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Aims Uncertainty exists over the importance of device-detected short-duration atrial arrhythmias. Continuous atrial diagnostics, through home monitoring (HM) technology (BIOTRONIK, Berlin, Germany), provides a unique opportunity to assess frequency and quantity of atrial fibrillation (AF) episodes defined as atrial high-rate events (AHRE). Methods and results Prospective data from 560 heart failure (HF) patients (age 67 ± 10 years, median ejection fraction 27%) patients with a cardiac resynchronization therapy (CRT) device capable of HM from two multi-centre studies were analysed. Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of >180 beats for at least 1% or total of 14 min per day. The primary endpoint was incidence of a thromboembolic (TE) event. Secondary endpoints were cardiovascular death, hospitalization because of AF, or worsening HF. Over a median 370-day follow-up AHRE occurred in 40% of patients with 11 (2%) patients developing TE complications and mortality rate of 4.3% (24 deaths, 16 with cardiovascular aetiology). Compared with patients without detected AHRE, patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications (P= 0.006). The majority of patients (73%) did not show a temporal association with the detected atrial episode and their adverse event, with a mean interval of 46.7 ± 71.9 days (range 0–194) before the TE complication. Conclusion In a high-risk cohort of HF patients, device-detected atrial arrhythmias are associated with an increased incidence of TE events. A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate. Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients. [ABSTRACT FROM PUBLISHER]

Background/Aims: The aim of the study was to characterize the whole cell current of the two-pore domain potassium channel TASK-1 (K2P3) in mouse ventricular cardiomyocytes (ITASK-1) and to analyze the cardiac phenotype of the TASK-1-/- mice. Methods and Results: We have quantified the ventricular ITASK-1 current using the blocker A293 and TASK-1-/- mice. Surface electrocardiogram recordings of TASK-1-/- mice showed a prolonged QTc interval and a broadened QRS complex. The differences in electrocardiograms between wild type and TASK-1-/- mice disappeared during sympathetic stimulation of the animals. Quantitative RT-PCR, patch clamp recordings and measurements of hemodynamic performance of TASK-1-/- mice revealed no major compensatory changes in ion channel transcription. Action potential recordings of TASK-1-/- mouse cardiomyocytes indicated that ITASK-1 modulates action potential duration. Our in vivo electrophysiological studies showed that isoflurane, which activates TASK-1, slowed heart rate and atrioventricular conduction of wild-type but not of TASK-1-/- mice. Conclusion: The results of an invasive electrophysiological catheter protocol in combination with the observed QRS time prolongation in the surface electrocardiogram point towards a regulatory role of TASK-1 in the cardiac conduction system. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Heart failure patients are often equipped with implanted devices and are frequently hospitalized due to volume overload. Reliable prediction of imminent fluid congestion has the potential to provide early detection of cardiac decompensation and therefore might be capable of enhancing therapy management. We investigated whether implant-based impedance (Z) measurement is closely correlated with directly assessed extravascular lung water and might thus be useful for patient monitoring. [ABSTRACT FROM PUBLISHER]

Background: Several studies showed the beneficial effect of pacemaker implantation on cognitive performance in patients with bradycardia. But it has never been investigated if patients with chronotropic incompetence may improve their cognitive performance if treated by a rate-adaptive system reacting to mental stress in comparison to the most frequently used accelerometer-driven pacing. Methods: The randomized, single-blind, multicenter COGNITION study evaluates if closed loop stimulation (CLS) offers incremental benefit in the speed of cognitive performance and the overall well-being of elderly patients with bradycardia compared with accelerometer-based pacing. Four hundred chronotropically incompetent patients older than 55 years will be randomized 3–6 weeks after implantation to CLS or accelerometer sensor. Follow-up visits are performed after 12 and 24 months. The speed of cognitive performance, which is the underlying function influencing all other aspects of cognitive performance, will be assessed by the number connection test, a standardized psychometric test for the elderly. Secondary endpoints include patient self-assessment of different aspects of health (by visual analogue scales), quality of life (by SF-8 health survey), the incidence of atrial fibrillation (episodes lasting for longer than 24 hours), and the frequency of serious adverse events. Conclusion: In the ongoing COGNITION study, we aim at long-term comparison of two rate-adaptive systems, focusing on the cognitive performance of the patients, which was neglected in the past evaluation of pacemaker sensors. [ABSTRACT FROM AUTHOR]

Aims: We compared pacing rate adaptation based on closed loop stimulation (CLS) or accelerometer sensor (AS) during acute mental and physical stress in the same patient. [ABSTRACT FROM PUBLISHER]

Cardiomyocytes are notoriously difficult to transfect using standard techniques unless viral vectors such as recombinant adenoviruses are used. Generation of recombinant adenoviruses is, however, a complex and timeconsuming procedure and not possible for every DNA construct. We therefore optimized DNA/polylysine/adenovirus complexing for efficient gene transfer in neonatal rat cardiomyocytes determining the critical parameters for this method. Importantly, not only the concentration of the various components but also the method used for plasmid purification is critical for this transfection technique. Cesium-chloride-purified DNA is inferior to anion-exchange methods for this purpose possibly because of altered ionic properties. In the second part of this study, we could demonstrate silent gene transfer into cardiomyocytes applying this optimized technique to plasmids encoding luciferase or ß-galactosidase cDNAs under the control of the cytomegalovirus immediate- early promoter. Phorbol myristate acetate and/or forskolin increased the amount of ß-galactosidase positive cells up to fivefold. Luciferase activity could even be increased as much as ninefold. These results demonstrate that the cytomegalovirus promoter is not maximally active in neonatal rat cardiomyocytes under basal conditions. In fact, a large proportion of cells is silently transfected and seems to express (an) inhibitor( s) of transcription from the CMV promoter that can be overcome by stimulation of cAMP- or protein kinase C-dependent pathways. [ABSTRACT FROM AUTHOR]

Voltage-gated Na[sup +] channels are composed of pore-forming α and auxiliary β subunits. The majority of Na[sup +] channels in the heart contain tetrodotoxin (TrX)-insensitive Na[sub v]1.5 α subunits, but TTXsensitive brain-type Na[sup +] channel α subunits are present and functionally important in the transverse tubules of ventricular myocytes. Sinoatrial (SA) nodal cells were identified in cardiac tissue sections by staining for connexin 43 (which is expressed in atrial tissue but not in SA node), and Na[sup +] channel localization was analyzed by immunocytochemical staining with subtype-specific antibodies and confocal microscopy. Brain-type TTX-sensitive Navl.1 and Na[sub v]1.3 α subunits and all four β subunits were present in mouse SA node, but Na[sub v]l.5 α subunits were not. Na[sub v]l.1 α subunits were also present in rat SA node. Isolated mouse hearts were retrogradely perfused in a Langendorff preparation, and electrocardiograms were recorded. Spontaneous heart rate and cycle length were constant, and heart rate variability was small under control conditions. In contrast, in the presence of 100 nM TTx to block TTX-sensitive Na[sup +] channels specifically, we observed a significant reduction in spontaneous heart rate and markedly greater heart rate variability, similar to sick-sinus syndrome in man. We hypothesize that brain-type Na[sup +] channels are required because their more positive voltage dependence of inactivation allows them to function at the depolarized membrane potential of SA nodal cells. Our results demonstrate an important contribution of TTX-sensitive brain-type Na[sup +] channels to SA nodal automaticity in mouse heart and suggest that they may also contribute to SA nodal function and dysfunction in human heart. [ABSTRACT FROM AUTHOR]

Examines the role of brain-type sodium channels in the coupling of cell surface depolarization in heart contraction. Reduction of left ventricular function; Presence of cardiac isoform in the intercalated disks; Properties of the sodium current in ventricular myocytes.