Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs). METHODS: A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants. RESULTS: Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression. CONCLUSION: We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.

Baseline left atrial low-voltage area predicts recurrence after pulmonary vein isolation: WAVE-MAP AF results.

AIMS: Electro-anatomical mapping may be critical to identify atrial fibrillation (AF) subjects who require substrate modification beyond pulmonary vein isolation (PVI). The objective was to determine correlations between pre-ablation mapping characteristics and 12-month outcomes after a single PVI-only catheter ablation of AF. METHODS AND RESULTS: This study enrolled paroxysmal AF (PAF), early persistent AF (PsAF; 7 days-3 months), and non-early PsAF (>3-12 months) subjects undergoing de novo PVI-only radiofrequency catheter ablation. Sinus rhythm (SR) and AF voltage maps were created with the Advisor HD Grid™ Mapping Catheter, Sensor Enabled™ for each subject, and the presence of low-voltage area (LVA) (low-voltage cutoffs: 0.1-1.5 mV) was investigated. Follow-up visits were at 3, 6, and 12 months, with a 24-h Holter monitor at 12 months. A Cox proportional hazards model identified associations between mapping data and 12-month recurrence after a single PVI procedure. The study enrolled 300 subjects (113 PAF, 86 early PsAF, and 101 non-early PsAF) at 18 centres. At 12 months, 75.5% of subjects were free from AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence. Univariate analysis found that arrhythmia recurrence did not correlate with AF diagnosis, but LVA was significantly correlated. Low-voltage area (<0.5 mV) >28% of the left atrium in SR [hazard ratio (HR): 4.82, 95% confidence interval (CI): 2.08-11.18; P = 0.0003] and >72% in AF (HR: 5.66, 95% CI: 2.34-13.69; P = 0.0001) was associated with a higher risk of AF/AFL/AT recurrence at 12 months. CONCLUSION: Larger extension of LVA was associated with an increased risk of arrhythmia recurrence. These subjects may benefit from substrate modification beyond PVI.

Comparison of gross pathology inspection and 9.4 T magnetic resonance imaging in the evaluation of radiofrequency ablation lesions in the left ventricle of the swine heart.

Aims: Gross pathology inspection (patho) is the gold standard for the morphological evaluation of focal myocardial pathology. Examination with 9.4 T magnetic resonance imaging (MRI) is a new method for very accurate display of myocardial pathology. The aim of this study was to demonstrate that lesions can be measured on high-resolution MRI images with the same accuracy as on pathological sections and compare these two methods for the evaluation of radiofrequency (RF) ablation lesion dimensions in swine heart tissue during animal experiment. Methods: Ten pigs underwent radiofrequency ablations in the left ventricle during animal experiment. After animal euthanasia, hearts were explanted, flushed with ice-cold cardioplegic solution to relax the whole myocardium, fixed in 10% formaldehyde and scanned with a 9.4 T magnetic resonance system. Anatomical images were processed using ImageJ software. Subsequently, the hearts were sliced, slices were photographed and measured in ImageJ software. Different dimensions and volumes were compared. Results: The results of both methods were statistically compared. Depth by MRI was 8.771 ± 2.595 mm and by patho 9.008 ± 2.823 mm; p = 0.198. Width was 10.802 ± 2.724 mm by MRI and 11.125 ± 2.801 mm by patho; p = 0.049. Estuary was 2.006 ± 0.867 mm by MRI and 2.001 ± 0.872 mm by patho; p = 0.953. The depth at the maximum diameter was 4.734 ± 1.532 mm on MRI and 4.783 ± 1.648 mm from the patho; p = 0.858. The volumes of the lesions calculated using a formula were 315.973 ± 257.673 mm3 for MRI and 355.726 ± 255.860 mm3 for patho; p = 0.104. Volume directly measured from MRI with the "point-by-point" method was 671.702 ± 362.299 mm3. Conclusion: Measurements obtained from gross pathology inspection and MRI are fully comparable. The advantage of MRI is that it is a non-destructive method enabling repeated measurements in all possible anatomical projections.

Mid-term success rate of single stage hybrid ablation of persistent and long-term persistent atrial fibrillation.

INTRODUCTION: Single stage thoracoscopic radiofrequency ablation (RFA) is a treatment method for persistent and long-term persistent atrial fibrillation (AF) offering the possibility for patients otherwise inconsolable by conventional catheter RFA. We present a pilot group of patients after the introduction of the new method at our clinical center. Patients group: A total of 52 patients aged 61.82 ± 9.7 years underwent single stage hybrid ablation (thoracoscopic isolation of pulmonary veins and box lesion followed by catheter verification of the surgical procedure effectivness) for symptomatic persistent and long-term persistent AF with significantly dilated left atrium 57.9 ± 11.0mm in the period September 2016-March 2019. RESULTS: The median duration of the procedure was 232 minutes and the median duration of hospitalization was 10 days. At discharge, 52 patients (100%) had sinus rhythm. 48 of 52 patients (92.3%) had a 6-month follow-up. 41 of 48 (85.4%) and 38 of 44 (86.4%) of patients were AF free at 3-month and 6-month follow-up, respectively. Acute complications were: one left atrial perforation resolved successfully by suture and one transient ischaemic attack without permanent sequelae. Late complications involved one massive pulmonary embolization and an atrioesophageal fistula. There was no periprocedural myocardial infarction or stroke with permanent sequelae. CONCLUSION: Hybrid thoracoscopic-catheter ablation performed during one procedure is an effective and relatively safe mini-invasive method of treatment for long-term persistent atrial fibrillation.

Randomized comparison of atrioventricular node re-entry tachycardia and atrial flutter catheter ablation with and without fluoroscopic guidance: ZeroFluoro study.

AIMS: Interventional cardiology procedures may expose patients and staff to considerable radiation doses. We aimed to assess whether exposure to ionizing radiation during catheter ablation of supraventricular tachycardia (SVT) can be completely avoided. METHODS AND RESULTS: In this prospective randomized study, patients with SVT (atrioventricular re-entrant tachycardia n = 94, typical atrial flutter n = 29) were randomly assigned in a 1:1 ratio to catheter ablation with conventional fluoroscopic guidance (CF group) or with the EnSite Precision mapping system [zerofluoro (ZF) group]. Acute procedural parameters, increased stochastic risk of cancer incidence and 6-month follow-up data were assessed. Between May 2019 and August 2020, 123 patients were enrolled. Clinical parameters were comparable. Median procedural time was 60.0 and 58.0 min, median fluoroscopy time and estimated median effective dose were 240 s vs. 0 and 0.38 mSv vs. 0 and arrhythmia recurrence was 5% and 7.9% in the CF and ZF groups, respectively. The acute success rate was 98.4% in both groups. No procedure-related complications were reported. At an average age of 55.5 years and median radiation exposure of 0.38 mSv, the estimate of increased incidence was approximately 1 in 14 084. The estimated mortality rate was 1 per 17 857 exposed persons. CONCLUSIONS: The procedural safety and efficacy of the zero-fluoroscopic approach are similar to those of conventional fluoroscopy-based ablation for atrioventricular nodal re-entrant tachycardia and atrial flutter. Under the assumption of low radiation dose, the excessive lifetime risk of malignancy in the CF group due to electrophysiology procedure is reasonably small, whilst totally reduced in zero fluoroscopy procedures.

Left atrium phasic impairments in paroxysmal atrial fibrillation patients assessed by cardiovascular magnetic resonance feature tracking.

Atrial fibrillation (AF) is an abnormal and irregular heartbeat caused by uncoordinated electrical impulses in the left atrium (LA), which could induce lasting changes in the heart tissue or could be a consequence of underlying cardiac disease. This study aimed to assess the left atrial phasic function and deformation in paroxysmal AF (PAF) patients-who had not received radiofrequency ablation and had no signs of permanent AF-using the cardiovascular magnetic resonance (CMR) feature-tracking (FT) technique. Fifty subjects (27 PAF patients and 23 controls) were included and examined with CMR. Their LA volume, LA function, LA longitudinal strain (LS) and LA strain rate were assessed in the LA reservoir, conduit, and contractile phases. PAF patients exhibited higher LA volumes than controls, while their LA emptying fraction and LA LS was significantly lower in all three phases. In contrast, the corresponding emptying volumes (total, passive and active) were similar in both groups. The LA volumetric rates from CMR-derived volume curves differed significantly in PAF patients vs controls in the reservoir and contractile phases. In contrast, the equivalent LV volumetric rates were similar. This study suggests that assessing the LA phasic function could offer insight into early LA impairments for PAF patients.

Reduced Radiation Exposure Protocol during Computer Tomography of the Left Atrium Prior to Catheter Ablation in Patients with Atrial Fibrillation.

(1) Background: Computer tomography (CT) is an imaging modality used in the pre-planning of radiofrequency catheter ablation (RFA) procedure in patients with cardiac arrhythmias. However, it is associated with a considerable ionizing radiation dose for patients. This study aims to develop and validate low-dose CT scanning protocols of the left atrium (LA) for RFA guidance. (2) Methods: 68 patients scheduled for RFA of atrial fibrillation were sequentially assigned to four groups of ECG-gated scanning protocols, based on the set tube current (TC): Group A (n = 20, TC = 33 mAs), Group B (n = 18, TC = 67 mAs), Group C (n = 10, TC = 135 mAs), and control Group D (n = 20, TC = 600 mAs). We used a 256-row multidetector CT with body weight-dependent tube voltage of 80 kVp (<70 kg), 100 kVp (70−90 kg), and 120 kVp (>90 kg). We evaluated scanning parameters including radiation dose, total scanning procedure time and signal-to-noise ratio (SNR). (3) Results: The average effective radiation dose (ED) was lower in Group A in comparison to Group B, C and D (0.83 (0.76−1.10), 1.55 (1.36−1.67), 2.91 (2.32−2.96) and 9.35 (8.00−10.04) mSv, p < 0.05). The total amount of contrast media was not significantly different between groups. The mean SNR was 6.5 (5.8−7.3), 7.1 (5.7−8.2), 10.8 (10.1−11.3), and 12.2 (9.9−15.7) for Group A, B, C and D, respectively. The comparisons of SNR in group A vs. B and C vs. D were without significant differences. (4) Conclusions: Optimized pre-ablation CT scanning protocols of the LA can reduce an average ED by 88.7%. Three dimensional (3D) models created with the lowest radiation protocol are useful for the integration of electro-anatomic-guided RFA procedures.

Efficacy and safety of novel temperature-controlled radiofrequency ablation system during pulmonary vein isolation in patients with paroxysmal atrial fibrillation: TRAC-AF study.

BACKGROUND AND PURPOSE: Saline-irrigated radiofrequency ablation (RFA) for atrial fibrillation (AF) is limited by the absence of reliable thermal feedback limiting the utility of temperature monitoring for power titration. The DiamondTemp (DT) ablation catheter was designed to allow efficient temperature-controlled irrigated ablation. We sought to assess the 1-year clinical safety and efficacy of the DT catheter in treating drug-refractory paroxysmal AF. METHODS: The TRAC-AF trial (NCT02821351) is a prospective, multi-center (n = 4), single-arm study which enrolled patients with symptomatic, drug-refractory, paroxysmal AF. Using the DT catheter, point-by-point ablation was performed around all pulmonary veins (PVs) to achieve PV isolation (PVI). Ablation was performed in a temperature-controlled mode (60 °C, max 50 W). Acute and chronic efficacy and safety was evaluated. RESULTS: Seventy-one patients (age 69.9 ± 11.0 years; 60.6% male) were ablated using the DT catheter. The mean fluoroscopy and RF ablation times were 9.3 ± 6.1 min and 20.6 ± 8.9 min, respectively. Acute isolation of all PVs was achieved in 100% of patients, and freedom from AF after 1 year was 70.6%. There were no steam pops, char, or coagulum on the catheter tip after ablation. There were few serious procedure/device-related adverse events including a single case of cardiac tamponade (1.4%) and transient ischemic attack (1.4). CONCLUSION: This first in man series demonstrates that temperature-controlled irrigated RFA with the DT catheter is efficient, safe, and effective in the treatment of paroxysmal AF. Randomized controlled trials are ongoing and will evaluate better the role of this catheter in relation to standard RFA. TRIAL REGISTRATION: Registered on the site ClinicalTrials.gov January 2016 with identifier: NCT02821351.

Correlation between electromechanical parameters (NOGA XP) and changes of myocardial ischemia in patients with refractory angina.

INTRODUCTION: Cell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness. AIM: Assessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy. MATERIAL AND METHODS: Thirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons. RESULTS: Global EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest R = -0.06; R = 0.2; R = -0.1 and at stress: R = 0.07, R = 0.09, R = -0.1, respectively; Segmental UV, BV, LLS at rest R = -0.2, R = 0.03, R = -0.4 and at stress R = 0.02, R = 0.2, R = -0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (p < 0.05). CONCLUSIONS: Electromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.

Widespread and sustained target engagement in Huntington's disease minipigs upon intrastriatal microRNA-based gene therapy.

Huntingtin (HTT)-lowering therapies hold promise to slow down neurodegeneration in Huntington's disease (HD). Here, we assessed the translatability and long-term durability of recombinant adeno-associated viral vector serotype 5 expressing a microRNA targeting human HTT (rAAV5-miHTT) administered by magnetic resonance imaging-guided convention-enhanced delivery in transgenic HD minipigs. rAAV5-miHTT (1.2 × 1013 vector genome (VG) copies per brain) was successfully administered into the striatum (bilaterally in caudate and putamen), using age-matched untreated animals as controls. Widespread brain biodistribution of vector DNA was observed, with the highest concentration in target (striatal) regions, thalamus, and cortical regions. Vector DNA presence and transgene expression were similar at 6 and 12 months after administration. Expression of miHTT strongly correlated with vector DNA, with a corresponding reduction of mutant HTT (mHTT) protein of more than 75% in injected areas, and 30 to 50% lowering in distal regions. Translational pharmacokinetic and pharmacodynamic measures in cerebrospinal fluid (CSF) were largely in line with the effects observed in the brain. CSF miHTT expression was detected up to 12 months, with CSF mHTT protein lowering of 25 to 30% at 6 and 12 months after dosing. This study demonstrates widespread biodistribution, strong and durable efficiency of rAAV5-miHTT in disease-relevant regions in a large brain, and the potential of using CSF analysis to determine vector expression and efficacy in the clinic.

Local electromechanical alterations determine the left ventricle rotational dynamics in CRT-eligible heart failure patients.

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients' grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

A Novel Temperature-Controlled Radiofrequency Catheter Ablation System Used to Treat Patients With Paroxysmal Atrial Fibrillation.

OBJECTIVES: DIAMOND-AF (DiamondTemp™ Ablation System for the Treatment of Paroxysmal Atrial Fibrillation) was a prospective, multicenter, noninferiority, randomized trial that compared the safety and effectiveness of the DTA system versus those of a force-sensing RF ablation system (control) for the treatment of patients with drug-refractory, recurrent, symptomatic paroxysmal atrial fibrillation (AF). BACKGROUND: Irrigated radiofrequency (RF) ablation catheters lose tissue temperature acuity, which is vital in assessing lesion formation. DiamondTemp Ablation (DTA) was designed to re-establish accurate tissue temperature measurements during ablation. METHODS: A total of 482 patients with paroxysmal AF were randomized (239 DTA, 243 control) to undergo pulmonary vein isolation and were followed up at 23 sites. Patients were screened for disease progression, cardiac characteristics, and prior interventions. Primary endpoints were effectiveness (freedom from atrial arrhythmia recurrence) and safety (composite of procedure- and device-related serious adverse events). RESULTS: The primary safety event rate was 3.3% in the DTA group versus 6.6% in the control group (p < 0.001 vs. 6.5% noninferiority margin). Primary effectiveness was met in 79.1% of DTA subjects and 75.7% of control subjects (p < 0.001 vs. -12.5% noninferiority margin). Secondary endpoint analysis found that off-drug effectiveness favored DTA compared with the control (142 [59.4%] vs. 120 [49.4%], respectively; p = 0.03). Total RF time and individual RF ablation duration were significantly shorter with less saline infused through the DTA catheter (p < 0.001). Both arms saw clinically meaningful improvements in quality of life at 12 months. CONCLUSIONS: Safety and efficacy of the DTA system proved noninferior to force-sensing RF ablation in a paroxysmal AF population. Efficiencies were observed using DTA with shorter total RF times, individual RF ablation durations, and less saline infusion. (DiamondTemp™ Ablation System for the Treatment of Paroxysmal Atrial Fibrillation; NCT03334630).

Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiac side effects of some pulmonary drugs are observed in clinical practice. Aminophylline, a methylxanthine bronchodilator with documented proarrhythmic action, may serve as an example. Data on the action of aminophylline on cardiac cell electrophysiology and contractility are not available. Hence, this study was focused on the analysis of changes in the beat rate and contraction force of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes in the presence of increasing concentrations of aminophylline (10 µM-10 mM in hPSC-CM and 8-512 µM in HL-1 cardiomyocytes). Basic biomedical parameters, namely, the beat rate (BR) and contraction force, were assessed in hPSC-CMs using an atomic force microscope (AFM). The beat rate changes under aminophylline were also examined on the HL-1 cardiac muscle cell line via a multielectrode array (MEA). Additionally, calcium imaging was used to evaluate the effect of aminophylline on intracellular Ca2+ dynamics in HL-1 cardiomyocytes. The BR was significantly increased after the application of aminophylline both in hPSC-CMs (with 10 mM aminophylline) and in HL-1 cardiomyocytes (with 256 and 512 µM aminophylline) in comparison with controls. A significant increase in the contraction force was also observed in hPSC-CMs with 10 µM aminophylline (a similar trend was visible at higher concentrations as well). We demonstrated that all aminophylline concentrations significantly increased the frequency of rhythm irregularities (extreme interbeat intervals) both in hPSC-CMs and HL-1 cells. The occurrence of the calcium sparks in HL-1 cardiomyocytes was significantly increased with the presence of 512 µM aminophylline. We conclude that the observed aberrant cardiomyocyte response to aminophylline suggests an arrhythmogenic potential of the drug. The acquired data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and describe cellular mechanisms of methylxanthine arrhythmogenesis. An AFM combined with hPSC-CMs may serve as a robust platform for direct drug effect screening.

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study.

INTRODUCTION: Pulsed field ablation (PFA) exploits the delivery of short high-voltage shocks to induce cells death via irreversible electroporation. The therapy offers a potential paradigm shift for catheter ablation of cardiac arrhythmia. We designed an AC-burst generator and therapeutic strategy, based on the existing knowledge between efficacy and safety among different pulses. We performed a proof-of-concept chronic animal trial to test the feasibility and safety of our method and technology. METHODS: We employed 6 female swine - weight 53.75 ± 4.77 kg - in this study. With fluoroscopic and electroanatomical mapping assistance, we performed ECG-gated AC-PFA in the following settings: in the left atrium with a decapolar loop catheter with electrodes connected in bipolar fashion; across the interventricular septum applying energy between the distal electrodes of two tip catheters. After procedure and 4-week follow-up, the animals were euthanized, and the hearts were inspected for tissue changes and characterized. We perform finite element method simulation of our AC-PFA scenarios to corroborate our method and better interpret our findings. RESULTS: We applied square, 50% duty cycle, AC bursts of 100 µs duration, 100 kHz internal frequency, 900 V for 60 pulses in the atrium and 1500 V for 120 pulses in the septum. The inter-burst interval was determined by the native heart rhythm - 69 ± 9 bpm. Acute changes in the atrial and ventricular electrograms were immediately visible at the sites of AC-PFA - signals were elongated and reduced in amplitude (p < 0.0001) and tissue impedance dropped (p = 0.011). No adverse event (e.g., esophageal temperature rises or gas bubble streams) was observed - while twitching was avoided by addition of electrosurgical return electrodes. The implemented numerical simulations confirmed the non-thermal nature of our AC-PFA and provided specific information on the estimated treated area and need of pulse trains. The postmortem chest inspection showed no peripheral damage, but epicardial and endocardial discolorations at sites of ablation. T1-weighted scans revealed specific tissue changes in atria and ventricles, confirmed to be fibrotic scars via trichrome staining. We found isolated, transmural and continuous scars. A surviving cardiomyocyte core was visible in basal ventricular lesions. CONCLUSION: We proved that our method and technology of AC-PFA is feasible and safe for atrial and ventricular myocardial ablation, supporting their systematic investigation into effectiveness evaluation for the treatment of cardiac arrhythmia. Further optimization, with energy titration or longer follow-up, is required for a robust atrial and ventricular AC-PFA.

Non-coding RNAs and Cardiac Arrhythmias.

Cardiac arrhythmias represent wide and heterogenic group of disturbances in the cardiac rhythm. Pathophysiology of individual arrhythmias is highly complex and dysfunction in ion channels/currents involved in generation or spreading of action potential is usually documented. Non-coding RNAs (ncRNAs) represent highly variable group of molecules regulating the heart expression program, including regulation of the expression of individual ion channels and intercellular connection proteins, e.g. connexins.Within this chapter, we will describe basic electrophysiological properties of the myocardium. We will focus on action potential generation and spreading in pacemaker and non-pacemaker cells, including description of individual ion channels (natrium, potassium and calcium) and their ncRNA-mediated regulation. Most of the studies have so far focused on microRNAs, thus, their regulatory function will be described into greater detail. Clinical consequences of altered ncRNA regulatory function will also be described together with potential future directions of the research in the field.

Bipolar ablation with contact force-sensing of swine ventricles shows improved acute lesion features compared to sequential unipolar ablation.

INTRODUCTION: Despite technical progress, ventricular tachycardia (VT) recurrence after unipolar ablation remains relatively high (12%-47%). Bipolar ablation has been proposed as an appealing solution that may overcome limitations associated with unipolar ablation settings. We designed an animal study to compare bipolar (BPA) vs sequential unipolar ablation (UPA) using contact force-sensing technology on both ablation catheters. METHODS: Twenty large white female pigs (6-months-old, 50-60 kg) underwent multiple RF ablations (30 W, 60 seconds, 30 mL/min irrigation) on the ventricular myocardium from the epicardial and endocardial sides. The hearts were fixed and scanned with high-resolution cardiac magnetic resonance imaging. Thermal lesions were located and characterized in volume, depth, width, and transmurality. RESULTS: Lesion volume was calculated as the sum of epicardial or endocardial conjoined/isolated lesions at one location. Linear dimensions (width and depth) were measured twice for each location, on the endocardial and epicardial side. We evaluated 35 lesions across the intraventricular septum (UPA, N = 17 vs BPA, N = 18). No difference in volume, linear dimensions or impedance drop was observed in this area between UPA and BPA. However, BPA required half RF time and showed an increased transmurality trend. We then analyzed 73 lesions from the endocardial side (UPA, N = 35 vs BPA, N = 38) and 50 from the epicardial side (UPA, N = 11 vs BPA N = 39) of the ventricular free walls. Lesion transmurality was markedly improved by BPA (P = .030, odds ratio, 23.73 [4.71,31.96]). Ventricular BPA lesions were significantly deeper on the epicardial side (P < .0001) and endocardial side (P = .015). CONCLUSION: Bipolar ablation is more likely to create transmural and epicardial lesions in the ventricle wall. Half the time is needed for the creation of comparably deep and large lesions.

Comparison of atrial fibrillation ablation efficacy using remote magnetic navigation vs. manual navigation with contact-force control.

AIMS: This study aims to compare procedural parameters and clinical efficacy of remote magnetic navigation (RMN) vs. manual navigation (MAN) approach for radiofrequency ablation (RFA) in patients with atrial fibrillation (AF). METHODS: 146 patients with AF were enrolled in the study. In the RMN group (n=57), patients were treated with the CARTO® 3 in combination with the Niobe ES system. In the MAN group (n=89), ablation was performed with the EnSite Velocity and TactiCath™ Quartz catheter with direct contact force measurement. Procedural time, ablation time, fluoroscopy time, radiation dose and ablation counts were measured and compared between the groups. Recurrence of AF was evaluated after 6 months of follow-up. RESULTS: Mean procedure times (236.87±64.31 vs. 147.22±45.19 min, P<0.05), counts of RF applications (74.30±24.77 vs. 49.15±20.33, P<0.05) and total RFA times (4323.39±1426.69 vs. 2780.53±1157.85 s, P<0.05) were all significantly higher in the RMN than in the MAN group, respectively. In the same order, mean X-ray dose (9722.6±7507.4 vs. 8087.9±6051.5 mGy/cm2, P=0.12) and mean total X-ray exposure time (8.07±4.20 vs. 9.54±5.47 min, P=0.08) were not statistically different. At 6-month follow-up, freedom from AF was similar in RMN and MAN group for paroxysmal (60.8% and 73%, respectively, P=0.42) and persistent AF (69.6% and 75.0%, respectively, P=0.77). CONCLUSIONS: Due to the fact that mid-term clinical outcomes showed no significant differences in AF recurrences between groups and manual ablation strategy provided more favorable results regarding acute procedural parameters, we can conclude that the remote magnetic navigation is not superior to the manual approach.

Serum Concentrations of Osteogenesis/Osteolysis-Related Factors and Micro-RNA Expression in ST-Elevation Myocardial Infarction.

BACKGROUND: Atherosclerosis and bone metabolism share similar molecular and cellular mechanisms. This study aims to evaluate (1) serum concentration of osteogenesis/osteolysis factors panel (Dickkopf-related protein 1 (DKK-1), TNF-α, N-terminal atrial natriuretic peptide (NT-proANP), thrombospondin-2 (TSP-2), osteoprotegerin (OPG), osteocalcin (OCN), osteopontin (OPN), fibroblast growth factor 23 (FGF-23), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), proprotein convertase subtilisin/kexin type 9 (PCSK9)), (2) serum expression levels of micro-RNA- (miR-) 24-1 and miR-6802, and (3) assess their correlation with myocardial injury and LV remodeling and function in the acute phase of STEMI and after 3 months. METHODS: Study enrolled 25 STEMI patients (mean age 55.4 ± 8.96 years). Blood samples were collected 4 days and 3 months after myocardial infarction. Serum concentrations of osteogenesis/osteolysis factors were measured using the Luminex assay. Analysis of miR-24-1, and miR-6802 expression was performed with qPCR. LV function and remodeling were assessed by MRI during index hospitalization and 3 months later. RESULTS: There were no significant differences in serum levels of osteogenesis/osteolysis factors and expression of miR-24-1 and miR-6802 between the acute phase and 3-month follow-up. The levels were similar in patients with at least ≥5% improvement of LVEF (n = 10) and those without improvement. There was a negative correlation between the OPG serum level and LVEF during the acute phase of myocardial infarction. CONCLUSIONS: In STEMI patients, serum concentrations of osteogenesis/osteolysis factors, as well as miR-24-1 and miR-6802 expression, do not change significantly within the 3-month follow-up and are not correlated with LV remodeling and function.

Comparing the incidence of ventricular arrhythmias during epicardial ablation in swine versus canine models.

BACKGROUND: Choosing the appropriate animal model for development of novel technologies requires an understanding of anatomy and physiology of these different models. There are little data about the characteristics of different animal models for the study of technologies used for epicardial ablation. We aimed to compare the incidence of ventricular arrhythmias during epicardial radiofrequency ablation between swine and canine models using novel epicardial ablation catheters. METHODS: We conducted a retrospective study using data obtained from epicardial ablation experiments performed on swine (Sus Scrofa) and canine (Canis familiaris) models. We compared the incidence of ventricular arrhythmias during ablation between swine and canine using multivariate regression analysis. Six swine and six canine animals underwent successful epicardial radiofrequency ablation. A total of 103 ablation applications were recorded. RESULTS: Ventricular arrhythmias requiring cardioversion occurred in 13.11% of radiofrequency ablation applications in swine and 9.75% in canine (relative risk: 117.6%, 95% confidence interval [CI]: 83.97-164.69, animal-based odds ratio [OR]: .55, 95% CI: .23-61.33; P = .184). When adjusting for application position, duration of ablation and power, the odds of developing potentially lethal ventricular arrhythmia in swine increased significantly compared to canine (OR: 3.60, 95% CI: 1.35-9.55; P = .010). CONCLUSIONS: The swine myocardium is more susceptible to developing ventricular arrhythmias compared to canine model during epicardial ablation. This issue should be carefully considered in future studies.