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Background Opioid treatment delays the onset of oral P2Y12 inhibitors in patients with acute ST-segment elevation myocardial infarction (STEMI), leading to suboptimal antithrombotic therapy during primary percutaneous coronary intervention (PPCI). Material and methods We retrospectively compared using a prolonged enoxaparin regimen (0.75 mg/kg bolus followed by 6-hour intravenous infusion) to using unfractionated heparin (UFH) with or without tirofiban in opioid-treated patients with STEMI who underwent PPCI. We compared the proportions of acute stent thrombosis (AST) and bleeding events according to the bleeding academic research consortium (BARC) within 24 hours post-PPCI. Results 270 opioid-treated patients with a mean age of 63 [SD ± 12] years were enrolled, of which 49 (18%) were with diabetes mellitus (DM). 90 (34%) patients (mean age 61 [SD ± 11] years) received enoxaparin, 110 (41%) (mean age 65 [SD ± 14] years) UFH with tirofiban, and 69 (25%) (mean age 63 [SD ± 12] years) UFH only. Compared to the other strategies, a higher proportion of DM was observed in the enoxaparin-treated group (21%). No AST was associated with enoxaparin compared to 2 (1.8%) events in UFH with tirofiban and 1 (1.4%) in UFH only. The rate of severe bleeding events (BARC 2 and 3) was significantly lower in the enoxaparin-treated patients than in UFH with tirofiban (0 (0%) vs. 8 (7%), P = 0.01). 3 enoxaparin-treated patients needed switching to tirofiban as a bailout strategy due to distal vessel embolisation. Conclusions The novel 6-hour enoxaparin regimen is safe during PPCI and was associated with fewer bleeding events than UFH with tirofiban.

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 ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Objectives: To identify factors associated with outcomes following rotational atherectomy (RA). Background: RA is an effective way to mechanically modify heavily calcified lesions before stenting; however its outcomes are not well defined. Methods and Results: Retrospective evaluation of all patients who underwent RA in three large UK centers (Leeds General Infirmary (LGI), Royal Infirmary of Edinburgh (RIE) and University Hospital of North Staffordshire (UHNS)) from March 2005 to January 2013. Five hundred and eighteen patients had RA with median follow-up period of 22 months. About 68.3% were male, 28.7% had DM and 34.6% were treated because of ACS. Stents were deployed in 97.3% of the patients while 30.7% of the procedures were performed transradially. Maximum burr was ≤1.75 mm in 85.5% and the mean SYNTAX score was 19.5 ± 11.6. Peri-procedural complications occurred in 6.4% and vascular access complications in 1.9%. Outcomes in the follow-up period were: MACE 17.8%, cardiac death 7.1%, MI 11.7%, TVR 7.5%, all-cause death 13.7%, definite stent thrombosis (ST) 1.4% and stroke 2.9%. Patients with intermediate and high SYNTAX scores were more likely to suffer MACE, cardiac death, MI, all-cause death and ST. Patients with a SYNTAX score >32 were also more likely to have a peri-procedural complication. Multiple logistic regression analysis showed that the presence of PVD (P = 0.026, OR = 2.0), DM (P = 0.008, OR = 2.1), ACS presentation (P = 0.011, OR = 2.1) and SYNTAX score ≥23 (P = 0.02, OR = 1.9) had a significant association with MACE. Conclusions: RA is safe and effective, with high rate of procedural success and relatively low incidence of MACE. PVD, DM, ACS presentation and SYNTAX score were significant predictors for MACE. © 2016 Wiley Periodicals, Inc.

Background: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. Methods: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. Results: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P =0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P >0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y 12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P 12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5–46.9) ng/L for clopidogrel, 22.4 (5.5–53.8) ng/L for T60, and 17.7 (8.1–43.5) ng/L for T90 ( P =0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P =0.09). Conclusions: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02327624.

Purpose To evaluate the technical performance of sensitivity encoding (SENSE)-accelerated myocardial perfusion magnetic resonance (MR) imaging and prospectively assess the diagnostic accuracy of this examination for depiction of significant coronary artery disease (CAD). Materials and methods All 102 subjects provided written informed consent, and the local ethics committee approved the study. A saturation-recovery segmented k-space gradient-echo pulse sequence was combined with SENSE to allow dynamic acquisition of myocardial perfusion data on four parallel short-axis MR image sections at every heartbeat. This technique was evaluated in 10 healthy volunteers and in 92 patients scheduled to undergo conventional coronary angiography. Gadopentetate dimeglumine was peripherally injected at rest and during adenosine-induced stress. The maximal upslope of the signal intensity-time profiles was plotted for 16 myocardial segments defined on three MR image sections, and a myocardial perfusion reserve index (MPRI) between stress and rest, normalized to the input function from the blood pool of the most basal section, was calculated. Areas under receiver operating characteristic curves (AUCs) were used to assess the diagnostic performance of cardiac MR imaging for depiction of greater than 70% CAD seen at coronary angiography, the reference standard. Results In volunteers, the mean myocardial enhancement was 2.1 +/- 1.2 (standard deviation), with homogeneous signal intensity distribution across the segments. The diagnostic accuracy of MPRI measurements was high (AUC, 0.908; sensitivity, 88% [52 of 59 patients]; specificity, 82% [27 of 33 patients]). Diagnostic performance was similar among separate analyses of the three coronary territories and among separate analyses of data in the patients with diabetes mellitus, left ventricular hypertrophy, or myocardial infarction. Conclusion Multisection myocardial perfusion MR imaging with SENSE is feasible and has high diagnostic accuracy in the detection of CAD.