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1. Digital consults to optimize guideline‐directed therapy: design of a pragmatic multicenter randomized controlled trial

Author

Jelle P. Man, Marcel G.W. Dijkgraaf, M. Louis Handoko, Frederik J. deLange, Michiel M. Winter, Marlies P. Schijven, Susan Stienen, Paola Meregalli, Wouter E.M. Kok, Dorianne I. Kuipers, Pim van derHarst, Maarten A.C. Koole, Steven A.J. Chamuleau, and Mark J. Schuuring

Subjects
Heart failure, Clinical trial, Guideline adherence, Digital health, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Many heart failure (HF) patients do not receive optimal guideline‐directed medical therapy (GDMT) despite clear benefit on morbidity and mortality outcomes. Digital consults (DCs) have the potential to improve efficiency on GDMT optimization to serve the growing HF population. The investigator‐initiated ADMINISTER trial was designed as a pragmatic multicenter randomized controlled open‐label trial to evaluate efficacy and safety of DC in patients on HF treatment. Methods and results Patients (n = 150) diagnosed with HF with a reduced ejection fraction will be randomized to DC or standard care (1:1). The intervention group receives multifaceted DCs including (i) digital data sharing (e.g. exchange of pharmacotherapy use and home‐measured vital signs), (ii) patient education via an e‐learning, and (iii) digital guideline recommendations to treating clinicians. The consults are performed remotely unless there is an indication to perform the consult physically. The primary outcome is the GDMT prescription rate score, and secondary outcomes include time till full GDMT optimization, patient and clinician satisfaction, time spent on healthcare, and Kansas City Cardiomyopathy Questionnaire. Results will be reported in accordance to the CONSORT statement. Conclusions The ADMINISTER trial will offer the first randomized controlled data on GDMT prescription rates, time till full GDMT optimization, time spent on healthcare, quality of life, and patient and clinician satisfaction of the multifaceted patient‐ and clinician‐targeted DC for GDMT optimization.

Published
2024
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2. Sex differences in circulating proteins in heart failure with preserved ejection fraction

Author

Susan Stienen, João Pedro Ferreira, Masatake Kobayashi, Gregoire Preud’homme, Daniela Dobre, Jean-Loup Machu, Kevin Duarte, Emmanuel Bresso, Marie-Dominique Devignes, Natalia López Andrés, Nicolas Girerd, Svend Aakhus, Giuseppe Ambrosio, Hans-Peter Brunner-La Rocca, Ricardo Fontes-Carvalho, Alan G. Fraser, Loek van Heerebeek, Gilles de Keulenaer, Paolo Marino, Kenneth McDonald, Alexandre Mebazaa, Zoltàn Papp, Riccardo Raddino, Carsten Tschöpe, Walter J. Paulus, Faiez Zannad, and Patrick Rossignol

Subjects
Medicine, Physiology, QP1-981
Abstract

Abstract Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

Published
2020
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3. Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure

Author

Masatake Kobayashi, Susan Stienen, Jozine M. terMaaten, Kenneth Dickstein, Nilesh J. Samani, Chim C. Lang, Leong L. Ng, Stefan D. Anker, Macro Metra, Gregoire Preud'homme, Kevin Duarte, Zohra Lamiral, Nicolas Girerd, Patrick Rossignol, Dirk J. vanVeldhuisen, Adriaan A. Voors, Faiez Zannad, and João Pedro Ferreira

Subjects
Heart failure, Renin, Aldosterone, Prediction model, Prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Activation of the renin–angiotensin–aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT‐CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all‐cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT‐CHF study, median renin and aldosterone levels were 85.3 (percentile25–75 = 28–247) μIU/mL and 9.4 (percentile25–75 = 4.4–19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted‐HR (95% CI) = 1.47 (1.16–1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted‐HR (95% CI) = 1.16 (0.93–1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT‐CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the “point” measurement of renin and aldosterone in HF is of limited clinical utility.

Published
2020
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4. External Validation of the ELAN‐HF Score, Predicting 6‐Month All‐Cause Mortality in Patients Hospitalized for Acute Decompensated Heart Failure

Author

Khibar Salah, Susan Stienen, Andreas H. M. Moons, Adrianus L. M. Bakx, Petra E. van Pol, R. A. Mikael Kortz, João Pedro Ferreira, Irene Marques, Jutta M. Schroeder‐Tanka, Jan T. Keijer, Antoni Bayes‐Genis, Yigal M. Pinto, Jan G. Tijssen, and Wouter E. Kok

Subjects
acute heart failure, external validation, NT‐proBNP, prognosis, risk score, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Our aim was to calibrate and externally revalidate the ELAN‐HF (European Collaboration on Acute Decompensated Heart Failure) score, to confirm and improve on a previous external validation of the risk score. Methods and Results The ELAN‐HF score predicts 6‐month all‐cause mortality in patients hospitalized for acute decompensated heart failure using absolute and percentage change of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels in addition to clinical variables. For the external validation, we used the PRIMA II (Can NT‐proBNP–Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) trial. For both data sets, observed versus predicted mortality was compared for the 4 risk categories; and the mean predicted mortality was plotted against the observed mortality with calculation of a correlation coefficient and SEE. The model discriminant ability was determined by comparing the C‐statistics for both data sets. The predicted versus actual 6‐month mortality values in the derivation cohort were 3.7% versus 3.6% for the low‐risk category, 9.4% versus 9.2% for the intermediate‐risk category, 24.2% versus 23.5% for the high‐risk category, and 54.2% versus 51.1% for the very‐high‐risk category. The correlation between predicted and observed mortality by deciles was 0.92, with an SEE of ±4%. In the validation cohort, predicted versus actual 6‐month mortality values were 3.0% versus 2.2% for the low‐risk category, 9.4% versus 8.2% for the intermediate‐risk category, 25.0% versus 22.9% for the high‐risk category, and 56.8% versus 53.6% for the very‐high‐risk category. The correlation between predicted and actual mortality by quintiles was 0.99, with an SEE of ±2%. There was no significant difference in C‐statistic between the derivation cohort (0.78; 95% CI, 0.74–0.82) and the validation cohort (0.77; 95% CI, 0.69–0.84; P=0.693). Conclusions Our study confirms that the ELAN‐HF score predicts accurately 6‐month mortality in patients hospitalized for acute decompensated heart failure with the use of easily obtained characteristics.

Published
2019
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5. Bias in natriuretic peptide-guided heart failure trials: time to improve guideline adherence using alternative approaches

Author

Muthiah Vaduganathan, Jean-Claude Tardif, Faiez Zannad, João Pedro Ferreira, Kirkwood F. Adams, Susan Stienen, Patrick Rossignol, James L. Januzzi, Ankeet S. Bhatt, BOZEC, Erwan, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Department of cardiology, Amsterdam University Medical Centers, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Physiology and Cardiothoracic Surgery Cardiovascular Research and Development Unit Faculty of Medicine University of Porto, Massachusetts General Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Montreal Heart Institute Coordinating Centre (MHICC), and Université de Montréal (UdeM)

Subjects
medicine.medical_specialty, Medical therapy, medicine.drug_class, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Biomarker-guided trials, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Bias, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Natriuretic peptides, Intensive care medicine, Guideline-directed, Heart Failure, Ejection fraction, business.industry, Guideline adherence, Stroke Volume, Biomarker, HFrEF, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adherence, Heart failure, Biomarker (medicine), Guideline Adherence, Cardiology and Cardiovascular Medicine, business
Abstract

Treatment of patients with heart failure with reduced ejection fraction (HFrEF) with currently available therapies reduces morbidity and mortality. However, implementation of these therapies is a problem with only few patients achieving guideline-recommended maximal doses of therapy. In an effort to improve guideline adherence and uptitration, several trials have investigated a biomarker-guided strategy (using natriuretic peptide targets in specific), but although conceptually promising, these trials failed to show a consistent beneficial effect on outcomes. In this review, we discuss different methodological issues that may explain the failure of these trials and offer potential solutions. Moreover, alternative approaches to increase heart failure guideline adherence are evaluated.

Published
2021
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6. Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure

Author

João Pedro Ferreira, Susan Stienen, Kenneth Dickstein, Faiez Zannad, Jozine M. ter Maaten, Chim C. Lang, Gregoire Preud'homme, Leong L. Ng, Nilesh J. Samani, Zohra Lamiral, Patrick Rossignol, Masatake Kobayashi, Adriaan A. Voors, M. Metra, Stefan D. Anker, Dirk J. van Veldhuisen, Kevin Duarte, Nicolas Girerd, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University Medical Center Groningen [Groningen] (UMCG), University of Bergen (UiB), Department of Cardiology, Stavanger University Hospital, Department of Cardiovascular Sciences [Leicester], University of Leicester, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, University of Dundee, Ninewells Hospital and Medical School [Dundee], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research (DZHK) partner site Berlin, University of Brescia, Civic Hospital of Brescia, This project was funded by a grant from the European Commission (FP7-242209-BIOSTAT-CHF, EudraCT 2010–020808–29). JPF, NG, PR and FZ are supported by 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. And by Contrat de Plan Etat-Région and FEDER Lorraine., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), European Project, Cardiovascular Centre (CVC), 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), BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, and EudraCT 2010–020808–29 - INCOMING

Subjects
medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, BASE-LINE, Renal function, Heart failure, 030204 cardiovascular system & hematology, THERAPY, DISEASE, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Mineralocorticoid receptor, LEFT-VENTRICULAR DYSFUNCTION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Prediction model, Internal medicine, Original Research Articles, Renin–angiotensin system, Renin, medicine, Humans, 030212 general & internal medicine, Original Research Article, Aldosterone, Mineralocorticoid Receptor Antagonists, PLASMA, business.industry, MORTALITY, medicine.disease, Prognosis, Angiotensin II, SPIRONOLACTONE, Pathophysiology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, ANGIOTENSIN-II, ADIPOSE-TISSUE, chemistry, lcsh:RC666-701, Spironolactone, Cardiology, Cardiology and Cardiovascular Medicine, business, SYSTEM
Abstract

Aims Activation of the renin-angiotensin-aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF.Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT-CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all-cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT-CHF study, median renin and aldosterone levels were 85.3 (percentile(25-75) = 28-247) mu IU/mL and 9.4 (percentile(25-75) = 4.4-19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted-HR (95% CI) = 1.47 (1.16-1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted-HR (95% CI) = 1.16 (0.93-1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT-CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies.Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the "point" measurement of renin and aldosterone in HF is of limited clinical utility.

Published
2020
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7. Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction

Author

Stephane Heymans, Kenneth McDonald, Marie-Dominique Devignes, Alexandre Mebazaa, Paolo Marino, Walter Paulus, Giuseppe Ambrosio, Loek van Heerebeek, Jean-Loup Machu, Carsten Tschöpe, Masatake Kobayashi, Alan G. Fraser, Svend Aakhus, Hans-Peter Brunner-La Rocca, Nicolas Girerd, Ricardo Fontes-Carvalho, Kevin Duarte, João Pedro Ferreira, Susan Stienen, Patrick Rossignol, Gilles W. De Keulenaer, Gregoire Preud'homme, Zoltán Papp, Emmanuel Bresso, Riccardo Raddino, Faiez Zannad, Daniela Dobre, Natalia López, 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), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 Physiology and Cardiothoracic Surgery Cardiovascular Research and Development Unit Faculty of Medicine University of Porto, Centre Psychothérapique de Nancy (CPN), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), 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)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), Department of Cardiology [Oslo], Oslo University Hospital [Oslo], ISB, Norwegian University of Science and Technology, Trondheim, Division of Cardiology, University of Perugia School of Medicine, Perugia, Department of Cardiology, Maastricht University Medical Center, Department of Surgery and Physiology, Cardiovascular Research Unit (UnIC), Faculty of Medicine, University of Porto, Wales Heart Research Institute [Cardiff] (WHRI), Cardiff University, Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, William Harvey Research Institute, Barts Heart Centre, Queen Mary University of London, Laboratory of Physiopharmacology, Antwerp University, and ZNA Hartcentrum, Clinical Cardiology, Università del Piemonte Orientale, Department of Translational Medicine, Azienda Ospedaliero Universitaria 'Maggiore della Carità', St Michael's Hospital Dun Laoghaire Co. Dublin, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis 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 Paris (UP), 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 de Paris (UP)-Université Sorbonne Paris Nord, Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Department of Cardiology, Spedali Civili di Brescia, Charité Campus Virchow-Klinikum (CVK), Department of Cardiology, Campus Virchow-Klinikum, Charite Universitaetsmedizin Berlin, Berlin Institute of Health – Center for Regenerative Therapies (BIH-BCRT), and the German Center for Cardiovascular Research (DZHK, Berlin partner site), Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, This study was supported by a grant from the European Union (FP7-HEALTH-2010-MEDIA), by the French Programme Hospitalier de Recherche Clinique (PHRC) and by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHU-0004), the GEENAGE (ANR-15-IDEX-04-LUE) program, by the Contrat de Plan Etat Région Lorraine and FEDER IT2MP.) N-LA was supported by a Miguel Servet contract CP13/00221 from the 'Instituto de Salud Carlos III-FEDER'. WJP and LvH were supported by CVON, Dutch Heart Foundation, The Hague, The Netherlands (RECONNECT and EARLY-HFpEF projects). AM received speaker's honoraria from Orion, Otsuka, Philips, Roche and Servier. AM received fees as member of advisory board and/or Steering Committee and/or research grant from Adrenomed, Epygon, Neurotronik, Roche, Sanofi and Sphyngotec. AM owns shares in S-Form Pharma. SS acknowledges funding received from the European Society of Cardiology in form of an ESC Research Grant (R-2018-18686). SH was supported by IMI2-CARDIATEAM (N° 821508), research grants from the Netherlands Organization for Scientific Research (NOW, Vidi 91796338), the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21, CVON Arena-PRIME, 2017-18 and the ERA-Net-CVD project MacroERA, 01KL1706, and FWO G091018N, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 261409,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDIA(2011), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Università degli Studi di Perugia = University of Perugia (UNIPG), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Antwerp (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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, BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, The MEtabolic Road to DIAstolic Heart Failure - MEDIA - - EC:FP7:HEALTH2011-01-01 - 2016-06-30 - 261409 - VALID, Centre Psychothérapique de Nancy [Laxou] (CPN), Academic Medical Center, ACS - Heart failure & arrhythmias, Physiology, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
Male, Proteomics, ANGIOPOIETIN RECEPTOR TIE-2, Health, Toxicology and Mutagenesis, Clinical Biochemistry, Disease, 030204 cardiovascular system & hematology, Logistic regression, Bioinformatics, Biochemistry, DISEASE, HFPEF, 0302 clinical medicine, biomarkers, cluster analysis, complex-network analysis, machine learning, phenotype, Pharmacology. Therapy, HEPARIN-BINDING PROTEIN, Diastolic heart failure, Middle Aged, Brain natriuretic peptide, Phenotype, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, PLASMA ANGIOPOIETIN-1, BRAIN NATRIURETIC PEPTIDE, 030220 oncology & carcinogenesis, L-SELECTIN, Female, Engineering sciences. Technology, EXPRESSION, GROWTH-FACTOR, DATABASE, Diastole, GRANULYSIN, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, medicine, Humans, Biology, Aged, Heart Failure, business.industry, Stroke Volume, medicine.disease, business, Heart failure with preserved ejection fraction
Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes. Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression. Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12–3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism. Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significance More insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolism Biomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials. Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

Published
2020
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8. Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction

Author

Faiez Zannad, João Pedro Ferreira, António S. Barros, Susan Stienen, Thomas Thum, Christian Bär, Bertram Pitt, Nicolas Girerd, Patrick Rossignol, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU 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), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], University of Amsterdam [Amsterdam] (UvA), Universidade do Porto, Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School [Hannover] (MHH), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, SS, JF, FZ and PR are supported by 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, and by the Contrat de plan Etat-lorraine and FEDER lorraine. SS received funding from the European Society of Cardiology in form of an ESC Research Grant (R-2018-18686). TT was supported by the German Research Foundation (DFG Th903/18-1) and the ERANet Grant EXPERT (BMBF, Germany, research grant ERA-CVD JTC2016 EXPERT, 01KL1711). AB was supported by DOCnet (NORTE-01-0145-FEDER-000003), by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE (ISITE),Lorraine Université d'Excellence(2016), Publica, DE CARVALHO, Philippe, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universidade do Porto = University of Porto, ANR-15-IDEX-0004,LUE,Isite LUE(2015), Cardiology, and ACS - Heart failure & arrhythmias

Subjects
medicine.medical_specialty, Cardiac fibrosis, Myocardial Infarction, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Mineralocorticoid receptor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes mellitus, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Mineralocorticoid Receptor Antagonists, Heart Failure, business.industry, medicine.disease, Eplerenone, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MicroRNAs, Heart failure, Cardiology, Biomarker (medicine), Cardiology and Cardiovascular Medicine, business, Type I collagen, medicine.drug
Abstract

Background After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results From the selected microRNAs, only mir-133a was associated with a PICP decrease (s-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. Conclusion Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

Published
2021
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9. Estimating the Lifetime Benefits of Treatments for Heart Failure

Author

Pardeep S. Jhund, Stuart J. Pocock, Brian Claggett, Kieran F. Docherty, Faiez Zannad, John J.V. McMurray, Scott D. Solomon, John Gregson, João Pedro Ferreira, Susan Stienen, Mark C. Petrie, Cardiology, ACS - Heart failure & arrhythmias, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 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), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 ), Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences. Amsterdam University Medical Center, University of Amsterdam, Cardiovascular Division Brigham and Women's Hospital 75 Francis Street Boston, Brigham and Women's Hospital [Boston], Department of Biostatistics, London School of Hygiene and Tropical Medicine, JPF & FZ are supported by ANR-15-RHU-0004 and ANR-15-IDEX-04-LUE. JJM, PSJ, and MCP are supported by BHF Grant RE/18/6/34217., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE (ISITE),Lorraine Université d'Excellence(2016), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)

Subjects
medicine.medical_specialty, Spironolactone, 030204 cardiovascular system & hematology, Lower risk, Placebo, HF, heart failure, Sacubitril, RMST, restricted mean survival time, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mini-Focus: Clinical Trial Considerations, Risk Factors, Internal medicine, Patient-Centered Care, medicine, Humans, 030212 general & internal medicine, NYHA, New York Heart Association, HFrEF, heart failure with reduced ejection fraction, Survival analysis, Mineralocorticoid Receptor Antagonists, Original Research, Heart Failure, survival models, business.industry, Hazard ratio, Absolute risk reduction, trials, Infant, Stroke Volume, treatment effects, HR, hazard ratio, Confidence interval, Eplerenone, 3. Good health, CI, confidence interval, Survival Rate, restricted mean survival time, Research Design, Relative risk, NNT, number needed to treat, NT-proBNP, N-terminal pro–B-type natriuretic peptide, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Objectives This study compared ways of describing treatment effects. The objective was to better explain to clinicians and patients what they might expect from a given treatment, not only in terms of relative and absolute risk reduction, but also in projections of long-term survival. Background The restricted mean survival time (RMST) can be used to estimate of long-term survival, providing a complementary approach to more conventional metrics (e.g., absolute and relative risk), which may suggest greater benefits of therapy in high-risk patients compared with low-risk patients. Methods Relative and absolute risk, as well as the RMST, were calculated in heart failure with reduced ejection fraction (HFrEF) trials. Results As examples, in the RALES trial (more severe HFrEF), the treatment effect metrics for spironolactone versus placebo on heart failure hospitalization and/or cardiovascular death were a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.5 to 0.77), number needed to treat = 9 (7 to 14), and age extension of event-free survival +1.1 years (−0.1 to + 2.3 years). The corresponding metrics for EMPHASIS-HF (eplerenone vs. placebo in less severe HFrEF) were 0.64 (0.54 to 0.75), 14 (1 to 22), and +2.9 (1.2 to 4.5). In patients in PARADIGM-HF aged younger than 65 years, the metrics for sacubitril/valsartan versus enalapril were 0.77 (95% CI: 0.68 to 0.88), 23 (15 to 44), and +1.7 (0.6 to 2.8) years; for those aged 65 years or older, the metrics were 0.83 (95% CI: 0.73 to 0.94), 29 (17 to 83), and +0.9 (0.2 to 1.6) years, which provided evidence of a greater potential life extension in younger patients. Similar observations were found for lower risk patients. Conclusions RMST event-free (and overall) survival estimates provided a complementary means of evaluating the effect of therapy in relation to age and risk. They also provided a clinically useful metric that should be routinely reported and used to explain the potential long-term benefits of a given treatment, especially to younger and less symptomatic patients., Central Illustration

Published
2020
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10. Eplerenone prevents an increase in serum carboxy‐terminal propeptide of procollagen type I after myocardial infarction complicated by left ventricular dysfunction and/or heart failure

Author

João Pedro Ferreira, Patrick Rossignol, Bertram Pitt, Pierpaolo Pellicori, Faiez Zannad, John G.F. Cleland, Nicolas Girerd, Susan Stienen, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University of Michigan [Ann Arbor], University of Michigan System, Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow and National Heart & Lung Institute, SS, JF, FZ and PR are supported by 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, and by the Contrat de plan Etat-lorraine and FEDER lorraine. SS received funding from the European Society of Cardiology in form of an ESC Research Grant, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and ANR-15-IDEX-0004,LUE (ISITE),Lorraine Université d'Excellence(2016)

Subjects
medicine.medical_specialty, Myocardial Infarction, Spironolactone, 030204 cardiovascular system & hematology, Procollagen Type I, Collagen Type I, Ventricular Dysfunction, Left, 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, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Protein precursor, ComputingMilieux_MISCELLANEOUS, Mineralocorticoid Receptor Antagonists, Heart Failure, business.industry, medicine.disease, R1, Peptide Fragments, Eplerenone, 3. Good health, Terminal (electronics), Heart failure, Cardiology, Cardiology and Cardiovascular Medicine, business, Procollagen, medicine.drug
Abstract

No abstract available.

Published
2020
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11. Sex differences in circulating proteins in heart failure with preserved ejection fraction

Author

Loek van Heerebeek, Kevin Duarte, Gregoire Preud'homme, Paolo Marino, Riccardo Raddino, Nicolas Girerd, Faiez Zannad, Emmanuel Bresso, Giuseppe Ambrosio, Zoltán Papp, Alexandre Mebazaa, Gilles W. De Keulenaer, Masatake Kobayashi, Alan G. Fraser, Daniela Dobre, Marie-Dominique Devignes, Ricardo Fontes-Carvalho, Carsten Tschöpe, Patrick Rossignol, Hans-Peter Brunner-La Rocca, João Pedro Ferreira, Natalia López Andrés, Susan Stienen, Svend Aakhus, Jean Loup Machu, Kenneth McDonald, Walter Paulus, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Universidade do Porto, Centre Psychothérapique de Nancy (CPN), 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), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Oslo University Hospital [Oslo], Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Department of Medicine [Perugia, Italy], Università degli Studi di Perugia (UNIPG), Department of Cardiology, Maastricht University Medical Center, Department of Surgery and Physiology, Cardiovascular Research Unit (UnIC), Faculty of Medicine, University of Porto, Wales Heart Research Institute [Cardiff] (WHRI), Cardiff University, Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Laboratory of Physiopharmacology, Antwerp University, and ZNA Hartcentrum, Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), St Michael's Hospital Dun Laoghaire Co. Dublin, 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 de Paris (UP)-Université Sorbonne Paris Nord, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis 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 Paris (UP), Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Department of Cardiology, Spedali Civili di Brescia, Charité Campus Virchow-Klinikum (CVK), Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, This study was supported by a grant from the European Union (FP7-HEALTH2010-MEDIA), by the French Programme Hospitalier de Recherche Clinique (PHRC), and by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir' program (reference: ANR-15-RHU-0004), the GEENAGE (ANR-15-IDEX-04-LUE) program, by the Contrat de Plan Etat Région Lorraine and FEDER IT2MP.N-LA was supported by a Miguel Servet contract CP13/00221 from the 'Instituto de Salud Carlos III-FEDER'. WJP and LvH were supported by VON,Dutch Heart Foundation, The Hague, The Netherlands (RECONNECT and EARLY-HFpEF projects). AM received speaker’s honoraria from Orion, Otsuka, Philips, Roche, and Servier. AM received fees as a member of the advisory board and/or Steering Committee and/or research grant from Adrenomed, Epygon, Neurotronik, Roche, Sanofi, and Sphyngotec. AM owns shares in SForm Pharma. SS acknowledges funding received from the European Society of Cardiology in the form of an ESC Research Grant (R-2018-18686)., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 261409,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDIA(2011), RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), Cardiologie, 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), Universidade do Porto = University of Porto, Centre Psychothérapique de Nancy [Laxou] (CPN), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), 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)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Perugia = University of Perugia (UNIPG), University of Antwerp (UA), 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Physiology, and ACS - Heart failure & arrhythmias

Subjects
Male, 0301 basic medicine, ACUTE MYOCARDIAL-INFARCTION, MATRIX METALLOPROTEINASES, DATABASE, [SDV]Life Sciences [q-bio], IGFBP3, Physiology, lcsh:Medicine, LIPOPROTEIN-LIPASE, lcsh:Physiology, Gender Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Endocrinology, LEPTIN, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Medicine, Myocardial infarction, Aged, Aged, 80 and over, Heart Failure, GENDER-DIFFERENCES, lcsh:QP1-981, business.industry, Proportional hazards model, Research, Leptin, MORTALITY, lcsh:R, Diastolic heart failure, WOMEN, Stroke Volume, MEN, medicine.disease, Pathophysiology, 030104 developmental biology, Gene Expression Regulation, ATHEROSCLEROSIS, Female, Human medicine, business, Heart failure with preserved ejection fraction, Biomarkers, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Extracellular matrix organization
Abstract

Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

Published
2020
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12. Mean BMI, visit-to-visit BMI variability and BMI changes during follow-up in patients with acute myocardial infarction with systolic dysfunction and/or heart failure: insights from the High-Risk Myocardial Infarction Initiative

Author

Bertram Pitt, Kenneth Dickstein, Faiez Zannad, João Pedro Ferreira, Nicolas Girerd, John J.V. McMurray, Zohra Lamiral, Susan Stienen, Kevin Duarte, Patrick Rossignol, Centre d'investigation clinique plurithématique Pierre Drouin (CIC-P), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Division of Cardiovascular and Medical Sciences, University of Glasgow, University of Michigan Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Stavanger, CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Contrat de Plan Etat Lorraine, FEDER, ANR-15-IDEX-04-LUE,LUE,Lorraine Université d'Excellence(2016), ANR: ANR-15-RHU-0004,Programme Investissement d'Avenir ANR-15-RHU-0004, 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), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, University of Michigan Medical School [Ann Arbor], ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), Graduate School, Amsterdam Cardiovascular Sciences, 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 Universidade do Porto

Subjects
Male, medicine.medical_specialty, Systolic dysfunction, [SDV]Life Sciences [q-bio], Myocardial Infarction, Acute myocardial infarction, 030204 cardiovascular system & hematology, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Internal medicine, Statistical significance, Outcome Assessment, Health Care, medicine, Humans, In patient, 030212 general & internal medicine, Myocardial infarction, Variability, Body mass index, Aged, Proportional Hazards Models, Heart Failure, business.industry, General Medicine, Middle Aged, medicine.disease, Prognosis, 3. Good health, Heart failure, Cardiology, Female, Patient status, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; BACKGROUND:In patients with acute myocardial infarction (MI), BMI 4%) were associated with increased event-rates, but lost statistical significance in sensitivity analysis including patients with ≥ 5 measurements or excluding patients with HF hospitalization, suggesting that BMI variability may be particularly associated with HF hospitalizations.CONCLUSION:Mean BMI

Published
2019
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13. Estimated Long-Term Survival With Eplerenone

Author

Faiez Zannad, João Pedro Ferreira, Susan Stienen, John Vincent, Benjamin Li, Nicolas Girerd, Patrick Rossignol, Martijn Busselen, Bertram Pitt, John J.V. McMurray, Graduate School, and Amsterdam Cardiovascular Sciences

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Myocardial Infarction, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Health Services Misuse, Time, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Long term survival, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Mineralocorticoid Receptor Antagonists, Randomized Controlled Trials as Topic, Heart Failure, Ejection fraction, business.industry, Stroke Volume, Middle Aged, medicine.disease, Eplerenone, Mineralocorticoid, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Despite Class I recommendations in current American College of Cardiology/American Heart Association guidelines for heart failure (HF) with reduced ejection fraction (HFrEF) and acute myocardial infarction (AMI) with left ventricular systolic dysfunction (LVSD) and/or HF [(1)][1], mineralocorticoid

Published
2019

14. Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction

Author

Wouter E.M. Kok, Susan Stienen, Khibar Salah, Marco Metra, Jan G.P. Tijssen, Valerio Verdiani, Yigal M. Pinto, Luc W. Eurlings, Antoni Bayes-Genis, Graduate School, ACS - Heart failure & arrhythmias, ACS - Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
Male, medicine.medical_specialty, Acute decompensated heart failure, acute decompensated Heart failure, medicine.drug_class, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, Humans, Medicine, In patient, 030212 general & internal medicine, Mortality prediction, Heart Failure and Cardiomyopathies, Aged, Aged, 80 and over, Heart Failure, Ejection fraction, business.industry, Stroke Volume, Middle Aged, medicine.disease, Peptide Fragments, Hospitalization, Survival Rate, NT-proBNP, preserved left ventricle ejection fraction, prognosis, Case-Control Studies, Relative risk, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

BackgroundWe assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).MethodsPatients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with ResultsDischarge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%–60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories.ConclusionsOur study highlights—after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF—the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF.

Published
2019

15. External Validation of the ELAN-HF Score, Predicting 6-Month All-Cause Mortality in Patients Hospitalized for Acute Decompensated Heart Failure

Author

João Pedro Ferreira, R. A. Mikael Kortz, Susan Stienen, Jan G.P. Tijssen, Jutta M. Schroeder-Tanka, Andreas H. M. Moons, Adrianus L. M. Bakx, Khibar Salah, Irene Marques, Petra E. van Pol, Wouter E.M. Kok, Jan T. Keijer, Yigal M. Pinto, Antoni Bayes-Genis, Graduate School, ACS - Heart failure & arrhythmias, Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
Male, medicine.medical_specialty, Acute decompensated heart failure, medicine.drug_class, acute heart failure, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Blood Pressure, 030204 cardiovascular system & hematology, risk score, NT‐proBNP, Risk Assessment, Severity of Illness Index, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, external validation, Internal medicine, Cause of Death, Natriuretic Peptide, Brain, Natriuretic peptide, Medicine, Edema, Humans, Urea, In patient, 030212 general & internal medicine, Mortality, Aged, Original Research, Heart Failure, Framingham Risk Score, business.industry, Significant difference, External validation, Age Factors, Reproducibility of Results, medicine.disease, Peptide Fragments, Hospitalization, NT-proBNP, Hospital admission, Acute Disease, Female, prognosis, Cardiology and Cardiovascular Medicine, business, All cause mortality, Hyponatremia
Abstract

Background Our aim was to calibrate and externally revalidate the ELAN‐HF (European Collaboration on Acute Decompensated Heart Failure) score, to confirm and improve on a previous external validation of the risk score. Methods and Results The ELAN‐HF score predicts 6‐month all‐cause mortality in patients hospitalized for acute decompensated heart failure using absolute and percentage change of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels in addition to clinical variables. For the external validation, we used the PRIMA II (Can NT‐proBNP–Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) trial. For both data sets, observed versus predicted mortality was compared for the 4 risk categories; and the mean predicted mortality was plotted against the observed mortality with calculation of a correlation coefficient and SEE. The model discriminant ability was determined by comparing the C‐statistics for both data sets. The predicted versus actual 6‐month mortality values in the derivation cohort were 3.7% versus 3.6% for the low‐risk category, 9.4% versus 9.2% for the intermediate‐risk category, 24.2% versus 23.5% for the high‐risk category, and 54.2% versus 51.1% for the very‐high‐risk category. The correlation between predicted and observed mortality by deciles was 0.92, with an SEE of ±4%. In the validation cohort, predicted versus actual 6‐month mortality values were 3.0% versus 2.2% for the low‐risk category, 9.4% versus 8.2% for the intermediate‐risk category, 25.0% versus 22.9% for the high‐risk category, and 56.8% versus 53.6% for the very‐high‐risk category. The correlation between predicted and actual mortality by quintiles was 0.99, with an SEE of ±2%. There was no significant difference in C‐statistic between the derivation cohort (0.78; 95% CI, 0.74–0.82) and the validation cohort (0.77; 95% CI, 0.69–0.84; P =0.693). Conclusions Our study confirms that the ELAN‐HF score predicts accurately 6‐month mortality in patients hospitalized for acute decompensated heart failure with the use of easily obtained characteristics.

Published
2019

16. Response by Kok and Stienen to Letter Regarding Article, 'NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?)'

Author

Wouter Kok, Susan Stienen, ACS - Heart failure & arrhythmias, Cardiology, Graduate School, and Amsterdam Cardiovascular Sciences

Subjects
Heart Failure, medicine.medical_specialty, Acute decompensated heart failure, medicine.drug_class, business.industry, medicine.disease, Patient Readmission, Peptide Fragments, law.invention, Randomized controlled trial, law, Physiology (medical), Internal medicine, Heart failure, Natriuretic Peptide, Brain, Hospital admission, medicine, Natriuretic peptide, Cardiology, Humans, N terminal pro b type natriuretic peptide, Cardiology and Cardiovascular Medicine, business
Published
2018

17. Serum Potassium Levels During Admissions for Acute Decompensated Heart Failure: Identifying Possible Threats to Outcome

Author

Susan Stienen, Khibar Salah, Wouter Kok, ACS - Heart failure & arrhythmias, Cardiology, Graduate School, and ACS - Amsterdam Cardiovascular Sciences

Subjects
Heart Failure, medicine.medical_specialty, Acute decompensated heart failure, business.industry, MEDLINE, 030204 cardiovascular system & hematology, medicine.disease, Hospitalization, 03 medical and health sciences, 0302 clinical medicine, Serum potassium, Heart failure, Internal medicine, Potassium, medicine, Cardiology, Humans, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Intensive care medicine
Published
2018

18. Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?

Author

Valerio Verdiani, Yigal M. Pinto, Luc W. Eurlings, Paulo Bettencourt, Khibar Salah, Antoni Bayes-Genis, Jan P. Tijssen, Luca Bettari, Susan Stienen, Marco Metra, Valentina Lazzarini, Joana Pimenta, and Wouter E.M. Kok

Subjects
medicine.medical_specialty, education.field_of_study, Acute decompensated heart failure, business.industry, Population, medicine.disease, Logistic regression, Surgery, Heart failure, Internal medicine, Attributable risk, Cardiology, Medicine, Population study, cardiovascular diseases, Cardiology and Cardiovascular Medicine, business, education, Prospective cohort study, Survival rate, hormones, hormone substitutes, and hormone antagonists
Abstract

Aims NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target. Methods and results Our study population was assembled from seven ADHF cohorts. We defined absolute ( 30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64–80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (∼60–70%) was observed for 70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets. Conclusion In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target.

Published
2015
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19. Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients

Author

Marco Metra, Paulo Bettencourt, Susan Stienen, Wouter E. Kok, Jan P. Tijssen, Valerio Verdiani, Khibar Salah, Luca Bettari, Antoni Bayes-Genis, Yigal M. Pinto, Luc W. Eurlings, Valentina Lazzarini, Joana Pimenta, Graduate School, Other departments, Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
Male, medicine.medical_specialty, acute decompensated heart failure, Acute decompensated heart failure, medicine.drug_class, Anemia, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, elderly, Patient Care Planning, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, Internal medicine, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Mortality, Diuretics, Intensive care medicine, Aged, Mineralocorticoid Receptor Antagonists, Proportional Hazards Models, Cause of death, Aged, 80 and over, Heart Failure, NT-proBNP targets, Proportional hazards model, business.industry, young, Age Factors, Middle Aged, medicine.disease, Peptide Fragments, Heart failure, Acute Disease, Disease Progression, Etiology, Population study, Female, Cardiology and Cardiovascular Medicine, business
Abstract

The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients. Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value of NT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients. Our study population comprised 7 ADHF cohorts. We defined absolute ( 30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age ≤75 years). Thereafter, we compared percentages of elderly and young patients attaining NT-proBNP levels (= attainability). A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT-proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levels and a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia at discharge. In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed to factors other than age

Published
2016

20. PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE AND ELEVATED TROPONIN T HAVE IMPROVED 180-DAY MORTALITY AND MORBIDITY AFTER CORONARY ANGIOGRAPHY

Author

Yigal M. Pinto, Wouter Kok, Hakim Aslaoui, and Susan Stienen

Subjects
Coronary angiography, medicine.medical_specialty, Acute decompensated heart failure, biology, business.industry, Internal medicine, medicine, Cardiology, biology.protein, medicine.disease, business, Cardiology and Cardiovascular Medicine, Troponin
Published
2015
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21. Response to: Letter to the editor regarding the manuscript 'Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-ProBNP target on the reduction of readmission and Mortality rAtes'

Author

Susan Stienen, Wouter E.M. Kok, Amsterdam Cardiovascular Sciences, Cardiology, and Graduate School

Subjects
Heart Failure, medicine.medical_specialty, Letter to the editor, Acute decompensated heart failure, business.industry, medicine.medical_treatment, Mortality rate, medicine.disease, Patient Readmission, Peptide Fragments, law.invention, Randomized controlled trial, law, Natriuretic Peptide, Brain, Practice Guidelines as Topic, medicine, Humans, Female, Molecular Targeted Therapy, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Reduction (orthopedic surgery)
Published
2015

22. Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis

Author

Marco Metra, Jan G.P. Tijssen, Carlo Lombardi, Khibar Salah, Yigal M. Pinto, Luc W. Eurlings, Susan Stienen, Wouter E.M. Kok, Graduate School, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Cardiologie, and RS: CARIM - R2 - Cardiac function and failure

Subjects
Male, medicine.medical_specialty, Time Factors, Acute decompensated heart failure, medicine.drug_class, Potassium, chemistry.chemical_element, Hypokalemia, Gastroenterology, Natriuretic Peptide, Cause of Death, Internal medicine, Natriuretic Peptide, Brain, 80 and over, Natriuretic peptide, Humans, Medicine, Prospective Studies, Intensive care medicine, Prospective cohort study, Survival rate, Aged, Netherlands, Aged, 80 and over, Heart Failure, business.industry, Medicine (all), Hazard ratio, Brain, Middle Aged, Prognosis, medicine.disease, Peptide Fragments, Survival Rate, Hospitalization, Italy, chemistry, Heart failure, Acute Disease, Disease Progression, Female, Biomarkers, Follow-Up Studies, Cardiology and Cardiovascular Medicine, medicine.symptom, business
Abstract

Background Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Methods Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. Results A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). Conclusions A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients.

Published
2015

23. N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Measurements Until a 30% Reduction Is Attained During Acute Decompensated Heart Failure Admissions and Comparison With Discharge NT-proBNP Levels. Implications for In-Hospital Guidance of Treatment

Author

Yigal M. Pinto, Salvatore Di Somma, Valentina Carubelli, Marco Metra, Jan P. Tijssen, Khibar Salah, Cathelijne Dickhoff, Laura Magrini, Susan Stienen, Wouter E.M. Kok, Amsterdam Cardiovascular Sciences, Cardiology, Graduate School, and Other departments

Subjects
Male, Acute decompensated heart failure, Severity of Illness Index, Cohort Studies, Patient Admission, Interquartile range, Natriuretic Peptide, Brain, Natriuretic peptide, 80 and over, Prospective Studies, Prospective cohort study, Aged, 80 and over, Statistics, Brain, Disease Management, Middle Aged, Prognosis, Patient Discharge, Cohort, NT-proBNP, acute decompensated heart failure, relative reduction, serial, Acute Disease, Aged, Biomarkers, Chi-Square Distribution, Feasibility Studies, Female, Heart Failure, Humans, Peptide Fragments, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Guidelines as Topic, Cardiology, Cardiology and Cardiovascular Medicine, hormones, hormone substitutes, and hormone antagonists, Cohort study, medicine.medical_specialty, medicine.drug_class, Natriuretic Peptide, Internal medicine, Severity of illness, medicine, Nonparametric, cardiovascular diseases, business.industry, medicine.disease, Surgery, Heart failure, business
Abstract

Background A >30% N-terminal pro–B-type natriuretic peptide (NT-proBNP) reduction at discharge in acute decompensated heart failure (ADHF) predicts a favorable prognosis. To study the feasibility of guiding ADHF treatment by measuring NT-proBNP well before discharge, we assessed at which moment during hospitalization patients attain a NT-proBNP reduction of >30% (target) and whether this target is still attained at discharge. Methods Twenty-five consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original cohort). NT-proBNP was measured daily until the target was attained, at clinical stability, and at discharge and was analyzed as percentages of patients on target. For comparison purposes, the same analysis was performed in individual patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in which NT-proBNP was measured from admission to day 3 and at discharge. Results In the original cohort of 25 patients (median age 70 years, 40% male), the cumulative percentage of patients attaining the target increased gradually during admission to 22 patients (88%) in a median of 3 days (interquartile range 2–5). In the comparison cohorts, a similar course was observed in patients attaining the target before discharge. Compared with levels measured at days 2 and 3, rebound NT-proBNP increases to levels off-target at discharge were seen in up to 33% of patients in the original and comparison cohorts. Conclusion A target >30% NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP increases to levels off-target occur in up to 33% of ADHF patients who initially attained target early during admission.

Published
2015

24. Are Changes in Serum Potassium Levels during Admissions for Acute Decompensated Heart Failure Irrelevant for Prognosis: The End of the Story?

Author

Khibar Salah, Susan Stienen, Wouter Kok, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Graduate School

Subjects
medicine.medical_specialty, Serum potassium, Acute decompensated heart failure, business.industry, Internal medicine, medicine, Cardiology, Cardiology and Cardiovascular Medicine, Intensive care medicine, medicine.disease, business
Published
2015

25. Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes

Author

Wouter E.M. Kok, Jan G.P. Tijssen, Cathelijne Dickhoff, Albertus J. Voogel, Adrianus L. M. Bakx, Jan T. Keijer, Andreas H. M. Moons, Jutta M. Schroeder-Tanka, Petra E. van Pol, Khibar Salah, R. A. Mikael Kortz, Paola G. Meregalli, Yigal M. Pinto, Susan Stienen, ACS - Amsterdam Cardiovascular Sciences, Cardiology, and Graduate School

Subjects
medicine.medical_specialty, Acute decompensated heart failure, Cost effectiveness, business.industry, Mortality rate, Retrospective cohort study, Brain natriuretic peptide, medicine.disease, law.invention, Randomized controlled trial, law, Heart failure, Emergency medicine, medicine, Clinical endpoint, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Background Hospital admissions for acute decompensated heart failure (ADHF) are frequent and are accompanied by high percentages of mortality and readmissions. Brain natriuretic peptide (BNP) and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP) are currently the best predictors of prognosis in heart failure (HF) patients. In the setting of chronic HF, studies that performed guidance of therapy by NT-proBNP have had only limited success. For patients with ADHF, retrospective studies have shown that a reduction in NT-proBNP of ≤30% during admission is a significant predictor of HF readmissions and mortality. These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions. Study design The PRIMA II is an investigator-initiated, multicenter, randomized, controlled, prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction during admission) on the reduction of readmission and mortality rates within 180 days. Consenting ADHF patients with NT-proBNP levels of >1,700 ng/L are eligible. After achieving clinical stability, a total of 340 patients are randomized to either NT-proBNP–guided or conventional treatment (1:1). The primary end point is dual, that is, a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days. Secondary end points are readmissions and/or mortality in 180 days, cost effectiveness of hospitalization days in 180 days, readmissions and mortality in 90 days, and quality of life. Conclusion The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP–guided therapy compared with conventional treatment in patients admitted for ADHF.

Published
2014

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