Ultra-high-frequency ECG volumetric and negative derivative epicardial ventricular electrical activation pattern.

From precordial ECG leads, the conventional determination of the negative derivative of the QRS complex (ND-ECG) assesses epicardial activation. Recently we showed that ultra-high-frequency electrocardiography (UHF-ECG) determines the activation of a larger volume of the ventricular wall. We aimed to combine these two methods to investigate the potential of volumetric and epicardial ventricular activation assessment and thereby determine the transmural activation sequence. We retrospectively analyzed 390 ECG records divided into three groups-healthy subjects with normal ECG, left bundle branch block (LBBB), and right bundle branch block (RBBB) patients. Then we created UHF-ECG and ND-ECG-derived depolarization maps and computed interventricular electrical dyssynchrony. Characteristic spatio-temporal differences were found between the volumetric UHF-ECG activation patterns and epicardial ND-ECG in the Normal, LBBB, and RBBB groups, despite the overall high correlations between both methods. Interventricular electrical dyssynchrony values assessed by the ND-ECG were consistently larger than values computed by the UHF-ECG method. Noninvasively obtained UHF-ECG and ND-ECG analyses describe different ventricular dyssynchrony and the general course of ventricular depolarization. Combining both methods based on standard 12-lead ECG electrode positions allows for a more detailed analysis of volumetric and epicardial ventricular electrical activation, including the assessment of the depolarization wave direction propagation in ventricles.

Nrf2 depletion in the context of loss-of-function Keap1 leads to mitolysosome accumulation.

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the principal determinant of the cellular redox homeostasis, contributing to mitochondrial function, integrity and bioenergetics. The main negative regulator of Nrf2 is Kelch-like ECH associated protein 1 (Keap1), a substrate adaptor for Cul3/Rbx1 ubiquitin ligase, which continuously targets Nrf2 for ubiquitination and proteasomal degradation. Loss-of-function mutations in Keap1 occur frequently in lung cancer, leading to constitutive Nrf2 activation. We used the human lung cancer cell line A549 and its CRISPR/Cas9-generated homozygous Nrf2-knockout (Nrf2-KO) counterpart to assess the role of Nrf2 on mitochondrial health. To confirm that the observed effects of Nrf2 deficiency are not due to clonal selection or long-term adaptation to the absence of Nrf2, we also depleted Nrf2 by siRNA (siNFE2L2), thus creating populations of Nrf2-knockdown (Nrf2-KD) A549 cells. Nrf2 deficiency decreased mitochondrial respiration, but increased the mitochondrial membrane potential, mass, DNA content, and the number of mitolysosomes. The proportion of ATG7 and ATG3 within their respective LC3B conjugates was increased in Nrf2-deficient cells with mutant Keap1, whereas the formation of new autophagosomes was not affected. Thus, in lung cancer cells with loss-of-function Keap1, Nrf2 facilitates mitolysosome degradation thereby ensuring timely clearance of damaged mitochondria.

Tin(II) cations stabilized by non-symmetric N,N',O-chelating ligands: synthesis and stability.

A series of novel non-symmetric neutral N,N',O-chelating ligands derived from the α-iminopyridine 2-(C(R1)N(C6H3-2,6-iPr2))-6-(R2R3PO)C5H3N (L1: R1 = H, R2 = R3 = Ph; L2: R1 = Me, R2 = R3 = Ph; L3: R1 = H; R2 = Ph, R3 = EtO; L4: R1 = Me, R2 = Ph, R3 = EtO; L5: R1 = H, R2 = R3 = iPrO; L6: R1 = Me, R2 = R3 = iPrO) were synthesized. Ligands L1-6 were reacted with SnCl2 and Sn(OTf)2 with the aim of studying the influence of different R2R3PO functional groups on the Lewis base mediated ionization of SnCl2 and Sn(OTf)2. While all ligands L1-6 provided the corresponding ionic tin(II) complexes [L1-6 → SnCl]+[SnCl3]- (1-6), only ligands L1, L4 and L6 were able to stabilize tin(II) dications [L1,4,6 → Sn(H2O)][OTf]2 (7-9). The auto-ionized compounds [L3-6 → SnCl]+[SnCl3]- possessing ethylphenyl phosphinate and diisopropylphosphite substituents undergo elimination of EtCl and iPrCl, respectively, yielding compounds 10-13. These can either be interpreted as neutral tin(II)phosphinate chloride (10, 11) and tin(II)phosphonate chloride (12, 13), respectively, containing Sn-O and Sn-Cl bonds, and a PO → SnCl2 interaction, or as zwitterionic compounds, where the positive charge of the central tin atom is compensated by an [OSnCl2]- anion. Finally, DFT studies were performed to better understand the steric and electronic properties of the ligands L1-6 as well as the nature of the bonds in the resulting products, with a particular focus on complexes 10-13.

Comparison of mononuclear and dinuclear copper(II) biomimetic complexes: spectroelectrochemical mechanistic study of their catalytic pathways.

Two catecholase-like biomimetic catalysts, namely, two dinuclear copper complexes [Cu2(L1)(OH)(H2O)(EtOH)][ClO4]2 (C1) and [Cu2Ac2O(L1)ClO4] (C2) with the 2,6-bis(4-methyl piperazin-1-yl-methyl)-4-formyl-phenoxy ligand (L1) together with the mononuclear complex Cu(ClO4)2(L2) (C3) containing ligand 1,2-(C5H4N-6-OCH3-2-CHN)2CH2CH2 (L2), were synthesized. Their catalytic pathways were investigated and compared. The evaluation of the catalytic activity of compound C1 (and C2, C3) using the Michaelis-Menten model was represented by values of KM = 272.93 (223.02; 1616) µmol L-1 and Vmax of 0.981 (1.617; 1.689) µmol L-1 s-1. The role of water content in the solvent is also discussed. The dinuclear complexes C1 and C2 were found to be more efficient catalysts than mononuclear complex C3. The mode of catalytic action was characterized via cyclic voltammetry, spectrophotometry, and UV-Vis spectroelectrochemistry. The catalytic mechanism of 3,5-di-tert butyl catechol oxidation in the presence of oxygen was proposed. The reaction circle was proved by the confirmation of the chemical reversibility of complex reduction. The advantage of the in situ spectroelectrochemical measurement enabled to control the reduction of quinone formed by the chemical reaction of catechol with oxygen in solution. At this step, the simultaneous change in the absorption spectrum indicated a change in the copper redox state of the catalyst.

Correction: Sýs et al. Bis(2,2'-bipyridil)Copper(II) Chloride Complex: Tyrosinase Biomimetic Catalyst or Redox Mediator? Materials 2021, 14, 113.

In the original publication [...].

Reduced Radiation Exposure Protocol during Computer Tomography of the Left Atrium Prior to Catheter Ablation in Patients with Atrial Fibrillation.

(1) Background: Computer tomography (CT) is an imaging modality used in the pre-planning of radiofrequency catheter ablation (RFA) procedure in patients with cardiac arrhythmias. However, it is associated with a considerable ionizing radiation dose for patients. This study aims to develop and validate low-dose CT scanning protocols of the left atrium (LA) for RFA guidance. (2) Methods: 68 patients scheduled for RFA of atrial fibrillation were sequentially assigned to four groups of ECG-gated scanning protocols, based on the set tube current (TC): Group A (n = 20, TC = 33 mAs), Group B (n = 18, TC = 67 mAs), Group C (n = 10, TC = 135 mAs), and control Group D (n = 20, TC = 600 mAs). We used a 256-row multidetector CT with body weight-dependent tube voltage of 80 kVp (<70 kg), 100 kVp (70−90 kg), and 120 kVp (>90 kg). We evaluated scanning parameters including radiation dose, total scanning procedure time and signal-to-noise ratio (SNR). (3) Results: The average effective radiation dose (ED) was lower in Group A in comparison to Group B, C and D (0.83 (0.76−1.10), 1.55 (1.36−1.67), 2.91 (2.32−2.96) and 9.35 (8.00−10.04) mSv, p < 0.05). The total amount of contrast media was not significantly different between groups. The mean SNR was 6.5 (5.8−7.3), 7.1 (5.7−8.2), 10.8 (10.1−11.3), and 12.2 (9.9−15.7) for Group A, B, C and D, respectively. The comparisons of SNR in group A vs. B and C vs. D were without significant differences. (4) Conclusions: Optimized pre-ablation CT scanning protocols of the LA can reduce an average ED by 88.7%. Three dimensional (3D) models created with the lowest radiation protocol are useful for the integration of electro-anatomic-guided RFA procedures.

The isoquinoline PRL-295 increases the thermostability of Keap1 and disrupts its interaction with Nrf2.

Transcription factor Nrf2 and its negative regulator Keap1 orchestrate a cytoprotective response against oxidative, metabolic, and inflammatory stress. Keap1 is a drug target, with several small molecules in drug development. Here, we show that the isoquinoline PRL-295 increased Keap1 thermostability in lysates from cells expressing fluorescently tagged Keap1. The thermostability of endogenous Keap1 also increased in intact cells and murine liver following PRL-295 treatment. Fluorescence Lifetime Imaging-Förster Resonance Energy Transfer (FLIM-FRET) experiments in cells co-expressing sfGFP-Nrf2 and Keap1-mCherry further showed that PRL-295 prolonged the donor fluorescence lifetime, indicating disruption of the Keap1-Nrf2 protein complex. Orally administered PRL-295 to mice activated the Nrf2transcriptional target NAD(P)H:quinone oxidoreductase 1 (NQO1) in liver and decreased the levels of plasma alanine aminotransferase and aspartate aminotransferase upon acetaminophen-induced hepatic injury. Thus, PRL-295 engages the Keap1 protein target in cells and in vivo, disrupting its interaction with Nrf2, leading to activation of Nrf2-dependent transcription and hepatocellular protection.

CDKL5 kinase controls transcription-coupled responses to DNA damage.

Mutations in the gene encoding the CDKL5 kinase are among the most common genetic causes of childhood epilepsy and can also give rise to the severe neurodevelopmental condition CDD (CDKL5 deficiency disorder). Despite its importance for human health, the phosphorylation targets and cellular roles of CDKL5 are poorly understood, especially in the cell nucleus. Here, we report that CDKL5 is recruited to sites of DNA damage in actively transcribed regions of the nucleus. A quantitative phosphoproteomic screen for nuclear CDKL5 substrates reveals a network of transcriptional regulators including Elongin A (ELOA), phosphorylated on a specific CDKL5 consensus motif. Recruitment of CDKL5 and ELOA to damaged DNA, and subsequent phosphorylation of ELOA, requires both active transcription and the synthesis of poly(ADP-ribose) (PAR), to which CDKL5 can bind. Critically, CDKL5 kinase activity is essential for the transcriptional silencing of genes induced by DNA double-strand breaks. Thus, CDKL5 is a DNA damage-sensing, PAR-controlled transcriptional modulator, a finding with implications for understanding the molecular basis of CDKL5-related diseases.

N-Donor stabilized tin(II) cations as efficient ROP catalysts for the synthesis of linear and star-shaped PLAs via the activated monomer mechanism.

α-Iminopyridine ligands L1 (2-(CHN(C6H2-2,4,6-Ph3))C5H4N), L2 (2-(CHN(C6H2-2,4,6-tBu3))C5H4N) and L3 (1,2-(C5H4N-2-CHN)2CH2CH2) differing by the steric demand of the substituent on the imine CHN group and by the number of donating nitrogen atoms were utilized to initiate a Lewis base mediated ionization of SnCl2 in an effort to prepare ionic tin(II) species [L1-3 → SnCl][SnCl3]. The reaction of L1 and L2 with SnCl2 led to the formation of neutral adducts [L1 → SnCl2] (2) and [L2 → SnCl2] (3). The preparation of the desired ionic compounds was achieved by subsequent reactions of 2 and 3 with an equivalent of SnCl2 or GaCl3. In contrast, ligand L3 containing four donor nitrogen atoms showed the ability to ionize SnCl2 and also Sn(OTf)2, yielding [L3 → SnCl][SnCl3] (7) and [L3 → Sn(H2O)][OTf]2 (8). The study thus revealed that the reaction is dependent on the type of the ligand. The prepared complexes 4-8 together with the previously reported [{2-((CH3)CN(C6H3-2,6-iPr2))-6-CH3O-C5H3N}SnCl][SnCl3] (1) were tested as catalysts for the ROP of L-lactide, which could operate via an activated monomer mechanism. Finally, a DFT computational study was performed to evaluate the steric and electronic properties of the ionic tin(II) species 1 and 4-8 together with their ability to interact with the L-lactide monomer.

Single-Chamber Cardiac Pacemaker Implantation in a Donkey with Complete AV Block: A Long-Term Follow-Up.

A five-month-old African jenny was presented with a history of exercise intolerance and syncopal episodes. Severe bradycardic arrhythmia due to a high-grade second-degree atrioventricular (AV) block with progression to complete AV block was diagnosed. The jenny underwent a transvenous single-chamber pacemaker implantation. The implantation procedure was performed in a lateral recumbency and the ventricular lead was inserted through the jugular vein. Positioning of the lead was guided by echocardiography. The pacemaker was programmed to VVI mode with a minimal ventricular rate of 40 pulses per minute, a pulse amplitude of 2.4 V, a pulse width of 0.5 ms and sensing amplitude of 2.5 mV. Short-term complications associated with the procedure included lead dislodgement and pacemaker pocket infection. The long-term outcome was satisfactory; the jenny showed improvement in heart function and quality of life after pacemaker implantation. The pulse generator replacement was performed twice (at nine-year intervals) and the intervention was always associated with a local inflammatory reaction around the pacing device. Cardiac examination 18 years after pacemaker implantation revealed no morphological changes in the heart; the electrode lead was still in the correct position and successful pacing and sensing of the ventricle were obtained. Regular follow-up checks are important to evaluate pacemaker function.

Preparation and Characterisation of Waste Poultry Feathers Composite Fibreboards.

The growth of poultry meat production is increasing industrial waste quantities every year. Feathers represent a huge part of the waste, and international directives and restrictions prevent landfilling of such biodegradable materials with high burning values. Furthermore, with their unique properties, poultry waste feathers are already a reliable resource for many byproducts, such as keratin extraction, fibres, hydrogel production, etc., all trying to achieve a high-added value. However, mass reduction of waste feathers into useful applications, such as development of alternative building materials, is also an important aspect. To take advantage of feathers' thermal insulation capabilities, sound damping, and biodegradability, we worked towards mixing waste feathers with wood residues (wood shavings, dust, and mixed residues) for production of composite fibreboards, comparable to the market's medium density fibreboards. The emphasis was to evaluate waste poultry feathers as the component of natural insulation composites, along with mixed waste wood residues, to improve their mechanical properties. Various composite fibreboards with different shares of wood and feathers were produced and tested for mechanical, thermal, and acoustic properties, and biodegradability, with comparison to typical particle boards on the market. The addition of waste feather fibres into the fibreboards' structure improved thermal insulation properties, and the biodegradability of fibreboards, but decreased their bending strength. The sound transition acoustic loss results of the presented combination fibreboards with added feathers improved at mid and high frequencies. Finally, production costs are estimated based on small scale laboratory experiments of feather processing (cleaning and drying), with the assumption of cost reduction in cases of large industrial application.

Bis(2,2'-bipyridil)Copper(II) Chloride Complex: Tyrosinase Biomimetic Catalyst or Redox Mediator?

In this article, construction of amperometric sensor(s) based on screen-printed carbon electrodes covered by thin layers of two types of carbon nanomaterials serving as amplifiers, and containing [Cu(bipy)2Cl]Cl∙5H2O complex is reported. Their performance and biomimetic activity towards two selected neurotransmitters (dopamine and serotonin) was studied mainly using flow injection analysis (FIA). The important parameters of FIA such as working potential, flow rate, and pH were optimized. The mechanism of the catalytic activity is explained and experimentally confirmed. It reveals that presence of hydrogen peroxide plays a crucial role which leads to answer the title question: can presented complex really be considered as a tyrosinase biomimetic catalyst or only as a redox mediator?

Novel ultra-high-frequency electrocardiogram tool for the description of the ventricular depolarization pattern before and during cardiac resynchronization.

INTRODUCTION: The present study introduces a new ultra-high-frequency 14-lead electrocardiogram technique (UHF-ECG) for mapping ventricular depolarization patterns and calculation of novel dyssynchrony parameters that may improve the selection of patients and application of cardiac resynchronization therapy (CRT). METHODS: Components of the ECG in sixteen frequency bands within the 150 to 1000 Hz range were used to create ventricular depolarization maps. The maximum time difference between the UHF QRS complex centers of mass of leads V1 to V8 was defined as ventricular electrical dyssynchrony (e-DYS), and the duration at 50% of peak voltage amplitude in each lead was defined as the duration of local depolarization (Vd). Proof of principle measurements was performed in seven patients with left (left bundle branch block) and four patients with right bundle branch block (right bundle branch block) before and during CRT using biventricular and His-bundle pacing. RESULTS: The acquired activation maps reflect the activation sequence under the tested conditions. e-DYS decreased considerably more than QRS duration, during both biventricular pacing (-50% vs -8%) and His-bundle pacing (-77% vs -13%). While biventricular pacing slightly increased Vd, His-bundle pacing reduced Vd significantly (+11% vs -36%), indicating the contribution of the fast conduction system. Optimization of biventricular pacing by adjusting VV-interval showed a decrease of e-DYS from 102 to 36 ms with only a small Vd increase and QRS duration decrease. CONCLUSIONS: The UHF-ECG technique provides novel information about electrical activation of the ventricles from a standard ECG electrode setup, potentially improving the selection of patients for CRT and application of CRT.

Feasibility of directional percutaneous epicardial ablation with a partially insulated catheter.

PURPOSE: To demonstrate the feasibility of directional percutaneous epicardial ablation using a partially insulated catheter. METHODS: Partially insulated catheter prototypes were tested in 12 (6 canine, 6 porcine) animal studies in two centers. Prototypes had interspersed windows to enable visualization of epicardial structures with ultrasound. Epicardial unipolar ablation and ablation between two electrodes was performed according to protocol (5-60 W power, 0-60 mls/min irrigation, 78 s mean duration). RESULTS: Of 96 epicardial ablation attempts, unipolar ablation was delivered in 53.1%. Electrogram evidence of ablation, when analyzable, occurred in 75 of 79 (94.9%) therapies. Paired pre/post-ablation pacing threshold (N = 74) showed significant increase in pacing threshold post-ablation (0.9 to 2.6 mA, P < .0001). Arrhythmias occurred in 18 (18.8%) therapies (11 ventricular fibrillation, 7 ventricular tachycardia), mainly in pigs (72.2%). Coronary artery visualization was variably successful. No phrenic nerve injury was noted during or after ablation. Furthermore, there were minimal pericardial changes with ablation. CONCLUSIONS: Epicardial ablation using a partially insulated catheter to confer epicardial directionality and protect the phrenic nerve seems feasible. Iterations with ultrasound windows may enable real-time epicardial surface visualization thus identifying coronary arteries at ablation sites. Further improvements, however, are necessary.

Electrochemical and Reactivity Studies of N→Sn Coordinated Distannynes.

Studies are focused on the redox potentials of N→Sn coordinated distannnynes {L1-3 Sn}2 (L1 =1, L2 =2 and L3 =3, in which L1 is [C6 H3 -2,6-(Me2 NCH2 )2 ]- , L2 is [C6 H2 -2,4-tBu2 -6-(Et2 NCH2 )]- and L3 is [C6 H2 -2,4-tBu2 -6-(DippN=CH)]- ; Dipp=2,6-diisopropylphenyl), containing the tin atom in oxidation state +I. Distannynes 1-3 were used as ligands for transition metals, and complexes [{L1 Sn}2 ⋅Fe(CO)4 ] (4) and [{L2 Sn}2 ⋅Fe(CO)4 ] (5) were prepared. The set of N→Sn coordinated distannynes 1-5 was studied by cyclic voltammetry measurements and the oxidation potentials of tin atoms in 1-5 were determined. The redox potentials are influenced by either ligands L1-3 or SnI →Fe coordination. Oxidation reactions of 1-3 were also studied. The reaction of 2 with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) provided mixed organotin oxide {(L2 SnO)(L2 )Sn(µ-O)}2 (6) as a consequence of the instability of the expected {L2 Sn⋅TEMPO} complex. To support this proposed mechanism, the N→Ge coordinated digermyne {L2 Ge}2 (7) was prepared. The reaction of 7 with TEMPO provided the expected complex {L2 Ge⋅TEMPO} (8).

Ventricular dyssynchrony assessment using ultra-high frequency ECG technique.

PURPOSE: The aim of this proof-of-concept study is to introduce new high-dynamic ECG technique with potential to detect temporal-spatial distribution of ventricular electrical depolarization and to assess the level of ventricular dyssynchrony. METHODS: 5-kHz 12-lead ECG data was collected. The amplitude envelopes of the QRS were computed in an ultra-high frequency band of 500-1000 Hz and were averaged (UHFQRS). UHFQRS V lead maps were compiled, and numerical descriptor identifying ventricular dyssynchrony (UHFDYS) was detected. RESULTS: An electrical UHFQRS maps describe the ventricular dyssynchrony distribution in resolution of milliseconds and correlate with strain rate results obtained by speckle tracking echocardiography. The effect of biventricular stimulation is demonstrated by the UHFQRS morphology and by the UHFDYS descriptor in selected examples. CONCLUSIONS: UHFQRS offers a new and simple technique for assessing electrical activation patterns in ventricular dyssynchrony with a temporal-spatial resolution that cannot be obtained by processing standard surface ECG. The main clinical potential of UHFQRS lies in the identification of differences in electrical activation among CRT candidates and detection of improvements in electrical synchrony in patients with biventricular pacing.

A Novel Defibrillation Tool: Percutaneously Delivered, Partially Insulated Epicardial Defibrillation.

INTRODUCTION: Epicardial defibrillation systems currently require surgical access. We aimed to develop a percutaneous defibrillation system with partially-insulated epicardial coils to focus electrical energy on the myocardium and prevent or minimize extra-cardiac stimulation. METHODS: We tested 2 prototypes created for percutaneous introduction into the pericardial space via a steerable sheath. This included a partially-insulated defibrillation coil and a defibrillation mesh with a urethane balloon acting as an insulator to the face of the mesh not in contact with the epicardium. The average energy associated with a chance of successful defibrillation 75% of the time (ED75) was calculated for each experiment. RESULTS: Of 16 animal experiments, 3 pig experiments had malfunctioning mesh prototypes such that results were unreliable; these were excluded. Therefore, 13 animal experiments were analyzed - 6 canines (29.8±4.0kg); 7 pigs (41.1±4.4kg). The overall ED75 was 12.8±6.7J (10.9±9.1J for canines; 14.4±3.9J in pigs [P=0.37]). The lowest ED75 obtained in canines was 2.5J while in pigs it was 9.5J. The lowest energy resulting in successful defibrillation was 2J in canines and 5J in pigs. There was no evidence of coronary vessel injury or trauma to extra-pericardial structures. CONCLUSION: Percutaneous, epicardial defibrillation using a partially insulated coil is feasible and appears to be associated with low defibrillation thresholds. Focusing insulation may limit extra-cardiac stimulation and potentially lower energy requirements for efficient defibrillation.

Prevalence and Predictors of Early Heart Failure With Preserved Ejection Fraction in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of diastolic dysfunction and heart failure. The purpose of this study was to identify independent predictors of early (ie, only exercise-induced) heart failure with preserved ejection fraction (HFpEF) and to describe the prevalence of early HFpEF among patients with paroxysmal AF. METHODS AND RESULTS: One hundred patients with paroxysmal AF and preserved left ventricular ejection fraction (LVEF) underwent catheterization for left atrial pressure (LAP) measurements at rest and at the peak of arm exercise (LAP-exe). Based on resting and exercise LAP values, the patients were divided into 3 groups. Sixty-one patients had no evidence of HFpEF (LAP at rest ≤15 mm Hg, LAP-exe <25 mm Hg). Twenty-five subjects had early HFpEF (LAP at rest ≤15 mm Hg, LAP-exe ≥25 mm Hg, prevalence 25%). Fourteen patients already had HFpEF at rest (LAP at rest >15 mm Hg). Multivariate exact logistic regression analysis identified age ≥58 years, LAP at rest ≥11 mm Hg, and peak systolic mitral annular velocity ≤9.3 cm/s to be independent predictors of early HFpEF. CONCLUSIONS: In patients with paroxysmal AF and preserved LVEF, there appears to be a clinically significant prevalence of early HFpEF.

Hydrosilylation of RN=CH Imino-Substituted Pyridines without a Catalyst.

Treatment of the neutral pyridine-based ligands L1 -L3 , bearing either one or two RN=CH imine moieties {where L1 and L2 are N,N-chelating ligands 2-(RN=CH)C5 H4 N (R=Ph (L1 ) or R=2,4,6-Ph3 C6 H2 (L2 )) and L3 is the N,N,N-chelating ligand 2,6-(RN=CH)2 C5 H3 N (R=2,6-iPr2 C6 H3 )}, with HSiCl3 yielded N→Si-coordinated silicon(IV) amides 2-{Cl3 SiN(R)CH2 }C5 H4 N (1, R=Ph; 2, R=2,4,6-Ph3 C6 H2 ) and 2-{Cl3 SiN(R)CH2 }-6-(RN=CH)C5 H4 N (3, R=2,6-iPr2 C6 H3 ). The organosilicon amides 1-3 are the products of spontaneous hydrosilylation of the RN=CH imine moiety induced by N→Si coordination of the proposed N,N-chelated chlorosilanes L1 →SiHCl3 (1 a), L2 →SiHCl3 (2 a), and L3 →SiHCl3 (3 a). Furthermore, the reaction of L3 with an excess of HSiCl3 provided the intramolecularly coordinated chlorosilicon diamide cyclo-{(C5 H3 N)-1,3-(CH2 NR)2 }SiCl2 (4) (R=2,6-iPr2 C6 H3 ) as the product of spontaneous reduction of both RN=CH imine moieties. The compounds have been characterized by NMR spectroscopy (1-4) and single-crystal X-ray diffraction analysis (1, 3, and 4). The mechanism of the hydrosilylation of the second RN=CH imine moiety in 3 by an excess of SiHCl3 has also been studied. The experimental work is supplemented by DFT calculations.

Improvement in the prediction of exercise-induced elevation of left ventricular filling pressure in patients with normal left ventricular ejection fraction.

BACKGROUND: Noninvasive diagnosis of exercise-induced elevation of left ventricular filling pressure is difficult and remains unsatisfactory. The aim of this study was to assess the accuracy of the ratio of early diastolic transmitral (E) to mitral annular (e') velocity and to determine new parameters or parameter combinations with the ability to predict exercise-induced left atrial pressure (LAP) elevation. METHODS AND RESULTS: Eighty patients with paroxysmal atrial fibrillation (AF) referred for catheter AF ablation underwent simultaneous exercise echocardiography and direct invasive LAP measurements, as well as a resting and postexercise biomarker analysis. Exercise E/e' ≥8.85 predicted exercise LAP ≥20 mm Hg with 61.5% sensitivity and 88.9% specificity (area under the curve [AUC], 0.76). Of all of the individual parameters tested, the best prediction was achieved with exercise E/s' (s'=peak systolic mitral annular velocity) ≥8.75 (sensitivity, 88.5%; specificity, 64.8%; positive predictive value, 54.8%; negative predictive value, 92.1%; AUC, 0.84). However, the combination of exercise E/A (A = late diastolic transmitral flow velocity) ≥1.22 + exercise E/e' ≥8.85 + exercise s'≤11.05 cm/s provided the most precise prediction of exercise LAP elevation (sensitivity, 84.6%; specificity, 79.6%; positive predictive value, 66.7%; negative predictive value, 91.5%; AUC, 0.90). CONCLUSIONS: Exercise E/e', when used as a sole parameter, was not sufficiently reliable to predict exercise-induced elevation of LAP. The application of a multivariate-adjusted combination of parameters appeared to be the preferable approach for the noninvasive prediction of exercise LAP elevation.