Current guidelines recommend use of heart valve centres (HVCs) to deliver optimal quality of care for patients with valve disease but there is no evidence to support this. The hypothesis of this ...study is that patient care with severe aortic stenosis (AS) will differ in HVCs compared with satellite centres. We aimed to compare the treatment of patients with AS at HVCs (tertiary care hospitals with full access to AS interventions) to satellites (hospitals without such access).
is a European, observational, prospective registry enrolling consecutive patients with newly diagnosed severe AS at four HVCs and 10 satellites. Clinical characteristics, interventions performed and outcomes up to 1 year by site-type were examined.
Among 790 patients, 594 were recruited in HVCs and 196 in satellites. At baseline, patients in HVCs had more severe valve disease (higher peak aortic velocity (4.3 vs 4.1 m/s; p=0.008)) and greater comorbidity (coronary artery disease (CAD) (44% vs 27%; p<0.001) prior myocardial infarction (MI) (11% vs 5.1%; p=0.011) and chronic pulmonary disease (17% vs 8.9%; p=0.007)) than those presenting in satellites. An aortic valve replacement was performed more often by month 3 in HVCs than satellites in the overall population (52.6% of vs 31.3%; p<0.001) and in symptomatic patients (66.7% vs 43.2%, p<0.001). One-year survival rate was higher for patients in HVCs than satellites (HR2.19; 95% CI 1.28 to 3.73 total population and 2.89 (95%CI 1.64 to 5.11) for symptomatic patients.
Our data support the implementation of referral pathways that direct patients to HVCs performing both surgery and transcatheter interventions.
NCT03112629.
BackgroundSevere aortic stenosis (AS) is one of the most common and most serious valve diseases. Without timely intervention with surgical aortic valve replacement or transcatheter aortic valve ...replacement, patients have an estimated survival of 2–3 years. Guidelines for the treatment of AS have been developed, but studies suggest that as many as 42% of patients with AS are not treated according to these recommendations.The aims of this registry are to delineate the caseload of patients with AS, outline the management of these patients and determine appropriateness of treatments in participating centres with and without onsite access to surgery and percutaneous treatments.Methods/designThe IMPULSE enhanced registry is an international, multicentre, prospective, observational cohort registry conducted at four central full access centres (tertiary care hospitals) and at least two satellite centres per hub (primary/secondary care hospitals). An estimated 800 patients will be enrolled in the registry and patient follow-up will last for 12 months.DiscussionIn addition to the primary aims determining the caseload management and outcome of patients with AS in primary, secondary and tertiary care settings, the registry will also determine a time course for the transition from asymptomatic to symptomatic status and the diagnostic steps, treatment decisions and the identification of decision-makers in tertiary versus primary/secondary care hospitals. The last patient will be enrolled in the registry in 2018 and results of the registry are anticipated in 2019.Registration numberNCT03112629.
Cardiac hypertrophy is a major predictor of heart failure and of morbidity and mortality in developed countries. Many hormones and growth factors induce cardiac hypertrophy via activation of members ...of the phospholipase C (PLC) family. The expression pattern of the PLCβ isozyme subfamily was investigated in neonatal rat cardiomyocytes after stimulation with different hypertrophic stimuli. Under control conditions and after stimulation with norepinephrine, cardiomyocytes expressed similar amounts of PLCβ3 mRNA. In the presence of fetal calf serum (FCS), additional expression of PLCβ1 was induced. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) both induced a substantial increase in PLCβ3 mRNA expression. The response to GH could not be abolished by the IGF-I receptor blocker IGF-I analogue indicating an IGF-I-independent action of GH. The upregulation of PLCβ3 by IGF-I was abolished by preincubation of cardiomyocytes with the IGF-I receptor antagonist IGF-I analogue, the tyrosine kinase inhibitor genistein, the extracellular signal-related kinase (ERK) inhibitor PD 98059, the phosphatidylinositol-3- (PI-3) kinase inhibitor wortmannin and the p70 S6 kinase inhibitor rapamycin. Induction of the immediate early genes c-myc, c-fos, and c-jun by IGF-I was abolished by preincubation with antisense oligos against PLCβ3. It is concluded that the expression of PLCβ isozymes in cardiomyocytes is differentially regulated by different hypertrophic stimuli. The upregulation of PLCβ3 by IGF-I is dependent on the activity of tyrosine kinase, ERK, PI3 kinase, and p70 S6 kinase and PLCβ3 expression seems to be required for the induction of immediate early genes by IGF-I. The involvement of the PLCβ subfamily in signal transduction of receptors other than G-protein-coupled receptors is suggested.
The effect of the antiarrhythmic drug amiodarone on the human myocardial β-adrenoceptor-G protein-adenylyl cyclase signalling cascade was investigated. Amiodarone had no effect on myocardial G ...proteins and maximal adenylyl cyclase activity, but acted as a β-adrenoceptor antagonist. This mechanism might be at least partially responsible for the beneficial effects of the drug in patients with arrhythmia and heart failure.
Diborynes, molecules containing homoatomic boron–boron triple bonds, have been investigated by Raman spectroscopy in order to determine the stretching frequencies of their central BB units as an ...experimental measure of homoatomic bond strengths. The observed frequencies between 1600 and 1750 cm–1 were assigned on the basis of DFT modeling and the characteristic pattern produced by the isotopic distribution of boron. This frequency completes the series of known stretches of homoatomic triple bonds, fitting into the trend established by the long-known stretching frequencies of CC and NN triple bonds in alkynes and dinitrogen, respectively. A quantitative analysis was carried out using the concept of relaxed force constants. The results support the classification of the diboryne as a true triple bond and speak to the similarities of molecules constructed from first-row elements of the p block. Also reported are the relaxed force constants of a recently reported diborabutatriene, which again fit into the trend established by the vibrational spectroscopy of organic cumulenes. As part of these studies, a new diboryne with decreased steric bulk was synthesized, and a computational study of the rotation of the stabilizing ligands indicated alkyne-like electronic isolation of the central B2 unit.
A series of 22 new bis(phosphine), bis(carbene), and bis(isonitrile) tetrahalodiborane adducts has been synthesized, either by direct adduct formation with highly sensitive B2X4 precursors (X=Cl, Br, ...I) or by ligand exchange at stable B2X4(SMe2)2 precursors (X=Cl, Br) with labile dimethylsulfide ligands. The isolated compounds have been fully characterized using NMR spectroscopy, elemental analysis, and, for 20 of these compounds, single‐crystal X‐ray diffraction, revealing an unexpected variation in the bonding motifs. In addition to the classical B2X4L2 diborane(4) bis‐adducts, certain more sterically demanding carbene ligands induce a halide displacement which led to the first halide‐bridged monocationic diboron species, B2X3L2A (A=BCl4, Br, I). Furthermore, low‐temperature 1:1 reactions of B2Cl4 with sterically demanding N‐heterocyclic carbenes led to the formation of kinetically unstable mono‐adducts, one of which was structurally characterized. A comparison of the NMR spectra and structural data of new and literature‐known bis‐adducts shows several trends pertaining to the nature of the halides and the stereoelectronic properties of the Lewis bases employed.
Introducing the diborane family: 22 tetrahalodiborane bis(base) adducts and two unstable mono(base) adducts were synthesized by the addition of carbenes, phosphines, and isonitriles to highly sensitive B2X4 or by ligand exchange at stable B2X4(SMe2)2 precursors. NMR spectroscopy and crystallographic studies revealed a variety of structural motifs, from sp2–sp3‐diboranes and sp3–sp3‐diboranes in staggered anti and gauche conformations to novel halide‐bridged diboron cations.
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