Benchmarking Belgian CRT practice against the rest of Europe: insights from the ESC-CRT survey II.

This subanalysis of the Euro-CRT survey II specifically focus on Belgian practice for CRT implantation. It explores Belgian adherence with the guidelines but also benchmark CRT practice in Belgium against the other European countries. Overall, Belgian management of CRT implantation is performed with great agreement with guidelines. This report could be used to provide guidance for both practical and economical approaches.

Small left atrium and mild mitral regurgitation predict super-response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) can result in profound reverse remodelling. The goal of this study was to identify factors predictive of such beneficial response. METHODS AND RESULTS: Super-response to CRT was defined as normalization or near normalization of left ventricular systolic function without recognized reversible causes of heart failure. In a retrospective study, we compared baseline demographic, electrocardiogram, and echocardiographic characteristics of super-responders (n = 21) with a population of unselected consecutive cardiac CRT patients (Control 1, n = 330) and another sex-, age-, and aetiology-matched control group (Control 2, n = 43). Compared with Control 1, super-responders had significantly smaller left ventricular end-diastolic diameter (65.4 ± 6.4 vs. 73.4 ± 9.3 mm, P = 0.0001), higher ejection fraction (0.25 ± 0.05 vs. 0.22 ± 0.04, P = 0.004), smaller degree of mitral regurgitation (MR; mean value 1.9 ± 0.9 vs. 2.6 ± 0.8, P = <0.0001), and smaller left atrium (LA; 42.8 ± 4.6 vs. 50.0 ± 6.5 mm, P < 0.0001). Septal flash and inter-ventricular mechanical dyssynchrony were both more frequent among super-responders than in Control 2 subjects (93.8 vs. 69.8%; P = 0.01, and 93.8 vs. 62.8%; P = 0.01, respectively). In a multivariate analysis, smaller LA diameter and milder MR remained independent predictors of super-response. CONCLUSION: Super-response to cardiac CRT was associated with less advanced left-sided structural involvement as described by echocardiography. In particular, smaller LA and milder MR were independent predictors of pronounced reverse remodelling.

MeRNA: a database of metal ion binding sites in RNA structures.

Metal ions are essential for the folding of RNA into stable tertiary structures and for the catalytic activity of some RNA enzymes. To aid in the study of the roles of metal ions in RNA structural biology, we have created MeRNA (Metals in RNA), a comprehensive compilation of all metal binding sites identified in RNA 3D structures available from the PDB and Nucleic Acid Database. Currently, our database contains information relating to binding of 9764 metal ions corresponding to 23 distinct elements, in 256 RNA structures. The metal ion locations were confirmed and ligands characterized using original literature references. MeRNA includes eight manually identified metal-ion binding motifs, which are described in the literature. MeRNA is searchable by PDB identifier, metal ion, method of structure determination, resolution and R-values for X-ray structure and distance from metal to any RNA atom or to water. New structures with their respective binding motifs will be added to the database as they become available. The MeRNA database will further our understanding of the roles of metal ions in RNA folding and catalysis and have applications in structural and functional analysis, RNA design and engineering. The MeRNA database is accessible at http://merna.lbl.gov.

ADME evaluation. 2. A computer model for the prediction of intestinal absorption in humans.

PURPOSE: To develop a computational method to rapidly evaluate human intestinal absorption, one of the drug properties included in the term ADME (Absorption, Distribution, Metabolism, Excretion). Poor ADME properties are the most important reason for drug failure in clinical development. METHODS: The model developed is based on a modified contribution group method in which the basic parameters are structural descriptors identified by the CASE program, together with the number of hydrogen bond donors. RESULTS: The human intestinal absorption model is a quantitative structure-activity relationship (QSAR) that includes 37 structural descriptors derived from the chemical structures of a data set containing 417 drugs. The model was able to predict the percentage of drug absorbed from the gastrointestinal tract with an r2 of 0.79 and a standard deviation of 12.32% of the compounds from the training set. The standard deviation for an external test set (50 drugs) was 12.34%. CONCLUSIONS: The availability of reliable and fast models like the one we propose here to predict ADME/Tox properties could help speed up the process of finding compounds with improved properties, ultimately making the entire drug discovery process shorter and more cost efficient.