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Myocardial interstitial fibrosis (MIF) occurs in several ischemic and non-ischemic cardiomyopathies and is associated with left ventricular dysfunction and progression to heart failure (HF). MIF exists in two types – reparative and reactive with different origin and molecular mechanisms. Although MIF arises mainly because of alterations in collagen turnover leading to collagen fiber accumulation, there are also qualitative changes in collagen fibers in cardiac diseases. There are several studies for cellular and molecular mechanisms and his role in cardiac function, biomarkers and potential target therapies.