PRADOC: A Multicenter Randomized Controlled Trial to Assess the Efficiency of PRADO-IC, a Nationwide Pragmatic Transition Care Management Plan for Hospitalized Patients With Heart Failure in France.

Background: The PRADO-IC (Programme de Retour à Domicile après une Insuffisance Cardiaque) is a transition care program designed to improve the coordination of care between hospital and home that was generalized in France in 2014. The PRADO-IC consists of an administrative assistant who visits patients during hospitalization to schedule follow-up visits. The aim of the present study was to evaluate the PRADO-IC program based on the hypotheses provided by health authorities.

Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome.

Background: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied.

Aim: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB.

Study and quantification of the enantiodiscrimination power of four polymeric chiral LLCs using NAD 2D-NMR.

Identifying and understanding the role of key molecular factors involved in the orientation/discrimination phenomena of analytes in polymer-based chiral liquid crystals (CLCs) are essential tasks for optimizing computational predictions (molecular dynamics simulation) of the existing orienting systems, as well as designing novel helically chiral polymers as new enantiodiscriminating aligning media. From this perspective, we propose to quantify and compare the enantiodiscrimination power of four homochiral polymer-based lyotropic liquid crystals (LLCs) toward a given chiral solute using their H residual quadrupolar couplings (H-RQCs) measured by anisotropic natural abundance deuterium 2D-NMR (ANAD 2D-NMR). Two families of chiral polymers are investigated in this study: (i) poly-peptide polymers (PBLG and PCBLL), and (ii) polyacetylene polymers (PDA and L-MSP, a new system never published so far).

Exploring the enantiomeric C position-specific isotope fractionation: challenges and anisotropic NMR-based analytical strategy.

Trying to answer the intriguing and fundamental question related to chiral induction/amplification at the origin of homochirality in Nature: "Is there a relationship between enantiomeric and isotopic fractionation of carbon 13 in chiral molecules?" is a difficult but stimulating challenge. Although isotropic C-PSIA NMR is a promising tool for the determination of (C/C) ratios capable of providing key C isotopic data for understanding the reaction mechanisms of biological processes or artificial transformations, this method does not provide access to any enantiomeric C isotopic data unless mirror-image isomers are first physically separated. Interestingly, C spectral enantiodiscriminations can be potentially performed in situ in the presence of enantiopure entities as chiral-europium complexes or chiral liquid crystals (CLCs).

Sacubitril-valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO-SAS study.

Aims: Optimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril-valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation.

Methods And Results: The ENTRESTO-SAS trial is a six-centre, prospective, open-label real-life cohort study (NCT02916160).

Deuterium Residual Quadrupolar Couplings: Crossing the Current Frontiers in the Relative Configuration Analysis of Natural Products.

The determination of the 3D structure (configuration and preferred conformation) of complex natural and synthetic organic molecules is a long-standing but still challenging task for chemists, with various implications in pharmaceutical sciences whether or not these substances have specific bioactivities. Nuclear magnetic resonance (NMR) in aligning media, either lyotropic liquid crystals (LLCs) or polymer gels, in combination with molecular modeling is a unique framework for solving complex structural problems whose analytical wealth lies in the establishment of nonlocal structural correlations. As an alternative to the already well-established anisotropic NMR parameters, such as RDCs (residual dipolar couplings) and RCSAs (residual chemical shift anisotropies), it is shown here that deuterium residual quadrupolar couplings (H-RQCs) can be extracted from H 2D-NMR spectra recorded at the natural abundance level in samples oriented in a homopolypeptide LLCs (poly-γ-benzyl-l-glutamate (PBLG)).

Telemonitoring versus standard care in heart failure: a randomised multicentre trial.

Aims: The aim was to assess the effect of a telemonitoring programme vs. standard care (SC) in preventing all-cause deaths or unplanned hospitalisations in heart failure (HF) at 18 months.

Methods And Results: OSICAT was a randomised, multicentre, open-label French study in 937 patients hospitalised for acute HF ≤12 months before inclusion.

Multinuclear NMR in polypeptide liquid crystals: Three fertile decades of methodological developments and analytical challenges.

NMR spectroscopy of oriented samples makes accessible residual anisotropic intramolecular NMR interactions, such as chemical shift anisotropy (RCSA), dipolar coupling (RDC), and quadrupolar coupling (RQC), while preserving high spectral resolution. In addition, in a chiral aligned environment, enantiomers of chiral molecules or enantiopic elements of prochiral compounds adopt different average orientations on the NMR timescale, and hence produce distinct NMR spectra or signals. NMR spectroscopy in chiral aligned media is a powerful analytical tool, and notably provides unique information on (pro)chirality analysis, natural isotopic fractionation, stereochemistry, as well as molecular conformation and configuration.

H and C NMR-Based Enantiodetection Using Polyacetylene versus Polypeptide Aligning Media: Versatile and Complementary Tools for Chemists.

Invited for this month's cover are the collaborating groups of Dr. Philippe Lesot (DR CNRS) at Université Paris-Sud/Université Paris-Saclay, France, and Professor Michael Reggelin at TU Darmstadt, Germany. The cover shows the proton-decoupled natural abundance deuterium (NAD-{ H}) Q-resolved Fz 2D-NMR spectrum of (±)-3-methylhexane measured in the anisotropic lyotropic chiral liquid-crystalline phase formed by a concentrated solution of a helically chiral polyarylacetylene in chloroform solvent.

H and C NMR-Based Enantiodetection Using Polyacetylene versus Polypeptide Aligning Media: Versatile and Complementary Tools for Chemists.

In this work, the practical/analytical potential of an L-valine-derived polyacetylene (PLA) lyotropic liquid crystal (LLC) is examined to spectrally discriminate enantiomers (racemic mixture) or enantiotopic directions of a large collection (23) of (pro)chiral model compounds (from rigid to flexible and polar to apolar ones), thus covering various important aspects of enantiomorphism. Experimental H-{ H} (deuterated analytes and at natural abundance level) and C-{ H} NMR results are discussed in terms of the difference of H-RQCs or C-RCSAs and compared to those obtained in polypeptide-type LLCs (PBLG). The analysis of the NMR results provides an overview of the enantiodifferentiation capabilities of PLA and gives useful/practical hints for the chemist to select the most appropriate chiral oriented system.

Impact of sacubitril-valsartan combination in patients with chronic heart failure and sleep apnoea syndrome: the ENTRESTO-SAS study design.

Aims: Sleep-disordered breathing (SDB) is a highly prevalent co-morbidity in patients with chronic heart failure (CHF) and can play a detrimental role in the pathophysiology course of CHF. However, the best way to manage SDB in CHF remains a matter of debate. Sacubitril-valsartan has been included in the 2016 European Society of Cardiology guidelines as an alternative to angiotensin-converting enzyme inhibitors to further reduce the risk of progression of CHF, CHF hospitalization, and death in ambulatory patients.

Integrated Computational Protocol for the Analysis of Quadrupolar Splittings from Natural-Abundance Deuterium NMR Spectra in (Chiral) Oriented Media.

Despite its low natural abundance, deuterium NMR spectroscopy in weakly oriented (chiral) solvents gives easy access to deuterium residual quadrupolar couplings ( H-RQCs). These are formally equivalent to one-bond residual dipolar couplings (( C- H)-RDCs) for calculation of the Saupe tensor, and provide similar information for the study of molecular structure and orientational behavior. Because the quadrupolar interaction is one order of magnitude larger than the dipolar one, H-RQC analysis is a much more sensitive tool for the detection of subtle structural differences and also tiny differences in molecular alignment, such as those observed for different enantiomers in chirally aligned media.

Detection of quadrupolar nuclei by ultrafast 2D NMR: exploring the case of deuterated analytes aligned in chiral oriented solvents.

Anisotropic (2)H ultrafast (ADUF) 2D NMR spectroscopy for studying analytes dissolved in chiral liquid crystals (CLC) is investigated for the first time and the analytical possibilities of this method are evaluated. We demonstrate that these unconventional sub-second 2D experiments are compatible with the basic gradient units (40-60 G cm(-1)) that are implemented in routine spectrometers and allow the recording of (2)H signals of weakly aligned deuterated solutes in sub-second experimental times.

Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data.

Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear.

Correlation 2D-NMR experiments involving both 13C and 2H isotopes in oriented media: methodological developments and analytical applications.

Correlation 2D-NMR experiments for (13)C and (2)H isotopes turn out to be powerful methods for the assignment of the quadrupolar doublets in the (2)H NMR spectra of isotopically modified (polydeuterated or perdeuterated) or unmodified solutes in homogeneously oriented solvents, such as thermotropic systems or lyotropic liquid crystals. We review here the different pulse sequences, which have been employed, their properties, and their most salient applications. These 2D-NMR sequences have been used for (i) (13)C-(2)H correlation with and without (1)H relay and (ii) (2)H-(2)H correlation with (13)C relay.

Antiplatelet drug response status does not predict recurrent ischemic events in stable cardiovascular patients: results of the Antiplatelet Drug Resistances and Ischemic Events study.

Background: The biological response to antiplatelet drugs has repeatedly been shown to predict the recurrence of major adverse cardiovascular events (MACEs). However, most studies involved coronary artery disease patients with recent vessel injury shortly after the initiation of antiplatelet therapy. Data on stable cardiovascular patients are scarce, and the added predictive value of specific assays (the vasodilator phosphoprotein assay for the clopidogrel response and serum thromboxane B2 for the aspirin response) and aggregation-based assays relative to common predictors has rarely been addressed.

Conformation and dynamics of 18-membered hexathiametacyclophanes: a two step racemization as studied by deuterium NMR in chiral lyotropic liquid crystals.

The conformation and interconversion dynamics of two derivatives of the 18-membered hexathia metacyclophane 1 and 2 were studied by (1)H NMR spectroscopy in isotropic solvents and by (2)H NMR in chiral liquid crystalline (CLC) solutions, as well as by molecular structure computations. For the analysis of the dynamic effects, we made use of the concepts of "average symmetry" and "isodynamic groups", introduced by Altmann (Altmann, Proc. R.

Admission NT-proBNP levels, renal insufficiency and age as predictors of mortality in elderly patients hospitalized for acute dyspnea.

Background: Assay of baseline B-type peptide (BNP and NT-proBNP) is useful for heart failure (HF) prognostication. In contrast, the prognostic value of NT-proBNP assay performed on admission of elderly subjects for acute dyspnea is uncertain. The aim of this study was to determine the vital prognostic value of NT-proBNP assay and other relevant variables available on admission in elderly patients hospitalized for acute dyspnea.

Use of N-terminal prohormone brain natriuretic peptide assay for etiologic diagnosis of acute dyspnea in elderly patients.

Background: B-type peptide assay (brain natriuretic peptide [BNP] and N-terminal prohormone brain natriuretic peptide [NT-proBNP]) is useful for the diagnosis of heart failure (HF), but few data are available on the use of these markers in elderly subjects. The aim of this study was to evaluate NT-proBNP assay for the diagnosis of acute left HF in patients older than 70 years hospitalized for acute dyspnea.

Methods: We prospectively enrolled 256 elderly patients with acute dyspnea.

Analysis of the 13C NMR spectra of molecules, chiral by isotopic substitution, dissolved in a chiral oriented environment: towards the absolute assignment of the pro-R/pro-S character of enantiotopic ligands in prochiral molecules.

We examined and discuss the proton- and deuterium-decoupled carbon-13 1D spectrum of a molecule, chiral by virtue of the isotopic substitution, dissolved in a chiral oriented medium which simultaneously exhibits chiral discrimination, enantiomeric enrichment and isotope effect. Using the 1-deutero-(2',3',4',5',6'-pentadeuterophenyl)phenylmethanol orientationally ordered in a chiral nematic liquid crystal as illustrative example, we point out three important features. First, we demonstrate that the absolute assignment of the pro-R/pro-S character may be derived from the absolute configuration of the isotopically chiral analogue.