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

European Journal of Heart Failure - Tập 21 Số 3 - Trang 272-285 - 2019
Rudolf A. de Boer1, Mihai Gheorghiade2, Johann Bauersachs3, Dirk L. Brutsaert2, John G.F. Cleland4, Javier Dı́ez5, Xiao-Jun Du6, Paul Ford7, Frank R. Heinzel8, Kenneth E. Lipson9, Theresa A. McDonagh10, Natalia López‐Andrés11, Ida G. Lunde12,13, Alexander R. Lyon14, Piero Pollesello15, Sanjay Prasad16, Carlo G. Tocchetti17, Manuel Mayr18, Joost P. G. Sluijter19, Thomas Thum20,21,22, Carsten Tschöpe8, Faı̈ez Zannad23,24, Wolfram‐Hubertus Zimmermann25,26, Frank Ruschitzka27, Gerasimos Filippatos28, Merry L. Lindsey29, Christoph Maack30, Stéphane Heymans31,32,33
1University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands
2Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
3Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
4Robertson Centre for Biostatistics & Clinical Trials University of Glasgow Glasgow UK
5Program of Cardiovascular Diseases, Center for Applied Medical Research, Departments of Nephrology, and Cardiology and Cardiac Surgery University Clinic, University of Navarra Pamplona Spain
6Baker Heart and Diabetes Institute, Melbourne, Australia
7Galecto Biotech Lund Sweden
8Department of Cardiology, Campus Virchow‐Klinikum Charite Universitaetsmedizin Berlin Berlin Germany
9FibroGen, Inc., San Francisco, CA, USA
10King's College Hospital, London, UK
11Cardiovascular Translational Research, Navarrabiomed, Complejo Hospitalario de Navarra Universidad Publica de Navarra Idisna Spain
12Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway
13University of Oslo
14Royal Brompton Hospital and Imperial College London, London, UK
15Orion Pharma, Espoo, Finland
16Royal Brompton and Harefield Hospital, London, UK
17Department of Translational Medical Sciences, Federico II University, Naples, Italy
18The James Black Centre, King’s College, University of London, London, UK
19University Medical Centre Utrecht, Experimental Cardiology Laboratory, UMC Utrecht Regenerative Medicine Center University Utrecht Utrecht The Netherlands
20DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
21Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
22REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany
23Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
24French-Clinical Research Infrastructure Network - F-CRIN [Paris]
25DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
26Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany
27Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
28Heart Failure Unit, Department of Cardiology, School of Medicine, Athens University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece
29Department 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
30Comprehensive Heart Failure Centre, University and University Hospital Würzburg, Würzburg, Germany
31Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
32Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
33The Netherlands Heart Institute, Nl‐HI Utrecht The Netherlands

Tóm tắt

AbstractFibrosis 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 infarctionand 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.

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European Journal of Heart Failure

Tập 21 Số 3

272-285

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