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Biomarkers Volume 25, 2020 - Issue 2
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Original Articles

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure)

Susan StienenCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; ORCID Iconhttp://orcid.org/0000-0002-5573-9377View further author information
ORCID Icon,
João Pedro FerreiraCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; ;Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal; View further author information
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Masatake KobayashiCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Gregoire Preud’hommeCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Daniela DobreCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; ;Clinical research and Investigation Unit, Psychotherapeutic Center of Nancy, Laxou, France; View further author information
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Jean-Loup MachuCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Kevin DuarteCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Emmanuel BressoEquipe CAPSID, LORIA (CNRS, Inria NGE, Université de Lorraine), Vandoeuvre-lès-Nancy, France; View further author information
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Marie-Dominique DevignesEquipe CAPSID, LORIA (CNRS, Inria NGE, Université de Lorraine), Vandoeuvre-lès-Nancy, France; View further author information
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Natalia LópezNavarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain; View further author information
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Nicolas GirerdCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Svend AakhusDepartment of Cardiology and Institute for Surgical Research, Oslo University Hospital, Oslo, Norway; ;ISB, Norwegian University of Science and Technology, Trondheim, Norway; View further author information
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Giuseppe AmbrosioDivision of Cardiology, University of Perugia School of Medicine, Perugia, Italy; View further author information
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Hans-Peter Brunner-La RoccaDepartment of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands; View further author information
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Ricardo Fontes-CarvalhoDepartment of Surgery and Physiology, Cardiovascular Research Unit (UnIC), Faculty of Medicine, University of Porto, Porto, Portugal; View further author information
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Alan G. FraserWales Heart Research Institute, Cardiff University, Cardiff, UK; View further author information
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Loek van HeerebeekDepartment of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands; View further author information
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Stephane HeymansDepartment of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; ;Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, Leuven, Belgium; ;William Harvey Research Institute, Barts Heart Centre, Queen Mary University of London, London, UK; View further author information
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Gilles de KeulenaerLaboratory of Physiopharmacology, Antwerp University, and ZNA Hartcentrum, Antwerp, Belgium; View further author information
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Paolo MarinoClinical Cardiology, Università del Piemonte Orientale, Department of Translational Medicine, Azienda Ospedaliero Universitaria “Maggiore della Carità”, Novara, Italy; View further author information
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Kenneth McDonaldSchool of Medicine and Medical Sciences, St Michael’s Hospital Dun Laoghaire Co. Dublin, Dublin, Ireland; View further author information
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Alexandre MebazaaDepartment of Anaesthesiology and Critical Care Medicine, Saint Louis and Lariboisière University Hospitals and INSERM UMR-S 942, Paris, France; View further author information
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Zoltàn PappDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; View further author information
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Riccardo RaddinoDepartment of Cardiology, Spedali Civili di Brescia, Brescia, Italy; View further author information
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Carsten TschöpeDepartment of Cardiology, Campus Virchow-Klinikum, C, Harite Universitaetsmedizin Berlin, Berlin Institute of Health – Center for Regenerative Therapies (BIH-BCRT), and the German Center for Cardiovascular Research (DZHK; Berlin partner site), Berlin, Germany; View further author information
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Walter J. PaulusAmsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, the NetherlandsView further author information
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Faiez ZannadCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; View further author information
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Patrick RossignolCHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre d’Investigation Clinique et Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; Correspondence[email protected]
View further author information
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Pages 201-211 | Received 30 Sep 2019, Accepted 26 Jan 2020, Published online: 16 Feb 2020

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MB Ferreira, M Kobayashi, RQ Costa, T Fonseca, M Brandão, JC Oliveira, A Marinho, H Cyrne Carvalho, P Rodrigues, F Zannad, P Rossignol, AS Barros & JP Ferreira. (2023) Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures. Scandinavian Journal of Rheumatology 52:6, pages 619-626.
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Articles from other publishers (22)

Claartje Meijs, M. Louis Handoko, Gianluigi Savarese, Robin W. M. Vernooij, Ilonca Vaartjes, Amitava Banerjee, Stefan Koudstaal, Jasper J. Brugts, Folkert W. Asselbergs & Alicia Uijl. (2023) Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review. Current Heart Failure Reports 20:5, pages 333-349.
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Teun B. Petersen, Marie de Bakker, Folkert W. Asselbergs, Magdalena Harakalova, K. Martijn Akkerhuis, Jasper J. Brugts, Jan van Ramshorst, R. Thomas Lumbers, Rachel M. Ostroff, Peter D. Katsikis, Peter J. van der Spek, Victor A. Umans, Eric Boersma, Dimitris Rizopoulos & Isabella Kardys. (2023) HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms. eBioMedicine 93, pages 104655.
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Dimitrios Farmakis, Jasper Tromp, Smaragdi Marinaki, Wouter Ouwerkerk, Christiane E. Angermann, Vasiliki Bistola, Ulf Dahlstrom, Kenneth Dickstein, Georg Ertl, Mathieu Ghadanfar, Mahmoud Hassanein, Achim Obergfell, Sergio V. Perrone, Eftihia Polyzogopoulou, Anja Schweizer, Ioannis Boletis, John G.F. Cleland, Sean P. Collins, Carolyn S.P. Lam & Gerasimos Filippatos. (2023) Impact of left ventricular ejection fraction phenotypes on healthcare resource utilization in hospitalized heart failure: a secondary analysis of REPORT‐HF . European Journal of Heart Failure 25:6, pages 818-828.
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Mariana Ribeiro Silva, Francisco Sampaio, Joana Braga, José Ribeiro & Ricardo Fontes-Carvalho. (2023) Left atrial strain evaluation to assess left ventricle diastolic dysfunction and heart failure with preserved ejection fraction: a guide to clinical practice. The International Journal of Cardiovascular Imaging 39:6, pages 1083-1096.
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Anthony E Peters, Jasper Tromp, Sanjiv J Shah, Carolyn S P Lam, Gregory D Lewis, Barry A Borlaug, Kavita Sharma, Ambarish Pandey, Nancy K Sweitzer, Dalane W Kitzman & Robert J Mentz. (2022) Phenomapping in heart failure with preserved ejection fraction: insights, limitations, and future directions. Cardiovascular Research 118:18, pages 3403-3415.
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Alberto Palazzuoli, Marco G.D. Buono, Gaetano Ruocco, Sergio Caravita, Antonio Abbate & Carl J. Lavie. (2023) The Conundrum of HFpEF Definition: Non-Invasive Assessment Uncertainties and Alternative Diagnostic Strategies. Current Problems in Cardiology 48:1, pages 101433.
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Lifen Xu, Melania Balzarolo, Emma L Robinson, Vera Lorenz, Giacomo Della Verde, Lydia Joray, Michika Mochizuki, Beat A Kaufmann, Gideon Valstar, Saskia C A de Jager, Hester M den Ruijter, Stephane Heymans, Otmar Pfister & Gabriela M Kuster. (2022) NOX1 mediates metabolic heart disease in mice and is upregulated in monocytes of humans with diastolic dysfunction. Cardiovascular Research 118:14, pages 2973-2984.
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Iris de Lange, Teun B. Petersen, Marie de Bakker, K. Martijn Akkerhuis, Jasper J. Brugts, Kadir Caliskan, Olivier C. Manintveld, Alina A. Constantinescu, Tjeerd Germans, Jan van Ramshorst, Victor A.W.M. Umans, Eric Boersma, Dimitris Rizopoulos & Isabella Kardys. (2022) Heart failure subphenotypes based on repeated biomarker measurements are associated with clinical characteristics and adverse events (Bio-SHiFT study). International Journal of Cardiology 364, pages 77-84.
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Liyan Huang, Lin Liang, Pengchao Tian, Lang Zhao, Yuyi Chen, Yan Huang, Qiong Zhou, Mei Zhai, Yuhui Zhang, Giuseppe Ambrosio & Jian Zhang. (2022) D‐dimer and outcomes in hospitalized heart failure patients across the ejection fraction phenotypes. ESC Heart Failure 9:5, pages 3060-3070.
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Paolo Morfino, Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Michele Emdin & Aldo Clerico. (2022) Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond. Journal of Cardiovascular Development and Disease 9:8, pages 256.
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Jin Sun, Hua Guo, Wenjun Wang, Xiao Wang, Junyu Ding, Kunlun He & Xizhou Guan. (2022) Identifying novel subgroups in heart failure patients with unsupervised machine learning: A scoping review. Frontiers in Cardiovascular Medicine 9.
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Antoni Bayes-Genis, Germán Cediel, Mar Domingo, Pau Codina, Evelyn Santiago & Josep Lupón. (2022) Biomarkers in Heart Failure with Preserved Ejection Fraction. Cardiac Failure Review 8.
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Masatake Kobayashi, Maria Betânia Ferreira, Rita Quelhas Costa, Tomás Fonseca, José Carlos Oliveira, António Marinho, Henrique Cyrne Carvalho, Nicolas Girerd, Patrick Rossignol, Faiez Zannad, Patrícia Rodrigues & João Pedro Ferreira. (2021) Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis. Frontiers in Cardiovascular Medicine 8.
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Lusha W. Liang & Yuichi J. Shimada. (2021) Endotyping in Heart Failure　― Identifying Mechanistically Meaningful Subtypes of Disease ―. Circulation Journal 85:9, pages 1407-1415.
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Alberto Palazzuoli, Sergio Caravita, Stefania Paolillo, Stefano Ghio, Carlo Gabriele Tocchetti, Gaetano Ruocco, Michele Correale, Giuseppe Ambrosio, Pasquale Perrone Filardi & Michele Senni. (2021) Current gaps in HFpEF trials: Time to reconsider patients' selection and to target phenotypes. Progress in Cardiovascular Diseases 67, pages 89-97.
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Giuseppe Ambrosio, Marisa G. Crespo Leiro, Lars H. Lund, Stefano Coiro, Andrea Cardona, Gerasimos Filippatos, Roberto Ferrari, Massimo F. Piepoli, Andrew J.S. Coats, Stefan D. Anker, Cécile Laroche, Luis Almenar-Bonet, Pentti Poder, David Bierge Valero, Anna Frisinghelli & Aldo P. Maggioni. (2021) Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry. European Journal of Internal Medicine 89, pages 65-75.
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Erberto Carluccio, Nicola Riccardo Pugliese, Paolo Biagioli, Cinzia Zuchi, Rosanna Lauciello, Anna Mengoni, Andreina D'Agostino, Gian Giacomo Galeotti, Frank Lloyd Dini & Giuseppe Ambrosio. (2021) Global longitudinal strain in heart failure with reduced ejection fraction: Prognostic relevance across disease severity as assessed by automated cluster analysis. International Journal of Cardiology 332, pages 91-98.
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Alan G. Fraser, Carsten Tschöpe & Rudolf A. Boer. (2021) Diagnostic recommendations and phenotyping for heart failure with preserved ejection fraction: knowing more and understanding less?. European Journal of Heart Failure 23:6, pages 964-972.
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Olivier Huttin, Alan G. Fraser, Lars H. Lund, Erwan Donal, Cecilia Linde, Masatake Kobayashi, Tamas Erdei, Jean‐Loup Machu, Kevin Duarte, Patrick Rossignol, Walter Paulus, Faiez Zannad & Nicolas Girerd. (2021) Risk stratification with echocardiographic biomarkers in heart failure with preserved ejection fraction: the media echo score. ESC Heart Failure 8:3, pages 1827-1839.
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Alberto Palazzuoli & Matteo Beltrami. (2021) Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes. Frontiers in Cardiovascular Medicine 8.
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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 & Patrick Rossignol. (2020) Sex differences in circulating proteins in heart failure with preserved ejection fraction. Biology of Sex Differences 11:1.
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