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.

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.

Twenty-five years of research on syncope.

Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.

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.

Respiratory cycle-dependent atrial tachycardia originating from the left atrial roof.

Respiratory cycle-dependent atrial tachycardia (RCAT) is rare. RCAT can be associated with severe symptoms and trigger atrial fibrillation. Focal radiofrequency ablation of RCAT can be a successful method of treatment. In the presented case RCAT originated from the roof of the left atrium - the site not previously reported in the literature. Ablation led to complete elimination of arrhythmia with no recurrence during follow up.

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.

Bipolar ablation of refractory atrial and ventricular arrhythmias: Importance of temperature values of intracardiac return electrodes.

INTRODUCTION: Bipolar radiofrequency catheter ablation (Bi-RFCA) emerged as an option for treatment of arrhythmias resistant to the conventional approach. Data on safety issues of Bi-RFCA, including temperature values of intracardiac return electrode (IRE) are lacking. OBJECTIVE: To determine the safety profile of Bi-RFCA regarding temperature measurements obtained from nonirrigated IRE of different sizes. METHODS: The study group consisted of consecutive patients after failed conventional RFCA who underwent Bi-RFCA. RESULTS: Out of 1510 RFCA performed in our center, 19 patients underwent Bi-RFCA due to refractory to previous RFCA ventricular arrhythmias (15 patients) or typical atrial flutter (four patients). Nonirrigated small (4 mm) and large (8 mm) tip catheters were used as IRE in 14 (including three cross-overs to 8 mm IRE) and five patients, respectively. A total number of 164 bipolar applications were performed (128 for 4 mm and 36 for 8 mm IRE). Maximal temperatures of 4 mm IRE were significantly higher than those of 8 mm IRE (63°C ± 16°C vs 43°C ± 4°C; P = .027). A significant rise of temperature and steam-pops, preventing further Bi-RFCA, occurred in seven patients treated with 4 mm IRE. Bi-RFCA using 4 mm IRE operated at significantly higher impedance values (211 ± 83 vs 143 ± 38; P = .04) and lower power values (mean 20 W ± 6 W vs 32 W ± 7 W, P = .0005; max 29 W ± 9 W vs 39 W ± 10 W, P = .027). CONCLUSION: The use of 8 mm IRE for Bi-RFCA is associated with lower temperatures of the catheter used as ground and lower incidence of steam-pops which may suggest a better safety profile than 4 mm IRE. Determination of safety/efficacy balance requires further studies.

Impact of monitoring on detection of arrhythmia recurrences in the ESC-EHRA EORP atrial fibrillation ablation long-term registry.

AIMS: Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation. METHODS AND RESULTS: The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan-Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P < 0.001). The rate of freedom from AF recurrences was 50.5% among patients using the ICM while it was 65.4%, 70.6%, and 72.8% using the TTMON, ECG, and Holter ECG, respectively. CONCLUSION: Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques.

Right atrial position of a return electrode for bipolar ablation of the left posterosuperior process ventricular tachycardia.

INTRODUCTION: Radiofrequency (RF) catheter ablation (RFCA) of ventricular tachycardia (VT) is an effective method of treatment. However, when arrhythmia has ischemic etiology and originates from the posterosuperior process (PSP) of the left ventricular (LV) base, ablation performed with conventional unipolar energy sources may be challenging or impossible. METHOD AND RESULT: A 67-year-old male after six unsuccessful RFCA for highly symptomatic VT originating from PSP of LV base underwent successful RFCA using multiple bipolar RF applications delivered between two electrodes located at LV endocardium and adjacent right atrial sites. CONCLUSION: This case report shows that bipolar RFCA can be used for safe and successful treatment of VT originating from deep PSP of LV base.

Statement by a Working Group conceived by the Polish National Consultants in Cardiology and Neurology addressing the use of implantable cardiac monitors in patients after ischaemic embolic stroke of undetermined source.

INTRODUCTION: Stroke remains one of the main causes of death and the most common cause of long-term disability in adults. Embolic strokes of undetermined source (ESUS) amount to a significant proportion of all ischaemic strokes. Detection of atrial fibrillation (AF) in this group of patients would allow for a major therapeutic decision to switch from antiplatelets to oral anticoagulants and therefore significantly reduce the risk of recurrence. STATE OF THE ART: Current technology allows long-term continuous ECG monitoring with different systems, including implantable cardiac monitors (ICM). However, in Poland lack of reimbursement does not allow their use in everyday clinical practice. CLINICAL IMPLICATIONS: This is a statement by a Working Group conceived by the Polish National Consultants in Cardiology and Neurology addressing the use of ICM in patients after ischaemic embolic strokes of undetermined source. The aim was to develop reasonable and comprehensive guidance on how to select and manage candidates for ICM in order to obtain the maximum benefit for Polish public health. FUTURE DIRECTIONS: This expert opinion is not intended as a guideline but it provides advice as to how to optimise the potential use of ICM in patients after ESUS in the Polish setting.

Prognostic value of noninvasive programmed stimulation in patients with implantable cardioverter defibrillator.

BACKGROUND: Implantable cardioverter defibrillator (ICD) offers an opportunity to examine vulnerability to ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether NIPS can predict VT/VF recurrences has not yet been established. PURPOSE: To examine the predictive value of NIPS for identification of patients with VT/VF recurrences. METHODS: The study group consisted of consecutive 105 ICD recipients included in the prospective NIPS-ICD study (ClinicalTrials ID: NCT02373306) (88 males, age 65 ± 11 years). The patients underwent NIPS using the protocol up to three premature extrastimuli at 600-500- and 400-ms drive cycle lengths. The endpoint of NIPS was induction of sustained VT or VF or completion of the protocol. RESULTS: VT/VF was induced in 29 (27.6%) patients. During a 12-month follow-up NIPS-inducible patients had significantly more frequently appropriate ICD therapy than noninducible patients (17% vs 4%, P = 0.023). NIPS-induced VT/VF had a sensitivity of 63%, specificity of 75%, positive predictive value of 17%, and negative predictive value of 96% for identification of patients with future VT/VF. Apart from NIPS, age ≥ 65 years, QRS duration, treatment with angiotensin-converting enzyme, history of coronary artery bypass grafting, history of VT/VF prior to NIPS, and prior appropriate ICD therapy were also associated with VT/VF recurrences. Multivariate analysis showed that, together with QRS duration, NIPS result was an independent predictor of future VT/VF. Predictive value of NIPS was significantly higher in ischemic than nonischemic patients. CONCLUSIONS: NIPS result is associated with future VT/VF. Noninducibility at NIPS identifies those patients with high accuracy who will have uneventful follow-up.

Noninvasive assessment of left atrial fibrosis. Correlation between echocardiography, biomarkers, and electroanatomical mapping.

AIM: Left atrial (LA) fibrosis promotes atrial fibrillation (AF), may predict poor radiofrequency catheter ablation (RFCA) outcome, and may be assessed invasively using electroanatomical mapping (EAM). Speckle tracking echocardiography (STE) enables quantitative assessment of LA function. The aim was to assess the relationship between LA fibrosis derived from EAM and LA echocardiographic parameters as well as biomarkers of fibrosis in patients with AF. METHODS: Sixty-six patients (64% males, mean age 56 ± 10) with nonvalvular AF treated with first RFCA were prospectively studied. Seventy-three percent of patients were in sinus rhythm at the time of examination. LA geometry, systolic, and diastolic function were assessed. In STE global, peak atrial longitudinal (PALS) and contractile (PACS) strain were calculated. LA stiffness index (LAs) - the ratio of E/e' to PALS - was assessed. The EAM of LA was build using Carto System before RFCA. Low amplitude potentials area (LAPA) was quantitatively analyzed and expressed as a percentage of LA surface using the cut-off <0.5 mV to detect potential sites of fibrosis. The serum concentrations of MMP-9, PIIINP, and TGFß1were estimated before RFCA. RESULTS: Pearson correlation analysis showed a significant correlation between LA diastolic function parameters: PALS (-0.54, P < .001), LAs (0.65, P < .001), and LAPA in patients who were in sinus rhythm. Also LA volume significantly correlated with LAPA (0.44, P < .002). None of biomarkers correlated with LAPA. CONCLUSION: Left atrial diastolic parameters derived from STE correlate well with the extent of LA fibrosis. Thus, STE may be useful in the noninvasive assessment of LA fibrosis and selection of candidates for RFCA.

Fragmented QRS complex in patients with implantable cardioverter defibrillator-Prevalence and predisposing factors.

BACKGROUND: Incidence of fragmented (fQRS) and predisposing factors in patients with implantable cardioverter-defibrillator (ICD) have not yet been established. Aim To examine incidence of fQRS, associated factors as well as predictive value in identifying site of coronary artery disease (CAD). METHODS: Consecutive patients with ICD. Retrospective analysis of demographic, clinical and ECG data. RESULTS: Of 382 patients, 163 (43%) had fQRS. They had more frequently history of MI, Q wave, lower left ventricular ejection fraction and prolonged ECG repolarisation indices. The presence of fQRS in more than one ECG localisation was associated with higher number of MI and ICD for secondary prevention. By combining fQRS with Q wave location, site of CAD could be predicted (total accuracy 84-95%). CONCLUSIONS: The fQRS is frequent in patients with ICD, especially those with CAD, more advanced cardiac disease and altered ECG repolarisation. The fQRS may improve ECG-based non-invasive identification of the site of CAD.

Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy.

BACKGROUND: Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters. METHODS: Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured. RESULTS: Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found. CONCLUSIONS: Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.