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

Oxidative Stress in Fetal Distress: Potential Prospects for Diagnosis

Our aim was to investigate the relation between fetal distress and oxidative stress. Fetal distress was associated with increased concentration of superoxide in the fetal blood and with significant increase of the level of H2O2 in both maternal and fetal blood. The activity of superoxide dismutase was increased roughly sixfold (p < 0.01) in the maternal [7330 ± 2240 U/g of hemoglobin in controls (C) and 36811 ± 16862 U/g in fetal distress (FD)] and fetal blood (C: 5930 ± 2641 U/g; FD: 41912 ± 17133 U/g). In contrast, fetal distress was related to a considerable decrease of catalase activity in both maternal (C: 26011 ± 8811 U/g; FD: 7212 ± 1270 U/g) and fetal blood (C: 37194 ± 9191 U/g; FD: 6173 ± 1965 U/g). From this we concluded that in fetal distress, the maternal and fetal bloods are exposed to superoxide- and H2O2-mediated oxidative stress, which could be initiated by hypoxic conditions in the fetal blood and placenta. A tremendous increase/decrease of the activities of superoxide dismutase/catalase in the blood of women bearing a distressed fetus in comparison to healthy subjects implies that the assessment of superoxide dismutase/catalase activity could be of use for establishing a timely and accurate ante- or intrapartum diagnosis of fetal distress

Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device

Objective: Atrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring. Methods: Twenty-five patients were monitored after an AF ablation procedure using the hand-held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation. Results: During months 1-2, 425 of 2942 hand-held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P LT .01) in 15 of 23 patients. Hotter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P LT .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holler detection by an average of 24 days. Conclusions: Wireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring. (C) 2012 Elsevier Inc. All rights reserved

Coronary Microcirculation: The Next Frontier in the Management of STEMI

Although the widespread adoption of timely invasive reperfusion strategies over the last two decades has significantly improved the prognosis of patients with ST-segment elevation myocardial infarction (STEMI), up to half of patients after angiographically successful primary percutaneous coronary intervention (PCI) still have signs of inadequate reperfusion at the level of coronary microcirculation. This phenomenon, termed coronary microvascular dysfunction (CMD), has been associated with impaired prognosis. The aim of the present review is to describe the collected evidence on the occurrence of CMD following primary PCI, means of assessment and its association with the infarct size and clinical outcomes. Therefore, the practical role of invasive assessment of CMD in the catheterization laboratory, at the end of primary PCI, is emphasized, with an overview of available technologies including thermodilution- and Doppler-based methods, as well as recently developing functional coronary angiography. In this regard, we review the conceptual background and the prognostic value of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), hyperemic microvascular resistance (HMR), pressure at zero flow (PzF) and angiography-derived IMR. Finally, the so-far investigated therapeutic strategies targeting coronary microcirculation after STEMI are revisited

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging

Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 &plusmn; 10 years; range: 27&ndash;74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression &ge;50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10&ndash;40 &mu;g/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 &plusmn; 0.16 vs. 2.78 &plusmn; 0.53; p &lt; 0.001). ROC analyses identified the optimal CFVR cut-off value &le; 2.1 obtained during high-dose dobutamine (&gt;20 &micro;g/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967&ndash;1.000; p &lt; 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values &le;2.1 (OR: 0.023; 95% CI: 0.001&ndash;0.534; p = 0.019; OR: 1.147; 95% CI: 1.042&ndash;1.263; p = 0.005; respectively). Conclusions: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off &le;2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications