Clinical and electrophysiologic characteristics of left septal atrial tachycardia

AbstractObjectivesIt was the purpose of this study to define the electrophysiologic (EP) identity of left septal atrial tachycardia (AT).BackgroundThe clinical and EP characteristics of this particular type of arrhythmia have not been fully described.MethodsA total of 120 patients with AT underwent invasive EP evaluation. Five patients (two men and three women; mean age 49 ± 15 years) with left septal AT were identified. Mapping of the right and left atrium was performed using conventional electrode catheters (five patients) and a three-dimensional electroanatomic mapping system (three patients) followed by radiofrequency (RF) ablation at the earliest site of local endocardial activation.ResultsFive tachycardias with a mean cycle length of 320 ± 94 ms were mapped, and the earliest endocardial electrogram occurred 22 ± 10 ms before the onset of the surface P-wave. Three left septal ATs were found to be originating from the left inferoposterior atrial septum and two from the left midseptum. During tachycardia, positive (three patients), biphasic negative-positive deflection (one patient), or isoelectric (one patient) P waves were recorded in lead V1. The inferior leads demonstrated a positive or biphasic P-wave morphology in four of five patients (80%). Four patients were given both adenosine and verapamil during AT. In three of four patients, verapamil successfully terminated AT after adenosine had failed. Adenosine successfully terminated AT in one of four patients. Successful RF ablation was performed in all patients (mean 2.2 ± 1.7 RF applications) without affecting atrioventricular conduction properties. No recurrence of AT was observed after a mean follow-up of 14 ± 8 months.ConclusionsLeft septal AT ablation is safe and effective. There was no consistent P-wave morphology associated with this particular type of AT. This arrhythmia appears to be resistant to adenosine and moderately responsive to calcium antagonists

Use of P wave configuration during atrial tachycardia to predict site of origin

Objectives.This study sought to construct an algorithm to differentiate left atrial from right atrial tachycardia foci on the basis of surface electrocardiograms (ECGs).Background.Atrial tachycardia is an uncommon form of supraventricular tachycardia, often resistant to drug therapy.Methods.A total of 31 consecutive patients with atrial tachycardia due to either abnormal automaticity or triggered rhythm underwent detailed atrial endocardial mapping and successful radiofrequency catheter ablation of a single atrial focus. P wave configuration was analyzed from 12-lead ECGs during tachycardia during either spontaneous or pharmacologically induced atrioventricular block. P waves inscribed above the isoelectric line (TP interval) were classified as positive, below as negative, above and below (or conversely, below and above) as biphasic and flat P waves as isoelectric (0). In 17 patients the tachycardia was located in the right atrium: crista terminalis (n = 4); right atrial appendage (n = 4); lateral wall (n = 4); posteroinferior right atrium (n = 3); tricuspid annulus (n = 1); and near the coronary sinus (n = 1). In 14 patients, atrial tachycardia was located in the left atrium: at the entrance of the right (n = 6) or left (n = 4) superior pulmonary veins; left inferior pulmonary vein (n = 1); inferior left atrium (n = 1); base of left atrial appendage (n = 1); and high lateral left atrium (n = 1).Results.There were no differences in P wave vectors between sites at the right atrial lateral wall versus the right atrial appendage or between sites at the entrance of right versus left superior pulmonary veins. However, analysis of P wave configuration showed that leads aVL and V1were most helpful in distinguishing right atrial from left atrial foci. The sensitivity and specificity of using a positive or biphasic P wave in lead aVL to predict a right atrial focus was 88% and 79%, respectively. The sensitivity and specificity of a positive P wave in lead V1in predicting a left atrial focus was 93% and 88%, respectively.Conclusions.1) Analyses of surface P wave configuration proved to be reasonably good in differentiating right atrial from left atrial tachycardia foci. 2) Leads II, III and aVF were helpful in providing clues for differentiating superior from inferior foci

Decentralized motion planning for multiple mobile robots: The cocktail party model

Abstract. This paper presents an approach for decentralized real-time motion planning for multiple mobile robots operating in a common 2-dimensional environment with unknown stationary obstacles. In our model, a robot can see (sense) the surrounding objects. It knows its current and its target’s position, is able to distinguish a robot from an obstacle, and can assess the instantaneous motion of another robot. Other than this, a robot has no knowledge about the scene or of the paths and objectives of other robots. There is no mutual communication among the robots; no constraints are imposed on the paths or shapes of robots and obstacles. Each robot plans its path toward its target dynamically, based on its current position and the sensory feedback; only the translation component is considered for the planning purposes. With this model, it is clear that no provable motion planning strategy can be designed (a simple example with a dead-lock is discussed); this naturally points to heuristic algorithms. The suggested strategy is based on maze-searching techniques. Computer simulation results are provided that demonstrate good performance and a remarkable robustness of the algorithm (meaning by this a virtual impossibility to create a dead-lock in a “random ” scene). Keywords: mobile robots, autonomous agents, decentralized intelligence, robot motion plannin

Mode of onset of torsade de pointes in congenital long QT syndrome

Objectives.We sought to describe the mode of onset of spontaneous torsade de pointes in the congenital long QT syndrome.Background.Contemporary classifications of the long QT syndrome (LQTS) refer to the congenital LQTS as “adrenergic dependent” and to the acquired LQTS as “pause dependent.” Overlap between these two categories has been recognized, and a subgroup of patients with “idiopathic pause-dependent torsade” has been described. However, it is not known how commonly torsade is preceded by pauses in the congenital LQTS.Methods.We reviewed the electrocardiograms (ECGs) of all our patients with congenital LQTS evaluated for syncope or sudden death (30 patients). Documentation of the onset of torsade de pointes was available for 15 patients. All these patients had “definitive LQTS” by accepted clinical and ECG criteria.Results.Pause-dependent torsade de pointes was clearly documented in 14 of the 15 patients (95% confidence interval 68% to 100%). The cycle length of the pause leading to torsade was 1.3 ± 0.2 times longer than the basic cycle length, and most pauses leading to torsade were unequivocally longer than the preceding basic cycle length (80% of pauses were >80 ms longer than the preceding cycle length).Conclusions.The “long-short” sequence, which has been recognized as a hallmark of torsade de pointes in the acquired LQTS, plays a major role in the genesis of torsade in the congenital LQTS as well. Our findings have important therapeutic implications regarding the use of pacemakers for prevention of torsade in the congenital LQTS

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Diagnosis, management, and outcomes of patients with syncope and bundle branch block

Although patients with syncope and bundle branch block (BBB) are at high risk of developing atrio-ventricular block, syncope may be due to other aetiologies. We performed a prospective, observational study of the clinical outcomes of patients with syncope and BBB following a systematic diagnostic approach. Patients with ≥1 syncope in the last 6 months, with QRS duration ≥120 ms, were prospectively studied following a three-phase diagnostic strategy: Phase I, initial evaluation; Phase II, electrophysiological study (EPS); and Phase III, insertion of an implantable loop recorder (ILR). Overall, 323 patients (left ventricular ejection fraction 56 ± 12%) were studied. The aetiological diagnosis was established in 267 (82.7%) patients (102 at initial evaluation, 113 upon EPS, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia-tachycardia (1), and non-arrhythmic (7). A pacemaker was implanted in 220 (68.1%), an implantable cardioverter defibrillator in 19 (5.8%), and radiofrequency catheter ablation was performed in 3 patients. Twenty patients (6%) had died at an average follow-up of 19.2 ± 8.2 months. In patients with syncope, BBB, and mean left ventricular ejection fraction of 56 ± 12%, a systematic diagnostic approach achieves a high rate of aetiological diagnosis and allows to select specific treatment

Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats

Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Dysregulated protein degradative pathways are increasingly recognized as mediators of human disease. This mechanism may have particular relevance to desmosomal proteins that play critical structural roles in both tissue architecture and cell-cell communication as destabilization/breakdown of the desmosomal proteome is a hallmark of genetic-based desmosomal-targeted diseases, such as the cardiac disease, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no information exists on whether there are resident proteins that regulate desmosomal proteome homeostasis. Here we uncovered a cardiac COP9 desmosomal resident protein complex, composed of subunit 6 of the COP9 signalosome (CSN6), that enzymatically restricted neddylation and targeted desmosomal proteome degradation. CSN6 binding, localization, levels and function were impacted in hearts of classic mouse and human models of ARVD/C impacted by desmosomal loss and mutations, respectively. Loss of desmosomal proteome degradation control due to CSN6 loss and human desmosomal mutations destabilizing CSN6 were also sufficient to trigger ARVD/C in mice. We identified a desmosomal resident regulatory complex that restricted desmosomal proteome degradation and disease

Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production

BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin