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, 21 (3), 272-285

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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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

Rudolf A de Boer et al. Eur J Heart Fail.

Abstract

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.

Keywords: Biomarkers; Fibroblast; Fibrosis; Heart failure; Imaging; Matrix; Prognosis.

Figures

Figure 1
Figure 1
Different forms of fibrosis are not mutually exclusive. The left panels show replacement (upper panel), reactive interstitial (middle), and perivascular (lower) fibrosis, with different cells playing the major role: fibroblasts (green), inflammatory cells (blue), and myocytes (red), with fibrillar debris interpositioned. In reality, in a typical failing heart, all forms may occur (middle panel and right histology panels). (Illustration: Maartje Kunen, Medical Visuals.)
Figure 2
Figure 2
Graphical depiction of time‐dependent fibrosis formation in the heart after acute injury such as myocardial infarction, longstanding injury such as hypertension, and intrinsic tissue changes during aging and senescence. The aetiological factors underpinning fibrosis, as well as the (physiological) need for a fibrotic reparative response will dictate the extent and timing of the fibrotic process. (Illustration: Maartje Kunen, Medical Visuals.) AngII, angiotensin II; CTGF, connective tissue growth factor; DAMPS, danger‐associated molecular patterns; ET‐1, endothelin‐1; IL, interleukin; L, lymphocyte; Ma, macrophage; MC, mast cell; MCP‐1, monocyte chemoattractant protein‐1; MF/MyoF, myofibroblast; MMP, matrix metalloproteinase; MV, microvessel; N, neutrophil; PAI, plasminogen activator inhibitor; PDGF, platelet‐derived growth factor; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinase; TNF, tumour necrosis factor.
Figure 3
Figure 3
Systemic biomarkers, measured in the plasma of patients with heart failure, ideally reflect changes in the heart muscle. For cardio‐specific biomarkers, such as natriuretic peptides and troponins, this is very accurate. However, for many (more novel) markers that are expressed by many organs outside the heart as well, the systemic levels only marginally reflects cardiac production. BNP, B‐type natriuretic peptide. (Illustration: Maartje Kunen, Medical Visuals.)

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References

    1. Heymans S, González A, Pizard A, Papageorgiou AP, López‐Andrés N, Jaisser F, Thum T, Zannad F, Díez J. Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential. Eur J Heart Fail 2015;17:764–771. - PubMed
    1. Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci 2014;71:549–574. - PMC - PubMed
    1. Creemers EE, Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure‐overloaded heart. Cardiovasc Res 2011;89:265–272. - PubMed
    1. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 2012;18:1028–1040. - PMC - PubMed
    1. Piek A, de Boer RA, Silljé HH. The fibrosis‐cell death axis in heart failure. Heart Fail Rev 2016;21:199–211. - PMC - PubMed

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