Figure 1. Proposed role of malignant myocardial fibrosis in aging-related atrial fibrillation (AF). An excessive myocardial collagen type-I deposition and cross-linking can form an anatomical obstacle of dense fibrosis (red color in the upper circle) and induce slow and heterogeneous conduction around it (black arrow in the upper circle), typical alterations of the arrhythmogenic substrate. Also, due to myofibroblast-cardiomyocyte coupling (lower circle) this particular form of fibrosis can partially depolarize the cardiomyocyte cell membrane, inducing both triggered activity and abnormal automaticity. In this way, malignant myocardial fibrosis fulfills the two key elements of the pathophysiology of AF, a triggering arrhythmia for its initiation and an impaired atrial conduction to perpetuate its perpetuation.