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Background: Although the satellite cell (SC) is a key regulator of muscle adaptation following exercise, the regulation of human muscle SC function in response to damaging exercise remains largely unexplored. STAT3 signalling, mediated via interleukin-6 (IL-6), has recently come to the forefront as a potential regulator of SC proliferation. The early response of the SC population in human muscle to muscle-lengthening contractions (MLC) as mediated by STAT3 has not been studied. Methodology/Principal Findings: Twelve male subjects (21 ± 2 y; 83 ± 12 kg) performed 300 maximal MLC of the quadriceps femoris at a velocity of 180˚·s-1 over a55° range of motion with muscle samples (vastus lateralis) and blood samples (antecubital vein) taken prior to exercise (PRE), 1 hour (T1), 3 hours (T3) and 24 hours (T24) post-exercise. Cytoplasmic and nuclear fractions of muscle biopsies were purified and analyzed for total and phosphorylated STAT3 (p-STAT3) by western blot. p-STAT3 was detected in cytoplasmic fractions across the time course, peaking at T24 (pcMYC, a STAT3 downstream gene, was significantly up-regulated in SCs at T24 versus PRE (pMYF5 mRNA was up-regulated at T24 (pMRF4 mRNA. Conclusions/Significant Findings: We have demonstrated that IL-6 mediated induction of STAT3 signaling occurred exclusively in the nuclei of SCs in response to MLC. An increase in the number of cMYC+ SCs indicated that human SCs were induced to proliferate under the control of STAT3 signaling. Master of Science (MS)

Pressure wire-based fractional flow reserve is considered the standard of reference for evaluation of the ischemic potential of coronary stenoses and the expected benefit from revascularization. Accordingly, its application in daily practice or for research purposes has to be as standardized as possible to avoid technical or operator-related artifacts in pressure recordings. This document proposes a standardized way of acquiring, recording, interpreting, and archiving the pressure tracings for daily practice and for the purpose of clinical research involving a core laboratory. Proposed standardized steps enhance the uniformity of clinical practices and data interpretation. (C) 2016 by the American College of Cardiology Foundation. Dr. Toth has a consultancy agreement with St. Jude Medical. Dr. Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical and Volcano/Philips outside of the submitted work; and has an institutional licensing and consulting agreement with Boston Scientific. Dr. Jeremias has reported speaker and consultant fees from Volcano Inc. and St. Jude Medical Inc. outside of the submitted work. Dr. Pellicano has been supported by a research grant provided by the Cardiopath PhD program. Dr. Vranckx has received speaking or consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and The Medicines Co. outside of the submitted work. Dr. Fearon has received research support from Medtronic and St. Jude Medical outside of the submitted work; and has received consultant fees from Medtronic, HeartFlow, and Cathworks. Dr. Barbato has received institutional research grants and speakers fees from St. Jude Medical outside of the submitted work. Dr. Kern has received consultant and speaker fees from St. Jude Medical, Volcano, Opsens, ACIST Medical, and Heartflow outside of the submitted work. Dr. Pijls is a consultant for St. Jude Medical, Opsens, and Boston Scientific outside of the submitted work; has received research grants from Medtronic; and is a shareholder for Philips, ASML, General Electric, and Heartflow. Dr. De Bruyne is a shareholder for Siemens, GE, Bayer, Philips, HeartFlow, Edwards Life Sciences, Sanofi, and Omega Pharma; and his institution has received grant support from Abbott, Boston Scientific, Biotronik, and St. Jude Medical and receives consulting fees on his behalf from St. Jude Medical, Opsens, and Boston Scientific outside of the submitted work.

We evaluated the clinical outcome of patients with moderate/severe aortic stenosis and significant coronary disease not treated according to guidelines, recommending combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). From 2002 to 2010, we assessed death up to 5 years in 650 patients with moderate/severe aortic stenosis and at least one coronary lesion (>50 %): 23 % were treated conservatively (MT), 17 % with percutaneous coronary intervention (PCI), 11 % with AVR, and 49 % with combined CABG and AVR. At a median follow-up of 58 months, overall death decreased over the groups (MT, 68 % vs. PCI, 44 % vs. AVR, 34 % vs. CABG and AVR, 23 %, p

Item does not contain fulltext BACKGROUND: The FIREHAWK is a drug-eluting stent with a fully biodegradable sirolimus-containing polymer coating localised to recessed abluminal grooves on the stent surface. We investigated clinical outcomes with this targeted, low-dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable polymer, everolimus-eluting stents in an all-comers population. METHODS: The TARGET All Comers study was a prospective, multicentre, open-label randomised non-inferiority trial done at 21 centres in ten European countries. Patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who qualified for percutaneous coronary intervention were randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was web-based, with random block allocation and stratification by centre and ST elevation myocardial infarction. Outcome assessors were masked to treatment allocation, but treating physicians and patients were not. The primary endpoint was target lesion failure at 12 months, a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation. The control event rate for XIENCE was assumed to be 7%, the non-inferiority margin was 3.5%, and the primary analysis was in the intention-to-treat population, censoring patients who did not have either an event before 365 days or contact beyond 365 days. Late lumen loss was the primary endpoint of an angiographic substudy designed to investigate the non-inferiority of the FIREHAWK compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov, number NCT02520180. FINDINGS: From Dec 17, 2015, to Oct 14, 2016, 1653 patients were randomly assigned to implantation of the FIREHAWK (n=823) or XIENCE (n=830). 65 patients in the FIREHAWK group and 66 in the XIENCE group had insufficient follow-up data and were excluded from the analyses. At 12 months, target lesion failure occurred in 46 (6.1%) of 758 patients in the FIREHAWK group and in 45 (5.9%) of 764 patients in the XIENCE group (difference 0.2%, 90% CI -1.9 to 2.2, pnon-inferiority=0.004, 95% CI -2.2 to 2.6, psuperiority=0.88). There were no differences in ischaemia-driven revascularisation or stent thrombosis rates at 12 months. 176 patients were included in the angiographic substudy, in which in-stent late lumen loss was 0.17 mm (SD 0.48) in the FIREHAWK group and 0.11 mm (0.52) in the XIENCE group (p=0.48), with an absolute difference of 0.05 mm (95% CI -0.09 to 0.18, pnon-inferiority=0.024). INTERPRETATION: In a broad all-comers population of patients requiring stent implantation for myocardial ischaemia, the FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of target lesion failure at 12 months and in-stent late lumen loss at 13 months. The FIREHAWK is a safe and effective alternative stent to treat patients with ischaemic coronary artery disease in clinical practice. FUNDING: Shanghai Microport Medical.

The aim of this review is to highlight the role of invasive functional evaluation in patients in whom coronary artery bypass graft (CABG) is indicated, and to examine the clinical evidence available in favour of fractional flow reserve (FFR) adoption in these patients, outline appropriate use, as well as point out potential pitfalls. FFR after CABG will also be reviewed, highlighting its correct interpretation and adoption when applied to both native coronary arteries and bypass grafts. Practice European guidelines support the use of FFR to complement coronary angiography with the highest degree of recommendation (Class IA) for the assessment of coronary stenosis before undertaking myocardial revascularization when previous non-invasive functional evaluation is unavailable or not conclusive. As a result, FFR has been adopted in routine clinical practice to guide clinicians decision as to whether or not perform a revascularization. Of note, due to the increasing confidence of the interventional cardiologists, FFR guidance is also being implemented to indicate or guide CABG. This is in anticipation of supportive clear-cut evidence, since recommendations for FFR adoption were based on randomized clinical trials investigating percutaneous coronary intervention (PCI) strategies in which patients with typical indications for CABG were excluded (e.g. left main disease, valvular disease, and coronary anatomy unsuitable for PCI). Based on the critical appraisal of the literature, FFR can play an important role in risk stratification and determining management strategy of patients either before or after CABG.