AstraZeneca, Biosensors, and The Medicines Company.

The findings indicate that GIK therapy may have an important role in reducing the in-hospital mortality after acute myocardial infarction. The value of this therapy in the era of thrombolysis and acute revascularization by primary angioplasty can be fully resolved only by conducting a large randomized mortality study.

AimsAtrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta-analysis to study the effects of the presence of AF on mortality in CHF patients. Methods and resultsA systematic MEDLINE search for all randomized trials and observational studies in which the influence of AF on CHF mortality was investigated and meta-analysis of the mortality data was performed. A total of 16 studies were identified of which 7 were randomized trials and 9 were observational studies including 30 248 and 23 721 patients, respectively. An adjusted meta-analysis of the data revealed that the presence of AF is associated with an adverse effect on total mortality with an odds ratio (OR) of 1.40 [95% confidence interval (CI) 1.32-1.48, P , 0.0001] in randomized trials and an OR of 1.14 (95% CI 1.03-1.26, P , 0.05) in observational studies. This increase in mortality associated with the presence of AF was observed in subgroups of CHF patients with both preserved and impaired left ventricular (LV) systolic function. ConclusionIn conclusion, meta-analysis of 16 studies involving 53 969 patients suggests that the presence of AF is associated with an adverse prognosis in CHF irrespective of LV systolic function.--

AimsTo investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease.Methods and resultsThe SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39–0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11–0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37–0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27–1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10–4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07–0.97, P = 0.045).ConclusionAt one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted.ClinicalTrials.gov IdentifierNCT02015832

Longitudinal stent deformation can occur secondary to a variety of mechanisms and identification is important as, left untreated, it may be associated with a risk of stent thrombosis. Although seen with several different stents, in our series it was more commonly observed with the Promus Element stent.

Objective A meta-analysis of all randomised controlled studies that compare outcomes of transradial versus the transfemoral route to better define best practice in patients with ST elevation myocardial infarction (STEMI). Design A Medline and Embase search was conducted using the search terms 'transradial,' 'radial', 'STEMI', 'myocardial' and 'infarction'. Setting Randomised controlled studies that compare outcomes of transradial versus the transfemoral route. Patients A total of nine studies were identified that consisted of 2977 patients with STEMI. Interventions Studies that compare outcomes of transradial versus the transfemoral route. Main outcome measures The primary clinical outcomes of interest were (1) mortality; (2) major adverse cardiac events (MACE); (3) major bleeding and (4) access site complications. Results Transradial PCI was associated with a reduction in mortality (OR 0.53, 95% CI 0.33 to 0.84; p¼0.008), MACE (OR 0.62, 95% CI 0.43 to 0.90; p¼0.012), major bleeding events (OR 0.63, 95% CI 0.35-1.12; p¼0.12) and access site complications (OR 0.30, 95% CI 0.19 to 0.48; p<0.0001) compared with procedures performed through the femoral route. Conclusions This meta-analysis demonstrates a significant reduction in mortality, MACE and major access site complications associated with the transradial access site in STEMI. The meta-analysis supports the preferential use of radial access for STEMI PCI.

Carbapenem-resistant (CRE) represent a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly being highlighted as important potential reservoirs. We investigated a large carbapenemase (KPC)-producing outbreak and wider CRE incidence trends in the Central Manchester University Hospital NHS Foundation Trust (CMFT) (United Kingdom) over 8 years, to determine the impact of infection prevention and control measures. Bacteriology and patient administration data (2009 to 2017) were linked, and a subset of CMFT or regional hospital KPC-producing isolates ( = 268) were sequenced. Control interventions followed international guidelines and included cohorting, rectal screening ( = 184,539 screens), environmental sampling, enhanced cleaning, and ward closure and plumbing replacement. Segmented regression of time trends for CRE detections was used to evaluate the impact of interventions on CRE incidence. Genomic analysis ( = 268 isolates) identified the spread of a KPC-producing outbreak clone (strain A, sequence type 216 [ST216]; = 125) among patients and in the environment, particularly on 2 cardiac wards (wards 3 and 4), despite control measures. ST216 strain A had caused an antecedent outbreak and shared its KPC plasmids with other lineages and species. CRE acquisition incidence declined after closure of wards 3 and 4 and plumbing replacement, suggesting an environmental contribution. However, ward 3/ward 4 wastewater sites were rapidly recolonized with CRE and patient CRE acquisitions recurred, albeit at lower rates. Patient relocation and plumbing replacement were associated with control of a clonal KPC-producing outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and the persistence of in, including pathogenic lineages, are of concern.

We investigated whether plasma long-chain sphingoid base (LCSB) concentrations are altered by transient cardiac ischemia during percutaneous coronary intervention (PCI) in humans and examined the signaling through the sphingosine-1-phosphate (S1P) cascade as a mechanism underlying the S1P cardioprotective effect in cardiac myocytes. Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) of 31 patients at 1 and 5 min and 12 h, following induction of transient myocardial ischemia during elective PCI. Coronary sinus levels of LCSB were increased by 1,072% at 1 min and 941% at 5 min (n = 7), while peripheral blood levels of LCSB were increased by 579% at 1 min, 617% at 5 min, and 436% at 12 h (n = 24). In cultured cardiac myocytes, S1P, sphingosine (SPH), and FTY720, a sphingolipid drug candidate, showed protective effects against CoCl induced hypoxia/ischemic cell injury by reducing lactate dehydrogenase activity. Twenty-five nanomolars of FTY720 significantly increased phospho-Pak1 and phospho-Akt levels by 56 and 65.6% in cells treated with this drug for 15 min. Further experiments demonstrated that FTY720 triggered nitric oxide release from cardiac myocytes is through pertussis toxin-sensitive phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase signaling. In ex vivo hearts, ischemic preconditioning was cardioprotective in wild-type control mice (Pak1f/f), but this protection appeared to be ineffective in cardiomyocyte-specific Pak1 knockout (Pak1cko) hearts. The present study provides the first direct evidence of the behavior of plasma sphingolipids following transient cardiac ischemia with dramatic and early increases in LCSB in humans. We also demonstrated that S1P, SPH, and FTY720 have protective effects against hypoxic/ischemic cell injury, likely a Pak1/Akt1 signaling cascade and nitric oxide release. Further study on a mouse model of cardiac specific deletion of Pak1 demonstrates a crucial role of Pak1 in cardiac protection against ischemia/reperfusion injury.