Normal values for Doppler echocardiographic assessment of prosthetic valve function after transcatheter aortic valve replacement: a systematic review and meta-analysis.

Transcatheter aortic valve replacement has emerged as valuable treatment modality for patients with severe aortic stenosis and an unacceptable risk/benefit ratio for open heart surgery, but particularities specific to TAVR and a rapidly growing number of available TAVR prosthesis make post-procedural assessment of valve function challenging. Aim of the present analysis was to collect and pool all available data currently in the literature regarding normal doppler values for transcatheter prosthetic heart valves and to provide a comprehensive overview. A PRISMA checklist-guided systematic review and meta-analysis of prospective observational studies or national and device specific registries or randomized clinical trials was conducted. Studies were identified by searching PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials and LILACs from January 2000 to March 2017. Out of 240 abstracts, 155 studies reporting echocardiographic parameter for twelve different valves prosthesis in a total of 27,159 patients were in included in this meta-analysis. The means and standard deviations of peak velocity, peak gradient, mean gradient and effective orifice were extracted and pooled from the included studies. The pooled means and standard deviations for all available TAVR prosthesis were classified according to implanted valve size and time since implantation. The present study firstly describes a pooled analysis of normal values for all available TAVR prosthesis in order to empower treating physicians with a reliable tool to perform follow-up echocardiographic assessment in TAVR patients and to safely identify patients with prostheses dysfunction.

Human epidermal growth factor receptor (EGFR) aligned on the plasma membrane adopts key features of Drosophila EGFR asymmetry.

The ability of epidermal growth factor receptor (EGFR) to control cell fate is defined by its affinity for ligand. Current models suggest that ligand-binding heterogeneity arises from negative cooperativity in signaling receptor dimers, for which the asymmetry of the extracellular region of the Drosophila EGFR has recently provided a structural basis. However, no asymmetry is apparent in the isolated extracellular region of the human EGFR. Human EGFR also differs from the Drosophila EGFR in that negative cooperativity is found only in full-length receptors in cells. To gain structural insights into the human EGFR in situ, we developed an approach based on quantitative Förster resonance energy transfer (FRET) imaging, combined with Monte Carlo and molecular dynamics simulations, to probe receptor conformation in epithelial cells. We experimentally demonstrate a high-affinity ligand-binding human EGFR conformation consistent with the extracellular region aligned flat on the plasma membrane. We explored the relevance of this conformation to ligand-binding heterogeneity and found that the asymmetry of this structure shares key features with that of the Drosophila EGFR, suggesting that the structural basis for negative cooperativity is conserved from invertebrates to humans but that in human EGFR the extracellular region asymmetry requires interactions with the plasma membrane.