Value of non-apical echocardiographic views in the up-grading of patients with aortic stenosis.

Purpose. Echocardiography assessment from apical five-chamber view (A5CV) is the standard technique for aortic stenosis (AS) grading. Data on non-apical views, such as right parasternal (RPV), subcostal (SCV) and suprasternal notch (SSNV), is scarce and constitutes the aim of our study. Methods. We designed an observational study that included patients with AS recruited prospectively in whom the stenosis was graded by echocardiography from A5CV and non-apical view. The value of non-apical views in up-grading the stenosis severity (primary objective), the prognostic relevance of such reclassification and the feasibility and reproducibility of non-apical views assessment (secondary objectives) was evaluated. Results. Feasibility of AS appraisal from RPV, SCV and SSNV was 78%, 81% and 56%, respectively (SCV vs SSNV, p = .009). AS were up-graded from non-apical views according to peak gradient, mean gradient, area and indexed area by 24%, 17%, 24% and 22%, respectively (p < .0001). Non-apical views reclassified from non-severe to severe AS, from low gradient severe to high gradient severe AS and from non-critical to critical AS 19%, 23% and 3% of cases (p < .0001). The 4-years hard cardiac events rate was 41% in patients with non-severe AS, 67% in patients with severe AS from non-apical views, 68% in patients with severe AS from A5CV and 80% in patients with severe AS from A5CV and non-apical views (p < .001). Reproducibility of AS evaluation from non-apical views was fair to excellent (intraclass correlation coefficients: SSNV = 0.44, RPV = 0.61, SCV = 0.92). Conclusion. Assessment of AS from non-apical views is feasible, reproducible and valuable over A5CV; its use is encouraged.

Structure-delivery relationships of lysine-based gemini surfactants and their lipoplexes.

The synthesis and properties of gemini surfactants of the type (R(1)(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R(1) = C8, C10, C12, C14, C16, and C18) and, for R(1) = C18, the degree of unsaturation. For R(1)(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared. The potential of the gemini surfactants to transfer polynucleotides across a cell membrane was investigated by transfection of HeLa cells with beta-galactosidase, both in the presence and absence of the helper lipid DOPE. Oleoyl was found to be by far the best hydrophobic tail for this biological activity, whereas the effect of the lysine stereochemistry was less pronounced. The effect of an optimum spacer length (n = 6) was observed only in the absence of helper lipid. The most active surfactant, i.e. the one with oleoyl chains and n = 6, formed liposomes with sizes in the range of 60-350 nm, and its lipoplex underwent a transition from a lamellar to a hexagonal morphology upon lowering the pH from 7 to 3.

Effect of beta-blocker dose on mortality after acute coronary syndrome.

INTRODUCTION: Beta-blocker doses that have been shown to be effective in randomized clinical trials are not commonly used in daily clinical practice. The aim of this study was to analyze whether there is a prognostic benefit of high rather than low doses of beta-blockers after an acute coronary syndrome (ACS). METHODS: In this retrospective cohort study, 2092 ACS patients discharged from hospital between June 2013 and January 2016 were classified according to the beta-blocker dose prescribed: high dose (≥50% of the target dose tested in clinical trials) and low dose (<50%). Two groups of 501 matched patients were obtained through propensity score matching according to treatment with high or low doses of beta-blockers. The prognostic impact (mortality) during follow-up of high vs. low dose was analyzed by Cox regression and represented by Kaplan-Meier curves. RESULTS: Of the 2092 patients, 80.5% were discharged under beta-blockers, with lower mortality during follow-up (18.6±9.7 months). Of the 1685 patients discharged under beta-blockers, only 31.4% received high doses. There were no differences in mortality during follow-up between patients under high-dose vs. low-dose beta-blockers (HR 0.935, 95% CI 0.628-1.392, p=0.740), and the equivalence between the two doses remained after propensity score matching (HR 1.183, 95% CI 0.715-1.958, p=0.513). CONCLUSION: No prognostic benefit was found in terms of mortality for high-dose vs. low-dose beta-blockers after an ACS.

Pulmonary vein stenosis: Etiology, diagnosis and management.

Pulmonary vein stenosis (PVS) is rare condition characterized by a challenging diagnosis and unfavorable prognosis at advance stages. At present, injury from radiofrequency ablation for atrial fibrillation has become the main cause of the disease. PVS is characterized by a progressive lumen size reduction of one or more pulmonary veins that, when hemodynamically significant, may raise lobar capillary pressure leading to signs and symptoms such as shortness of breath, cough, and hemoptysis. Image techniques (transesophageal echocardiography, computed tomography, magnetic resonance and perfusion imaging) are essential to reach a final diagnosis and decide an appropriate therapy. In this regard, series from referral centers have shown that surgical and transcatheter interventions may improve prognosis. The purpose of this article is to review the etiology, assessment and management of PVS.

Gemini surfactants: new synthetic vectors for gene transfection.

The superior surfactant properties of cationic gemini surfactants are applied to the complex problem of introducing genes into cells. Of almost 250 new compounds tested, of some 20 different structural types, a majority showed very good transfection activity in vitro. The surfactant is shown to bind and compact DNA efficiently, and structural studies and calculations provide a working picture of the "lipoplex" formed. The lipoplex can penetrate the outer membranes of many cell types, to appear in the cytoplasm encapsulated within endosomes. Escape from the endosome--a key step for transfection--may be controlled by changes in the aggregation behavior of the lipoplex as the pH falls. The evidence suggests that DNA may be released from the lipoplex before entry into the nucleus, where the new gene can be expressed with high efficiency.