Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology

• Published in: European Journal of Heart Failure
• Main Authors: de Boer, Rudolf, A, de Keulenaer, Gilles, Bauersachs, Johann, Brutsaert, Dirk, Cleland, John, G, Diez, Javier, Du, Xiao‐jun, Ford, Paul, Heinzel, Frank, R, Lipson, Kenneth, E, Mcdonagh, Theresa, Lopez-Andres, Natalia, Lunde, Ida, G, Lyon, Alexander, R, Pollesello, Piero, Prasad, Sanjay, K, Tocchetti, Carlo, G, Mayr, Manuel, Sluijter, Joost P.G., Thum, Thomas, Tschöpe, Carsten, Zannad, Faiez, Zimmermann, Wolfram‐hubertus, Ruschitzka, Frank, Filippatos, Gerasimos, Lindsey, Merry, L, Maack, Christoph, Heymans, Stephane
• Other Authors: University Medical Center Groningen Groningen (UMCG), University of Antwerp (UA), Medizinische Hochschule Hannover = Hannover Medical School (MHH), University of Glasgow, Center for Applied Medical Research Plamplona (CIMA), Universidad de Navarra Pamplona (UNAV), Clínica Universidad de Navarra Pamplona, Baker Heart and Diabetes Institute (AUSTRALIA), Galecto Biotech AB Gothenburg, Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital Berlin, FibroGen Inc., King's College Hospital (KCH), Universidad Pública de Navarra Espagne = Public University of Navarra (UPNA), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra Espagne = Public University of Navarra (UPNA)-Universidad de Navarra Pamplona (UNAV)-Clínica Universidad de Navarra Pamplona, University of Oslo (UiO), Oslo University Hospital Oslo, Royal Brompton Hospital, Orion Pharma, University of Naples Federico II = Università degli studi di Napoli Federico II, King‘s College London, University Medical Center Utrecht (UMCU), Institute of Molecular and Translational Therapeutic Strategies (IMTTS), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Centre d'investigation clinique plurithématique Pierre Drouin Nancy (CIC-P), Centre d'investigation clinique Nancy (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists Vandoeuvre-les-Nancy (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu Nancy, French-Clinical Research Infrastructure Network - F-CRIN Paris (Cardiovascular & Renal Clinical Trialists - CRCT ), University Medical Center Göttingen (UMG), University hospital of Zurich Zurich, “Attikon” University Hospital, University of Mississippi Medical Center (UMMC), Julius-Maximilians-Universität Würzburg = University of Würzburg (JMU), University Hospital Wuerzburg / Universitäts­klinikum Würzburg, Maastricht University Maastricht, Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven), The Netherlands Heart Institute, R.A.d.B. is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11); and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). J.B. is supported is supported by the Deutsche Forschungsgemeinschaft (DFG), Clinical Research Group 311 (KFO 311) ‘(Pre)terminal heart and lung failure: unloading and repair’ (DFG; TP1, BA 1742/9-1) and ‘MR-Focus’‘ (DFG BA 1742/8-1). J.S. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (consolidator grant Evicare #725229) and by the Netherlands Heart Foundation (CVON-HUSTCARE). M.M. is a BHF Chair Holder (CH/16/3/32406), with BHF program grant support (RG/16/14/32397), and was awarded a BHF Special Project grant to participate in the ERA-CVD Translational Grant MacroERA. M.M. and T.T. are members of a network funded by the Foundation Leducq. C.G.T. is supported by a Federico II University/Ricerca di Ateneo grant. S.H. has received funding from the European Union Commission's Seventh Framework programme under grant agreement n. 305507 (HOMAGE), n. 602904 (FIBROTARGETS) and FP7-Health-2013-Innovations-1 n. 602156 (HECATOS), CVON2016-Early HFPEF, 2015-10, and CVON SHE-PREDICTS-HF, grant 2017-21. C.M. is supported by the DFG (Ma 2528/7-1, SFB 894, TRR-219) and the Federal Ministry of Education and Science (BMBF; 01EO150, CF.3, RC2)., European Project: 305507, European Project: 602904,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,FIBRO-TARGETS(2013), European Project: 602156,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,HECATOS(2013)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2019
• Subjects: Fibrosis; Heart failure; Biomarkers; Fibroblast; Matrix; Prognosis; Imaging; [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; SCAR
• Online Access: https://hal.univ-lorraine.fr/hal-03764243; https://hal.univ-lorraine.fr/hal-03764243/document; https://hal.univ-lorraine.fr/hal-03764243/file/European%20J%20of%20Heart%20Fail%20-%202019%20-%20de%20Boer%20-%20Towards%20better%20definition%20%20quantification%20and%20treatment%20of%20fibrosis%20in%20heart.pdf; https://doi.org/10.1002/ejhf.1406

International audience Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins - resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research.