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• High coercivity is required only at the magnet's edges in wind turbine generators. • Several NdFeB materials with distinct properties can be arranged in a single magnet. • Conventional and SPS sintering are viable for preparation of multicomponent magnets. • Nonuniform distribution of magnetization is favorable for the target applications. Magnetic remanence (B r) and coercivity (H c) of hard magnets play a crucial role in electro-mechanical devices like electrical motors or generators. Elevated remanence ensures high efficiency of the device, and large coercivity protects the magnet from demagnetization. Usually, the increase of one comes at the cost of the other, such that the material optimization has a trade-off character. In this work, we demonstrate that in many electrical machines which use permanent magnets, high coercivity is required mainly at the edges of the magnet. This enables us to design a novel form of a permanent magnet, called a multicomponent magnet, where the sides of the magnet have high coercivity, while the central part is characterized by high remanence. Such multicomponent magnets are realized by two independent methods, namely, conventional high-temperature sintering and Spark Plasma Sintering (SPS). The magnetic and mechanical performances are suitable for applications, and simulation results using the magnetic characteristics of the multicomponent geometry predict its benefit on the device functionality. Further tuning of the geometry of the multicomponent permanent magnets opens avenues for promising applications, particularly in electrical motors for electrical vehicles. [ABSTRACT FROM AUTHOR]

Background: PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States., Methods: The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022. The key safety end point was defined as all-cause death, ischemic stroke, systemic embolism, or device or procedure-related events requiring open cardiac surgery or major endovascular intervention between device implantation and hospital discharge. Major adverse events were reported at hospital discharge, 45 days, and 1 year., Results: Among 97 185 patients in the Left Atrial Appendage Occlusion registry undergoing WATCHMAN FLX, successful implantation occurred in 97.5% (n=94 784) of patients. The key safety end point occurred in 0.45% of patients. At 45 days post-procedure, all-cause death occurred in 0.81% patients, ischemic stroke in 0.23%, major bleeding in 3.1%, pericardial effusion requiring intervention in 0.50%, device-related thrombus in 0.44%, and device embolism in 0.04% patients. No peri-device leak was observed in 83.1% of patients at 45 days. At 1 year, the rate of all-cause death was 8.2%, the rate of any stroke was 1.5% (ischemic stroke, 1.2%), and major bleeding occurred in 6.4% of patients., Conclusions: In a large contemporary cohort of patients with the WATCHMAN FLX device, the rates of implant success and clinical outcomes through 1 year were comparable with the PINNACLE FLX study, demonstrating that favorable outcomes achieved in the pivotal approval study can be replicated in routine clinical practice.

Background: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy., Study Design: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding., Conclusions: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF., Clinical Trial Registration: NCT04394546., Competing Interests: Disclosures Dr Kar is a consultant to BSC, Abbott Vascular, Medtronic, LAMINAR, V-wave, Intershunt Highlife, co-principal investigator of the CHAMPION AF and REPAIR-MR studies and a steering committee member for the Triluminate and RELIEVE HF trials. Dr Doshi serves as a consultant to BSC, Biosense Webster, Abbott Vascular, Conformal and is co-principal investigator of the CHAMPION AF study. Dr Alkhouli is on the advisory board for BSC and received institutional research grant from BSC. Dr Camm received personal fees from Anthos, Menarini, Bayer, Daiichi Sankyo, Pfizer, Abbott and BSC. Dr Coylewright received research funding from BSC and Edwards Life Sciences and is a consultant for BSC, Edwards Life Sciences, Occlutech and Medtronic. Dr Gibson received research grant support payable to his institution and consulting fees from J&J, BMS, Diachi Sankyo, CeleCor and Merck. Dr Granger receives consulting fees from Abbvie, Abiomed, Alnylam Pharmaceuticals, Anthos, Bayer Corporation, Boehringer Ingelheim, BSC, Bristol Myers Squibb, Cardionomics, CeleCor Therapeutics, Janssen Pharmaceutical, Medscape, LLC, Medtronic, Inc., Merck, Nation Institutes of Health, Novo Nordisk, Novartis Pharmaceutical Company, PLX Pharma, Pfizer, Philips, REATA and NephroSynergy. He has an equity in Tenac.io. and salary funded by Duke grants sponsored by Boehinger Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, FDA, Janssen Pharmaceuticals, Novartis Pharmaceutical Company, Pfizer, and Philips. Dr Gurol received research funding from NIH and the hospital he is affiliated to received research funding from AVID, Pfizer and BSC. Dr Huber is on the Watchman Advisory Board. Dr Mansour is a consultant: for BSC. Dr Nair is an advisory board member and consultant for, and received research grant support from Biosense Webster, BSC, Abbott and Medtronic. Dr Natale is a consultant for Abbott, Baylis, Biosense Webster, BSC, Biotronik and Medtronic. Dr Pocock is a consultant for BSC. Dr Reddy serves as a consultant to, and has received grant support from, BSC. He reports additional disclosures unrelated to this manuscript: Consultant for and has equity in Ablacon, Acutus Medical, Affera, Medtronic, Apama Medical, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; Consultant for AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; Equity in Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. Dr Saliba is on the advisory board for BSC. Dr Christen and Allocco are full-time employees with an equity interest in BSC. Dr Ellenbogen received research support/lecture fees/honorarium and is a consultant for BSC. Dr Leon received clinical research grants to Columbia University from Abiomed-J&J, Abbott, BSC, Edwards and Medtronic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The FLXibility Post-Approval Study collected data on unselected patients implanted with a WATCHMAN FLX in a commercial clinical setting., Methods and Results: Patients were implanted with a WATCHMAN FLX per local standard of care, with a subsequent first follow-up visit from 45 to 120 days post-implant and a final follow-up at 1-year post-procedure. A Clinical Event Committee adjudicated all major adverse events and TEE/CT imaging results were adjudicated by a core laboratory. Among 300 patients enrolled at 17 centres in Europe, the mean age was 74.6 ± 8.0 years, mean CHA2DS2-VASc score was 4.3 ± 1.6, and 62.1% were male. The device was successfully implanted in 99.0% (297/300) of patients. The post-implant medication regimen was DAPT for 87.3% (262/300). At first follow-up, core-lab adjudicated complete seal was 88.2% (149/169), 9.5% (16/169) had leak <3 mm, 2.4 (4/169) had leak ≥3 mm to ≤5 mm, and 0% had >5 mm leak. At 1 year, 93.3% (280/300) had final follow-up; 60.5% of patients were on a single antiplatelet medication, 21.4% were on DAPT, 5.6% were on direct oral anticoagulation, and 12.1% were not taking any antiplatelet/anticoagulation medication. Adverse event rates through 1 year were: all-cause death 10.8% (32/295); CV/unexplained death 5.1% (15/295); disabling and non-disabling stroke each 1.0% (3/295, all non-fatal); pericardial effusion requiring surgery or pericardiocentesis 1.0% (3/295); and device-related thrombus 2.4% (7/295)., Conclusion: The WATCHMAN FLX device had excellent procedural success rates, high LAA seal rates, and low rates of thromboembolic events in everyday clinical practice., Competing Interests: Conflict of interest. T.R.B.: proctoring/consultancy honoraria (Boston Scientific). M.G.: proctoring/consultancy honoraria (Abbott, Boston Scientific), research grants (Boston Scientific). J.E.N.K.: procotoring/consultancy honoraria (Abbott, Boston Scientific), research grants (Abbott, Boston Scientific). T.S.: proctoring/consultancy honoraria (Boston Scientific). M.S.: nothing to disclose. G.C.: proctoring/consultancy honoraria (Abbott, Boston Scientific, Lifetech). M.B.: Speaker honoraria and study support (Abbott, Boston Scientific, Daiichi, Medtronic, MSD/Pfizer). D.H.-S.: proctoring/advisory board honoraria (Abbott, Boston Scientific, Eclipse Medical). T.C.: salary and equity (Boston Scientific Corporation). D.J.A.: salary and equity (Boston Scientific Corporation)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Intracardiac echocardiography (ICE) is increasingly used to guide left atrial appendage closure (LAAC)., Objectives: The aim of this study was to investigate the efficacy and safety of ICE-guided LAAC with the Watchman FLX device., Methods: The ICE LAA (I Can See Left Atrial Appendage) study was a prospective, multicenter study with independent adjudication of echocardiographic data by a core laboratory and clinical events by a clinical events committee. Patients with atrial fibrillation with CHA 2 DS 2 -VASc scores ≥2 and clinical indications for LAAC were eligible. Preplanning with either cardiac computed tomography or transesophageal echocardiography (TEE) within 7 days prior to LAAC was mandatory. Intraprocedural ICE was carried out from the left atrium. The primary outcome was the rate of significant peridevice leaks (>5 mm) at 45-day TEE., Results: A total of 100 patients were enrolled. The mean age was 76 ± 8 years, the mean CHA 2 DS 2 -VASc score was 4.0 ± 1.5, and the mean HAS-BLED score was 2.5 ± 0.9. The incidence of the primary outcome of significant peridevice leak (>5 mm) was 0%; all patients evaluated by TEE at 45 days had effective LAAC. All patients received Watchman FLX devices, and technical success was 100%. The number of devices per case was 1.0 ± 0.1. ICE successfully guided the assessment of device release criteria, including device compression (19.2% ± 7.1%; recommended range: 10%-30%). No subject required conversion to TEE. Procedural complications were 4 access-site bleeds. There was no stroke, transient ischemic attack, systemic embolization, pericardial effusion, device embolization, or device-related thrombus during the procedure or 45-day follow-up., Conclusions: ICE can be used to successfully guide LAAC with the Watchman FLX, with excellent procedural success, a high rate of effective LAAC, and minimal periprocedural complications. (I Can See Left Atrial Appendage [ICELAA] Clinical Study; NCT04196335)., Competing Interests: Funding Support and Author Disclosures The ICE LAA study was supported by Boston Scientific. Dr Nielsen-Kudsk is a proctor and an investigator for Abbott and Boston Scientific. Dr Berti is a proctor for Abbott and Boston Scientific. Dr Caprioglio has received speaker honoraria from Abbott, Philips, and GE Healthcare. Dr Ronco has received speaker honoraria from Abbott and GE Healthcare. Dr Arzamendi is a proctor for Abbott and Boston Scientific. Dr Betts is a proctor for Boston Scientific. Dr Tondo is a proctor for Abbott and Boston Scientific. Drs Christen and Allocco are full-time employees of and stockholders in Boston Scientific., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background The PINNACLE FLX (Protection Against Embolism for Non-valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next-generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2-year outcomes with this next-generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA 2 DS 2 -VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA 2 DS 2 -VASc, 4.2±1.5), the secondary efficacy end point of 2-year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1-sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two-year rates of adverse events were as follows: 9.3% all-cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device-related thrombi after 1 year. Conclusions The secondary end point of 2-year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next-generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O 2 . Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions., Competing Interests: LC, DR, and TB are employees of Olea Medical, a company developing the OleaSphere platform including pipelines for ischemic penumbra. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chalet, Boutelier, Christen, Raguenes, Debatisse, Eker, Becker, Nighoghossian, Cho, Canet-Soulas and Mechtouff.)

Background: Transcatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve., Methods: The primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months., Results: The study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P < 0.001 in a paired analysis). In the overall population, paravalvular leak was evaluated at 1 year as none/trace in 60.5%, mild in 37.0%, and moderate in 2.5%; no patients had severe PVL., Conclusions: One-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve., (© 2021. The Author(s).)

This article presents an open source software able to convert, display, and process medical images. It differentiates itself from the existing software by its ability to design complex processing pipelines and to wisely execute them on a large databases. An MP3 pipeline can contain unlimited homemade or ready-made processes and can be carried out with a parallel execution system. As a viewer, MP3 allows display of up to four images together and to draw Regions Of Interest (ROI). Two applications showing the strengths of the software are presented as examples: a preclinical study involving Magnetic Resonance Imaging (MRI) data and a clinical one involving Computed Tomography (CT) images. MP3 is downloadable at https://github.com/nifm-gin/MP3., (Copyright © 2020 Brossard, Montigon, Boux, Delphin, Christen, Barbier and Lemasson.)

Background: High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Consumption of dark chocolate, which is high in flavonoids that may reduce CVD risk, is an attractive intervention to reduce to BP. Additionally, the use of mobile health (mHealth) technologies (eg, telehealth, smartphones, and wearable devices) can improve outcomes in patients with CVD., Objective: The purpose of this study was to investigate the impact of dark chocolate intake on BP, subject use of mHealth, and integration of mHealth into a clinical trial., Methods: The COCOA-BP (ChOcolate COnsumption And Blood Pressure) study was a prospective, single-center, pre-/postintervention study that enrolled 62 healthy volunteers. The study consisted of 3 phases: smartwatch/smart BP monitor familiarization and washout from chocolate (week 1); control (week 2); and intervention (weeks 3 and 4). During the intervention phase, subjects consumed 50 g of dark chocolate per day. The primary endpoint was change in resting systolic BP between the intervention and control phases. Additional endpoints included device accuracy and correlation with physical activity., Results: Mean resting systolic BP was 116.4 mm Hg before chocolate intake among 62 participants (mean age 37 years; 61% female). After chocolate intake, mean resting systolic BP was 116.0 mm Hg (difference -0.4; P = .69). These findings suggest that 2 weeks of dark chocolate intake did not reduce resting systolic BP. There was poor agreement between mHealth device and standard (nurse-performed) measurements., Conclusion: In this study, short-term dark chocolate intake did not seem to reduce BP. mHealth technology shows great potential for use in clinical studies, but challenges related to device accuracy and compliance need to be addressed., (© 2020 The Author(s).)

Objectives: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice., Background: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%., Methods: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups., Results: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups., Conclusions: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease., (© 2018 Wiley Periodicals, Inc.)

Background: While extended dual antiplatelet therapy (DAPT) with aspirin and a platelet (P2Y 12 ) inhibitor after percutaneous coronary intervention (PCI) reduces the risk of stent thrombosis (ST) and myocardial infarction (MI), it also increases bleeding. Newer generation drug-eluting stents with bioabsorbable polymer coatings may reduce thrombotic events and allow abbreviated DAPT in selected patients. The EVOLVE Short DAPT study is designed to evaluate the safety of 3-month DAPT in high bleeding risk subjects treated with the SYNERGY bioabsorbable polymer everolimus-eluting stent., Trial Design: EVOLVE Short DAPT is a prospective, single-arm, international study that enrolled 2009 high risk bleeding subjects (defined as age ≥75 years, chronic anticoagulation, major bleeding within 12 months, history of stroke, renal insufficiency/failure, or thrombocytopenia) who underwent PCI with the SYNERGY stent. Subjects presenting with acute MI or complex lesions were excluded. After 3 months treatment with DAPT (except those on anticoagulant in whom aspirin is optional), subjects free from stroke, MI, revascularization or ST will be eligible to discontinue P2Y 12 inhibitor, but continue aspirin. Co-primary endpoints assessed between 3-15 months are: i) death/MI compared for non-inferiority with propensity-adjusted historical group receiving 12-month DAPT, and ii) definite/probable ST compared to a performance goal. The secondary endpoint is the rate of bleeding in subjects not receiving chronic anticoagulation compared for superiority against a propensity-adjusted historical control., Conclusion: The EVOLVE Short DAPT study will prospectively define the safety of DAPT discontinuation at 3 months in high bleeding risk patients treated with the SYNERGY stent., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

Aims: Long-term data on bioabsorbable polymer-coated everolimus-eluting stents (BP-EES) are limited. The EVOLVE trial compared the safety and efficacy of two dose formulations of the SYNERGY BP-EES with the permanent polymer-coated PROMUS Element EES (PE)., Methods and Results: The EVOLVE study was a prospective, multicentre, non-inferiority trial that randomised 291 patients with de novo coronary lesions (length: ≤28 mm; diameter: ≥2.25 to ≤3.5 mm) to receive PE (n=98), SYNERGY (n=94), or SYNERGY half-dose (n=99). At five years, there were no significant differences in the rates of TLF or individual components between groups. TLR rates trended lower in both SYNERGY arms than in the PE arm (TLR: 1.1% SYNERGY and 1.0% SYNERGY half-dose vs. 6.1% PE; p=0.07 and p=0.06, respectively). TVR was numerically lower in the SYNERGY arms compared to the PE arm (TVR: 3.3% SYNERGY and 4.2% SYNERGY half-dose vs. 10.2% PE; p=0.06 and p=0.11, respectively). No incidence of stent thrombosis was reported in any arm up to five years., Conclusions: The EVOLVE trial represents the longest-term follow-up of the SYNERGY stent available to date, demonstrating its continued safety and efficacy for the treatment of selected de novo atherosclerotic lesions up to five years.

Purpose: To simultaneously assess reproducibility of three MRI transverse relaxation parameters ( R2', R2*, and R 2 ) for brain tissue oxygenation mapping and to assess changes in these parameters with inhalation of gases that increase and decrease oxygenation, to identify the most sensitive parameter for imaging brain oxygenation., Materials and Methods: Forty-eight healthy subjects (25 male, ages 35 ± 8 years) were scanned at 3.0 Tesla, each with one of four gases (mildly and strongly hypercapnic and hypoxic) administered in a challenge paradigm, using a gas delivery setup designed for patient use. Cerebral blood flow mapping with arterial spin labeling, and simultaneous R2', R2*, and R 2 mapping with gradient-echo sampling of free induction decay and echo (GESFIDE) were performed. Reproducibility in air and gas-induced changes were evaluated using nonparametric analysis with correction for multiple comparisons., Results: Our gas delivery setup achieved stable gas challenges as shown by physiological monitoring. Test-retest variability of R2', R2*, and R 2 were found to be 0.24 s -1 (8.6% of mean), 0.24 s -1 (1.3% of mean), and 0.15 s -1 (1.0% of mean), respectively. Strong hypoxia produced the most conclusive oxygenation-driven relaxation change, inducing increases in R2' (25 ± 13%, P = 0.03), R2* (5 ± 2%, P = 0.02), and R 2 (2 ± 2%, NS)., Conclusion: We benchmarked the intra-scan test-retest variability in GESFIDE-based transverse relaxation rate mapping. Using a reliable framework for gas challenge paradigms, we recommend strong hypoxia for validating oxygenation mapping methods, and the use of tissue R2' change, instead of R2* or R 2 , as a metric for studying brain tissue oxygenation using transverse relaxation methods., Level of Evidence: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:704-714., (© 2017 International Society for Magnetic Resonance in Medicine.)

This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence., (Copyright © 2017. Published by Elsevier Inc.)

Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (P a CO 2 ) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R 2  = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2' differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s -1 , p < 0.001), indicating reduced oxygenation in abnormal regions. Cerebrovascular reserve was lower in angiographically abnormal regions (21 ± 38 vs. 41 ± 26%, p = 0.001). All regions showed trend toward significantly improved oxygenation post-acetazolamide. Regions with poorer cerebrovascular reserve had lower baseline oxygenation (Kendall's τ = -0.24, p = 0.003). A number of angiographically abnormal regions demonstrated preserved cerebrovascular reserve, likely due to the presence of collaterals. Finally, of the concurrently measured relaxation rates, R2' was superior for oxygenation assessment.

Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

Aims: Bioabsorbable polymer drug-eluting stents (DES) may reduce the inflammation and delayed healing associated with some permanent polymer-coated DES. Whether late clinical outcomes are improved, particularly among patients with medically treated diabetes, is unknown. Therefore, we analysed outcomes from a pre-specified substudy of the EVOLVE II trial to evaluate the safety and effectiveness of the SYNERGY stent in patients with diabetes mellitus., Methods and Results: SYNERGY is a thin-strut, platinum-chromium everolimus-eluting stent with an ultra-thin bioabsorbable poly(DL-lactide-co-glycolide) abluminal polymer. The EVOLVE II randomised, controlled trial proved the non-inferiority of the SYNERGY versus the PROMUS Element Plus stent for one-year target lesion failure (TLF: ischaemia-driven target lesion revascularisation [ID-TLR], target vessel myocardial infarction [TVMI], or cardiac death). The pre-specified EVOLVE II diabetes substudy prospectively pooled randomised patients with diabetes (N=263) with a sequential single-arm diabetic cohort (n=203). The substudy primary endpoint was one-year TLF compared with a pre-specified performance goal (14.5%). The primary endpoint occurred in 7.5% of SYNERGY-treated patients with diabetes, significantly less than the performance goal (p<0.0001). The two-year rate of TLF was 11.2% (cardiac death 1.5%, TVMI 6.4%, ID-TLR 6.8%) and definite/probable stent thrombosis occurred in 1.1% of patients., Conclusions: The EVOLVE II diabetes substudy demonstrates the efficacy and safety of the SYNERGY stent in patients with medically treated diabetes.

Several MR methods have been proposed over the last decade to obtain quantitative estimates of the tissue blood oxygen saturation (StO2) using a quantification of the blood oxygen level dependent effect. These approaches are all based on mathematical models describing the time evolution of the MR signal in biological tissues in the presence of magnetic field inhomogeneities. Although the experimental results are very encouraging, possible biases induced by the model assumptions have not been extensively studied. In this study, a numerical approach was used to examine the influence on T(2)*, blood volume fraction, and StO2 estimates of possible confounding factors such as water diffusion, intravascular signal, and presence of arterial blood in the voxel. To evaluate the impact of the vessel geometry, straight cylinders and realistic data from two-photon microscopy for microvascular geometry were compared. Our results indicate that the models are sufficiently realistic, based on a good correlation between ground truth and MR estimates of StO2., (Copyright © 2011 Wiley Periodicals, Inc.)

Blood oxygen saturation (SO(2)) is a promising parameter for the assessment of brain tissue viability in numerous pathologies. Quantitative blood oxygenation level-dependent (qBOLD)-like approaches allow the estimation of SO(2) by modelling the contribution of deoxyhaemoglobin to the MR signal decay. These methods require a high signal-to-noise ratio to obtain accurate maps through fitting procedures. In this article, we present a version of the qBOLD method at long TE taking into account separate estimates of T(2), total blood volume fraction (BV(f)) and magnetic field inhomogeneities. Our approach was applied to the brains of 13 healthy rats under normoxia, hyperoxia and hypoxia. MR estimates of local SO(2) (MR&#95;LSO(2)) were compared with measurements obtained from blood gas analysis. A very good correlation (R(2) = 0.89) was found between brain MR&#95;LSO(2) and sagittal sinus SO(2)., (Copyright © 2010 John Wiley & Sons, Ltd.)

The aim of this work focuses on the description of the short-term response of a 9L brain tumor model and its vasculature to microbeam radiation therapy (MRT) using magnetic resonance imaging (MRI). Rat 9L gliosarcomas implanted in nude mice brains were irradiated by MRT 13 days after tumor inoculation using two orthogonal arrays of equally spaced 28 planar microbeams (25 microm width, 211 microm spacing and dose 500 Gy). At 1, 7 and 14 days after MRT, apparent diffusion coefficient, blood volume and vessel size index were mapped by MRI. Mean survival time after tumor inoculation increased significantly between MRT-treated and untreated groups (23 and 28 days respectively, log-rank test, p < 0.0001). A significant increase of apparent diffusion coefficient was observed 24 h after MRT in irradiated tumors versus non-irradiated ones. In the untreated group, both tumor size and vessel size index increased significantly (from 7.6 +/- 2.2 to 19.2 +/- 4.0 mm(2) and +23%, respectively) between the 14th and the 21st day after tumor cell inoculation. During the same period, in the MRT-treated group, no difference in tumor size was observed. The vessel size index measured in the MRT-treated group increased significantly (+26%) between 14 and 28 days of tumor growth. We did not observe the significant difference in blood volume between the MRT-treated and untreated groups. MRT slows 9L tumor growth in a mouse brain but MRI results suggest that the increase in survival time after our MRT approach may be rather due to a cytoreduction than to early direct effects of ionizing radiation on tumor vessels. These results suggest that MRT parameters need to be optimized to further damage tumor vessels.