Role of catheter location on local impedance measurements and clinical outcome with the new direct sense technology in cardiac ablation procedures.

Background: A novel catheter technology (direct sense, DS) enables periprocedural local impedance (LI) measurement for estimation of tissue contact during radiofrequency ablation (RFA) for real-time assessment of lesion generation. This measure reflects specific local myocardial conduction properties in contrast to the established global impedance (GI) using a neutral body electrode. Our study aimed to assess representative LI values for the cardiac chambers, to evaluate LI drop in response to RF delivery and to compare those values to established GI measures in patients undergoing RFA procedures. Methods and Results: Seventy-three patients undergoing RFA with the DS technology were included. Within the cardiac chambers, baseline LI was significantly different, with the highest values in the left atrium (LA 107.5 ± 14.3 Ω; RV 104.6 Ω ± 12.9 Ω; LV 100.7 Ω ± 11.7 Ω, and RA 100.5 Ω ± 13.4 Ω). Baseline LI was positively correlated to the corresponding LI drop during RF delivery (R2 = 0.26, p = 0.01) representing a promising surrogate of lesion generation. The observed mean LI drop (15.6 ± 9.5 Ω) was threefold higher as GI drop (4.9 ± 7.4 Ω), p < 0.01. We evaluated the clinical outcome in a subgroup of patients undergoing DS-guided pulmonary vein isolation, which was comparable regarding arrhythmia recurrence to a conventional ablation cohort (57 % vs 50 %, p = 0.2). Conclusion: We provide detailed information on LI measures in electrophysiological procedures with significant differences within the cardiac chambers highlighting that RFA-related LI drop can serve as a promising surrogate for real-time assessment of lesion generation. Guiding the electrophysiologist in RFA procedures, this additional information promises to improve safety profile and success rates in the interventional treatment of arrhythmias.

High-density Mapping Guided Pulmonary Vein Isolation for Treatment of Atrial Fibrillation - Two-year clinical outcome of a single center experience.

Pulmonary vein isolation (PVI) as interventional treatment for atrial fibrillation (AF) aims to eliminate arrhythmogenic triggers from the PVs. Improved signal detection facilitating a more robust electrical isolation might be associated with a better outcome. This retrospective cohort study compared PVI procedures using a novel high-density mapping system (HDM) with improved signal detection vs. age- and sex-matched PVIs using a conventional 3D mapping system (COM). Endpoints comprised freedom from AF and procedural parameters. In total, 108 patients (mean age 63.9 ± 11.2 years, 56.5% male, 50.9% paroxysmal AF) were included (n = 54 patients/group). Our analysis revealed that HDM was not superior regarding freedom from AF (mean follow-up of 494.7 ± 26.2 days), with one- and two-year AF recurrence rates of 38.9%/46.5% (HDM) and 38.9%/42.2% (COM), respectively. HDM was associated with reduction in fluoroscopy times (18.8 ± 10.6 vs. 29.8 ± 13.4 min; p < 0.01) and total radiation dose (866.0 ± 1003.3 vs. 1731.2 ± 1978.4 cGy; p < 0.01) compared to the COM group. HDM was equivalent but not superior to COM with respect to clinical outcome after PVI and resulted in reduced fluoroscopy time and radiation exposure. These results suggest that HDM-guided PVI is effective and safe for AF ablation. Potential benefits in comparison to conventional mapping systems, e.g. arrhythmia recurrence rates, have to be addressed in randomized trials.

Critical inflammatory mechanisms underlying arrhythmias.

During the past few decades, cardiovascular research has increasingly focused on systemic inflammatory mechanisms, particularly in the field of atherosclerosis but also in association with cardiac arrhythmogenesis. Objective inflammatory markers including C­reactive protein and cytokines, also called "biomarkers," seem to serve as predictors of onset and prognosis of cardiac arrhythmias. This review gives an overview of potential mechanisms underlying inflammatory processes and arrhythmias, especially atrial fibrillation, which is the most common sustained arrhythmia in daily clinical routine. The association between inflammatory pathways and cardiac arrhythmia is highly complex and includes direct as well as indirect pathways. While past research into arrhythmia focused on fibrosis, altered action potential properties, and ischemia, novel concepts include coagulation and inflammation in cardiac tissue. The underlying mechanisms are altered electrophysiological properties, including ion channel disturbance, early and late afterdepolarizations, as well as enhanced fibrosis and structural remodeling in cardiomyopathies. These pathophysiological factors favor the occurrence of ectopic pacemakers as well as re-entry tachycardia. Further studies are essential to better understand the main inflammatory signal cascades and the exact proarrhythmic effect of interacting key mediators. This will facilitate the evaluation of future anti-inflammatory therapeutic approaches for arrhythmias, analogous to recent developments in atherosclerosis.

Inhibition of cardiac Kv1.5 and Kv4.3 potassium channels by the class Ia anti-arrhythmic ajmaline: mode of action.

Ajmaline is a class Ia anti-arrhythmic compound that is widely used for the diagnosis of Brugada syndrome and the acute treatment of atrial or ventricular tachycardia. For ajmaline, inhibitory effects on a variety of cardiac K(+) channels have been observed, including cardiac Kv1 and Kv4 channels. However, the exact pharmacological properties of channel blockade have not yet been addressed adequately. Using two different expression systems, we analysed pharmacological effects of ajmaline on the potassium channels Kv1.5 and Kv4.3 underlying cardiac I Kur and I to current, respectively. When expressed in a mammalian cell line, we find that ajmaline inhibits Kv1.5 and Kv4.3 with an IC50 of 1.70 and 2.66 µM, respectively. Pharmacological properties were further analysed using the Xenopus expression system. We find that ajmaline is an open channel inhibitor of cardiac Kv1.5 and Kv4.3 channels. Whereas ajmaline results in a mild leftward shift of Kv1.5 activation curve, no significant effect on Kv4.3 channel activation could be observed. Ajmaline did not significantly affect channel inactivation kinetics. Onset of block was fast. For Kv4.3 channels, no significant effect on recovery from inactivation or channel deactivation could be observed. Furthermore, there was no use-dependence of block. Taken together, we show that ajmaline inhibits cardiac Kv1.5 and Kv4.3 channels at therapeutic concentrations. These data add to the current understanding of the electrophysiological basis of anti-arrhythmic action of ajmaline.

Acute and subacute effects of the selective serotonin-noradrenaline reuptake inhibitor duloxetine on cardiac hERG channels.

Duloxetine is a selective serotonin-noradrenaline reuptake inhibitor approved for treatment of major depressive disorder. So far, duloxetine has been found to be well tolerated and reported cardiac side effects were negligible. However, pharmacological effects on cardiac hERG channels have not been properly addressed yet. hERG channels were expressed in Xenopus oocytes and a human embryonic kidney (HEK) cell line. Currents were measured using voltage clamp and patch clamp techniques. Channel surface expression was quantified using Western blot analysis. We found that duloxetine inhibits heterologously expressed hERG channels in a concentration-dependent manner, yielding an IC50 of 142.8 µM in Xenopus oocytes. Inhibitory effects were even more pronounced when using a mammalian cell line resulting in a 34 or 59% current decrease by 10 or 30 µM duloxetine, respectively. Duloxetine did not affect channel activation or inactivation kinetics. However, channel deactivation was accelerated by duloxetine. We further showed that inhibition occurs in the open and inactivated, but not closed, states. There was no frequency dependence of block. However, effects of duloxetine were significantly attenuated when using the hERG pore mutants Y652A and F656A. Subacute effects of duloxetine on hERG channel expression were analyzed using the Western blot technique. We found that incubation with duloxetine results in a concentration-dependent decrease of channel surface expression. Whereas inhibitory effects of duloxetine seem negligible under therapeutically relevant concentrations, hERG block should be considered in cases of duloxetine overdose and when administering duloxetine to patients susceptible to drug-induced QT prolongation.