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Eur J Heart Fail. 2019 Mar;21(3):272-285. doi: 10.1002/ejhf.1406. Epub 2019 Feb 4.

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.

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University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, The Netherlands.
Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Robertson Centre for Biostatistics & Clinical Trials, University of Glasgow, Glasgow, UK.
Program of Cardiovascular Diseases, Center for Applied Medical Research, Departments of Nephrology, and Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Pamplona, Spain.
Baker Heart and Diabetes Institute, Melbourne, Australia.
Galecto Biotech, Lund, Sweden.
Department of Cardiology, Campus Virchow-Klinikum, Charite Universitaetsmedizin Berlin, Berlin, Germany.
FibroGen Inc., San Francisco, CA, USA.
King's College Hospital, London, UK.
Cardiovascular Translational Research, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Publica de Navarra, Idisna, Spain.
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
Royal Brompton Hospital, and Imperial College London, London, UK.
Orion Pharma, Espoo, Finland.
Royal Brompton and Harefield Hospital, London, UK.
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
The James Black Centre, King's College, University of London, London, UK.
University Medical Centre Utrecht, Experimental Cardiology Laboratory, UMC Utrecht Regenerative Medicine Center, University Utrecht, Utrecht, The Netherlands.
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany.
DZHK (German Center for Cardiovascular Research) partner site Berlin, Berlin, Germany.
Centre d'Investigation Clinique, CHU de Nancy, Nancy, France.
Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany.
DZHK (German Center for Cardiovascular Research) partner site Göttingen, Göttingen, Germany.
Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.
Heart Failure Unit, Department of Cardiology, School of Medicine, Athens University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center and Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA.
Comprehensive Heart Failure Centre, University and University Hospital Würzburg, Würzburg, Germany.
Department 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, KU Leuven, Leuven, Belgium.
The Netherlands Heart Institute, Nl-HI, Utrecht, The Netherlands.


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.


Biomarkers; Fibroblast; Fibrosis; Heart failure; Imaging; Matrix; Prognosis

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