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The vicious cycle of arrhythmia and myocardial fibrosis

Cardiac remodelling includes changes in the myocytic compartment (cardiomyocyte hypertrophy) as well as changes in the non-myocytic compartment (myocardial fibrosis).1 Various ‘drivers’ may underpin the remodelling process, and it has been postulated that some triggers have more effects on cardiomyocytes whilst others are more specific to changes outside the cardiomyocyte, but in fact, there is intense cross talk between the two, and several studies have demonstrated that remodelled cardiomyocytes cause fibroblast proliferation and production of extracellular matrix (ECM).2–4 When a certain threshold is reached, rhythm disturbances, like atrial fibrillation (AF), may develop, and not surprisingly, AF is an important risk factor of heart failure (HF) development. In both animal models and in humans, AF tends to show a strong correlation with cardiac fibrosis and, indeed, myocardial fibrosis is an important substrate for the development of AF.2,4 Fibrosis creates re-entry circuits in the myocardium, enhances automaticity and hinders adequate action potential conduction in cardiomyocytes by interfering with ion channels, ion pumps and gap junction proteins.2,4 Thereby, myocardial fibrosis disturbs normal electrophysiology, leading to various rhythm disturbances including AF. As discussed, cross talk between pathophysiological remodelled cardiomyocytes and myofibroblasts exists, but does this also account for irregular contracting cardiomyocytes, hereby creating their own substrate? Possibly, the stressed irregular contracting cardiomyocytes promote the development of myocardial fibrosis. Therewith, a vicious cycle of arrhythmia and fibrosis could exist, similar to the vicious cycle of fibrosis and cell death that has been suggested for the development of HF.4 In this issue of the Journal, Slawik and colleagues report on a cell culture model assessing the influence of irregular paced