Abstract
For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an increased amount of fibrous tissue. However, fibrosis is not a singular entity. Various forms can be distinguished, that differ in distribution: replacement fibrosis, endomysial and perimysial fibrosis, and perivascular, endocardial, and epicardial fibrosis. These different forms typically result from diverging pathophysiological mechanisms and can have different consequences for conduction. The impact of fibrosis on propagation depends on exactly how the patterns of electrical connections between myocytes are altered. We will therefore first consider the normal patterns of electrical connections and their regional diversity as determinants of propagation. Subsequently, we will summarize current knowledge on how different forms of fibrosis lead to a loss of electrical connectivity in order to explain their effects on propagation and mechanisms of arrhythmogenesis, including ectopy, reentry, and alternans. Finally, we will discuss a histological quantification of fibrosis. Because of the different forms of fibrosis and their diverging effects on electrical propagation, the total amount of fibrosis is a poor indicator for the effect on conduction. Ideally, an assessment of cardiac fibrosis should exclude fibrous tissue that does not affect conduction and differentiate between the various types that do; in this article, we highlight practical solutions for histological analysis that meet these requirements.
Highlights
Fibrous tissue forms the skeleton of the heart, providing the myocardial stiffness and mechanical stability required for normal cardiac function (Figure 1)
Not explicitly investigated in the context of ectopic activity, it is likely that increased fibrosis has effects similar to decreased gap junctional coupling: the corresponding loss of electrical connections would allow for the democratic synchronization of proarrhythmic events within a diseased tissue area and heterogeneity in coupling to the surrounding normal myocardium would facilitate the propagation of ectopic activity
The total relative area occupied by fibrous tissue was unaltered after 6 months of AF, but there was an increase in endomysial fibrosis, quantified as myocyte-to-myocyte distance in the outer 0.5–1 mm across the atrial walls [62]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Bundles of myocytes are ensconced by perimysial fibrous tissue. Fibrosis is a pathological increase in the amount of fibrous tissue. In the heart, both normal and excess fibrous tissue consist primarily of the fibrillar collagen types I and III [3]. All the types of normal fibrous tissue mentioned above can increase in volume in response to pathological conditions. Perimysial and endomysial fibrosis have been called ‘reactive fibrosis’ This is distinctly different from reparative or replacement fibrosis, which is the final stage of the wound healing process after myocyte apoptosis or necrosis, most notably after myocardial infarction (Figure 1) [2]. Acellular preparation after digestion of cells fibrous showing perimysial sheets (p) and myocytes within bundles (left panel).
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