Rationale Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. Objective To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). Methods and Results We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes. Conclusions Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.

There is a paucity of data describing acute kidney injury (AKI) following transcatheter aortic valve implantation and its impact on mortality remains unknown. We therefore evaluate the incidence, predictors and impact of AKI following transcatheter aortic valve implantation. We searched MEDLINE for studies from 2008 to 2013, evaluating AKI after transcatheter aortic valve implantation. All studies were compared according to the incidence, predictors and impact of AKI following transcatheter aortic valve implantation. AKI was diagnosed according to the Valve Academic Research Consortium definition using the RIFLE criteria. Thirteen studies with more than 1900 patients were included. AKI occurred in 8.3-57% of the patients. The following factors were associated with AKI: blood transfusion; transapical access; preoperative creatinine concentration; peripheral vascular disease; hypertension; and procedural bleeding events. The 30-day mortality rate in patients with AKI ranged from 13.3% to 44.4% and was 2-6-fold higher than in patients without AKI. The amount of contrast agent used was not associated with the occurrence of AKI. AKI is a common complication, with an incidence of 8.3-57% following transcatheter aortic valve implantation. Patients with AKI had higher 30-day and late mortality rates. However, AKI was related to the amount of contrast volume used in only one study.