce preventive strategies in females.
Published: 2022

35. Prognostic relevance of magnesium alterations in patients with a myocardial infarction and left ventricular dysfunction: insights from the EPHESUS trial

Author: Pieter Martens, João Pedro Ferreira, John Vincent, Paula Abreu, Martijn Busselen, Wilfried Mullens, Wai Hong Wilson Tang, Michael Böhm, Bertram Pitt, Faiez Zannad, Patrick Rossignol, Ziekenhuis Oost-Limburg (ZOL), Hasselt University (UHasselt), Cleveland Clinic, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Pfizer, Saarland University [Saarbrücken], University of Michigan [Ann Arbor], University of Michigan System, The EPHESUS trial was sponsored by Pfizer, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), BOZEC, Erwan, and Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID
Subjects: electrolytes. ClinicalTrials.gov identifier: NCT00232180, systolic dysfunction, heart failure, General Medicine, Spironolactone, Prognosis, Critical Care and Intensive Care Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Ventricular Dysfunction, Left, hypomagnesemia, Treatment Outcome, myocardial infarction, hypermagnesemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Magnesium, Cardiology and Cardiovascular Medicine, eplerenone, Mineralocorticoid Receptor Antagonists
Abstract: Aims Magnesium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). The relation between serum magnesium and clinical outcomes is insufficiently elucidated in this population. Methods and results The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hypomagnesemia and hypermagnesemia were defined as a serum magnesium 1.10 mmol/L, respectively. Linear mixed models and time-dependent Cox regression analysis were used to determine the effect of eplerenone on magnesium changes and the prognostic importance of magnesium. The co-primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV hospitalization. A total of 5371 patients had a post-baseline magnesium measurement. At baseline, 231 (4.3%) patients had hypomagnesemia and 271 (5.0%) patients had hypermagnesemia. During a median follow-up of 16 months, 682 (13%) developed hypomagnesemia and 512 (9.5%) hypermagnesemia. Eplerenone treatment did not result in a different magnesium level during follow-up (P = 0.14). After covariate adjustment hypo- and hypermagnesemia were not associated with a higher risk of CV events. Magnesium levels did not modulate the effect of a high potassium (>5 mmol/L) or low potassium ( 0.1 for all primary and secondary endpoints). Conclusion In patients with MI complicated by LVSD or HF, magnesium alterations were not associated with clinical outcomes nor did they influence the effect of eplerenone. Serum magnesium did not modulate the effect of potassium changes on clinical outcome or the treatment effect of eplerenone. ClinicalTrials.gov identifier NCT00232180.
Published: 2022

36. Metabolic Syndrome and the Risk of Preclinical Heart Failure: Insights after 17 Years of Follow-Up from the STANISLAS Cohort

Author: Abhinav Sharma, Amir Razaghizad, João Pedro Ferreira, Jean-Loup Machu, Erwan Bozec, Nicolas Girerd, Patrick Rossignol, Faiez Zannad, McGill University Health Center [Montreal] (MUHC), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), McGill University = Université McGill [Montréal, Canada], Universidade do Porto = University of Porto, The STANISLAS study is sponsored by Nancy CHRU. This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004), and by the French PIA project 'Lorraine Université d’Excellence,' reference ANR-15-IDEX-04-LUE. It is also supported by the European Fibro-Targets Project (Grant agreement No. SP7#602904), European HOMAGE project (Grant agreement No. Heart 'Omics' in Ageing, 7th Framework Program Grant # 305,507), the MEDIA project (Européen 'Cooperation'—Theme 'Health'/FP7-HEALTH-2010-single-stage (reference: 261409), FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), and the Fondation de Recherche en Hypertension Artérielle., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project: SP7#602904, European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), and European Project: 261409,EU FP 7 MEDIA project
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Preclinical heart failure, Heart failure, Pharmacology (medical), Cardiology and Cardiovascular Medicine, Metabolic syndrome
Abstract: Background: We used data from people initially free of clinical cardiovascular disease to evaluate the association between metabolic syndrome (MS) and incident preclinical heart failure (pHF). Methods and Results: STANISLAS was a familial, single-center, longitudinal prospective cohort study composed of 1,006 families from Nancy, France (median follow-up, 17 years [1993–2016]). Age- and sex-adjusted logistic regression and inverse probability weighting models were used to evaluate the association between MS and pHF, which was defined by diastolic dysfunction, atrial enlargement, ventricular hypertrophy, or elevated natriuretic peptides. Among 944 people who were adults at the first and final visit, those with baseline MS were more likely to be older (63 vs. 61 vs. 59 years of age) and male (73% vs. 55% vs. 45%) compared to people who developed incident MS and people who had no baseline MS, respectively. Furthermore, compared to people without baseline MS, the risk of pHF was numerically larger among people with baseline MS (adjusted odds ratio [aOR] 2.27, 95% CI: 1.07–4.81) and people who developed incident MS (aOR 1.56, 95% CI: 1.00–2.43). Concerning the metabolic determinants of MS, the risk of pHF was most elevated in people with baseline hypertension (aOR 3.19, 95% CI: 1.80–5.63) and elevated waist circumference (aOR 2.59, 95% CI: 1.47–4.57). Conclusion: Overall, HF is an important public health concern given the high risk of mortality when patients with MS or elevated fasting glucose become established with the disease. Early aggressive lifestyle modification and medical intervention among patients free of cardiovascular disease with an obese-hypertensive phenotype may be warranted to prevent HF development.
Published: 2022

37. Urinary Marker Profiles in Heart Failure with Reduced Versus Preserved Ejection Fraction

Author: Koen W. Streng, Hans L. Hillege, Jozine M. ter Maaten, Dirk J. van Veldhuisen, Kenneth Dickstein, Nilesh J. Samani, Leong L. Ng, Marco Metra, Gerasimos S. Filippatos, Piotr Ponikowski, Faiez Zannad, Stefan D. Anker, Peter van der Meer, Chim C. Lang, Adriaan A. Voors, Kevin Damman, University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), Stavanger University Hospital, University of Bergen (UiB), University of Leicester, Glenfield Hospital, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Università degli Studi di Brescia = University of Brescia (UniBs), National and Kapodistrian University of Athens (NKUA), University of Athens, Attikon Hospital, University of Cyprus = Université de Chypre, Wrocław Medical University, Cardiology Department, Military Hospital, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Center for Biomaterial Development and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Institute for Polymer Research, GKSS Research Center GmbH, Teltow, Germany, University of Dundee, This work was supported by the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014-11 RECONNECT] and a grant from the European Commission [FP7-242209-BIOSTAT-CHF]. There is no relation with industry., and European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010)
Subjects: Heart failure, Proximal tubule, Renal function, Urinary markers, [SDV]Life Sciences [q-bio], Heart failure Renal function Urinary markers Proximal tubule, Genetics, Pharmaceutical Science, Molecular Medicine, Cardiology and Cardiovascular Medicine, Genetics (clinical)
Abstract: Background Recent data suggest different causes of renal dysfunction between heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We therefore studied a wide range of urinary markers reflecting different nephron segments in heart failure patients. Methods In 2070, in chronic heart failure patients, we measured several established and upcoming urinary markers reflecting different nephron segments. Results Mean age was 70 ± 12 years, 74% was male and 81% (n = 1677) had HFrEF. Mean estimated glomerular filtration rate (eGFR) was lower in patients with HFpEF (56 ± 23 versus 63 ± 23 ml/min/1.73 m2, P = 0.001). Patients with HFpEF had significantly higher values of NGAL (58.1 [24.0–124.8] versus 28.1 [14.6–66.9] μg/gCr, P P = 0.001). These differences were more pronounced in patients with an eGFR > 60 ml/min/1.73m2. Conclusions HFpEF patients showed more evidence of tubular damage and/or dysfunction compared with HFrEF patients, in particular when glomerular function was preserved.
Published: 2023

38. Albuminuria as a marker of systemic congestion in patients with heart failure

Author: Eva M Boorsma, Jozine M ter Maaten, Kevin Damman, Bart J van Essen, Faiez Zannad, Dirk J van Veldhuisen, Nilesh J Samani, Kenneth Dickstein, Marco Metra, Gerasimos Filippatos, Chim C Lang, Leong Ng, Stefan D Anker, John G Cleland, Pierpaolo Pellicori, Ron T Gansevoort, Hiddo J L Heerspink, Adriaan A Voors, Johanna E Emmens, BOZEC, Erwan, University Medical Center Groningen [Groningen] (UMCG), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Department of Cardiovascular Sciences [Leicester], University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Stavanger University Hospital, Università degli Studi di Brescia = University of Brescia (UniBs), National and Kapodistrian University of Athens (NKUA), University of Athens, Attikon Hospital, University of Dundee, Ninewells Hospital and Medical School [Dundee], Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: EXCRETION, SICKLE-CELL-DISEASE, MODELS, PROTEINURIA, PRESSURE, DIAGNOSIS, EJECTION FRACTION, PREVALENCE, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PULMONARY-HYPERTENSION, Central venous pressure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, HOSPITALIZATION, Cardiorenal interaction, Congestion, Albuminuria, Biomarkers, Cardiology and Cardiovascular Medicine
Abstract: Aims Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated. Methods and results Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumin–creatinine ratio (UACR) >30 mg/gCr and >300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4% and 10.0%, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P < 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95% confidence interval 0.35–0.53, P < 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings. Conclusion In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.
Published: 2023

39. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author: Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Dartigeas, Caroline, Schneider, Christof, Mottok, Anja, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Tournilhac, Olivier, Bernhart, Stephan H., Chteinberg, Emil, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Ammerpohl, Ole, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, Stilgenbauer, Stephan, Publica, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Service d'hématologie [Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institute of pathology [Würzburg], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Epigenomics, Chronic lymphocytic leukaemia, Lymphoma, B-Cell, B-Zell-Lymphom, biostatistics, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Biochemistry, Genetics and Molecular Biology, integrative genomics, DDC 570 / Life sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:570, ddc:610, Transcriptomics, Epigenetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, B-cell lymphoma, Gene Expression Profiling, Computational Biology, classifiers, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computational biology and bioinformatics, DLBCL, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic lymphocytic leukemia, Epigenetics, Richter syndrome, DDC 610 / Medicine & health, CLL
Abstract: Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis., publishedVersion
Published: 2023

40. Rationale and design of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) in patients with high-risk diabetic cardiomyopathy

Author: James L. Januzzi, Javed Butler, Stefano Del Prato, Justin A. Ezekowitz, Nasrien E. Ibrahim, Carolyn S.P. Lam, Gregory D. Lewis, Thomas H. Marwick, Julio Rosenstock, W.H. Wilson Tang, Faiez Zannad, Francesca Lawson, Riccardo Perfetti, Alessia Urbinati, BOZEC, Erwan, Massachusetts General Hospital [Boston], Baim Institute for Clinical Research Boston MA, Harvard Medical School [Boston] (HMS), Baylor Scott and White Research Institute, University of Mississippi Medical Center (UMMC), University of Pisa - Università di Pisa, University of Alberta, Harvard T.H. Chan School of Public Health, National Heart Centre Singapore (NHCS), Duke-National University of Singapore Graduate Medical School, Baker Heart and Diabetes Institute (AUSTRALIA), Dallas Diabetes Research Center at Medical City, Cleveland Clinic, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Applied Therapeutics, and The ARISE-HF Trial is sponsored by Applied Therapeutics, Inc. Dr. Januzzi is fundedin part by the Hutter Family Professorship
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Background: Diabetic cardiomyopathy (DbCM) is a specific form of heart muscle disease that may result in substantial morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). Hyperactivation of the polyol pathway is one of the primary mechanisms in the pathogenesis of diabetic complications, including development of DbCM. There is an unmet need for therapies targeting the underlying metabolic abnormalities that drive this form of Stage B heart failure (HF).Methods: Aldose reductase (AR) catalyzes the first and rate-limiting step in the polyol pathway, and AR inhibition has been shown to reduce diabetic complications, including DbCM in animal models and in patients with DbCM. Previous AR inhibitors (ARIs) were limited by poor specificity resulting in unacceptable tolerability and safety profile. AT-001 is a novel investigational highly specific ARI with higher binding affinity and greater selectivity than previously studied ARIs. ARISE-HF (NCT04083339) is an ongoing Phase 3 randomized, placebo-controlled, double blind, global clinical study to investigate the efficacy of AT-001 (1000 mg twice daily [BID] and 1500 mg BID) in 675 T2DM patients with DbCM at high risk of progression to overt HF. ARISE-HF assesses the ability of AT-001 to improve or prevent decline in exercise capacity as measured by functional capacity (changes in peak oxygen uptake [peak VO2]) over 15 (and possibly 27) months of treatment. Additional endpoints include percentage of patients progressing to overt HF, health status metrics, echocardiographic measurements, and changes in cardiacbiomarkers.Results: The ARISE-HF Trial is fully enrolled.Conclusions: This report describes the rationale and study design of ARISE-HF.
Published: 2023

41. Comparison of Proteomic Measurements Across Platforms in the Atherosclerosis Risk in Communities (ARIC) Study

Author: Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Olive Tang, Morgan E Grams, Adrienne Tin, Chiadi E Ndumele, Faiez Zannad, David J Couper, Weihong Tang, Elizabeth Selvin, Josef Coresh, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Baylor College of Medicine (BCM), Baylor University, University of Mississippi Medical Center (UMMC), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). Research reported in this publication was supported by the NIH/NHLBI grants T32HL007024 (Rooney), K24HL152440 (Selvin), R01-HL134320 (Ballantyne and Selvin), R01-HL146907 (Ndumele), NIH/NIDDK grant R01DK089174 (Selvin), and the American Heart Association grant 20SFRN35120152. The research leading to these results has received funding from the European Union Commission’s Seventh Framework Programme under grant agreement No. 305507 (HOMAGE [Heart Omics in Ageing consortium])., European Project: 305507, BOZEC, Erwan, and HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Biochemistry (medical), Clinical Biochemistry, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: Background The plasma proteome can be quantified using different types of highly multiplexed technologies, including aptamer-based and proximity-extension immunoassay methods. There has been limited characterization of how these protein measurements correlate across platforms and with absolute measures from targeted immunoassays. Methods We assessed the comparability of (a) highly multiplexed aptamer-based (SomaScan v4; Somalogic) and proximity-extension immunoassay (OLINK Proseek® v5003; Olink) methods in 427 Atherosclerosis Risk in Communities (ARIC) Study participants (Visit 5, 2011–2013), and (b) 18 of the SomaScan protein measurements against targeted immunoassays in 110 participants (55 cardiovascular disease cases, 55 controls). We calculated Spearman correlations (r) between the different measurements and compared associations with case-control status. Results There were 417 protein comparisons (366 unique proteins) between the SomaScan and Olink platforms. The average correlation was r = 0.46 (range: −0.21 to 0.97; 79 [19%] with r ≥ 0.8). For the comparison of SomaScan and targeted immunoassays, 6 of 18 assays (growth differentiation factor 15 [GDF15], interleukin-1 receptor-like 1 [ST2], interstitial collagenase [MMP1], adiponectin, leptin, and resistin) had good correlations (r ≥ 0.8), 2 had modest correlations (0.5 ≤ r < 0.8; osteopontin and interleukin-6 [IL6]), and 10 were poorly correlated (r < 0.5; metalloproteinase inhibitor 1 [TIMP1], stromelysin-1 [MMP3], matrilysin [MMP7], C-C motif chemokine 2 [MCP1], interleukin-10 [IL10], vascular cell adhesion protein 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], interleukin-18 [IL18], tumor necrosis factor [TNFα], and visfatin) overall. Correlations for SomaScan and targeted immunoassays were similar according to case status. Conclusions There is variation in the quantitative measurements for many proteins across aptamer-based and proximity-extension immunoassays (approximately 1/2 showing good or modest correlation and approximately 1/2 poor correlation) and also for correlations of these highly multiplexed technologies with targeted immunoassays. Design and interpretation of protein quantification studies should be informed by the variation across measurement techniques for each protein.
Published: 2023

42. Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure

Author: Markousis-Mavrogenis, George, Minich, Waldemar B, Al-Mubarak, Ali A, Anker, Stefan D, Cleland, John G F, Dickstein, Kenneth, Lang, Chim C, Leong L, Ng, Samani, Nilesh J, Zannad, Faiez, Metra, Marco, Seemann, Petra, Hoeg, Antonia, Lopez, Patricio, van Veldhuisen, Dirk J, de Boer, Rudolf A, Voors, Adriaan A, van der Meer, Peter, Schomburg, Lutz, Bomer, Nils, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], ImmunometriX GmbH i.L., Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University Medical Center Göttingen (UMG), University of Glascow, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Bergen (UiB), Stavanger University Hospital, University of Dundee, Department of Cardiovascular Sciences [Leicester], University of Leicester, NIHR Leicester Cardiovascular Biomedical Research Unit, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Brescia, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), and European Project
Subjects: immune system, Physiology, Physiology (medical), [SDV]Life Sciences [q-bio], autoimmunity, M2, beta 1, beta 2, beta 3, Cardiology and Cardiovascular Medicine, beta 1 beta 2 beta 3 M2 immune system autoimmunity
Abstract: AimsThe importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF.Methods and resultsSerum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04–1.81), P = 0.024] and HF rehospitalization [1.57 (1.13–2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05–2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function.ConclusionsAAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated.
Published: 2023

43. Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial

Author: João Sérgio Neves, Francisco Vasques‐Nóvoa, Marta Borges‐Canha, Ana Rita Leite, Abhinav Sharma, Davide Carvalho, Milton Packer, Faiez Zannad, Adelino Leite‐Moreira, João Pedro Ferreira, BOZEC, Erwan, Cardiovascular R&D Centre-UnIC@RISE, Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, McGill University Health Center [Montreal] (MUHC), DREAM-CV Lab, McGill University = Université McGill [Montréal, Canada], Baylor Heart and Vascular Institute, Baylor University Medical Center, Imperial College London, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), and This study was supported by national funds through FCT Fundação para a Ciência e Tecnologia, I.P., under the scope of the Cardiovascular R&D Center – UnIC (UIDB/00051/2020 and UIDP/00051/2020).
Subjects: Endocrinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Endocrinology, Diabetes and Metabolism, Internal Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Aim: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF).Materials and methods: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression.Results: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047).Conclusions: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.
Published: 2023

44. Do individual constraints induce flexibility of visual field dependence following a virtual immersion? Effects of perceptive style and cybersickness

Author: Luca Fantin, Gwenaelle Ceyte, Elodie Maïni, Gabriela Hossu, Hadrien Ceyte, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences du Sport-Santé de Paris (I3SP - URP3625), Université Paris Cité (UPCité), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Human-Computer Interaction, Perceptive style, [SCCO]Cognitive science, Cybersickness, Computer Graphics and Computer-Aided Design, Visual cues, Software, Field dependence, Virtual reality, Virtual immersion
Abstract: International audience; Accurately perceiving the gravitational direction is key to successful interaction in our terrestrial environment. In this context field dependence (FD), the importance given to static and/or dynamic visual cues has largely been discussed. Although first considered a trait, several studies suggest FD be flexible in response to postural or visual contexts and to poor virtual reality user experience. The aim of this study was therefore to determine the influence of a disruptive virtual immersion on the level of static and dynamic FD. Forty-five participants were exposed to a virtual maritime environment for up to 14 min. Cybersickness and sense of presence were measured. Before and after virtual immersion, the rod and frame test and the rod and disk test were performed to assess static and dynamic FD, respectively. We demonstrated a significant decrease in both levels of FD after immersion in initially more dependent participants. Decrease in static FD was explained by high initial static FD and severe cybersickness, while decrease in dynamic FD was only explained by the initial level of dynamic FD. In this study, we provide evidence confirming FD flexibility, likely reflecting an adaptation process to environmental or individual-related constraints. Yet, static and dynamic FD seems to rely on separate mechanisms, highlighting the necessity to specify which characteristic of visual information (static or dynamic) individuals depend on when assessing their FD. Our results question the reliability of virtual reality for perceptive or motor diagnoses without considering its consequences, specifically in vulnerable populations such as the elderly.
Published: 2023

45. Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction

Author: Javed Butler, Milton Packer, Gerasimos Filippatos, Joao Pedro Ferreira, Cordula Zeller, Janet Schnee, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Stefan D Anker, BOZEC, Erwan, University of Mississippi Medical Center (UMMC), Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton, National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Attikon University Hospital, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Boehringer Ingelheim International GmbH, University of Heidelberg, Medical Faculty, London School of Hygiene and Tropical Medicine (LSHTM), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Funding for the EMPEROR trials was provided by Boehringer Ingelheim and Eli Lilly and Company., and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Ejection fraction, animal structures, Empagliflozin, Stroke Volume, Heart failure, 030204 cardiovascular system & hematology, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, 03 medical and health sciences, 0302 clinical medicine, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Sex, 030212 general & internal medicine, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine
Abstract: Aims No therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium–glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes. Methods and results A pooled analysis was performed on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9718 patients; 4860 empagliflozin and 4858 placebo), and patients were grouped based on ejection fraction: Conclusion The magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions Key Question How does ejection fraction influence the effects of empagliflozin in patients with heart failure and either a reduced or a preserved ejection fraction? Key Finding The magnitude of the effect of empagliflozin on heart failure outcomes and health status was similar in patients with ejection fractions Take Home Message The consistency of the response in patients with ejection fractions of
Published: 2021

46. Staphylococcus aureus endocarditis: Identifying prognostic factors using a method derived from morbidity and mortality conferences

Author: Benjamin Lefèvre, Antoine Legoff, Mathilde Boutrou, François Goehringer, Willy Ngueyon-Sime, Catherine Chirouze, Matthieu Revest, Véronique Vernet Garnier, Xavier Duval, François Delahaye, Vincent Le Moing, Christine Selton-Suty, Laura Filippetti, Bruno Hoen, Nelly Agrinier, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des maladies infectieuses, Hopital Andree Rosemond, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Cardiologie [CHRU Nancy], Université de Lorraine, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, and Association pour l’Etude et la Prévention de l’Endocardite Infectieuse (AEPEI)
Subjects: Staphylococcus aureus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, morbidity and mortality conference method, infective endocarditis, [SDV]Life Sciences [q-bio], morbidity and mortality, prognostic factors, conference method, General Medicine, survival, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectivesLethality of Staphylococcus aureus (Sa) infective endocarditis (IE) is high and might be due to yet unidentified prognostic factors. The aim of this study was to search for new potential prognostic factors and assess their prognostic value in SaIE.Materials and methodsWe used a two-step exploratory approach. First, using a qualitative approach derived from mortality and morbidity conferences, we conducted a review of the medical records of 30 patients with SaIE (15 deceased and 15 survivors), randomly extracted from an IE cohort database (NCT03295045), to detect new factors of possible prognostic interest. Second, we collected quantitative data for these factors in the entire set of SaIE patients and used multivariate Cox models to estimate their prognostic value.ResultsA total of 134 patients with modified Duke definite SaIE were included, 64 of whom died during follow-up. Of the 56 candidate prognostic factors identified at the first step, 3 had a significant prognostic value in multivariate analysis: the prior use of non-steroidal anti-inflammatory drugs [aHR 3.60, 95% CI (1.59–8.15), p = 0.002]; the non-performance of valve surgery when indicated [aHR 1.85, 95% CI (1.01–3.39), p = 0.046]; and the decrease of vegetation size on antibiotic treatment [aHR 0.34, 95% CI (0.12–0.97), p = 0.044].ConclusionWe identified three potential SaIE prognostic factors. These results, if externally validated, might eventually help improve the management of patients with SaIE.
Published: 2022

47. Head-to-head comparison of diagnostic scores for acute heart failure in the emergency department: results from the PARADISE cohort

Author: Tahar Chouihed, Aurélie Bannay, Patrick Rossignol, Anne Delaruelle, Nicolas Girerd, Deborah Jaeger, Adrien Bassand, Gaetan Giacomin, Yann Roth, Masatake Kobayashi, Charlène Duchanois, Kevin Duarte, BOZEC, Erwan, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service d’Accueil des urgences [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), K team (Data Science, Knowledge, Reasoning and Engineering), Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'Evaluation et Information Médicales [CHRU Nancy], Université de Lorraine (UL), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Data Science, Knowledge, Reasoning and Engineering (K Team)
Subjects: medicine.medical_specialty, Head to head, Population, 030204 cardiovascular system & hematology, Diagnostic tools, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, Humans, Prospective Studies, education, Heart Failure, education.field_of_study, business.industry, 030208 emergency & critical care medicine, Emergency department, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Clinical trial, Dyspnea, Heart failure, Acute Disease, Cohort, Emergency Medicine, Emergency Service, Hospital, business, Area under the roc curve
Abstract: BREST and PREDICA scores have recently emerged for the diagnosis of acute heart failure (AHF) in the emergency department (ED). This study aimed to perform a head-to-head comparison in a large contemporary cohort. BREST and PREDICA scores were calculated from, respectively, 11 and 8 routine clinical variables recorded in the ED in 1386 patients from the PArADIsE cohort. The diagnostic performance of the scores for adjudicated AHF diagnosis was assessed by the area under the ROC curve (AUC). Acute HF diagnosis was adjudicated according to the European Society of Cardiology criteria and BNP levels. A BREST score ≤ 3 or PREDICA score ≤ 1 was associated with low probabilities of AHF (5.7% and 2.6%, respectively). Conversely, a BREST score ≥ 9 or PREDICA score ≥ 5 was associated with a high risk of AHF diagnosis (77.3% and 66.9%, respectively) although more than half of the population was within the "gray zone" (4-8 and 2-4 for the BREST and PREDICA scores, respectively). Diagnostic performances of both scores were good (AUC 79.1%, [66.1-82.1] for the BREST score and 82.4%, [79.8-85.0] for the PREDICA score). PREDICA score had significantly higher diagnostic performance than BREST score (increase in AUC 3.3 [0.8-5.8], p = 0.009). Our study emphasizes the good diagnostic performance of both BREST and PREDICA scores, albeit with a significantly higher diagnostic performance of the PREDICA score. Yet, more than half of the population was classified within the "gray zone" by these scores; additional diagnostic tools are needed to ascertain AHF diagnosis in the ED in a majority of patients. Clinical trial registration: NCT02800122.
Published: 2021

48. Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction

Author: Subodh Verma, Milton Packer, Stefan D. Anker, Carolyn S.P. Lam, Daniel Cotton, Stuart J. Pocock, Martina Brueckmann, David Sim, Janet Schnee, Javed Butler, Egon Pfarr, Gerasimos Filippatos, João Pedro Ferreira, Hiroyuki Tsutsui, Faiez Zannad, Naveed Sattar, Cardiovascular Centre (CVC), National Heart Centre Singapore (NHCS), University Medical Center Groningen [Groningen] (UMCG), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Boehringer Ingelheim International GmbH, Department of Cardiovascular Medicine, Kyushu University, Higashi-ku, Kyushu University [Fukuoka], Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Mississippi State University [Mississippi], Attikon University Hospital, National and Kapodistrian University of Athens (NKUA), London School of Hygiene and Tropical Medicine (LSHTM), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, St. Michael's Hospital, University of Toronto, University of Heidelberg, Medical Faculty, Boehringer Ingelheim Pharmaceuticals, Inc, Baylor University Medical Center, Baylor College of Medecine, Imperial College London, and The EMPEROR-Reduced trial was funded by Boehringer Ingelheim and Eli Lilly (EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977)
Subjects: Relative risk reduction, Ethnic group, Empagliflozin, Fast Track Clinical Research, Heart failure, 030204 cardiovascular system & hematology, Placebo, Racial differences, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Ethnicity, Medicine, Humans, In patient, AcademicSubjects/MED00200, 030212 general & internal medicine, Benzhydryl Compounds, 10. No inequality, Heart Failure and Cardiomyopathies, Ejection fraction, business.industry, Geographic differences, Stroke Volume, medicine.disease, 3. Good health, Cardiology and Cardiovascular Medicine, business, Demography
Abstract: Aims The aim of this article is to explore the influence of region and race/ethnicity on the effects of empagliflozin in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) trial. Methods and results Of 3730 patients, 1353 (36.3%) were enrolled in Europe, 1286 (34.5%) in Latin America, 425 (11.4%) in North America, and 493 (13.2%) in Asia; 2629 (70.5%) were White, 257 (6.9%) Black, and 672 (18.0%) Asian. Placebo event rates (per 100 patient-years) for cardiovascular death or heart failure (HF) hospitalization varied by region (Asia 27.7, North America 26.4, Latin America 21.4, and Europe 17.5) and race/ethnicity (Black 34.4, Asian 24.3, and White 18.7); driven by differences in HF hospitalization. The ratio of total HF hospitalization to cardiovascular death varied from 5.4 in Asia and 4.8 in North America to 2.1 in Europe; and from 4.8 in Black and 4.2 in Asian to 2.2 in White patients. Groups with the highest ratio had the greatest reduction in the primary outcome with empagliflozin. Inclusion of outpatient worsening HF episodes added more events in Europe vs. other regions; enhanced the placebo event rates in Europe vs. other regions; and increased the relative risk reduction with empagliflozin in Europe from 6% to 26%. Conclusions There were notable differences in the placebo event rates for major HF events across diverse regions and race/ethnic groups. The benefit of empagliflozin was most pronounced in groups with the highest ratio of HF hospitalization to cardiovascular death. Regional differences were attenuated when the definition of HF events was expanded to include outpatient worsening HF events., Graphical Abstract Effect of empagliflozin by region and race in EMPEROR-Reduced. Inclusion of outpatient events in the extended composite endpoint attenuated the between-region differences in the effect of empagliflozin seen in the primary outcome of EMPEROR-Reduced.
Published: 2021

49. Lung ultrasound in outpatients with heart failure: the wet‐to‐dry HF study

Author: Pedro Moliner, Julio Núñez, Mar Domingo, Pau Codina, Carmen Rivas, Beatriz González, Josep Lupón, Evelyn Santiago-Vacas, Giosafat Spitaleri, Marta de Antonio, V. Diaz, P Velayos, Laura Conangla, Nicolas Girerd, Antoni Bayes-Genis, Germán Cediel, Germans Trias i Pujol Hospital, Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Biomedical Research Institute [Valencia, Spain] (INCLIVA ), Universitat de València (UV), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project, Barcelona Autonomous University, Université de Barcelonne, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque - - MR-focus2015 - ANR-15-CE14-0032 - AAPG2015 - VALID, Exploring new pathways in age-related heart diseases - - EXPERT2016 - ANR-16-ECVD-0002 - ERA-CVD - VALID, Contrat de Plan Etat Lorraine IT2MP - INCOMING, and Entreprises lorraines, parties prenantes et Développement Durable (FEDER) (Région Lorraine) - INCOMING
Subjects: Male, medicine.medical_specialty, Heart failure, 030204 cardiovascular system & hematology, Pulmonary congestion, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Interquartile range, Internal medicine, Outpatients, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, Decompensation, 030212 general & internal medicine, Lung, Ultrasonography, Heart Failure, Lung ultrasound, business.industry, Hazard ratio, Original Articles, Prognosis, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, RC666-701, Ambulatory, Cardiology, Original Article, Female, Cardiology and Cardiovascular Medicine, business, After treatment
Abstract: The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme (reference: ANR-15-RHUS-0004), by the French PIA project 'Lorraine Université d'Excellence' (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. Aims: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. Methods and results: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B-lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right-sided, left-sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all-cause death or HF-related hospitalization. Two hundred and thirty-three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B-line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B-lines (20.6 ± 11), followed by left-sided (19.7 ± 11.6) and right-sided (13.5 ± 9.8). B-lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6-40)]. B-lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01-1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B-line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01-1.07), P = 0.014], with a 4% increase risk per B-line added. B-lines correlated significantly with CA125 (R = 0.30, P = 0.001). Conclusions: Lung ultrasound supports the diagnostic work-up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short-term events.
Published: 2021

50. Mediators of the improvement in heart failure outcomes with empagliflozin in the EMPA‐REG OUTCOME trial

Author: Anne Pernille Ofstad, Afshin Salsali, Erich Bluhmki, Martin Schumacher, Christoph Wanner, John M. Lachin, Silvio E. Inzucchi, Stefan Hantel, Kristin Ohneberg, Jyothis T. George, Claudia Schmoor, David Fitchett, Faiez Zannad, Bernard Zinman, St. Michael's Hospital, Yale University School of Medicine, Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], University Hospital of Würzburg, University of Freiburg [Freiburg], Clinical Trials Center, Freiburg University Medical Center, Boehringer Ingelheim Norway KS, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Boehringer Ingelheim International GmbH, Biostatistics Center, The George Washington University, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), This analysis was funded by Boehringer Ingelheim. TheEMPA-REG OUTCOME trial was funded by BoehringerIngelheim and Eli Lilly., Yale School of Medicine [New Haven, Connecticut] (YSM), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), and BOZEC, Erwan
Subjects: medicine.medical_specialty, Population, Empagliflozin, Renal function, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucosides, Diabetes mellitus, Internal medicine, Heart rate, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, 030212 general & internal medicine, Benzhydryl Compounds, education, Heart Failure, education.field_of_study, business.industry, Proportional hazards model, Diabetes, SGLT2 inhibitor, Original Articles, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Diabetes Mellitus, Type 2, chemistry, RC666-701, Heart failure, Cardiology, Mediation analysis, Uric acid, Original Article, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Aims: In the EMPA-REG OUTCOME trial, empagliflozin reduced risk of death from heart failure (HF) or hospitalization for heart failure (HHF) versus placebo in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease. We evaluated post hoc the degree to which covariates mediated the effects of empagliflozin on HHF or HF death.Methods and results: A mediator had to fulfil the following criteria: (i) affected by active treatment, (ii) associated with the outcome, and finally (iii) adjustment for it results in a reduced treatment effect compared with unadjusted analysis. Potential mediators were calculated as change from baseline or updated mean and evaluated in univariable analyses as time-dependent covariates in Cox regression of time to HHF or HF death; those with the largest mediating effects were then included in a multivariable analysis. Increases in heart rate, log urine albumin-to-creatinine ratio (UACR), waist circumference, and uric acid were associated with increased risk of HHF or HF death; increases in high-density lipoprotein cholesterol, estimated glomerular filtration rate, haematocrit, haemoglobin, and albumin were associated with reduced risk of HHF or HF death. In univariable analyses, change from baseline in haematocrit, haemoglobin, albumin, uric acid, and logUACR mediated 51%, 54%, 23%, 24%, and 27% of the risk reduction with empagliflozin versus placebo, respectively. Multivariable analysis including haemoglobin, logUACR, and uric acid mediated 85% of risk reduction with similar results when updated means were evaluated.Conclusions: Changes in haematocrit and haemoglobin were the most important mediators of the reduction in HHF and death from HF in patients with T2DM and established CV disease treated with empagliflozin. Albumin, uric acid, and logUACR had smaller mediating effects in this population.
Published: 2021

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