4.6 Review

Diffuse myocardial fibrosis: mechanisms, diagnosis and therapeutic approaches

Journal

NATURE REVIEWS CARDIOLOGY
Volume 18, Issue 7, Pages 479-498

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41569-020-00504-1

Keywords

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Funding

  1. Spanish Ministry of Science, Innovation and Universities (Instituto de Salud Carlos III) [CIBERCV CB16/11/00483, PI17/01999, PI18/01469]
  2. FEDER funds
  3. ERA-CVD Joint Transnational Call 2016 LYMIT-DIS [AC16/00020]
  4. LIPCAR-HF [AC16/00016]
  5. European Commission [848109]
  6. Direccion General de Industria, Energia e Innovacion, Gobierno de Navarra, Spain [0011-1411-2018-000053]

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Diffuse myocardial fibrosis is a common lesion in chronic cardiac diseases, resulting from excessive deposition of collagen fibers throughout the myocardium. The composition and properties of the fibers play a role in the detrimental effects on cardiac function and clinical outcomes in patients with heart failure. Various clinicopathological phenotypes of diffuse myocardial fibrosis exist, and understanding the mechanisms and potential therapeutic strategies is essential for personalizing prevention and reversal in patients with heart failure.
Diffuse myocardial fibrosis resulting from the excessive deposition of collagen fibres through the entire myocardium is encountered in a number of chronic cardiac diseases. This lesion results from alterations in the regulation of fibrillary collagen turnover by fibroblasts, facilitating the excessive deposition of type I and type III collagen fibres within the myocardial interstitium and around intramyocardial vessels. The available evidence suggests that, beyond the extent of fibrous deposits, collagen composition and the physicochemical properties of the fibres are also relevant in the detrimental effects of diffuse myocardial fibrosis on cardiac function and clinical outcomes in patients with heart failure. In this regard, findings from the past 20 years suggest that various clinicopathological phenotypes of diffuse myocardial fibrosis exist in patients with heart failure. In this Review, we summarize the current knowledge on the mechanisms and detrimental consequences of diffuse myocardial fibrosis in heart failure. Furthermore, we discuss the validity and usefulness of available imaging techniques and circulating biomarkers to assess the clinicopathological variation in this lesion and to track its clinical evolution. Finally, we highlight the currently available and potential future therapeutic strategies aimed at personalizing the prevention and reversal of diffuse myocardial fibrosis in patients with heart failure. In this Review, Diez and colleagues summarize the mechanisms of diffuse myocardial fibrosis in heart failure, discuss imaging techniques and circulating biomarkers to characterize the variability of this lesion in patients, and highlight the available and potential future therapeutic strategies for personalizing the prevention and reversal of diffuse myocardial fibrosis.

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