ATLAS is one of the four major LHC experiments, designed to cover a wide range of physics topics. In order to cope with a rate of 40MHz and 25 interactions per bunch crossing, the ATLAS trigger ...system is divided in three different levels. The jet selection starts at first level with dedicated processors that search for high ET hadronic energy depositions. At the LVL2, the jet signatures are verified with the execution of a dedicated, fast jet reconstruction algorithm, followed by a calibration algorithm. Three possible granularities have been proposed and are being evaluated: cell based (standard), energy sums calculated at each Front-End Board and the use of the LVL1 Trigger Towers. In this presentation, the design and implementation of the jet trigger of ATLAS will be discussed in detail, emphasazing the major difficulties of each selection step. The performance of the jet algorithm, including timing, efficiencies and rates will also be shown, with detailed comparisons of the different unpacking modes.
Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted ...therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension.
PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174.
The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was –15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, –15·2 (0·9) mm Hg for aprocitentan 25 mg, and –11·5 (0·9) mm Hg for placebo, for a difference versus placebo of –3·8 (1·3) mm Hg (97·5% CI –6·8 to –0·8, p=0·0042) and –3·7 (1·3) mm Hg (–6·7 to –0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was –4·2 mm Hg (95% CI –6·2 to –2·1) and –5·9 mm Hg (–7·9 to –3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p<0·0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12·5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment.
In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40.
Idorsia Pharmaceuticals and Janssen Biotech.
Clinic-ambulatory blood pressure (BP) difference is influenced by patients- and device-related factors and inadequate clinic-BP measurement. We investigated whether nonadherence to antihypertensive ...medications may also influence this difference in a post hoc analysis of the DENERHTN trial (Renal Denervation for Hypertension). We pooled the data of 77 out of 106 evaluable patients with apparent resistant hypertension who received a standardized antihypertensive treatment and had both ambulatory BP and drug-screening results available at baseline after 1 month of standardized triple therapy and at 6 months on a median of 5 antihypertensive drugs. After drug assay samplings on study visits, patients took their antihypertensive treatment under supervision immediately after the start of the ambulatory BP recording, and supine clinic BP was measured 24 hours post-dosing; both allowed to calculate the clinic minus daytime ambulatory systolic BP (SBP) difference (clinic-SBP-day-SBP). A total of 29 (37.7%) were found nonadherent to medications at baseline and 38 (49.4%) at 6 months. At baseline, the mean clinic-SBP-day-SBP difference in the nonadherent group was 12.7 mm Hg (95% CI, 7.8-17.7 mm Hg,
<0.001). In contrast, clinic SBP was almost identical to day-SBP in the adherent group (clinic-SBP-day-SBP difference, 0.1 mm Hg; 95% CI, -3.3 to 3.5 mm Hg;
=0.947). Similar observations were made at 6 months. Using receiver operating characteristics curves, we found that a 6 mm Hg cutoff of clinic-SBP-day-SBP difference had 67% sensitivity and 69% specificity to predict nonadherence to the triple therapy at baseline. In conclusion, a large clinic-SBP-day-SBP difference may help discriminating between adherence and nonadherence to treatment in patients with resistant hypertension. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.
Abstract Aim To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to CT-angiography (CTA) for endoleak detection and aneurismal sac diameter measurement in the follow-up after ...endovascular abdominal aortic aneurysm repair (EVAR). Methods From January 2006 to December 2010, 395 patients underwent EVAR follow-up with both CTA and CEUS. The diameter of the aneurismal sac and the presence of endoleaks were evaluated in all the 395 paired examinations. Results Bland–Altman plots showed a good agreement in aneurismal sac diameter evaluation between the two imaging modalities. The mean diameter was 54.93 mm (standard deviation (SD) ±12.57) with CEUS and 56.01 mm (SD ± 13.23) with CTA. The mean difference in aneurismal sac diameter was −1.08 mm ± 3.3543 (95% confidence interval (CI), −0.75 to −1.41), in favour of CTA. The number of observed agreement in endoleak detection was 359/395 (90.89%). The two modalities detected the same type I and type III endoleaks. McNemar’s χ2 test confirmed that CTA and CEUS are equivalent in endoleak detection. Conclusions CEUS demonstrated to be as accurate as CTA in endoleak detection and abdominal aortic aneurysm diameter measurements during EVAR follow-up, without carrying the risks of radiation exposure or nephrotoxicity. Even if it cannot be proposed as the sole imaging modality during follow-up, our analysis suggests that it should have a major role.
Background: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied.
...Methods: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE.
Results: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27–18.1), with no differences in bleeding.
Conclusions: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation.
The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for ...resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control.
One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients.
The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients.
In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.
Abstract
Background
Current data regarding the impact of diabetes mellitus (DM) on cardiovascular mortality in patients with aortic stenosis (AS) are restricted to severe AS or aortic valve ...replacement (AVR) trials.
Purpose
To investigate cardiovascular mortality according to DM across the entire spectrum of AS outpatients.
Methods
Between May 2016 and December 2017, patients with mild (peak aortic velocity=2.5–2.9m/s), moderate (3–3.9m/s) and severe (≥4m/s) AS graded by echocardiography were included during outpatient cardiology visits in the Nord-Pas-de-Calais region in France and followed-up for modes of death.
Results
Among 2,703 patients, 820 (30.3%) had DM, mean age was 76±10.8 years with 46.6% of women and a relatively high prevalence of underlying cardiovascular diseases. There were 200 cardiovascular deaths prior to AVR during the 2.1 years (IQR 1.4–2.7) follow-up period. In adjusted analyses, DM was significantly associated with cardiovascular mortality (HR=1.40, 95% CI 1.04–1.89; P=0.029). In mild or moderate AS, the cardiovascular mortality of diabetic patients was similar to that of nondiabetic patients (Figuer 1). In severe AS, DM was associated with higher cardiovascular mortality (HR=2.65, 95% CI 1.50–4.68; P=0.001). This was almost exclusively related to a higher risk of death from heart failure (HR=2.61, 95% CI 1.15–5.92; P=0.022) and sudden death (HR=3.33, 95% CI 1.28–8.67; P=0.014) (Figure 2).
Conclusion
The effect of DM on cardiovascular mortality varied across AS severity. Despite no association between DM and outcomes in mild/moderate AS patients, DM was strongly associated with death from heart failure and sudden death in severe AS patients.
Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Fédération Française de Cardiologie
The prevention of venous thromboembolic disease is less studied in medical patients than in surgery.
We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin ...(UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deep-vein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded.
Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both cases), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH (4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049).
This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.
Abstract
Background
To date, there is little data regarding the clinical significance of myocardial work (MW) parameters after a stable period following acute myocardial infarction (AMI).
Purpose
To ...investigate the additional prognostic value of MW parameters following AMI.
Methods
Between 2018 and 2020, 244 patients admitted in cardiac intensive care unit of a university hospital for AMI were included. One-month following AMI, a comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure and unplanned coronary revascularisation.
Results
At 1 month, half of the population was symptomatic (NYHA≥II), and medical therapy was almost optimized (ACEi/ARB in 95.5%, beta-blockers in 96.3%, DAPT in 94.7% and statins in 97.1%). After a median follow-up of 681 IQR 538–840 days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5±14.2 vs. 58.1±12.1 years, P=0.005) with higher prevalence of hypertension (65.4 vs. 36.2%, P=0.004), more impaired LV function as assessed by left ventricular ejection fraction (LVEF) (P=0.07), global longitudinal strain (GLS) (P=0.03) or MW parameters (P=0.01 for global work efficiency (GWE)), and greater LV and LA dilations (P=0.06 for LVEDVi and P=0.03 for LAVi). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P=0.02). A GWE value <91% was selected to identify patients at higher ME risk (HR 95% CI) = 2.94 (1.36–6.35), P=0.0041) (Figure 1 & 2).
Conclusion
Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE <91% can improve the post-AMI patient risk stratification.
Funding Acknowledgement
Type of funding sources: None.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke ...recurrence in patients with PFO-associated cryptogenic stroke.
We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I
=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I
=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I
=12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I
=77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I
=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I
=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.
PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation.
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