Diffuse myocardial fibrosis: mechanisms, diagnosis and therapeutic approaches

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, Díez 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. Key points Diffuse myocardial fibrosis is characterized by excessive diffuse interstitial and perivascular deposition of highly crosslinked collagen fibres (type I collagen) and other components of the extracellular matrix. Diffuse myocardial fibrosis is present in nearly all chronic cardiac diseases and impairs cardiac function and therefore has a crucial role in the development of heart failure and its outcomes and is an important global health problem. Modification of the biosynthetic properties of cardiac fibroblasts that result in the alteration of fibrillary collagen turnover are the major determinants in the pathogenesis of diffuse myocardial fibrosis. Diffuse my