Towards better definition, quantification and treatment of fibrosis in heart failure
Rudolf A de Boer, Gilles De Keulenaer, Johann Bauersachs, Dirk Brutsaert, John G Cleland, Javier Diez, Xiao-Jun Du, Paul Ford, Frank R Heinzel, Kenneth E Lipson, Theresa McDonagh, Natalia Lopez-Andres, Ida G Lunde, Alexander R Lyon, Piero Pollesello, Sanjay K Prasad, Carlo G Tocchetti, Manuel Mayr, Joost P G Sluijter, Thomas Thum, Carsten Tschöpe, Faiez Zannad, Wolfram-Hubertus Zimmermann, Frank Ruschitzka, Gerasimos Filippatos, Merry L Lindsey, Christoph Maack, Stephane Heymans
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.
CITATION Eur J Heart Fail. 2019 Mar;21(3):272-285. doi: 10.1002/ejhf.1406. Epub 2019 Feb 4.