106 Determinants of B-type natriuretic peptide levels and left atrial volume in stable patients in sinus rhythm: an echocardiographic-catheterization study

BackgroundB-type natriuretic peptide (BNP) (Advia Centaur System) and left atrial volume index (LAVi) are regarded as powerful markers of global myocardial function. Several confounding factors are known to potentially influence this relation. The aim of the present study was to evaluate the determinants of BNP and LAVi in the same population of stable patients referred for catheterism.Methods74 consecutive patients were included. Exclusion criteria were arrhythmias, acute coronary syndrome, exacerbation of heart failure and severe left-sided valve disease. All the data were obtained within the same morning for each patient. All following variables were tested: age, gender, body mass index, systolic arterial pressure, heart rate, LV ejection fraction (LVEF), LV mass index (LVM), significant mitral regurgitation (MR), serum hemoglobin (Hb), creatinine clearance (CC), LV end-diastolic pressure (LVEDP), extent of coronary disease.ResultsUnivariate determinants of BNP were age, LVEF, LVM, MR, LVEDP, extent of coronary disease, Hb and CC. By multiple regression analysis, the independant determinants of BNP were age, LVEDP and LVEF (p<0,005 for all). Univariate determinants of LAVI were age, significant MR, LVM, LVEF and LVEDP. By multiple regression analysis, the independent predictors were LVM and LVEDP (p=0,001 for all). BNP was not predicted by LAVi in the multivariate model.ConclusionOur study confirms that both BNP and LAVi can be used as markers of global myocardial dysfunction in stable patients in sinus rhythm. However, age must be taken into consideration before interpreting BNP results

Anticoagulant selection in relation to the SAMe-TT₂R₂ score in patients with atrial fibrillation:The GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.</p

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation:results from phase II/III of the GLORIA-AF registry

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1–3) and 1 (IQR 0–2), respectively (p &lt; 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21–2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641–0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377

Variabilité de la réactivité plaquettaire au cours du temps chez les patients coronariens sous bithérapie antiagrégante

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Shared subgenome dominance following polyploidization explains grass genome evolutionary plasticity from a seven protochromosome ancestor with 16K protogenes

Modern plant genomes are diploidized paleopolyploids. We revisited grass genome paleohistory in response to the diploidization process through a detailed investigation of the evolutionary fate of duplicated blocks. Ancestrally duplicated genes can be conserved, deleted, and shuffled, defining dominant (bias toward duplicate retention) and sensitive (bias toward duplicate erosion) chromosomal fragments. We propose a new grass genome paleohistory deriving from an ancestral karyotype structured in seven protochromosomes containing 16,464 protogenes and following evolutionary rules where 1) ancestral shared polyploidizations shaped conserved dominant (D) and sensitive (S) subgenomes, 2) subgenome dominance is revealed by both gene deletion and shuffling from the S blocks, 3) duplicate deletion/movement may have been mediated by single-/double-stranded illegitimate recombination mechanisms, 4) modern genomes arose through centromeric fusion of protochromosomes, leading to functional monocentric neochromosomes, 5) the fusion of two dominant blocks leads to supradominant neochromosomes (D + D = D) with higher ancestral gene retention compared with D + S = D (i.e., fusion of blocks with opposite sensitivity) or even S + S = S (i.e., fusion of two sensitive ancestral blocks). A new user-friendly online tool named "PlantSyntenyViewer," available at http://urgi.versailles.inra.fr/synteny-cereal, presents the refined comparative genomics data

Identification of two thaumatin-like proteins (TLPs) in the pollination drop of hybrid yew that may play a role in pathogen defence during pollen collection.

We describe the proteomic identification of two pathogenesis-related group 5 (PR-5) proteins, an acidic thaumatin-like protein (TLP) and a basic TLP isolated from the pollination drop of hybrid yew (Taxus x media Rehder). The basic TLP (TxmTLPb) was the most abundant protein in the yew pollination drop based on protein spot size after two-dimensional electrophoresis. The acidic TLP (TxmTLPa) is also a major protein component of the yew ovular secretion and appears to be encoded by a number of mRNAs transcribed from a TLP gene family that has undergone limited sequence divergence. We have sequenced five acidic TLP-encoding cDNAs (TxmTLPa-1,2,3,4 and 5) isolated from the yew ovule that vary from each other by no more than five out of 233 amino acid residues in their predicted protein sequences. All of the cDNA variants encode TLPs possessing the 16 conserved cysteine residues and five charged amino acid side chains associated with antifungal activity. Amplification of genomic DNA with TxmTLPa primers indicated that at least 11 acidic TLPs with highly similar amino acid sequences may be expressed in yew tissues. Antibodies against TLPs confirmed the identity of TxmTLPa and TxmTLPb in the yew pollination drop and detected TLPs in the ovular secretions of four other species from three other conifer families. Our results suggest that TLPs are a conserved component of conifer ovular secretions and are involved in broad spectrum pathogen defence of ovules.Peer reviewed: YesNRC publication: Ye

Characterization of HIV-1 diversity in various compartments at the time of primary infection by ultradeep sequencing

International audienceWe used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log10 copies/mL [IQR: 5.5-6.95] in PL, 4.9 log10 copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log10 copies/mL [IQR: 4.46-5.09] in SAL. Median HIV-1 DNA was 4.1 log10 copies/106 PBMCs [IQR: 3.15-4.15] in WB and 2.6 log10 copies /106 Cells [IQR: 2.23-2.75] in NSC. The median overall diversity per patient varied from 0.0005 to 0.0232, suggesting very low diversity, confirmed by the clonal aspect of most of the phylogenetic trees. One single haplotype was present in all compartments for five patients in the earliest stage of infection. Evidence of higher diversity was established for two patients in PL and WB, suggesting compartmentalization. Our study shows low diversity of the env gene in the first stages of infection followed by the rapid establishment of cellular reservoirs of the virus. Such clonality could be exploited in the search for early patient-specific therapeutic solutions

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial

International audienceAccording to recent literature, pretreatment with a P2Y12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y12 ADP receptor antagonist pretreatment

Predictors of Clinical Success After Transcatheter Paravalvular Leak Closure: An International Prospective Multicenter Registry

International audienceBackground: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure. Methods: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry ( Fermeture de Fuite ParaProthétique , FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death. Results: We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively ( P =0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively ( P =0.371); and clinical success rates of 70.3% and 88.0%, respectively ( P =0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0–25.0]; P= 0.002; 3.6 [1.1–11.1]; P =0.036; and 3.7 [1.2–11.9]; P =0.025; respectively). Conclusions: Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT0508913