Synthesis, spectroscopic findings and crystal engineering of Pb(ii)-Salen coordination polymers, and supramolecular architectures engineered by σ-hole/spodium/tetrel bonds: a combined experimental and theoretical investigation.

Spontaneous self-assembly is one of the available synthetic routes to achieve structurally versatile and unique crystal complexes with selected metal-ligand combinations in the spirit of pseudohalides. In this endeavour, we designed a novel 1D coordination polymer (CP), [(Cd)(Pb)(L)(η1-NCS)(η1-SCN)] n (1), using a compartmental Salen ligand (H3L) in the presence of NaSCN. The characterization of the CP was accomplished using several spectroscopic techniques: MALDI-TOF, PXRD, SEM, EDX mapping, and single-crystal X-ray crystallography. The CP crystallizes in the monoclinic space group P21/c with Z = 4. SCXRD reveals Cd(ii) and Pb(ii) metal ions fulfilled distorted square pyramidal and hemi-directed coordination spheres. Cd(ii) is placed in the inner N2O2 and heavier Pb(ii) in the outer O4 compartments of the de-protonated form of the ligand [L]2-. Supramolecular interactions in the intricate crystal structure produced attractive molecular architectures of the compound. The flexible aliphatic -OH pendent group coordinates with the Pb(ii) ions. This unique binding further elevates the supramolecular crystal topographies. The supramolecular interactions were authenticated by Hirshfeld surface analysis (HSA). The observation of the recurring unconventional tetrel bonds was rationalized by DFT calculations and surface plots of molecular electrostatic potential (MEP). In the 1D polymeric chain in the complex, the O-atom of the -OH groups shows a tetrel bonding interaction with the Pb atom. We have found that the combination of QTAIM/NCI and QTAIM/ELF plots helps reveal the nature of these contacts. Moreover, the QTAIM/ELF plot determines the donor-acceptor interaction between the O-atom and the Pb atom, establishing the σ-hole. Agreeably, the σ-hole interaction also helps Pb(ii) serve as a Lewis acid in the complex. Finally, spodium and tetrel bonds are formed, possible thanks to a hemi-directional coordination sphere of the Pb atoms in the polymer described.

A Computational Study of the Electrophysiological Substrate in Patients Suffering From Atrial Fibrillation.

In the context of cardiac electrophysiology, we propose a novel computational approach to highlight and explain the long-debated mechanisms behind atrial fibrillation (AF) and to reliably numerically predict its induction and sustainment. A key role is played, in this respect, by a new way of setting a parametrization of electrophysiological mathematical models based on conduction velocities; these latter are estimated from high-density mapping data, which provide a detailed characterization of patients' electrophysiological substrate during sinus rhythm. We integrate numerically approximated conduction velocities into a mathematical model consisting of a coupled system of partial and ordinary differential equations, formed by the monodomain equation and the Courtemanche-Ramirez-Nattel model. Our new model parametrization is then adopted to predict the formation and self-sustainment of localized reentries characterizing atrial fibrillation, by numerically simulating the onset of ectopic beats from the pulmonary veins. We investigate the paroxysmal and the persistent form of AF starting from electro-anatomical maps of two patients. The model's response to stimulation shows how substrate characteristics play a key role in inducing and sustaining these arrhythmias. Localized reentries are less frequent and less stable in case of paroxysmal AF, while they tend to anchor themselves in areas affected by severe slow conduction in case of persistent AF.

Arrhythmogenic response to isoproterenol testing vs. exercise testing in arrhythmogenic right ventricular cardiomyopathy patients.

Aims: To compare the arrhythmic response to isoproterenol and exercise testing in newly diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results: We studied isoproterenol [continuous infusion (45 µg/min) for 3 min] and exercise testing (workload increased by 30 W every 3 min) performed in consecutive newly diagnosed ARVC patients. Both tests were evaluated with regard to the incidence of (i) polymorphic premature ventricular contractions (PVCs) and couplet(s) or (ii) sustained or non-sustained ventricular tachycardia (VT) with left bundle branch block [excluding right ventricular outflow tract VT]; and compared to a control group referred for the evaluation of PVCs without structural heart disease. Thirty-seven ARVC patients (63.5% male, age 38 ± 16 years) were included. The maximal sinus rhythm heart rate achieved during isoproterenol testing was significantly lower compared to exercise testing (149 ± 17 bpm vs. 166 ± 19 bpm, P < 0.0001). However, the incidence of polymorphic ventricular arrhythmias was much higher during isoproterenol testing compared to exercise testing [33/37 (89.2%) vs. 16/37 (43.2%), P < 0.0001]. Interestingly, isoproterenol testing was arrhythmogenic in all 15 patients in whom baseline PVCs were reduced or suppressed during exercise testing. During both isoproterenol and exercise testing, control group presented a low incidence of ventricular arrhythmias compared to ARVC patients (8.1% vs. 89.2%, P < 0.0001 and 2.7% vs. 43.2%, P < 0.0001, respectively). Conclusions: The incidence of polymorphic ventricular arrhythmias is significantly higher during isoproterenol compared to exercise testing in newly diagnosed ARVC patients, suggesting its potential utility for the diagnosis.

Donor-acceptor interactions in tri(phosphonio)methanide dications [(Ph3P)2CP(X)Ph2]2+ (X = H, Me, CN, NCS, OH, Cl, OTf, F).

The impact of the strongly electron donating carbodiphosphorane moiety in the series of tri(phosphonio)methanide dications as triflate salts [(Ph3P)2CP(X)Ph2][OTf]2 (X = H, Me, CN, NCS, OH, Cl, OTf, F) deriving from [(Ph3P)2CPPh2][OTf] (19[OTf]) is presented. The influence of the introduced substituents X on the electronic structures of these dications is investigated by means of detailed NBO analysis, NMR spectroscopy and X-ray analysis.

Diagnostic yield of cardiovascular magnetic resonance in young-middle aged patients with high-grade atrio-ventricular block.

BACKGROUND: Atrio-ventricular block (AVB) is a rare finding in young or middle-aged adults, often leading to pacemaker implantation (PM) without further investigation. We sought to assess the diagnostic role of cardiovascular magnetic resonance (CMR) in young and middle-aged adults with high-grade AVB. METHODS: We consecutively enrolled young-middle aged (18-65years) patients with high grade AVB referred to CMR after standard clinical assessment (history, electrocardiogram and cardiac rhythm monitoring) prior to PM implantation. Cine and post-contrast imaging were performed in a 1.5T scanner. RESULTS: 34 patients (59% male, mean age 42±12years) with high grade AVB were referred to CMR for suspected ischemic heart disease (IHD)(n=4) and non-ischemic heart disease (NIHD)(n=20); no clear cause was found in 9 patients prior to CMR and 1 patient had suspected lung disease. A pathologic substrate was found on CMR in 15 patients (44%), while a structurally normal heart was reported in 18 (53%). Non-specific findings were reported in 1 patient (3%). There was a fair agreement between CMR and echocardiographic findings (Cohen's kappa 0.243), and CMR provided an entirely new diagnosis in 34% of patients. As compared to the standard clinical assessment, CMR had an additional role in 65% of patients and guided further testing (genetic testing, extra-cardiac imaging) in 9%. CONCLUSIONS: CMR found a pathologic substrate in 44% of patients, mainly NIHD (32%). Half of the patients (53%) had a structurally normal heart. When added to the standard clinical assessment, CMR had an incremental diagnostic role in two thirds of patients.

Carbodiphosphorane mediated synthesis of a triflyloxyphosphonium dication and its reactivity towards nucleophiles.

A carbodiphosphorane ((Ph3P)2C) mediated synthesis of the first triflyloxyphosphonium dication (12+) bearing two electrophilic sites is presented. Depending on the nucleophile, 12+ reacts selectively either at the sulfur atom of the triflyloxy moiety or at the directly attached phosphorus atom. In substitution reactions at the phosphorus atom the triflyloxy moiety serves as a leaving group and enables the synthesis of rare examples of pseudo-halophosphonium dications.

Accuracy of the pacemaker-mediated tachycardia algorithm in Boston Scientific devices.

INTRODUCTION: The incidence of pacemaker-mediated tachycardia (PMT) varies as a function of patient characteristics, device programming and algorithm specificities. We investigated the efficacy of the Boston Scientific algorithm by reviewing PMT episodes in a large device population. METHODS: In this multicenter study, we included 328 patients implanted with a Boston Scientific device: 157 non-dependent patients with RYTHMIQ™ activated (RYTHMIQ group), 76 patients with permanent AV-conduction disorder (AV-block group) and 95 Cardiac Resynchronization Therapy patients (CRT group). For each patient, we reviewed the last 10 remote monitoring-transmitted EGMs diagnosed as PMT. RESULTS: We analyzed 784 PMT episodes across 118 patients. In the RYTHMIQ group, the diagnosis of PMT was correct in most episodes (80%) of which 69% was directly related to the prolongation of the AV-delay associated with the RYTHMIQ algorithm. The usual triggers for PMT were also observed (PVC 16%, PAC 9%). The remainder of the episodes (20%) in RYTHMIQ patients and most episodes of AV-block (66%) and CRT patients (74%) were incorrectly diagnosed as PMT during sinus tachycardia at the maximal tracking rate. The inappropriate intervention of the algorithm during exercise causes non-conducted P-waves, loss of CRT (sustained in six patients) and may have been pro-arrhythmogenic in one patient (induction of ventricular tachycardia). CONCLUSION: Algorithms to minimize ventricular pacing can occasionally have unintended consequences such as PMT. The PMT algorithm in Boston Scientific devices is associated with a high rate of incorrect PMT diagnosis during exercise resulting in inappropriate therapy with non-conducted P-waves, loss of CRT and limited risk of pro-arrhythmic events.

Implantable cardioverter defibrillators in octogenarians: clinical outcomes from a single center.

AIMS: Limited data exist on outcomes in very elderly ICD recipients. We describe outcomes in new ICD and Cardiac Resynchronisation Therapy with Defibrillator (CRT-D) implants in octogenarians at our institution. METHODS: Patients aged 80 years and above who underwent de novo ICD or CRT-D implantation from January 2006 to July 2012 were identified. Clinical data were collected from the procedural record, medical and ICD notes. Baseline characteristics were compared using independent sample t test for continuous variables and Fisher's exact test for categorical variables. Kaplan-Meier curves were constructed. RESULTS: Ten per cent of all new ICD/CRT-D implants were aged 80 years and over. Median age was 83.0 years. Median follow-up was 29 months. Death occurred in 17 (34%). Median time to death was 23 months. Three deaths (6%) occurred within 12 months of ICD implantation. Appropriate therapy (ATP or shock) occurred in 19 (38%). Inappropriate therapy occurred in 6 (12%). Rates of appropriate shocks and inappropriate therapy (shocks and ATP) and significant valvular incompetence were higher amongst deceased patients (P=0.03 OR 5.9 95% CI 1.3-27) and (P=0.02 OR 12 95% CI 1.3-112). Univariate analysis identified diuretic use (P=0.008 95% C.I. 0.05 to 0.63) and appropriate shock (P= 0.025 95% C.I. 1.25 to 26.3) as predictors of mortality. CONCLUSION: Octogenarians make up a small but increasing number of ICD recipients. This study highlights high survival rates at one year with acceptable rates of appropriate and inappropriate device therapy. Ongoing debate regarding the appropriateness of ICD in very elderly patients is warranted.

Screening for atrial fibrillation in patients with obstructive sleep apnoea to reduce ischaemic strokes.

Obstructive sleep apnoea is an independent risk factor for stroke. A number of different mechanisms have been identified which link OSA and stroke including hypertension and oxidative stress. Atrial fibrillation (AF) is likely to play a role in the development of stroke in patients with OSA. Indeed, patients with OSA have a higher incidence of AF than the general population. Given the higher constellation of cardiovascular co-morbidities seen in patients with OSA, we believe that a strategy of actively screening for the presence of AF in patients with OSA and initiating oral anticoagulation therapy when appropriate may reduce the burden of stroke in this population. This is a question that needs to be addressed in a clinical trial.

Substituent effects in cation-π interactions revisited: a general approach based on intrinsic properties of the arenes.

The controversial proposal that substituent effects in cation-π interactions can be attributed mainly to electrostatic effects between the ion and local dipoles has been theoretically studied by analyzing 171 aromatics interacting with Na(+). Our results stress the importance of both electrostatic and π-polarization effects to properly describe cation-π interactions.

Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

Acute autonomic neuropathy. Its occurrence in infectious mononucleosis.

A 13-year-old girl with acute onset of symptoms limited to autonomic dysfunction was found to be suffering from infectious mononucleosis. With symptomatic therapy, improvement gradually occurred over a period of seven months. The documentation of this case widens the spectrum of disorders to be considered as a cause of so-called acute pandysautonomia or autonomic neuropathy.