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To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes.The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-βThe 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-βOur study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

Objectives The aims of this study were to document the prevalence of concomitant tricuspid regurgitation (TR) before and after transcatheter aortic valve replacement (TAVR), to quantify potential eligibility for transcatheter tricuspid valve intervention (TTVI), and to report clinical outcomes as a function of the severity of TR and potential candidacy for TTVI. Background The importance of concomitant TR in patients with severe aortic stenosis undergoing TAVR remains unclear. Methods In a prospective TAVR registry, the severity of TR before and after TAVR was retrospectively evaluated in an echocardiography core laboratory. Results Among 2,008 eligible patients, 1,659 patients (82.6%) had mild or less TR, 242 (12.1%) had moderate TR, 57 (2.8%) had severe TR, and 50 (2.5%) had massive TR. More than one-half of patients with moderate or greater TR had a reduction in TR, while a small proportion of patients with severe or less of TR had worsening of TR after TAVR. In contrast to TR at baseline, severe TR (adjusted HR [HRadjusted]: 1.90; 95% CI: 1.03-3.49) and massive TR (HRadjusted: 2.17; 95% CI: 1.10-4.30) after TAVR conferred an increased risk for mortality compared with mild or less TR at 1 year after TAVR. After TAVR, 63 patients (3.1%) were deemed potential candidates for TTVI. They had a 2-fold increased risk for mortality between 30 days and 1 year (HRadjusted: 1.93; 95% CI: 1.15-3.25) and a higher risk for persistent heart failure symptoms (adjusted risk ratio: 2.80; 95% CI: 1.78-4.40). Conclusions A non-negligible proportion of patients were considered potential candidates for TTVI after TAVR and had impaired prognosis and persistently impaired functional status at 1 year. (SwissTAVI Registry; NCT01368250 )

Aims To investigate the variability between site and core laboratory (CL) calculation of the anatomical SYNTAX score (SS) based on coronary computed tomography angiography (CTA) alone and functional SS based on coronary CTA and fractional flow reserve derived from computed tomography (FFRCT) in the SYNTAX III trial. Methods and results The SYNTAX III trial was a multicentre, international study that included 223 patients with three-vessel disease with or without left main involvement. Functional SS was computed by subtracting non-flow limiting stenoses (FFRCT > 0.80) from anatomical SS. SS was combined with clinical information to generate the SYNTAX score II (SS II) that provides treatment recommendations. The mean anatomical SS based on coronary CTA alone was 33.4 ± 12.7 by sites and 37.1 ± 13.4 by CL (P Conclusion The mean anatomical SS derived from coronary CTA alone and functional SS based on coronary CTA and FFRCT were higher when assessed by the CL than by the sites themselves. However, substantial agreement in treatment recommendation by SS II between sites and CL was demonstrated. Clinical Trials.gov Identifier NCT02385279.

Background The value of antitachycardia pacing (ATP) in the overall cohort of primary prevention patients who receive implantable cardioverter-defibrillators (ICDs) remains uncertain. ATP success reported in prior trials potentially included a large number of patients receiving unnecessary ATP for arrhythmias that may have self-terminated owing to the prematurity of the intervention. Although some patients derive benefit from initial ATP in terminating rapid ventricular arrhythmias and thereby preventing shocks, there are limited data allowing us to identify those patients a priori. Objective The purpose of APPRAISE ATP is to understand the role of ATP in primary prevention patients currently indicated for ICD therapy in a large prospective randomized controlled trial with modern programming parameters. Methods The study is a global, prospective, randomized, multicenter clinical trial conducted at up to 150 sites globally, enrolling approximately 2600 subjects The primary endpoint of the trial is time to first all-cause shock in a 2-arm study with an equivalent study design in which the incidence of all-cause shocks will be compared between primary prevention subjects programmed with shocks only vs subjects programmed to standard therapy (ATP and shock). Results An Electrogram and Device Interrogation Core Laboratory will review interrogation data to determine primary endpoints that occur in APPRAISE ATP. Their decisions are based on independent physician review of the data from device interrogation. Conclusion The ultimate purpose of the study is to aid clinicians in the selection of ICD technologies based on hard endpoint evidence across the spectrum of indications for primary prevention implantation.

Background Coronary computed tomographic angiography (CCTA) provides a non-invasive assessment of the coronary artery tree. Computed Tomography - adapted Leaman Score (CT-LeSc) has been shown to be an independent predictor of cardiac events in coronary artery disease (CAD) patients with a score greater than 5 (high). Purpose To investigate the relationship between CT-LeSc and the progression of CAD and to provide vessel- and segment-level CAD qualification and quantification at baseline and 7-year follow-up. Methods Patients with multivessel CAD and CCTA assessments at baseline and follow-up were included. The CT-LeSc analysis was performed in a paired fashion. The patient-level scores and the differences between each phase were assessed by 2 analysts in an independent core laboratory. Results This study analyzed 248 coronary segments from 17 patients with a mean follow-up interval of 7.5 ± 0.6 years. The mean CT-LeSc at baseline and follow-up were 14.6 ± 4.2 and 16.9 ± 1.5, respectively, with an absolute increase of 2.3 ± 1.8. The mean cumulative increase of new lesions was 0.2 ± 0.2 per year. Over time, 14.6% of the non-obstructive lesions became obstructive, and 15.0% of the non-calcified plaques became calcified. There were 29 new lesions found at follow-up, and out of these, 16 were obstructive and 19 were non-calcified. Conclusion In patients at high risk for cardiac events, as determined by CT-LeSc, there was an increase in CT-LeSc, obstructive lesions, and calcified plaques over the 7-year follow-up period. Most of the new lesions were obstructive and non-calcified. This is the first report showing long-term serial imaging CCTA changes in a high-risk population.

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

Objective Fenestrated endovascular aneurysm repair (FEVAR) is a well established treatment for complex abdominal aortic aneurysms (AAAs). FEVAR with custom made devices (CMDs) has limitations in both the emergency and elective settings due to time consuming manufacture. “Off the shelf” (OTS) fenestrated stent grafts are a potential solution. The primary goal was to evaluate the five year outcome of the COOK Zenith p-Branch OTS device at a single centre. Methods Patients with juxtarenal AAA meeting the inclusion criteria for the COOK Zenith p-Branch device were enrolled in a prospective, non-randomised, non-comparative trial from July 2012 to September 2015. Demographic, anatomical, procedure related, and five year follow up data were collected, analysed, and adjudicated by a core laboratory. The primary aims were to assess intervention free survival and overall survival at five years. Results Twenty-three patients were treated and 21 completed follow up. Mean time to p-Branch implantation after patient presentation was 28 hours (range 0–122 hours) in emergency cases and 67 days (range 20–112 days) in elective cases. Median procedure time was 283 minutes (range 161–475 minutes) and technical success was 91%. Mean follow up was 45 months (standard deviation ± 24.4 months). The most common adverse events were renal injuries. Primary target vessel patency was 96.4% and 94.0% after one and five years respectively. Mean time to first re-intervention was 469 days (range 0–1 567 days). Survival during the follow up period was 76%, with no aneurysm related deaths. Conclusion FEVAR with the COOK Zenith p-Branch device is safe and effective for juxtarenal AAA in a selected patient population, in both elective and emergency settings. Long term outcomes are acceptable although inferior to CMDs. Mid and long term outcomes emphasise the p-Branch as a possible endovascular treatment for juxtarenal aortic pathology where CMD is not an option. Further innovation to address target vessel complications is needed, as these seem more prevalent than after repair with CMDs.

Aims Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS). Methods and results Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age ( Conclusion Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.

INTRODUCTION The pneumatic tube system (PTS) is widely used for sample delivery. We aimed to investigate the impacts of PTS on hemostasis assays. METHODS Triplicate samples from 30 healthy volunteers were delivered to the core laboratory manually by human courier or via the 500 m long-distance PTS or via the 1000 m long-distance PTS. Comparisons of 19 hemostasis tests were conducted. RESULTS Although PT, INR, APTT, FII, FV, FVII FIX, FX, FXII, DD, α2-PI, and PC had statistical significance (all P

Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to describe echocardiographic normal values in adults and to compare races and nationalities using a uniform acquisition and measurement protocol. This report focuses on left ventricular (LV) diastolic function. Methods: WASE is an international, cross-sectional study. Participants were enrolled with equal distribution according to age and gender. Echocardiograms were analyzed in a core laboratory based on the latest American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Left ventricular diastolic function was assessed by E, E/A, e' velocities, E/e', left atrial volume index (LAVI), and tricuspid regurgitation velocity. Determination of LV diastolic function was made using the algorithm proposed by the guidelines. Results: A total of 2,008 subjects from 15 countries were enrolled. The majority were of white or Asian race (42.8%, 41.8%, respectively). E and E/e' were higher in female patients, while LAVI was similar in both genders. Consistent increase in E/e' and decrease in E/A, E, and e' were found as age increased. The upper limit of normal for LAVI was higher in WASE compared with the guidelines. The lower limits of normal for e' were smaller in elder groups than those in the guidelines, while the upper limits of normal for E/e' were below the guideline values. These findings suggest that the cutoff value for LAVI should be shifted upward and age-specific cutoff values for e' should be considered. In WASE

Background The presence of tricuspid regurgitation (TR) may affect prognosis in patients with mitral regurgitation (MR). Objectives This study sought to determine the impact of TR on outcomes in patients with heart failure and severe secondary MR randomized to guideline-directed medical therapy (GDMT) or edge-to-edge repair with the MitraClip in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. Methods A total of 614 patients with symptomatic heart failure with moderate to severe (3+) or severe (4+) secondary MR were randomized to maximally tolerated GDMT plus MitraClip or GDMT alone; 599 had core laboratory evaluable echocardiograms. Patients were divided into 2 groups by baseline TR severity: none/trace/mild TR (≤Mild TR) (n = 501 [83.6%]) and moderate/severe TR (≥Mod TR) (n = 98 [16.4%]). Two-year composite endpoints of death or heart failure hospitalization (HFH) and the individual endpoints were analyzed. Results Patients with ≥Mod TR were more likely to be New York Heart Association functional class III/IV (p Conclusions Patients with severe secondary MR who also had ≥Mod TR had worse clinical and echocardiographic characteristics and worse clinical outcomes compared to those with ≤Mild TR. Within the COAPT trial, MitraClip improved outcomes in patients with and without ≥Mod TR severity compared with GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079 )

Objectives Accurate hematologic test interpretation based on normative reference standards is critical to ensure appropriate clinical decision making. However, healthy pediatric reference data for most hematology parameters are lacking. To address this gap, this study establishes age- and sex-specific hematologic reference standards in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents. Methods Fresh whole blood samples collected from a total of 566 healthy children and adolescents (birth to Results Reference value distributions for most hematology parameters demonstrated dynamic changes across the pediatric age range with significant age-specific differences observed for 39 of the 47 parameters examined. Sex-specific differences were also observed for eight hematologic parameters, primarily during and after puberty. Conclusions This study establishes a robust database of pediatric reference standards for 47 hematologic parameters in the CALIPER cohort for the first time. These comprehensive reference value data sets report potentially important and physiologically relevant trends in hematologic markers, clearly demonstrating the need for pediatric reference standards for hematologic test interpretation.

Objectives: The aim of this study was to assess acute regurgitation following transcatheter aortic valve replacement, comparing different implanted transcatheter heart valves. Background: Regurgitation following transcatheter aortic valve replacement influences all-cause mortality. Thus far, no quantitative comparison of regurgitation among multiple commercially available transcatheter heart valves has been performed. Methods: Aortograms from a multicenter cohort of consecutive 3,976 transcatheter aortic valve replacements were evaluated in this pooled analysis. A total of 2,258 (58.3%) were considered analyzable by an independent academic core laboratory using video densitometry. Results of quantitative regurgitation are shown as percentages. The valves evaluated were the ACURATE (n = 115), Centera (n = 11), CoreValve (n = 532), Direct Flow Medical (n = 21), Evolut PRO (n = 95), Evolut R (n = 295), Inovare (n = 4), Lotus (n = 546), Lotus Edge (n = 3), SAPIEN XT (n = 239), and SAPIEN 3 (n = 397). For the main analysis, only valves with more than 50 procedures (7 types) were used. Results: The Lotus valve had the lowest mean regurgitation (3.5 ± 4.4%), followed by Evolut PRO (7.4 ± 6.5%), SAPIEN 3 (7.6 ± 7.1%), Evolut R (7.9 ± 7.4%), SAPIEN XT (8.8 ± 7.5%), ACURATE (9.6 ± 9.2%) and CoreValve (13.7 ± 10.7%) (analysis of variance p < 0.001). The only valves that statistically differed from all their counterparts were Lotus (as the lowest regurgitation) and CoreValve (the highest). The proportion of patients presenting with moderate or severe regurgitation followed the same ranking order: Lotus (2.2%), Evolut PRO (5.3%), SAPIEN 3 (8.3%), Evolut R (8.8%), SAPIEN XT (10.9%), ACURATE (11.3%), and CoreValve (30.1%) (chi-square p < 0.001). Conclusions: In this pooled analysis stemming from daily clinical practice, the Lotus valve was shown to have the best immediate sealing. This analysis reflects the objective evaluation of regurgitation by an academic core laboratory (nonsponsored) in a real-world cohort of patients using a quantitative technique.

Adisa Kuršumović,1 Gerrit Joan Bouma,2 Larry E Miller,3 Richard Assaker,4 Erik Van de Kelft,5 Robert Hes,6 Jenny C Kienzler7 1Department of Neurosurgery, Donauisar Klinikum Deggendorf, Deggendorf, Germany; 2Department of Neurosurgery, OLVG-West and Academic Medical Center, Amsterdam, the Netherlands; 3Miller Scientific, Johnson City, TN, USA; 4Department of Neurosurgery, Centre Hospitalier Régional Universitaire de Lille, Lille, France; 5Department of Neurosurgery, AZ Nikolaas, Sint-Niklaas and University of Antwerp, Antwerpen, Belgium; 6Department of Neurosurgery, AZ Klina, Brasschaat, Belgium; 7Department of Neurosurgery, Kantonsspital Aarau, Aarau, SwitzerlandCorrespondence: Adisa KuršumovićDepartment of Neurosurgery, Donauisar Klinikum Deggendorf, Deggendorf, GermanyEmail kursumovic@hotmail.comObjective: Vertebral endplate disruptions (VEPD) are common findings on imaging after lumbar surgery. The objective of this study was to explore the clinical implications of VEPD development following lumbar discectomy with or without implant with a bone-anchored annular closure device (ACD).Methods: This was a multicenter randomized controlled trial of patients with large postsurgical annular defects after limited lumbar discectomy who were randomized to additionally receive an ACD or no additional treatment. VEPD were identified on computed tomography and confirmed by an imaging core laboratory. Clinical outcomes included recurrent herniation, reoperation, Oswestry Disability Index, leg pain, and back pain. Patient follow-up in this study was 3 years.Results: In the ACD group (n=272), the risk of reoperation was lower in patients with vs without VEPD (8% vs 24%, p< 0.01), but no other clinical outcomes differed when stratified by VEPD prevalence or size. In the Control group (n=278), the risk of symptomatic reherniation was higher in patients with VEPD (41% vs 23%, p< 0.01) and patients with the largest VEPD had the highest reoperation rates. Patient-reported outcomes were not associated with VEPD prevalence or size in the Control group.Conclusion: VEPD had no significant influence on patient-reported outcomes at 3 years after lumbar discectomy. VEPD increased the risk of recurrence in patients treated with lumbar discectomy only, but had no negative influence in patients treated with the ACD.Keywords: annular closure, disc herniation, lumbar discectomy, randomized controlled trial, sciatica, vertebral endplate &nbsp

Optical coherence tomography (OCT) provides excellent image resolution, however OCT optimal acquisition is essential but could be challenging owing to several factors. We sought to assess the quality of OCT pullbacks and identify the causes of suboptimal image acquisition. We evaluated 784 (404 pre-PCI; 380 post-PCI) coronary pullbacks from an anonymized OCT database from our Cardiovascular Imaging Core Laboratory. Imaging of the region-of-interest (ROI—lesion or stented segment plus references) was incomplete in 16.1% pullbacks, caused by pullback starting too proximal (63.7%), inappropriate pullback length (17.1%) and pullback starting too distal (11.4%). The quality of image acquisition was excellent in 36.3% pullbacks; whereas 4% pullbacks were unanalyzable. Pullback quality was most commonly affected by poor blood displacement from inadequate contrast volume (27.4%) or flow (25.6%), followed by artifacts (24.1%). Acquisition mode was ‘High-Resolution’ (54 mm) in 74.4% and ‘Survey’ (75 mm) in 25.6% of cases. The 54 mm mode was associated with incomplete ROI imaging (p = 0.020) and inadequate contrast volume (p = 0.035). We observed a substantial frequency of suboptimal image acquisition and identified its causes, most of which can be addressed with minor modifications during the procedure, ultimately improving patient outcomes.

B cells are important in immunity to both SARS-CoV-2 infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyse serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients, and find the global BCR repertoire differs between them. Following infection, IgG1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination the proportion of IgD/M BCRs increase, SHM is unchanged and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post-infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, whilst a more focused response after vaccination mainly targets the spike’s receptor-binding domain. Thus the nature of SARS-CoV-2 exposure differentially impacts BCR repertoire development, potentially informing vaccine strategies., Graphical Abstract, Kotagiri et al. find that SARS-CoV-2 infection versus vaccination induces distinct changes in the B cell receptor repertoire, including prominent clonal expansion in IgA and IgM after infection, but IgG after vaccination. A broad anti-spike response to infection contrasts with a narrower RBD-focused one after vaccination, potentially informing vaccination strategies.

The non-invasive self-monitoring of blood glucose (SMBG) has been the subject of intense investigation over recent decades. We conducted a pilot study designed to examine a novel non-invasive glucometer, the HGR GWave, utilizing radiofrequency (RF) sensing. Blood glucose levels assessed by this HGR prototype were compared to measurements performed by a hexokinase core laboratory assay during an oral glucose tolerance test (oGTT) for 5 subjects with type 2 diabetes. The HGR glucose meter readings were also compared to two Abbot Freestyle® glucose meters, which were also used for calibration. The accuracy of the results was evaluated through the calculation of relative absolute difference (RAD), specified percentage differences between 43 reference glucose measurements, and using comparator measurements. The median RAD was −4.787. We detected 79.04%, 92.99% and 97.64% of HGR readings within ±10%, ±15% and ±20% of the reference glucose measurements. The HGR readings had a high correlation with reference lab glucose measurements with R2 = 0.924 (95% CI 0.929–0.979, p &lt, 0.0001). When compared to the Freestyle® glucose meters 94.3% and 100% of the readings were within ±5% and ±10%, with R2 = 0.975 (0.975–0.994, 0.0001). The HGR prototype glucose meter was found to be accurate in detecting real-time blood glucose during an oGTT in this small pilot study. A study with a broader range of blood glucose levels is needed to further assess its accuracy and its suitability for clinical use.

Two recently published JNIS commentaries1 2 on eligibility criteria for the clinical trials on patients with large core, acute ischemic stroke (AIS) with large vessel occlusion have caused some debate. Five trials were included.1 Our ongoing trial, ANGEL-ASPECT (NCT 04551664), which represents the only large core trial currently ongoing in the Chinese population, was not included in the discussion. One issue of the debate is the addition of CT perfusion (CTP)/diffusion-weighted image of magnetic resonance imaging (DWI-MRI) to the inclusion criteria, which only the SELECT-2 trial chose to adopt. This raised concern about whether patients already known to benefit from endovascular thrombectomy (EVT) are being randomized to EVT treatment or no treatment. Like the SELECT-2 trial, our ANGEL-ASPECT trial also added CTP/DWI-MRI to our inclusion criteria, but in a manner different from SELECT-2. Here we review the merits of ANGEL-ASPECT’s design and suggest that it be included in the discussion of patient selection criteria in large core trials. The ANGEL-ASPECT trial is an ongoing, multicenter, randomized controlled trial (RCT) currently being conducted in China and sponsored by Beijing Tiantan Hospital. Patients are enrolled according to a prespecified protocol. Each randomized patient is qualified by two core laboratory members who are available at all hours to calculate Alberta Stroke Program Early CT Score (ASPECTS) and infarct core volume using the specialized RAPID software. As for the other five trials discussed in the commentary by Jadhav et al ,1 the primary goal of our trial is to determine whether EVT will benefit or harm patients with AIS and large vessel occlusion and a ‘large core’ infarct. While the ANGEL-ASPECT and SELECT-2 trials both include core volume as defined by CTP in the inclusion criteria in addition to ASPECTS, the other four trials define large core using only ASPECTS. The …

Background: The potential advantages for conscious sedation (CS) as compared to general anesthesia (GA) have not been evaluated in studies with core laboratory echocardiographic assessments and monitored end points. We compared CS versus GA for SAPIEN 3 transcatheter aortic valve replacement in patients at intermediate- and low-surgical risk. Methods: This analysis included patients in the PARTNER 2 (Placement of Aortic Transcatheter Valve Trial) intermediate-risk registry and the PARTNER 3 randomized low-risk study. CS was compared to GA with respect to death, stroke, bleeding, paravalvular regurgitation, length of stay, and costs. Outcomes were assessed by a core echocardiographic laboratory, and clinical events were independently adjudicated. Results: Baseline characteristics were similar between the CS and GA groups. Postprocedure hospital length of stay was significantly shorter for CS versus GA both in intermediate-risk patients (4.4±0.2 and 5.2±0.2 days, respectively, P P Conclusions: The selective use of CS is associated with shorter procedure times, shorter intensive care unit and hospital length of stay, lower costs, and no difference in clinical outcomes to 1 year, including ≥moderate paravalvular regurgitation. Our data demonstrate similar safety profiles with both approaches and support the continued use of CS for most patients undergoing the procedure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03222128 and NCT02675114.

Background Biological specimens from patients who have received radiopharmaceuticals are often collected for diagnostic testing and sent to clinical laboratories. Residual radiation has long been assumed to be minimal. However, literature is sparse and may not represent the specimen volumes or spectrum of radionuclides currently seen at National Cancer Institute (NCI)–designated cancer centers. This study examined the radiopharmaceuticals associated with patient specimens received in the hospital core laboratory and assessed the potential risk of external radiation exposure to laboratory personnel. Methods The types and amounts of radiopharmaceuticals administered in a large metropolitan hospital system were retrospectively examined over a 20-month study period. The associated biological specimens sent to the largest core laboratory in the system for testing were evaluated. In addition, manual survey meter assessment of random clinical specimens and weekly wipe tests were performed for 44 weeks, and wearable and environmental dosimeters were placed for 6 months. Results Over 11 000 specimens, collected within 5 physical half-lives of radiopharmaceutical administration, were processed by our laboratory. Manual survey meter assessment of random clinical specimens routinely identified radioactive specimens. If held in a closed palm for >2 min, many samples could potentially deliver a 0.02 mSv effective dose of radiation. Conclusions The laboratory regularly receives radioactive patient specimens without radioactive labels. Although the vast majority of these are blood specimens associated with low-dose diagnostic radiopharmaceuticals, some samples may be capable of delivering a significant amount of radiation. Recommendations for laboratories associated with NCI cancer centers are given.

Purpose of Review APS ACTION is an international research network created to design and conduct large-scale, multicenter research in persistently antiphospholipid antibody (aPL)–positive patients. Given the expanding research activities of the network in the last decade since its creation, the purpose of this article is to review the scientific contributions of APS ACTION as well as future directions. Recent Findings APS ACTION has achieved increased international collaboration with internal and external investigators for outcome, interventional, and mechanistic antiphospholipid syndrome (APS) studies. This has been linked to substantial progress in Core laboratory work, which has demonstrated that laboratories can achieve good agreement in performance of aPL assays by use of the same reagents, analyzer type, and protocols. Summary APS ACTION will continue to identify gaps in the existing aPL/APS literature, design mechanistic studies to elucidate underlying mechanisms, and conduct prospective, large-scale clinical studies, all for the ultimate goal of early diagnosis and improved management of aPL-positive patients.

Stress echocardiography (SE) assesses for flow-limiting coronary artery disease (CAD) and requires expertise to interpret. Clinical trials use core laboratories to ensure that interpretations are accurate and reproducible. We determined agreement between site and core laboratory SE interpretations

International audience; Objectives: The purpose of this study is to report the 1-year results of the CENTERA-EU trial.Background: The CENTERA transcatheter heart valve (THV) (Edwards Lifesciences, Irvine, California) is a low-profile (14-F eSheath compatible), self-expanding nitinol valve, with a motorized delivery system allowing for repositionability. The 30-day results of the CENTERA-EU trial demonstrated the short-term safety and effectiveness of the valve.Methods: Implantations were completed in 23 centers in Europe, Australia, and New Zealand. Transfemoral access was used in all patients. Echocardiographic outcomes were adjudicated by a core laboratory at baseline, discharge, 30 days, 6 months, and 1 year. Major adverse clinical events were adjudicated by an independent clinical events committee.Results: Between March 2015 and July 2016, 203 high-risk patients (age 82.7 ± 5.5 years, 67.5% women, 68.0% New York Heart Association functional class III or IV, Society of Thoracic Surgeons score 6.1 ± 4.2%) with severe, symptomatic aortic stenosis underwent transcatheter aortic valve replacement with the CENTERA THV. The primary endpoint of the study was 30-day mortality (1.0%). At 1 year, overall mortality was 9.1%, cardiovascular mortality was 4.6%, disabling stroke was 4.1%, new permanent pacemakers were implanted in 6.5% of patients at risk, and cardiac-related rehospitalization was 6.8%. Hemodynamic parameters were stable at 1 year, with a mean aortic valve gradient of 8.1 ± 4.7 mm Hg, a mean effective orifice area of 1.7 ± 0.42 cm2, and no incidences of severe or moderate aortic regurgitation.Conclusions: The CENTERA-EU trial demonstrated mid-term safety and effectiveness of the CENTERA THV, with low mortality, sustained improvements in hemodynamic performances, and low incidence of permanent pacemaker implantations in high-risk patients with symptomatic aortic stenosis. (Safety and Performance of the Edwards CENTERA-EU Self-Expanding Transcatheter Heart Valve [CENTERA-2]; NCT02458560).

Objectives The authors investigated 1-year outcomes after transcaval access and closure for transcatheter aortic valve replacement (TAVR), using commercially available nitinol cardiac occluders off-label. Background Transcaval access is a fully percutaneous nonfemoral artery route for TAVR. The intermediate-term fate of transcaval access tracts is not known. Methods The authors performed a prospective, multicenter, independently adjudicated trial of transcaval access, using Amplatzer nitinol cardiac occluders (Abbott Vascular, Minneapolis, Minnesota), among subjects without traditional transthoracic (transapical or transaortic) access options. One-year clinical follow-up included core laboratory analysis of serial abdominal computed tomography (CT). Results 100 subjects were enrolled. Twelve-month mortality was 29%. After discharge, there were no vascular complications of transcaval access. Among 83 evaluable CT scans after 12 months, 77 of fistulas (93%) were proven occluded, and only 1 was proven patent. Fistula patency was not associated with overall survival (p = 0.37), nor with heart failure admissions (15% if patent vs. 23% if occluded; p = 0.30). There were no cases of occluder fracture or migration or visceral injury. Conclusions Results are reassuring 1 year after transcaval TAVR and closure using permeable nitinol occluders off-label. There were no late major vascular complications. CT demonstrated spontaneous closure of almost all fistulas. Results may be different in a lower-risk cohort, with increased operator experience, and using a dedicated transcaval closure device. (Transcaval Access for Transcatheter Aortic Valve Replacement in People With No Good Options for Aortic Access; NCT02280824)

Background and Purpose— The safety and efficacy of mechanical thrombectomy in patients with acute ischemic stroke has been demonstrated. However, the impact of stent retriever size on clinical and angiographic outcomes is not well established. Methods— This was a retrospective ad hoc analysis of data from the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry—a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever. An independent core laboratory, blinded to clinical outcomes, reviewed all procedures and angiographic data to classify stent retriever size, targeted clot location, recanalization after each pass, and the number of stent retriever passes. The primary angiographic end point was first-pass effect (FPE) as determined by a core laboratory and defined as achieving near-complete revascularization (modified Thrombolysis in Cerebral Infarction ≥2c) after the first pass without the use of rescue therapy. Rates of modified FPE were also assessed, defined as meeting all criteria for FPE but achieving modified Thrombolysis in Cerebral Infarction ≥2b after first pass. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site. Outcome comparisons were made across the stent retriever size groups and adjusted for baseline characteristics. Results— Of 715 patients, a 4×20 stent retriever was used in 201 (28%) patients, 4×40 was used in 270 (38%) patients, and 6×30 was used in 244 (34%) patients. The 4×40 group had the highest rate of FPE ( P =0.003 versus 6×30) and modified FPE ( P =0.038 versus 4×20; P =0.0001 versus 6×30). Final revascularization was not significantly different across the groups, and there were no significant differences in functional dependence or mortality at 90 days post-procedure. Use of the longer stent retriever (4×40) was an independent predictor of achieving modified FPE ( P =0.037 versus 6×30; P =0.037 versus 4×20). Conclusions— The longer stent retriever (4×40) demonstrated the highest rate FPE and modified FPE compared with larger diameter or shorter stent retrievers, suggesting that their routine use may improve early revascularization success. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Recently, instantaneous wave-free ratio (iFR) or diastolic pressure-ratio (dPR) have been used in practice. For these indices, the reliability of electrocardiography (ECG)-independent algorithm for pressure-only data is essential. The current study sought to compare the current to a new ECG-independent algorithm for calculating resting physiologic indices. The main purpose of developing a new ECG-independent algorithm was to raise the detection rates over the entire heart cycle despite irregular heartbeats. Both iFR and dPR were calculated from resting pressure tracings using current and new algorithms by a core laboratory in 975 vessels (393 patients). The diagnostic performance of resting physiologic indices with a new algorithm to predict fractional flow reserve (FFR) was compared with the current algorithm. Both algorithms provided nearly identical values of iFR or dPR without systemic bias. iFR and dPR, which were calculated using current and new ECG-independent algorithms, provided comparable discrimination ability and diagnostic performance to predict functionally significant stenosis defined by FFR≤0.80. However, detection rates of the new algorithm were significantly higher than current algorithm in the patients with irregular heartbeats (for per patient [59.5% vs. 83.8%] and per unit-heartbeats analysis [84.3% vs. 90.3%]), such as arterial fibrillation or multiple premature ventricular contractions.

Background: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCT in Japan are scarce, so we assessed the clinical impact of using FFRCT in a Japanese population. Methods and Results: The ADVANCE registry is an international prospective FFRCT registry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCT occurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT ≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT >0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCT were medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCT within 90 days. Conclusions: In this Japanese population, FFRCT modified the treatment strategy in more than half of the patients. FFRCT showed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

OBJECTIVES: We evaluated the diagnostic performance of quantitative flow ratio (QFR) assessment of nonculprit lesions (NCLs) based on acute setting angiograms obtained in patients with ST-segment elevation myocardial infarction (STEMI) with QFR, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) in the staged setting as reference.BACKGROUND: QFR is an angiography-based approach for the functional evaluation of coronary artery lesions.METHODS: This was a post-hoc analysis of the iSTEMI study. NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 13 days) follow-up. Acute and staged QFR values were computed in a core laboratory based on the coronary angiography recordings. Diagnostic cut-off values were ≤0.80 for QFR and FFR, and ≤0.89 for iFR.RESULTS: Staged iFR and FFR data were available for 146 NCLs in 112 patients in the iSTEMI study. Among these, QFR analysis was feasible in 103 (71%) lesions assessed in the acute setting with a mean QFR value of 0.82 (IQR: 0.73-0.91). Staged QFR, FFR, and iFR were 0.80 (IQR: 0.70-0.90), 0.81 (IQR: 0.71-0.88), and 0.91 (IQR: 0.87-0.96), respectively. Classification agreement of acute and staged QFR was 93% (95%Cl: 87-99). The classification agreement of acute QFR was 84% (95%CI: 76-90) using staged FFR as reference and 74% (95%CI: 65-83) using staged iFR as reference.CONCLUSIONS: Acute QFR showed a very good diagnostic performance with staged QFR as reference, a good diagnostic performance with staged FFR as reference, and a moderate diagnostic performance with staged iFR as reference.

This study was performed to determine if baseline aortic regurgitation (AR) affects the deleterious effects of postprocedure paravalvular leak following transcatheter aortic valve implantation (TAVI). We evaluated the effect of baseline AR on mortality in a large cohort of patients randomized to transcatheter or surgical aortic valve replacement (SAVR). The analysis cohort comprised 739 patients who underwent attempted TAVI (n = 386) or SAVR (n = 353) in the CoreValve US Pivotal High Risk Trial and had baseline AR measurements. Patients were stratified by the severity of baseline AR into those with none and/or trace and those with ≥mild AR. Echocardiographic measurements were assessed by an independent core laboratory. Of the 386 TAVI patients, 204 (52.9%) had none and/or trace at baseline AR; 182 (47.2%) had ≥mild AR. Of the 353 SAVR patients, 169 (47.9%) had none and/or trace and 184 (52.1%) ≥mild AR. The presence of ≥mild baseline AR was associated with lower all-cause mortality at 1 year following TAVI (9.4% vs 18.6%, p = 0.008) or SAVR (13.3% vs 24.4%, p = 0.009). Mortality remained lower in the ≥mild baseline AR patients at 3 years after SAVR (p = 0.011), but not TAVI. In conclusion, baseline AR appears to provide a protective effect on survival and quality of life in both TAVI and SAVR patients at 1 year; this effect persists out to 3 years in SAVR patients.

Background: Coronary angiography-derived fractional flow reserve (caFFR) measurements have shown good correlations and agreement with invasive wire-based fractional flow reserve (FFR) measurements. However, few studies have examined the diagnostic performance of caFFR measurements before and after percutaneous coronary intervention (PCI). This study sought to compare the diagnostic performance of caFFR measurements against wire-based FFR measurements in patients before and after PCI.Methods: Patients who underwent FFR-guided PCI were eligible for the acquisition of caFFR measurements. Offline caFFR measurements were performed by blinded hospital operators in a core laboratory. The primary endpoint was the vessel-oriented composite endpoint (VOCE), defined as a composite of vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization.Results: A total of 105 pre-PCI caFFR measurements and 65 post-PCI caFFR measurements were compared against available wire-based FFR measurements. A strong linear correlation was found between wire-based FFR and caFFR measurements (r = 0.77; p < 0.001) before PCI, and caFFR measurements also showed a high correlation (r = 0.82; p < 0.001) with wire-based FFR measurements after PCI. A total of 6 VOCEs were observed in 61 patients during follow-up. Post-PCI FFR values (≤0.82) in the target vessel was the strongest predictor of VOCE [hazard ratio (HR): 5.59; 95% confidence interval (CI): 1.12–27.96; p = 0.036). Similarly, patients with low post-PCI caFFR values (≤0.83) showed an 8-fold higher risk of VOCE than those with high post-PCI caFFR values (>0.83; HR: 8.83; 95% CI: 1.46–53.44; p = 0.017).Conclusion: The study showed that the caFFR measurements were well-correlated and in agreement with invasive wire-based FFR measurements before and after PCI. Similar to wire-based FFR measurements, post-PCI caFFR measurements can be used to identify patients with a higher risk for adverse events associated with PCI.

Objective Patients in the Valiant Evo U.S. and international clinical trials had positive short-term outcomes; however, late structural failures, including type IIIb endoleaks have been recently discovered. Type IIIb endoleaks are serious adverse events because the repressurization of the aneurysm sac increases the risk of rupture. The purpose of the present study was to detail the imaging patterns associated with the structural failures with the aim of increasing awareness of failing graft presentation, early recognition, and prompt treatment. Methods The Valiant Evo clinical trial was a prospective, single-arm investigation of a thoracic stent graft system. With the recent late structural failures, sites were requested to submit all available imaging studies to date to allow the core laboratory to assess for structural failures such as type IIIb endoleaks, stent ring fractures, and stent ring enlargement. Of the 100 patients originally enrolled in the trial from 2016 to 2018, the core laboratory assessed the imaging studies performed at ≥1 year for 83 patients. Results No structural failures of the graft were reported through 1 year of follow-up. At 1 to 4 years, graft structural failures were detected in 11 patients with descending thoracic aortic aneurysms. Of the 11 patients, 5 had a type IIIb endoleak. Four of the five had imaging findings showing stent fractures consistent with the location of the graft seam and one had a type IIIb endoleak attributed to calcium erosion with no stent fracture or ring enlargement. Of the four patients with stent fracture in line with the graft seam, three underwent a relining procedure that successfully excluded the type IIIb endoleak. One of these three patients died 4 days later of suspected thoracic aortic rupture because the distal thoracic endovascular aortic repair extension had been landed in a previously dissected and fragile section of the aorta. The remaining six patients had had stent ring enlargement. One of the six patients had had persistent aneurysm expansion from the time of implantation onward and had died of unknown causes. The remaining five patients have continued to be monitored. Conclusions In the present preliminary analysis, the imaging patterns associated with type IIIb endoleaks, stent fractures, and stent ring enlargement appear to be related to the loss of seam integrity or detachment of the stent rings from the surface of the graft material. The imaging patterns we have detailed should be closely monitored using computed tomography angiography surveillance to allow structural failures to be promptly identified and treated.

BackgroundThe degree of reperfusion is the most important modifiable predictor of 3 month functional outcome and mortality in ischemic stroke patients treated with mechanical thrombectomy. Whether the beneficial effect of reperfusion also leads to a reduction in long term mortality is unknown.MethodsPatients undergoing mechanical thrombectomy between January 2010 and December 2018 were included. The post-thrombectomy degree of reperfusion and emboli in new territories were core laboratory adjudicated. Reperfusion was evaluated according to the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Vital status was obtained from the Swiss population register. Adjusted hazard ratios (aHRs) using time split Cox regression models were calculated. Subgroup analyses were performed in patients with borderline indications.ResultsOur study included 1264 patients (median follow-up per patient 2.5 years). Patients with successful reperfusion had longer survival times, attributable to a lower hazard of death within 0–90 days and for >90 days to 2 years (aHR 0.34, 95% CI 0.26 to 0.46; aHR 0.37, 95% CI 0.22 to 0.62). This association was homogeneous across all predefined subgroups (p for interaction >0.05). Among patients with successful reperfusion, a significant difference in the hazard of death was observed between eTICI2b50 and eTICI3 (aHR 0.51, 95% CI 0.33 to 0.79). Emboli in new territories were present in 5% of patients, and were associated with increased mortality (aHR 2.3, 95% CI 1.11 to 4.86).ConclusionSuccessful, and ideally complete, reperfusion without emboli in new territories is associated with a reduction in long term mortality in patients treated with mechanical thrombectomy, and this was evident across several subgroups.

Proximal aortic neck dilatation (PND) affects a considerable proportion of patients undergoing endovascular aneurysm repair (EVAR) and is associated with increased rates of type I endoleak (EL1), migration, and reinterventions. Although there are numerous studies investigating PND following the placement of endografts that utilize self-expanding stent (SES) technology, there are few reports for patients treated with endografts that utilize polymer-filled rings. The purpose of this study is to examine PND and graft migration after EVAR with the Ovation stent graft.The study comprised patients who underwent EVAR as part of the prospective, international, multicenter Ovation stent graft trial. A clinical events committee adjudicated adverse events through 1 year, an independent imaging core laboratory analyzed imaging through 5 years, and a data safety and monitoring board provided study oversight. Neck diameter was measured at the level of the lowest renal artery. PND was defined as neck enlargement of 3 mm or more. Graft migration was defined as distal movement10 mm or movement ≤10 mm when resulting in secondary intervention.A total of 238 patients received this device during the study period. Patients were predominantly male (81%), with a mean age of 73 ± 8 years. Median follow-up was 58 months (IQR 36-60). Almost half the patients (110 patients, 46%) had challenging anatomy; defined as outside the instructions for use (IFU) with other commercially available stent grafts. 41 patients (17.2%) had a proximal neck length10 mm and 93 (39%) had a minimum access vessel diameter6 mm. The technical success rate was 100%. The 1-, 3- and 5-year overall survival rates were 96.6%, 86.2% and 74.9%, respectively. The immediate postoperative proximal neck diameter ranged from 16 mm to 31 mm with a mean of 22.4 ± 3 mm. During follow-up, ten patients (4.2%) developed PND. Freedom from PND estimates at 1, 3 and 5 years were 97.7%, 96%, and 93.6%, respectively. None of the patients developed endograft migration.The use of the Ovation stent graft was associated with low rates of PND despite challenging neck anatomy in 17% of patients. No graft migration was observed. The design of this endograft may explain its superiority to SES in preventing neck dilatation and migration even in patients with challenging neck anatomy. This is important, as we continue to see significant late failures of EVAR due to proximal neck degeneration.

Residual or newly acquired leaks are routinely appraised after left atrial appendage closure (LAAC). The Watchman and the Amulet are the two most frequently used devices for LAAC but no randomized study has so far assessed their comparative leak rates after intervention. The "Comparison of Amplatzer Amulet vs Watchman devices in patients undergoing left atrial appendage closure" (Swiss-Apero, clinicaltrial.gov NCT03399851) is an academic-sponsored multicenter, randomized clinical trial comparing Amulet versus Watchman/FLX devices among patients undergoing a clinically indicated LAAC. The study is designed to assess the superiority of Amulet vs. Watchman/FLX in terms of leaks detected by cardiac computed tomography angiography (CCTA) at 45 days (primary endpoint) and 13 months (secondary endpoint) after intervention by an imaging Core Laboratory. The Swiss-Apero study is the first randomized clinical trial comparing Amulet and Watchman/FLX with respect to the prevalence of post-procedural leak as assessed with CCTA.

Aims: Based on the aortic pressure waveform, a specially-designed computational fluid dynamic (CFD) method was proposed to determine coronary angiography-derived diastolic pressure ratio (caDPR) without using invasive pressure wire. The aim of the study is to retrospectively assess diagnostic performance of the caDPR in the catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). Methods and results: Patients with diagnosis of stable or unstable angina pectoris were enrolled in six centers. Wire-derived FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline caDPR was assessed in blinded fashion against wire-derived FFR at an independent core laboratory. A total of 330 patients who met the inclusion/exclusion criteria were enrolled from June 26 to December 18, 2018. Offline computed caDPR and wire-derived FFR were compared in 328 interrogated vessels. The caDPR with a cutoff value of 0.89 shows diagnostic accuracy of 87.7%, sensitivity of 89.5%, specificity of 86.8%, and AUC of 0.940 against the wire-derived FFR with a cutoff value of 0.80. Conclusions: Using wired-based FFR as the standard reference, there is good diagnostic performance of the novel-CFD-design caDPR. Hence, caDPR could enhance the hemodynamic assessment of coronary lesions.

Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective alternative to surgery in this high-risk population.The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety.The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory.At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year.Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757).

Background Bioresorbable scaffolds (BRS) were introduced to overcome the limitations of permanent metallic stent implantation. Optical coherence tomography (OCT) can provide important insights on vessel wall healing at follow-up. We compared OCT-assessed healing at 6 months after implantation of everolimus-eluting BRS and everolimus-eluting metallic stents (EES) in patients treated for acute myocardial infarction (AMI). Methods ISAR-Absorb MI is a multicentre, 2:1 randomized trial comparing outcomes of patients with AMI stented with BRS or conventional EES. Angiographic surveillance was planned for all patients at 6–8 months follow-up; surveillance with OCT at follow-up was discretionary. For the present analysis, patients with OCT follow-up were included and images analyzed at a core laboratory. Tissue characterization using grey-scale signal intensity (GSI) analysis was done for neointimal regions of interest (ROI) with thickness of 100 to 400 µm. ROI’s were classified as mature using a cut-off GSI score of 109.7. Generalized linear mixed model was used as appropriate. Results 70 patients in the BRS arm and 32 patients in the EES arm had OCT available for analysis at a median follow-up of 216 days. Minimum lumen area [5.13 (3.95, 6.70) vs. 4.93 (3.84, 6.99) mm2] and minimum stent area [5.78 (4.88, 7.34) vs. 6.39 (4.77, 7.45) mm2] were comparable between BRS and EES. In total 2,237 frames with 19,827 struts were assessed. Overall strut coverage was better with BRS compared to EES (97.5% vs. 90.9%, p Conclusions In selected patients undergoing OCT imaging at 6–8 months after implantation of BRS and conventional EES for AMI, we observed generally favorable healing characteristics with high rates of strut coverage and fewer areas of immature neointimal areas with BRS in comparison to EES.

Background/Purpose This sub-analysis of the prospective Low Risk TAVR (LRT) trial determined anatomical characteristics associated with hypoattenuated leaflet thickening (HALT), which may contribute to early transcatheter heart valve (THV) degeneration. Methods/Materials The LRT trial enrolled 200 low-risk patients between February 2016 and February 2018. All subjects underwent baseline and 30-day CT studies, analyzed by an independent core laboratory. Additional measurements, namely THV expansion, eccentricity, depth, and commissural alignment, were made by consensus of three independent readers. HALT was observed only in the Sapien 3 THV, so Evolut valves were excluded from this analysis. Results In the LRT trial, 177 subjects received Sapien 3 THVs, of whom 167 (94.3%) had interpretable 30-day CTs and were eligible for this analysis. Twenty-six subjects had HALT (15.6%). Baseline characteristics were similar between groups. There was no difference in THV size implanted and baseline aortic-root geometry between groups. In patients who developed HALT, THV implantation depth was shallower than in patients who did not develop HALT (2.6±1.1 mm HALT versus 3.3±1.8 mm no-HALT, p=0.03). There were more patients in the HALT group with commissural malalignment (40% vs. 28%; p=0.25), but this did not reach statistical significance. In a univariable regression model, no predetermined variable were shown to independently predict the development of HALT. Conclusions This study did not find anatomical or THV implantation characteristics that predicted the development of HALT at 30 days. This study cannot exclude subtle effects or interaction between factors because of the small number of events. Summary This sub-analysis of the prospective Low Risk TAVR trial found that hypoattenuated leaflet thickening (HALT) was associated with shallower transcatheter heart valve implantation. No predictors of HALT were found in a univariable regression analysis.

BACKGROUND Critical culprit lesion locations (CCLL) such as left main (LM) and proximal left anterior descending (LAD) are associated with worse clinical outcome in myocardial infarction without cardiogenic shock (CS). AIMS We aimed to assess whether CCLL identify a subgroup of patients with poorer prognosis when presenting with CS. METHODS In the CULPRIT-SHOCK trial, a core laboratory reviewed all coronary angiograms to identify CCLL. A CCLL was defined as a culprit lesion with a >70% diameter stenosis of the LM, LM equivalent (>70% diameter stenosis of both proximal LAD and proximal circumflex), proximal LAD or last remaining vessel. We evaluated the primary study endpoint of the CULPRIT-SHOCK trial according to CCLL. RESULTS A total of 269 (43%) out of 626 patients eligible for this analysis had a CCLL. Death or renal replacement therapy within 30 days, death within 30 days and death within one year were significantly higher in the CCLL than in the non-CCLL group (58.4% vs 43.4%, p

Tricuspid regurgitation (TR) is a prevalent disease with limited treatment options.This is the first 30-day report of the U.S. single-arm, multicenter, prospective CLASP TR early feasibility study of the PASCAL transcatheter valve repair system in the treatment of TR.Patients with symptomatic TR despite optimal medical therapy, reviewed by the local heart team and central screening committee, were eligible for the study. Data were collected at baseline, discharge, and the 30-day follow-up and were reviewed by an independent clinical events committee and echocardiographic core laboratory. Feasibility endpoints included safety (composite major adverse event [MAE] rate), echocardiographic, clinical, and functional endpoints.Of the 34 patients enrolled in the study, the mean age was 76 years, 53% were women, the mean Society of Thoracic Surgeons score was 7.3%, 88% had atrial fibrillation/flutter, 97% had severe or greater TR, and 79% had New York Heart Association (NYHA) functional class III/IV symptoms. Twenty-nine patients (85%) received implants; at 30 days, 85% of them achieved a TR severity reduction of at least 1 grade, with 52% with moderate or less TR (p 0.001). The MAE rate was 5.9%, and none of the patients experienced cardiovascular mortality, stroke, myocardial infarction, renal complication, or reintervention. Eighty-nine percent of the patients improved to NYHA functional class I/II (p 0.001), the mean 6-min walk distance improved by 71 m (p 0.001), and the mean Kansas City Cardiomyopathy Questionnaire score improved by 15 points (p 0.001).In this early experience, the repair system performed as intended, with substantial TR reduction, favorable safety results with a low MAE rate, no mortality or reintervention, and significant improvements in functional status, exercise capacity, and quality of life. (Edwards CLASP TR EFS [CLASP TR EFS]; NCT03745313).

IntroductionCoronary CT angiography (CCTA) is widely used for non-invasive coronary artery evaluation, but it is limited in identifying the nature of functional characteristics that cause ischaemia. Recent computational fluid dynamic (CFD) techniques applied to CCTA images permit non-invasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischaemia. However, this technology has limitations, such as long computational time and the need for expensive equipment, which hinder widespread use.Methods and analysisThis study is a prospective, multicentre, comparative and confirmatory trial designed to evaluate the diagnostic performance of HeartMedi V.1.0, a novel CT-derived FFR measurement for the detection of haemodynamically significant coronary artery stenoses identified by CCTA, based on invasive FFR as a reference standard. The invasive FFR values ≤0.80 will be considered haemodynamically significant. The study will enrol 184 patients who underwent CCTA, invasive coronary angiography and invasive FFR. Computational FFR (c-FFR) will be analysed by CFD techniques using a lumped parameter model based on vessel length method. Blinded core laboratory interpretation will be performed for CCTA, invasive coronary angiography, invasive FFR and c-FFR. The primary objective of the study is to compare the area under the receiver–operator characteristic curve between c-FFR and CCTA to non-invasively detect the presence of haemodynamically significant coronary stenosis. The secondary endpoints include diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value and correlation of c-FFR with invasive FFR.Ethics and disseminationThe study has ethic approval from the ethics committee of Seoul National University Bundang Hospital (E-1709/420-001) and informed consent will be obtained for all enrolled patients. The result will be published in a peer-reviewed journal.Trial registration numberKCT0002725; Pre-results.

Objective Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Patients with small AAAs are managed with careful surveillance and it is a common concern that their anatomy may change with AAA growth, and their option for EVAR may become limited. Device innovation has resulted in expanded ranges of anatomy that may be eligible for EVAR. This study sought to identify changes in anatomic eligibility for repair with contemporary endovascular devices in AAA patients, monitored by computed tomography scan over the course of 2 years. Methods Patients from the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT, NCT01756833) were included in this analysis. Females had baseline AAA maximum transverse diameter between 3.5 and 4.5 cm, and males had baseline maximum transverse diameter between 3.5 and 5.0 cm. Patients were included in this analysis if they completed pre-enrollment and 2-year follow-up computed tomography imaging. Pertinent anatomic measurements were performed on a postprocessing workstation in a centralized imaging core laboratory. EVAR candidacy was determined by measuring proximal aortic neck diameter, AAA length, and infrarenal neck angulation. Patients were considered to be eligible for EVAR if they qualified for at least one of the seven studied devicesʼ instructions for use at baseline and at 2 years. A paired t test analysis was used to detect differences in aortic measurements over 2 years, and the McNemar test was used to compare eligibility over 2 years. Results We included 192 patients in this analysis—168 male and 24 female. Of these patients, 85% were eligible for EVAR at baseline and 85% after 2 years of follow-up (P = 1.00; 95% confidence interval –0.034 to 0.034). Of the 164 EVAR candidates at baseline, 160 (98%) remained eligible over 2 years of surveillance. Insufficient neck length was the most common reason for both ineligibility at baseline (18 of 28 patients) as well as loss of candidacy over 2 years (3 of 4 patients). Conclusions The majority of patients eligible for EVAR when entering a surveillance program for small AAA remain eligible after 2 years. Substantial changes in AAA neck anatomy resulting in loss of EVAR treatment options are infrequent. Patients with anatomic AAA progression beyond EVAR eligibility remain candidates for complex EVAR and open repair.

AIMS: We aimed to investigate the association between the use and findings of IVUS with clinical outcomes in the PCI arm of a randomised trial of LMS PCI.METHODS AND RESULTS: The NOBLE trial randomised patients with LMS disease to treatment by PCI or CABG. Of 603 patients treated by PCI, 435 (72%) underwent post-PCI IVUS assessment, 224 of which were analysed in a core laboratory. At five years, the composite of MACCE was 18.9% if post-PCI IVUS was performed versus 25.0% if it was not performed (p=0.45, after adjustment). Overall repeat revascularisation was not reduced (10.6% vs 16.5%, p=0.11); however, LMS TLR was (5.1% vs 11.6%, p=0.01) if IVUS was used. For comparison of stent expansion, LMS MSA was split into tertiles. We found no significant difference in MACCE, death, myocardial infarction or stent thrombosis between tertiles. There was a significant difference between the lower and upper tertiles for repeat revascularisation (17.6% vs 5.2%, p=0.02) and LMS TLR (12.2% vs 0%, p=0.002).CONCLUSIONS: Post-PCI IVUS assessment and adequate stent expansion are not associated with reduced MACCE; however, there is an association with reduced LMS TLR. The use of intracoronary imaging to prevent stent underexpansion in LMS PCI is likely to improve outcomes.

BACKGROUND Differences between resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have not been sufficiently discussed. This study aimed to investigate if there is a difference in diagnostic performance between RFR and dPR for the functional lesion assessment and to assess if there are specific characteristics for discordant revascularization decision-makings between RFR and dPR.Methods and Results:A total of 936 intermediate lesions in 776 patients who underwent measurements of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were retrospectively studied. Physiological indices were measured from anonymized pressure recordings at an independent core laboratory. Both RFR and dPR measures were highly correlated (r=0.997, P

Objectives The new European In Vitro Diagnostic (IVD) Regulation 2017/746 (IVDR) restricts the use of lab-developed tests (LDT) after 26th May 2022. There are no data on the impact of the IVDR on laboratories in the European Union. Methods Laboratory tests performed in UZ Leuven were divided in four groups: core laboratory, immunology, special chemistry, and molecular microbiology testing. Each test was classified as Conformité Européenne (CE)-IVD, modified/off-label CE-IVD, commercial Research Use Only (RUO) or LDT. Each matrix was considered a separate test. Results We found that 97.6% of the more than 11.5 million results/year were generated with a CE-IVD method. Of the 922 different laboratory tests, however, only 41.8% were CE-IVD, 10.8% modified/off-label CE-IVD, 0.3% RUO, and 47.1% LDT. Off-label CE-IVD was mainly used to test alternative matrices not covered by the claim of the manufacturer (e.g., pleural or peritoneal fluid). LDTs were mainly used for special chemistry, flow cytometry, and molecular testing. Excluding flow cytometry, the main reasons for the use of 377 LDTs were lack of a CE-IVD method (71.9%), analytical requirements (14.3%), and the fact the LDT was in use before CE-IVD available (11.9%). Conclusions While the large majority of results (97.6%) were generated with a CE-IVD method, only 41.8% of laboratory tests were CE-IVD. There is currently no alternative on the market for 71.5% of the 537 LDTs performed in our laboratory which do not fall within the scope of the current IVD directive (IVDD). Compliance with the IVDR will require a major investment of time and effort.

Objectives Preanalytical factors, such as hemolysis, affect many components of a test panel. Machine learning can be used to recognize these patterns, alerting clinicians and laboratories to potentially erroneous results. In particular, machine learning might identify which cases of elevated potassium from a point-of-care (POC) basic metabolic panel are likely erroneous. Methods Plasma potassium concentrations were compared between POC and core laboratory basic metabolic panels to identify falsely elevated POC results. A logistic regression model was created using these labels and the other analytes on the POC panel. Results This model has high predictive power in classifying POC potassium as falsely elevated or not (area under the curve of 0.995 when applied to the test data set). A rule-in and rule-out approach further improves the model’s applicability with a positive predictive value of around 90% and a negative predictive value near 100%. Conclusions Machine learning has the potential to detect laboratory errors based on the recognition of patterns in commonly requested multianalyte panels. This could be used to alert providers at the POC that a result is suspicious or used to monitor the quality of POC results.

The number of onsite clinical microbiology laboratories in hospitals is decreasing, likely related to the business model for laboratory consolidation and labor shortages, and this impacts a variety of clinical practices, including that of banking isolates for clinical or epidemiologic purposes. To determine the impact of these trends, infectious disease (ID) physicians were surveyed regarding their perceptions of offsite services. Clinical microbiology practices for retention of clinical isolates for future use were also determined. Surveys were sent to members of the Infectious Diseases Society of America’s (IDSA) Emerging Infections Network (EIN). The EIN is a sentinel network of ID physicians who care for adult and/or pediatric patients in North America and who are members of IDSA. The response rate was 763 (45%) of 1,680 potential respondents. Five hundred forty (81%) respondents reported interacting with the clinical microbiology laboratory. Eighty-six percent of respondents thought an onsite laboratory very important for timely diagnostic reporting and ongoing communication with the clinical microbiologist. Thirty-five percent practiced in institutions where the core microbiology laboratory has been moved offsite, and an additional 7% (n = 38) reported that movement of core laboratory functions offsite was being considered. The respondents reported that only 24% of laboratories banked all isolates, with the majority saving isolates for less than 30 days. Based on these results, the trend toward centralized core laboratories negatively impacts the practice of ID physicians, potentially delays effective implementation of prompt and targeted care for patients with serious infections, and similarly adversely impacts infection control epidemiologic investigations.

Background Sex difference in fractional flow reserve ( FFR ) and resting index has not been fully clarified. We sought to investigate the impact of sex on the discordance of revascularization decision making between FFR and diastolic pressure ratio during the diastolic wave‐free period ( dPR WFP ). Methods and Results A total of 759 angiographically intermediate lesions with 30% to 80% diameter stenosis by quantitative coronary angiography in 577 patients in whom FFR and dPR WFP were measured were investigated. dPR WFP was measured during the wave‐free window of 5 heart cycles at an independent core laboratory. FFR ≤0.80 and dPR WFP ≤0.89 were considered positive studies. A total of 164 vessels in 126 women (21.6%) and 595 vessels in 451 men (78.4%) were included. In lesions with negative dPR WFP , positive FFR was less frequently observed in women (13 of 73; 17.8%) than in men (97 of 286; 33.9%) ( P =0.009). In lesions with positive dPR WFP , the frequency of negative FFR was observed in 22 of 91 vessels (24.2%) in women and 51 of 309 vessels (16.5%) in men, which did not reach statistical significance ( P =0.098). In multivariable analyses, female sex was independently associated with FFR ‐ dPR WFP discordance both in negative dPR WFP cohort (odds ratio, 0.44; 95% CI , 0.21–0.98; P =0.036) and in positive dPR WFP cohort (odds ratio, 2.41; 95% CI , 1.17–4.96; P =0.017) after adjustment for age, weight, quantitative coronary angiography data, and baseline physiological indexes. Conclusions The frequency of FFR ‐ dPR WFP discordance was significantly associated with sex, which may indicate potential shift of optimal threshold of either FFR or dPR WFP , or both of them, according to sex.