Revascularization in multivessel disease: Comparison between two-year outcomes of coronary bypass surgery and stenting

AbstractObjective: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. Methods: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. Results: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). Conclusion: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients.J Thorac Cardiovasc Surg 2003;125:809-2

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote 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. METHODS: We 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. FINDINGS: Between 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. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

The wrecker's daughter: and other tales of the forest, the shore, and the ocean.

Also pub. under title: Forest and shore, or Legends of the Pine tree state.The scenes of these tales are laid in Maine: the 2d in Falmouth (now Portand) and Buxton, the 4th in New Gloucester, the 5th in Machias, the 6th in Freeport.The wrecker's daughter.--The scout.--The light-keeper.--The settlers.--The liberty pole.--The storm at sea.--The Canadian captive.Mode of access: Internet

Multifocal Severe Coronary Artery Vasospasm Mistaken for Diffuse Atherosclerosis: A Case Report

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Spontaneous severe multivessel coronary artery vasospasm is a rare but important cause of morbidity. One-third of patients have normal coronary vasculature, and these pose a significant therapeutic dilemma as lack of clinical suspicion might potentially lead to unnecessary revascularization therapies. A patient with resting chest pain and ischaemic electrocardiography demonstrated severe coronary obstruction at catheter angiography. Preangioplasty further information highlighted spasm as the likely cause and the angiographic abnormalities resolved post intracoronary nitrate. This paper emphasises thorough history-taking and judicious use of nitrates during diagnostic coronary angiography in such patients. This may negate the need for more complex cardiac interventions. 1

Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial

Objective To compare the clinical, angiographic, neurocognitive, and quality of life outcomes of off-pump coronary artery bypass surgery with conventional coronary artery bypass grafting surgery using cardiopulmonary bypass. Design Randomised controlled clinical trial. Setting Tertiary cardiothoracic centre in Middlesex, England. Participants 168 patients (27 women) requiring primary isolated coronary artery bypass grafting surgery. Interventions Patients were randomised to conventional coronary artery bypass grafting surgery using cardiopulmonary bypass (n = 84) or off-pump coronary artery bypass surgery (n = 84), carried out by one surgeon. Angiographic examination was carried out at three months postoperatively. Neurocognitive tests were carried out at baseline and at six weeks and six months postoperatively. Main outcome measures Clinical outcome, graft patency at three months, neurocognitive function at six weeks and six months, and health related quality of life. Results Graft patency was evaluated by angiography in 151 (89.9%) patients and was similar between the cardiopulmonary bypass and off-pump groups (risk difference - 1%, 95% confidence interval - 5% to 4%), with the off-pump group considered the treatment group. Patients in the off-pump group required fewer blood transfusions (1.7 units v 1.0 unit, P = 0.02), shorter duration of mechanical ventilation (7.7 hours v 3.9 hours, P = 0.03), and shorter hospital stay (10.8 days v 8.9 days). Scores for neurocognitive function showed a significant difference in three memory subtests at six weeks and two memory subtests at six months in favour of the off-pump group. Conclusions Patients who underwent off-pump coronary artery bypass surgery showed similar patency of grafts, better clinical outcome, shorter hospital stay, and better neurocognitive function than patients who underwent conventional coronary artery bypass grafting surgery using cardiopulmonary bypass

Direct targets of pStat5 signalling in erythropoiesis

Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: similar to 15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25), epigenetic regulation (Suv420h2), and EpoR turnover (Clint1/EpsinR). Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors