Bipolar catheter ablation with dedicated radiofrequency system for highly refractory ventricular arrhythmia-Does the rate of success depend on arrhythmia origin?

INTRODUCTION: Despite rapid technological progress, some arrhythmias are still resistant to standard unipolar ablation. These include arrhythmias arising from the base of the heart, cardiac crux, or epicardium. Bipolar radiofrequency ablation (B-RFA) may be useful in some cases, however, data on the efficacy of this approach in various arrhythmia localizations are scarce. The aim of this study was to assess the efficacy of B-RFA in patients with ventricular arrhythmias originating from various locations, occurring refractory to standard unipolar ablation approaches. METHODS: An observational, single center study was conducted over a 30-month period. B-RFA were performed using dedicated radio frequency (RF) generator and electroanatomic mapping system. RESULTS: Twenty-four procedures, in 23 patients with a median (range) of 1 (1-2) previously failed unipolar ablation procedures, were included in the final analysis. There were 12 ablations of ventricular arrhythmias originating from interventricular septum with an acute success rate of 75%, and 12 from left ventricular (LV) summit with an acute success rate of 58%. The midterm success rate (median interquartile range follow-up of 205 days [188-338]) was 66% and 50%, respectively. CONCLUSIONS: B-RFA is a promising method of catheter ablation for refractory cardiac arrhythmias. A higher success rate was observed in ablation for difficult ventricular arrhythmias originating from interventricular septal region than LV summit.

Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Bipolar ablation of therapy-refractory ventricular arrhythmias: application of a dedicated approach.

AIMS: Bipolar radiofrequency ablation (B-RFA) has been reported as a bail-out strategy for the treatment of therapy refractory ventricular arrhythmias (VA). Currently, existing setups have not been standardized for B-RFA, while the impact of conventional B-RFA approaches on lesion formation remains unclear. METHODS AND RESULTS: (i) In a multicentre observational study, patients undergoing B-RFA for previously therapy-refractory VA using a dedicated B-RFA setup were retrospectively analysed. (ii) Additionally, in an ex vivo model lesion formation during B-RFA was evaluated using porcine hearts. In a total of 26 procedures (24 patients), acute success was achieved in all 14 ventricular tachycardia (VT) procedures and 7/12 procedures with premature ventricular contractions (PVC), with major complications occurring in 1 procedure (atrioventricular block). During a median follow-up of 211 days in 21 patients, 6/11 patients (VT) and 5/10 patients (PVC) remained arrhythmia-free. Lesion formation in the ex vivo model during energy titration from 30 to 50 W led to similar lesion volumes compared with initial high-power 50 W B-RFA. Lesion size significantly increased when combining sequential unipolar and B-RFA (1429 mm3 vs. titration 501 mm3 vs. B-RFA 50 W 423 mm3, P < 0.001), an approach used in overall 58% of procedures and more frequently applied in procedures without VA recurrence (92% vs. 36%, P = 0.009). Adipose tissue severely limited lesion formation during B-RFA. CONCLUSION: Using a dedicated device for B-RFA for therapy-refractory VA appears feasible and safe. While some patients need repeat ablation, success rates were encouraging. Sequential unipolar and B-RFA may be favourable for lesion formation.

Cardioneuroablation - Induced shift in sinus node activation: A new parameter of vagal denervation?

Experimental studies demonstrated a shift in the leading pacemaker site based on parasympathetic or sympathetic dominance. Radiofrequency catheter ablation of ganglionated plexi (GP) might be used to overcome deleterious effects of enhanced parasympathetic tone. Herein, we present two patients who underwent GP ablation due to cardioinhibitory type reflex syncope and symptomatic bradycardia, respectively. In both cases complete vagal denervation was achieved and was associated with a cranial shift of sinus node activation area with corresponding changes in surface P wave morphology. This unique phenomenon needs to be confirmed in the larger prospective study.

Magnetic Core-Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma-Material Characterization, Theoretical Analysis and Pharmacokinetics.

The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core-shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two Kd and two Bmax values: Kd (1) = 0.319 µg L-1 and Bmax (1) = 0.240 µg g-1, and Kd (2) = 34.6 µg L-1 and Bmax (2) = 5.82 µg g-1. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.

Diagnostic value of implantable loop recorder in patients undergoing cryoballoon ablation of atrial fibrillation.

BACKGROUND: Due to limited data, implantable loop recorders (ILR) are not currently recommended by the guidelines to routinely monitor patients after atrial fibrillation (AF) ablation. AIMS: To validate the diagnostic value of ILR after AF ablation, modern generation ILRs (LINQ) were implanted in patients scheduled for cryoballoon ablation of AF (CBA). METHODS: We included 29 patients with frequent and symptomatic episodes of paroxysmal AF. ILR was implanted 3 months prior to CBA, and data were collected before and for 6 months after the procedure. The device was programmed to maximize sensitivity of AF/ atrial tachycardia (AT) detection. All EGM recordings were "manually" assessed and annotated as true AF, pseudo AF, unrecognized AF, and episodes with no EGM available. Duration and episode-based standard performance metrics were evaluated. RESULTS: A total number of 5,842 episodes were recorded. A total of 4,403 episodes were true AF, 453 episodes were pseudo AF, and 986 episodes had no EGM available. The device did not recognize 144 episodes of AF. Duration-based sensitivity was 95.2%, duration-based specificity 99.9%, duration-based PPV 99.2%, duration-based NPV 99.9%, episode-based sensitivity 98.0%, and episode-based PPV 91.0%. Misdiagnosis happened in 1 in 10 episodes. Total data review time was 166 hr. CONCLUSIONS: Implantable loop recorders is a valuable tool in evaluation of AF episodes in patients undergoing CBA. However, for high precision all recorded episodes need to be evaluated "manually." The memory storage space is too low for frequent AF episodes, resulting in overwriting of stored EGMs and data loss.

Characterization of In Vitro and In Vivo Metabolism of Antazoline Using Liquid Chromatography-Tandem Mass Spectrometry.

Antazoline (ANT) was recently shown to be an effective and safe antiarrhythmic drug in the termination of atrial fibrillation. However, the drug is still not listed in clinical guidelines. No data on ANT metabolism in humans is available. We used liquid chromatography coupled with tandem mass spectrometry to identify and characterize metabolites of ANT. We analyzed plasma of volunteers following a single intravenous administration of 100 mg of ANT mesylate and in in vitro cultures of human hepatocytes. We revealed that ANT was transformed into at least 15 metabolites and we investigated the role of cytochrome P450 isoforms. CYP2D6 was the main one involved in the fast metabolism of ANT. The biotransformation of ANT by CYP2C19 was much slower. The main Phase I metabolite was M1 formed by the removal of phenyl and metabolite M2 with hydroxyl in the para position of phenyl. Glucuronidation was the leading Phase II metabolism. Further study on pharmacokinetics of the metabolites would allow us to better understand the activity profile of ANT and to predict its potential clinical applications. Ultimately, further investigation of the activity profile of the new hydroxylated M2 metabolite of ANT might result in an active substance with a different pharmacological profile than the parent molecule, and potentially a new drug candidate.