Does upgrade to tri-ventricular pacemaker improve long-term clinical response in non-responders to biventricular cardiac resynchronization therapy?

Up to one third of patients with biventricular (BiV) cardiac resynchronization therapy (CRT) are non-responders.1 § Greater clinical response to CRT has been shown in patients given TriV CRT compared to BiV CRT as de novo device therapy. 2 This abstract investigates if upgrade to TriV CRT in non-responders to BiV CRT will improve long-term clinical outcom

Pulmonary Vein Isolation using a High Density Mesh Ablator Catheter: Incorporation of three-Dimensional Navigation and Mappin

Background: We evaluated the use of a novel High Density Mesh Ablator (HDMA) catheter in combination with three-dimensional navigation for the treatment of paroxysmal atrial fibrillation. Methods: The HDMA catheter was used to carry out pulmonary vein isolation in a consecutive series of patients. Three-dimensional geometry of the left atrial-pulmonary vein (LA-PV) junctions were first created with the HDMA catheter. Ostial, proximal and distal sites within the pulmonary veins were tagged with catheter shadows on the created geometry to allow for re-interrogation of these exact sites after ablation. Results: The HDMA catheter was successfully used to create three dimensional geometry of the LA-PV junction in a total of 20 pulmonary veins which involved 5 patients. In all cases, ostial ablation alone was sufficient to achieve electrical isolation. No significant pulmonary vein stenosis was seen acutely after ablation. Conclusion: We describe the successful use of the novel HDMA catheter to create three-dimensional geometry of the LA-PV junction to assist with pulmonary vein isolation

Increase in organization index predicts atrial fibrillation termination with flecainide post-ablation: spectral analysis of intracardiac electrograms

Aims: The mechanism of the action of flecainide in the termination of human atrial fibrillation (AF) is not fully understood. We studied the acute effects of flecainide on AF electrograms in the time and frequency domain to identify factors associated with AF termination. Methods and results: Patients who were still in AF at the end of catheter ablation for AF were given intravenous flecainide. Dominant frequency (DF) and organization index (OI) were obtained by fast Fourier transform of electrograms from the coronary sinus catheter over 10 s in AF, before and after flecainide infusion. Mean AF cycle length (CL) was also calculated. Twenty-six patients were studied (16 paroxysmal AF and 10 persistent AF). Seven converted to sinus rhythm (SR) with flecainide. In all patients, mean CL increased from 211 ± 44 to 321 ± 85 ms ( P \u3c 0.001). Mean DF decreased from 5.2 ± 1.03 to 3.6 ± 1.04 Hz ( P \u3c 0.001). Mean OI was 0.33 ± 0.13 before and 0.32 ± 0.11 after flecainide ( P = 0.90). Comparing patients who converted to SR with those who did not, OI post-flecainide was 0.41 ± 0.12 vs. 0.29 ± 0.10 ( P = 0.013), and the relative change in OI was 29 ± 33 vs. −3.9 ± 27% ( P = 0.016), respectively. No significant difference was noted in the change in CL and DF in the two groups. Conclusion: Increase in OI, independent of changes to CL and DF, appears critical to AF termination with flecainide. Increase in OI holds promise as a sensitive predictor of AF termination

Electrophysiological effects of nicotinic and electrical stimulation of intrinsic cardiac ganglia in the absence of extrinsic autonomic nerves in the rabbit heart

BackgroundThe intrinsic cardiac nervous system is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function.ObjectiveThe goals of this study were to provide a complete picture of the neurotransmitter/neuromodulator profile of the rabbit intrinsic cardiac nervous system and to determine the influence of spatially divergent ganglia on cardiac electrophysiology.MethodsNicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff-perfused rabbit heart. Functional effects on sinus rate and atrioventricular conduction were measured. Immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase, and/or neuronal nitric oxide synthase (nNOS) was performed using whole mount preparations.ResultsStimulation within all ganglia produced either bradycardia, tachycardia, or a biphasic brady-tachycardia. Electrical stimulation of the right atrial and right neuronal cluster regions produced the largest chronotropic responses. Significant prolongation of atrioventricular conduction was predominant at the pulmonary vein-caudal vein region. Neurons immunoreactive (IR) only for ChAT, tyrosine hydroxylase, or nNOS were consistently located within the limits of the hilum and at the roots of the right cranial and right pulmonary veins. ChAT-IR neurons were most abundant (1946 ± 668 neurons). Neurons IR only for nNOS were distributed within ganglia.ConclusionStimulation of intrinsic ganglia, shown to be of phenotypic complexity but predominantly of cholinergic nature, indicates that clusters of neurons are capable of independent selective effects on cardiac electrophysiology, therefore providing a potential therapeutic target for the prevention and treatment of cardiac disease

A systematic review of the spectrum of cardiac arrhythmias in Sub-Saharan Africa

Major structural cardiovascular diseases are associated with cardiac arrhythmias, but their full spectrum remains unknown in sub-Saharan Africa (SSA), which we addressed in this systematic review. Atrial fibrillation/atrial flutter (AF/AFL) prevalence is 16–22% in heart failure, 10–28% in rheumatic heart disease, 3–7% in cardiology admissions, but <1% in the general population. Use of oral anticoagulation is heterogenous (9–79%) across SSA. The epidemiology of sudden cardiac arrest/death is less characterized in SSA. Cardiopulmonary resuscitation is challenging, owing to low awareness and lack of equipment for life-support. About 18% of SSA countries have no cardiac implantable electronic devices services, leaving hundreds of millions of people without any access to treatment for advanced bradyarrhythmias, and implant rates are more than 200-fold lower than in the western world. Management of tachyarrhythmias is largely non-invasive (about 80% AF/AFL via rate-controlled strategy only), as electrophysiological study and catheter ablation centers are almost non-existent in most countries

A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

Background: In order to facilitate implementation of precision medicine in clinical management of cancer, there is a need to harmonise and standardise the reporting and interpretation of clinically relevant genomics data. / Methods: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to propose a classification system for molecular aberrations based on the evidence available supporting their value as clinical targets. A group of experts from several institutions was assembled to review available evidence, reach a consensus on grading criteria and present a classification system. This was then reviewed, amended and finally approved by the ESMO TR and PM WG and the ESMO leadership. / Results: This first version of the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) defines six levels of clinical evidence for molecular targets according to the implications for patient management: tier I, targets ready for implementation in routine clinical decisions; tier II, investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed; tier III, clinical benefit previously demonstrated in other tumour types or for similar molecular targets; tier IV, preclinical evidence of actionability; tier V, evidence supporting co-targeting approaches; and tier X, lack of evidence for actionability. / Conclusions: The ESCAT defines clinical evidence-based criteria to prioritise genomic alterations as markers to select patients for targeted therapies. This classification system aims to offer a common language for all the relevant stakeholders in cancer medicine and drug development

Potential application of digitally linked tuberculosis diagnostics for real-time surveillance of drug-resistant tuberculosis transmission: Validation and analysis of test results

YesBackground: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. Objective: We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. Methods: We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance–determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains’ available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. Results: The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers’ claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results. Conclusions: We propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking.KCN was supported by Erasmus Mundus Joint Doctorate Fellowship grant 2016-1346, and BCdJ, LR, and CJM were supported by European Research Council-INTERRUPTB starting grant 311725

Enhancement of Antiferromagnetic Correlations Induced by Nonmagnetic Impurities: Origin and Predictions for NMR Experiments

Spin models that have been proposed to describe dimerized chains, ladders, two dimensional antiferromagnets, and other compounds are here studied when some spins are replaced by spinless vacancies, such as it occurs by $Zn$ doping. A small percentage of vacancies rapidly destroys the spin gap, and their presence induces enhanced antiferromagnetic correlations near those vacancies. The study is performed with computational techniques which includes Lanczos, world-line Monte Carlo, and the Density Matrix Renormalization Group methods. Since the phenomenon of enhanced antiferromagnetism is found to occur in several models and cluster geometries, a common simple explanation for its presence may exist. It is argued that the resonating-valence-bond character of the spin correlations at short distances of a large variety of models is responsible for the presence of robust staggered spin correlations near vacancies and lattice edges. The phenomenon takes place regardless of the long distance properties of the ground state, and it is caused by a ``pruning'' of the available spin singlets in the vicinity of the vacancies. The effect produces a broadening of the low temperature NMR signal for the compounds analyzed here. This broadening should be experimentally observable in the structurally dimerized chain systems $Cu(NO_3)_2\cdot2.5H_2O$, $CuWO_4$, $(VO)_2P_2O_7$, and $Sr_{14}Cu_{24}O_{41}$, in ladder materials such as $Sr Cu_2 O_3$, in the spin-Peierls systems $CuGeO_3$ and $NaV_2 O_5$, and in several others since it is a universal effect common to a wide variety of models and compounds.Comment: 18 pages revtex with 26 figures include

Cardiac innervation in acute myocardial ischaemia/reperfusion injury and cardioprotection

Acute myocardial infarction (AMI) and the heart failure (HF) that often complicates this condition, are among the leading causes of death and disability worldwide. To reduce myocardial infarct (MI) size and prevent heart failure, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). In this regard, targeting cardiac innervation may provide a novel therapeutic strategy for cardioprotection. A number of cardiac neural pathways mediate the beneficial effects of cardioprotective strategies such as ischaemic preconditioning and remote ischaemic conditioning, and nerve stimulation may therefore provide a novel therapeutic strategy for cardioprotection. In this article, we provide an overview of cardiac innervation and its impact on acute myocardial IRI, the role of extrinsic and intrinsic cardiac neural pathways in cardioprotection, and highlight peripheral and central nerve stimulation as a cardioprotective strategy with therapeutic potential for reducing MI size and preventing HF following AMI. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225