First, we have conducted an exploratory study using anonymized surgical leftover material from patients undergoing AVR. As such, our study has been able to provide the first characterization of the PF exosomal compartment but not to investigate its biomarker value. Prospective studies collecting clinical samples and data (at baseline and follow-up) from surgical and non-surgical patients are next required. Interestingly, the PF represents a leftover material from most cardiac surgeries and is also sampled for diagnostic purposes in non-surgical patients.39, 40 However, this fluid is not always accessible, thus limiting the translational potential to particular clinical conditions and to restricted time windows. Second, we have focused on the proangiogenic actions elicited by PF exosomes. We already know that PF exosomes are taken up by additional types of heart cells (C.B., unpublished data) and further studies will be necessary to disclose their full spectrum of actions. Third, we have concentrated our attention on miRNAs. However, other molecular components of the exosome cargo could contribute to the angiogenic effects of exosomes as well as representing potential biomarkers. Fourth, and conversely, extracellular miRNAs are not only contained in exosomes, and the fundamental and translational importance of miRNAs carried via different transporter systems is not to be neglected.