Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells.

The generation of effective and safe nanoagents for biological applications requires their physicochemical characteristics to be tunable, and their cellular interactions to be well characterized. Here, the controlled synthesis is developed for preparing high-aspect ratio gold nanotubes (AuNTs) with tailorable wall thickness, microstructure, composition, and optical characteristics. The modulation of optical properties generates AuNTs with strong near infrared absorption. Surface modification enhances dispersibility of AuNTs in aqueous media and results in low cytotoxicity. The uptake and trafficking of these AuNTs by primary mesothelioma cells demonstrate their accumulation in a perinuclear distribution where they are confined initially in membrane-bound vesicles from which they ultimately escape to the cytosol. This represents the first study of the cellular interactions of high-aspect ratio 1D metal nanomaterials and will facilitate the rational design of plasmonic nanoconstructs as cytosolic nanoagents for potential diagnosis and therapeutic applications.BLF-Papworth Fellowship from the British Lung Foundation and the Victor Dahdaleh Foundation

Clinical trials update from European Society of Cardiology meeting 2008: TIME-CHF, BACH, BEAUTIFUL, GISSI-HF, and HOME-HF

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the European Society of Cardiology meeting which was held in Munich, Germany from 30th August to 3rd September 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. The TIME-CHF study failed to show that BNP guided therapy was superior to usual care in patients with heart failure. The BACH study suggested that a new biomarker, MR-proANP, was as good as BNP for the diagnosis of heart failure in patients presenting with breathlessness. Ivabradine failed to reduce the incidence of cardiovascular events in patients with coronary artery disease and left ventricular systolic dysfunction in the BEAUTIFUL study, but patients with higher heart rates might have benefited. In GISSI-HF, n–3 PUFA reduced mortality and cardiovascular hospitalisation by a small amount compared to placebo in patients with chronic heart failure, but rosuvastatin had no effect on clinical outcomes. In the HOME-HF study, telemonitoring support failed to reduce the time to first re-hospitalisation or death, or days alive and out of hospital, compared with usual care

Clinical trials update from the European Society of Cardiology Heart Failure meeting 2011: TEHAF, WHICH, CARVIVA, and atrial fibrillation in GISSI-HF and EMPHASIS-HF

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the European Society of Cardiology Heart Failure meeting held in Gothenburg, Sweden in May 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In the TEHAF study, use of the Health Buddy ® monitoring system failed to reduce the number of HF admissions compared with usual care but a subgroup of patients with more recently diagnosed HF may have benefited. In the WHICH study, some reductions in the rate of hospital stay were observed in patients who underwent a nurse-led home-based intervention programme following a hospital admission for an acute HF exacerbation, compared with patients who were followed in a specialized outpatient clinic. Results from CARVIVA-HF suggest that ivabradine alone or in combination with carvedilol is safe and effective for improving exercise capacity and quality of life in HF patients on optimized angiotensin-converting enzyme inhibitor therapy. In the GISSI-HF study there was no difference in atrial fibrillation (AF) occurrence between the n-3 polyunsaturated fatty acids and placebo groups. In EMPHASIS-HF the incidence of new onset AF or flutter was reduced in patients with mild HF randomized to eplerenone compared with placebo

Clinical trials update from the American College of Cardiology Meeting 2011: STICH, NorthStar, TARGET, and EVEREST II

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual American College of Cardiology meeting held in New Orleans in 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The STICH trial failed to show a benefit of revascularization on all-cause mortality in patients with HF and coronary artery disease; however, cardiovascular deaths were reduced compared with medical therapy alone. Results from the NorthStar study suggest that patients with clinically stable systolic HF, who are on optimal medical therapy, including those with elevated amino-terminal B-type natriuretic peptide levels, may not benefit from long-term follow-up in an HF clinic. Results from the TARGET study demonstrate that targeted left ventricular lead placement using speckle tracking echocardiography is feasible in patients undergoing implantation of a cardiac resynchronization therapy device and is associated with an enhanced response. Two-year follow-up data from EVEREST II show that although a catheter-based mitral valve repair procedure using the MitraClip ® system was less effective at reducing mitral regurgitation than conventional surgery, similar improvements in clinical outcomes were observed with fewer short-term adverse events

Clinical trials update from heart rhythm 2008 and heart failure 2008: ATHENA, URGENT, INH study, HEART and CK-1827452

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Rhythm Society meeting in San Francisco, USA and the Heart Failure Association meeting of the European Society of Cardiology which was held in Milan, Italy in June 2008. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. The ATHENA study showed that dronedarone reduced the incidence of the composite outcome of cardiovascular hospitalisation or death, in patients with atrial fibrillation or flutter, 29% of whom had a history of heart failure, compared with placebo. The URGENT study demonstrated that treatment of acute heart failure with standard therapy, including intravenous diuretics and nitrates, leads to a rapid resolution of breathlessness in the sitting position but that orthopnoea often persists. The INH study showed that a disease management programme could reduce mortality compared to usual care but not hospitalisation rates. The HEART study failed to recruit its planned number of patients, although it is the largest randomised trial of revascularisation in heart failure reported to date. At a median follow-up of 5 years no difference in mortality was observed but the study lacked power to provide a conclusive result. The selective myosin activator CK-1827452 produced a concentration dependent increase in systolic ejection time, stroke volume and fractional shortening in patients with heart failure compared to placebo

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the β 1 adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group. © 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Clinical trials update from the American Heart Association Meeting 2010: EMPHASIS-HF, RAFT, TIM-HF, Tele-HF, ASCEND-HF, ROCKET-AF, and PROTECT

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Chicago in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In patients with mild heart failure (HF), EMPHASIS-HF showed that the addition of eplerenone to standard therapy was well tolerated and reduced both the risk of death and hospitalization. The addition of cardiac resynchronization therapy to implantable cardioverter defibrillator (ICD) therapy reduced the incidence of all-cause mortality and HF hospitalizations in patients with NYHA class IIIII HF compared with ICD alone in RAFT. Telemonitoring failed to improve outcome compared with a high standard of conventional care in patients with chronic HF (TIM-HF study) and a telephone-based interactive voice response system failed to improve outcome in patients recently hospitalized for HF (Tele-HF study). ASCEND-HF suggested that nesiritide was ineffective but safe in patients with acute decompensated HF. ROCKET-AF suggests that the factor-Xa inhibitor rivaroxaban may be as effective as warfarin in patients with atrial fibrillation. The PROTECT study provided more data to suggest that amino-terminal B-type natriuretic peptide guided therapy may be beneficial in patients with left ventricular systolic dysfunction

Clinical trials update from the European Society of Cardiology Meeting 2011: ARISTOTLE, SMART-AV: QLV substudy, SHIFT: echocardiography and quality of life substudies, European CRT Survey, and Basic Science Update

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the European Society of Cardiology meeting held in Paris, France in August 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from ARISTOTLE suggest that apixaban is more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Electrical dyssynchrony, measured by the time from onset of electrical activity on the surface ECG to activation of myocardium by intrinsic conduction at the pacing site (QLV), was a strong and independent predictor of improvement in ventricular function after cardiac resynchronization therapy (CRT) in an observational analysis of a subgroup of patients from the SMART-AV study. Subgroup analyses from SHIFT suggest that heart rate reduction with ivabradine causes favourable left ventricular remodelling and improves quality of life in patients with symptomatic systolic heart failure and an increased heart rate. The European CRT Survey reported outcome data

Clinical trials update from the American Heart Association 2007: CORONA, Rethin0, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American Heart Association 2007. These should be considered as preliminary data, as analyses may change in the final publication. Rosuvastatin did not reduce mortality compared to placebo in patients with heart failure and left ventricular systolic dysfunction due to ischaemic heart disease in the CORONA study. Results of RethinQ provide equivocal evidence of benefit from CRT in patients with heart failure, echocardiographic dyssynchrony and QRS interval <130 ms. In the MASCOT study, the addition of atrial overdrive pacing did not reduce the incidence of permanent atrial fibrillation in patients receiving CRT. The AF‐CHF study failed to show a benefit of rhythm control over rate control in patients with heart failure and atrial fibrillation. Self‐management skills training and education had no benefit on the combined outcome of death or heart failure hospitalisation, compared with education alone in heart failure patients in the HART study. Microvolt T‐wave alternans testing failed to identify patients at increased risk of life‐threatening ventricular arrhythmias in the MASTER study. POISE suggests that initiating metoprolol therapy shortly prior to non‐cardiac surgery increases the risk of hypotension, stroke and death, despite reducing the risk of myocardial infarction. Three trials of stem cell therapy in post‐MI patients gave conflicting results

Clinical trials update from the American College of Cardiology 2008: carisma, trends, meta-analysis of cox-2 studies, hat, on-target, hyvet, accomplish, momentum, protect, horizon-hf and reverse

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. CARISMA investigated the use of implantable loop recorders for detecting life-threatening arrhythmias in patients with LVSD after MI and found that brady- and ventricular tachy-arrhythmias predicted an adverse prognosis. The TRENDS study showed that the burden of atrial fibrillation detected by pacemakers or defibrillators predicted the risk of embolic events but not with sufficient precision to justify changes in anti-thrombotic management. A meta-analysis of six trials reported an increased cardiovascular risk associated with celecoxib, particularly for heart failure, which was related to dose and baseline cardiovascular risk. The HAT study failed to show a benefit of providing post-MI patients with a home defibrillator. MOMENTUM, a study of a device designed to augment aortic blood flow, was stopped early due to increased bleeding risk. Results from PROTECT support the use of rolofylline 30 mg/day in acute heart failure, a definitive study is now underway. Istaroxime, an agent that appears to have both inotropic and lusitropic effects, improved haemodynamics when added to standard therapy in patients stabilised after admission with heart failure in HORIZON-HF. The REVERSE study suggested that CRT improves ventricular function and reduces morbidity even in patients with few or no symptoms of heart failure and may delay or prevent worsening heart failure