Long-Term Changes in Estimated Glomerular Filtration Rate in Left Ventricular Assist Device Recipients: A Longitudinal Joint Model Analysis.

Background Advanced kidney disease is often a relative contraindication to left ventricular assist device (LVAD) implantation because of concerns for poor outcomes including worsening kidney disease. Data are lacking on long-term changes and sex-based differences in estimated glomerular filtration rate (eGFR), with published data limited by potential bias introduced by the competing risks of death and heart transplantation. Methods and Results We conducted a longitudinal analysis of 288 adults receiving durable continuous-flow LVADs from January 2010 to December 2017 at a single center. A joint model was constructed to evaluate change in eGFR over 2 years, the prespecified primary outcome, adjusted for the competing risks of death and heart transplantation. Median baseline eGFR was 60 mL/min per 1.73 m2 (interquartile range 42-78). At 2 years, 74 patients died and 104 received a heart transplant. In unadjusted analysis, LVAD recipients had a modest initial increase in eGFR of ≈2 mL/min per 1.73 m2 within the first 6 months after implantation, followed by a decrease in eGFR below baseline values at 1 and 2 years. Men experienced an eGFR decline of 5 to 10 mL/min per 1.73 m2 over the first year which then stabilized, while women had an ≈5 mL/min per 1.73 m2 increase in eGFR within the first 6 months followed by decline towards baseline eGFR levels (interaction P=0.005). Conclusions Estimated GFR remains relatively stable in most patients following LVAD implantation. Larger studies are needed to investigate sex-based differences in eGFR and to evaluate eGFR trajectory and mortality in LVAD recipients with lower eGFR.

Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a are mediated by suppression of PTEN and activation of PI3K dependent signaling.

OBJECTIVE: Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. APPROACHES AND RESULTS: To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phospho-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. CONCLUSIONS: miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression.