Outcomes in patients with dual antegrade conduction in the atrioventricular node: insights from a multicentre observational study

Background Supraventricular tachycardias induced by dual antegrade conduction via the atrioventricular (AV) node are rare but often misdiagnosed with severe consequences for the affected patients. As long-term follow-up in these patients was not available so far, this study investigates outcomes in patients with dual antegrade conduction in the AV node. Methods and results In this multicentre observational study, patients from six European centres were studied. Catheter ablation was performed in 17 patients (52 +/- 16 years) with dual antegrade conduction via both AV nodal pathways between 2012 and 2018. Patients with the final diagnosis of a manifest dual AV nodal non-re-entrant tachycardia had a mean delay of the correct diagnosis of over 1 year (range 2-31 months). Two patients received prescription of non-indicated oral anticoagulation, two further patients suffered from inappropriate shocks of an implantable cardioverter defibrillator. In 12 patients, a co-existence of dual antegrade and re-entry conduction in the AV node was present. Mean fast pathway conduction time was 138 +/- 61 ms and mean slow pathway conduction time was 593 +/- 134 ms. Successful radiofrequency catheter ablation was performed in all patients. Post-procedurally oral anticoagulation was discontinued, without detection of cerebrovascular events or atrial fibrillation during a long-term follow-up of median 17 months (range 6-72 months). Conclusion This first multicentre study investigating patients with supraventricular tachycardia and dual antegrade conduction in the AV node demonstrates that catheter ablation is safe and effective while long-term patient outcome is good. Autonomic tone dependent changes in ante- vs. retrograde conduction via slow and/or fast pathway can challenge the diagnosis and therapy in some patients. [GRAPHICS]

A novel algorithm for 3-D visualization of electrogram duration for substrate-mapping in patients with ischemic heart disease and ventricular tachycardia

Background Myocardial slow conduction is a cornerstone of ventricular tachycardia (VT). Prolonged electrogram (EGM) duration is a useful surrogate parameter and manual annotation of EGM characteristics are widely used during catheter-based ablation of the arrhythmogenic substrate. However, this remains time-consuming and prone to inter-operator variability. We aimed to develop an algorithm for 3-D visualization of EGM duration relative to the 17-segment American Heart Association model. Methods To calculate and visualize EGM duration, in sinus rhythm acquired high-density maps of patients with ischemic cardiomyopathy undergoing substrate-based VT ablation using a 64- mini polar basket-catheter with low noise of 0.01 mV were analyzed. Using a custom developed algorithm based on standard deviation and threshold, the relationship between EGM duration, endocardial voltage and ablation areas was studied by creating 17-segment 3-D models and 2-D polar plots. Results 140,508 EGMs from 272 segments (n = 16 patients, 94% male, age: 66±2.4, ejection fraction: 31±2%) were studied and 3-D visualization of EGM duration was performed. Analysis of signal processing parameters revealed that a 40 ms sliding SD-window, 15% SD-threshold and >70 ms EGM duration cutoff was chosen based on diagnostic odds ratio of 12.77 to visualize rapidly prolonged EGM durations. EGMs > 70 ms matched to 99% of areas within dense scar (<0.2 mV), in 95% of zones within scar border zone (0.2-1.0 mV) and detected ablated areas having resulted in non-inducibility at the end of the procedure. Ablation targets were identified with a sensitivity of 65.6% and a specificity of 94.6% avoiding false positive labeling of prolonged EGMs in segments with healthy myocardium. Conclusion The novel algorithm allows rapid visualization of prolonged EGM durations. This may facilitate more objective characterization of arrhythmogenic substrate in patients with ischemic cardiomyopathy.PeerReviewe

Repolarization indicates electrical instability in ventricular arrhythmia originating from papillary muscle

AimsCardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood.Methods and resultsVentricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity.ConclusionRT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesi

Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n=7) or ANG II (n=9) for 8weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 +/- 5.3 to 111.8 +/- 6.9mmHg (P=0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 +/- 12.6g to 131 +/- 18.7g after 7weeks (P=0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II-treated animals compared to the control group (18 +/- 4mm vs. 13 +/- 2mm, respectively, P=0.002). However, ANG II-treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high-sensitivity C-reactive protein and urinary 8-iso-prostaglandin F-2 were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep

Cardiac glial cells release neurotrophic S100B upon catheter-based treatment of atrial fibrillation

Atrial fibrillation (AF), the most common sustained heart rhythm disorder worldwide, is linked to dysfunction of the intrinsic cardiac autonomic nervous system (ICNS). The role of ICNS damage occurring during catheter-based treatment of AF, which is the therapy of choice for many patients, remains controversial. We show here that the neuronal injury marker S100B is expressed in cardiac glia throughout the ICNS and is released specifically upon catheter ablation of AF. Patients with higher S100B release were more likely to be AF free during follow-up. Subsequent in vitro studies revealed that murine intracardiac neurons react to S100B with diminished action potential firing and increased neurite growth. This suggests that release of S100B from cardiac glia upon catheter-based treatment of AF is a hallmark of acute neural damage that contributes to nerve sprouting and can be used to assess ICNS damage

Long-term efficacy and safety of radiofrequency catheter ablation of atrial fibrillation in patients with cardiac implantable electronic devices and transvenous leads

Introduction Long-term efficacy and safety are uncertain in patients with cardiac implantable electronic devices (CIED) and transvenous leads (TVL) undergoing radiofrequency catheter ablation of atrial fibrillation (AF). Thus, we assessed the outcome of AF ablation in those patients during long-term follow-up using continuous atrial rhythm monitoring (CARM). Methods and Results A total of 190 patients (71.3 +/- 10.7 years; 108 (56.8% men) were included in this study. At index procedure 81 (42.6%) patients presented with paroxysmal AF and 109 (57.4%) with persistent AF. The ablation strategy included pulmonary vein isolation in all patients and biatrial ablation of complex fractionated electrograms with additional ablation lines, if appropriate. AF recurrences were assessed by CARM- and CIED-related complications by device follow-up. After a mean follow-up of 55.4 +/- 38.1 months, freedom of AF was found in 86 (61.4%) and clinical success defined as an AF burden less than or equal to 1% in 101 (72.1%) patients. Freedom of AF was reported in 74.6% and 51.9% (P = 0.006) and clinical success in 89.8% and 59.3% (P < 0.001) of patients with paroxysmal and persistent AF, respectively. In 3 of 408 (0.7%) ablation procedures, a TVL malfunction occurred within 90 days after catheter ablation. During long-term follow-up 9 (4.7%) patients showed lead dislodgement, 2 (1.1%) lead fracture, and 2 (1.1%) lead insulation defect not related to the ablation procedure. Conclusion Our findings using CARM demonstrate long-term efficacy and safety of radiofrequency catheter ablation of AF in patients with CIED and TVL