impact-intracardiac-neurons-on-cardiac-electrophysiology

Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an <em>Ex Vivo</em> Langendorff System

Since its invention in the late 19th century, the Langendorff ex vivo heart perfusion system continues to be a relevant tool for studying a broad spectrum ...

University Hospital Hamburg-Eppendorf

Recently, a new image integration module (IIM, CartoUnivu™ Module) has been introduced to combine and merge fluoroscopy images with 3-dimensional-(3D)-electroanatomical maps (Carto® 3 System) into an accurate 3D view. The aim of the study was to investigate the influence of IIM on the fluoroscopy exposure during pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) in a prospective randomized trial.

Reduction of Radiation Exposure in Atrial Fibrillation Ablation Using a New Image Integration Module: A Prospective Randomized Trial in Patients Undergoing Pulmonary Vein Isolation.

To investigate whether percutaneous left atrial appendage (LAA) closure guided by automated real-time integration of 2D-/3D-transesophageal echocardiography (TEE) and fluoroscopy imaging results in decreased radiation exposure.

Left Atrial Appendage Closure Guided by Integrated Echocardiography and Fluoroscopy Imaging Reduces Radiation Exposure.

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 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (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 ± 4 mm vs. 13 ± 2 mm, 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 F2α 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. 

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

Comparative data of early recurrence rates of atrial fibrillation (ERAF) following second-generation cryoballoon (CB-G2) and radiofrequency current (RFC) ablation for pulmonary vein isolation (PVI) in paroxysmal AF (PAF) are rare. We randomized PAF patients into either PVI with CB-G2 (group 1) or PVI with a combined RFC-approach applying contact force (CF) with the endpoint of unexcitability (group 2) to investigate ERAF.

Influence of energy source on early atrial fibrillation recurrences: a comparison of cryoballoon vs. radiofrequency current energy ablation with the endpoint of unexcitability in pulmonary vein isolation.

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 arrhythmogenesis.

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias.

During ablation in the vicinity of the coronary arteries establishing a safe distance from the catheter tip to the relevant vessels is mandatory and usually assessed by fluoroscopy alone. The aim of the study was to investigate the feasibility of an image integration module (IIM) for continuous monitoring of the distance of the ablation catheter tip to the main coronary arteries during ablation of ventricular arrhythmias (VA) originating in the sinus of valsalva (SOV) and the left ventricular summit part of which can be reached via the great cardiac vein (GCV).

Image integration into 3-dimensional-electro-anatomical mapping system facilitates safe ablation of ventricular arrhythmias originating from the aortic root and its vicinity.

The need for transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (CA-AF) is still being questioned. The aim of this study is to analyze patients' (patients) risk factors of left atrial appendage thrombus (LAAT) prior to CA-AF in daily clinical practice, according to oral anticoagulation (OAC) strategies recommended by current guidelines.

Risk stratification of patients with left atrial appendage thrombus prior to catheter ablation of atrial fibrillation: An approach towards an individualized use of transesophageal echocardiography.

Finding the right timing in cryoballoon ablation for pulmonary vein isolation.

BACKGROUND Recent evidence indicates that sympathetic/parasympathetic coactivation (CoA) is causally linked to changes in heart rate (HR) dynamics. Whether this is relevant for patients with atrial fibrillation (AF) is unknown. MATERIAL AND METHODS In patients with paroxysmal AF (n=26) and age-matched controls, (n=10) we investigated basal autonomic outflow and HR dynamics during separate sympathetic (cold hand immersion) and parasympathetic activation (O2-inhalation), as well as during CoA (cold face test). In an additional cohort (n=7), HR response was assessed before and after catheter-based pulmonary vein isolation (PVI). Ultra-high-density endocardial mapping was performed in patients (n=6) before and after CoA. RESULTS Sympathetic activation increased (control: 74±3 vs. 77±3 bpm, p=0.0098; AF: 60±2 vs. 64±2 bpm, p=0.0076) and parasympathetic activation decreased HR (control: 71±3 vs. 69±3 bpm, p=0.0547; AF: 60±1 vs. 58±2 bpm, p<0.0009), while CoA induced a paradoxical HR increase in patients with AF (control: 73±3 vs. 71±3 bpm, p=0.084; AF: 59±2 vs. 61±2 bpm, p=0.0006), which was abolished after PVI. Non-linear parameters of HR variability (SD1) were impaired during coactivation in patients with AF (control: 61±7 vs. 69±6 ms, p=0.042, AF: 44±32 vs. 32±5 ms, p=0.3929). CoA was associated with a shift of the earliest activation site (18±4 mm) of the sinoatrial nodal region, as documented by ultra-high-density mapping (3442±343 points per map). CONCLUSIONS CoA perturbs HR dynamics and shifts the site of earliest endocardial activation in patients with paroxysmal AF. This effect is abolished by PVI, supporting the value of emerging methods targeting the intrinsic cardiac autonomic nervous system to treat AF. CoA might be a valuable tool to assess cardiac autonomic function in a clinical setting.

Article	Year
Reduction of Radiation Exposure in Atrial Fibrillation Ablation Using a New Image Integration Module: A Prospective Randomized Trial in Patients Undergoing Pulmonary Vein Isolation. Journal of cardiovascular electrophysiology\| PubMed ID: 25807878	2015
Left Atrial Appendage Closure Guided by Integrated Echocardiography and Fluoroscopy Imaging Reduces Radiation Exposure. PloS one\| PubMed ID: 26465747	2015
Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model. Physiological reports\| PubMed ID: 27613823	2016
Influence of energy source on early atrial fibrillation recurrences: a comparison of cryoballoon vs. radiofrequency current energy ablation with the endpoint of unexcitability in pulmonary v... Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology\| PubMed ID: 27742775	2018
Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias. Nature communications\| PubMed ID: 28128201	2017
Image integration into 3-dimensional-electro-anatomical mapping system facilitates safe ablation of ventricular arrhythmias originating from the aortic root and its vicinity. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology\| PubMed ID: 28340078	2018
Risk stratification of patients with left atrial appendage thrombus prior to catheter ablation of atrial fibrillation: An approach towards an individualized use of transesophageal echocardio... Journal of cardiovascular electrophysiology\| PubMed ID: 28635023	2017
Finding the right timing in cryoballoon ablation for pulmonary vein isolation. International journal of cardiology\| PubMed ID: 29425571	2018
Sympathetic and Parasympathetic Coactivation Induces Perturbed Heart Rate Dynamics in Patients with Paroxysmal Atrial Fibrillation. Medical science monitor : international medical journal of experimental and clinical research\| PubMed ID: 29641513	2018

Christian Eickholt

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