Heart failure (HF), being a complex pathology that derives from several different conditions such as idiopathic cardiomyopathy, myocardial infarction (MI), inflammatory diseases, pressure overload and volume overload [1], is one of the main causes of morbidity and mortality worldwide. Despite distinct etiologies of cardiac disease, they all share a common myocardial response at molecular, cellular and biochemical levels [2], which lead to clinical manifestations due to major morphological alterations of the heart. The end result is the impairment of cardiac pumping capacity accompanied by genetic re-programming of fetal genes, higher vulnerability to necrotic or apoptotic gene programs and dysfunctional vascular remodeling [3].

Cardiomyocytes (CMs), the major cardiac contractile cellular unit, are unable to complete the cell cycle division after the perinatal period and respond to chronic stress conditions by becoming hypertrophic. This growth is beneficial at onset as it improves cardiac contractility, but becomes detrimental when prolonged and eventually leads to HF [4]. The profound changes that the myocardium undergoes during HF result not only from a direct response of the CMs but are rather a concerted reaction involving all other cardiac cell types such as endothelial cells (ECs), fibroblasts (FBs), smooth muscle cells (SMCs) and immune cells. Cell-to-cell interactions are fundamental not only to maintain tissue and organ integrity and homeostasis but also to induce adaptive changes in response to external stimuli. Cells can interact in many different ways including direct cell-to-cell communication, release of chemical compounds, electrical stimuli, extracellular matrix (ECM) interactions and long-distance communication. As short-range communication is often not sufficient to respond to specific stimuli [5], in the past decade more interest has been directed to the contribution of extracellular vesicles (EVs) which have been found to be released by most cell types and detected in most body fluids [[6],[7],[8],[9],[10]]. By allowing long-range cellular communication, EVs could therefore, account for horizontal gene transfer between cells [11]. The aim of the present review is to critically review the current research on EVs, mainly exosomes, their ability to alter cardiac function and the mechanisms driving their effects in the context of heart failure.