SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Elevated BNP and NT-proBNP levels identify patients undergoing major noncardiac surgery at high risk of cardiac mortality, all-cause mortality, and MACE.

Transgenic technology has been revolutionised by the development of techniques that allow temporo-spatial control of gene deletion or expression in transgenic animals. The ability to switch gene expression 'on' or 'off' in restricted tissues at specific times allows unprecedented flexibility for exploring gene function in both health and disease. As use of these techniques grows in all areas of biomedical research, an understanding of this topic is essential. In this review we examine the theory, application and limitations of these strategies, with particular reference to endocrine research.

We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS.

Abstract-Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2)27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR(mRen2)27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 ␣ and 3 ␤ integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only ␣V was significantly raised. In conjunction, we confirmed elevated integrin ␣V protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. ␤1 and ␤3, but not ␤5 integrin subunits were coprecipitated with integrin ␣V and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of ␣V␤3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertensioninduced increases in wall stress. We have established that the only upregulated integrin, the ␣V subunit of integrin ␣V␤3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific ␣V␤3-extracellular matrix interactions are likely to allow vascular smooth muscle cell-length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state. A lthough the causes of high blood pressure may vary, sustained hypertension is associated with changes in cardiovascular structure. 1 These can be seen from the left ventricle down to the resistance vessels, and there is a strong relationship between left ventricular mass and small artery structure. 2,3 Resistance to blood flow is provided by arteries with an internal diameter (ID) of Յ300 m, 4 and in subcutaneous vessels, there is clear evidence for an increased media thickness:lumen diameter ratio in essential hypertension, which is proportional to the severity of the blood pressure. 1,5,6 Such findings appear to be representative of other vascular beds, with similar results being reported in the small intestine and the heart. 7,8 The nature of the structural change that is effected by hypertension is a rearrangement of the preexisting material in the vascular wall without a major hypertrophic response. 9 This has been termed eutrophic inward remodeling, which is initiated by vascular smooth muscle cell (VSMC)-length autoregulation. 10 Constriction causes shortening of VSMCs and a return to normal length after dissipation of the stimulus; however, prolonged constriction causes cells to increase in overlap. This functional adaptation to prolonged vasoconstriction is thought to occur because it is an energetically favored mechanism to preserve a reduced lumen diameter for long periods. 10 All models of hypertension appear to demonstrate eutrophic remodeling in small arteries, although to differing extents. ...

The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95–3.44; p < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45–2.06; p = 0.00001), Troponin (HR 1.65; 95% CI 1.31–2.07; p < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27–2.61; p < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status.

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The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).