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Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 1. European Regional Development Fund - Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) 2. Specific University Research provided by MŠMT, No.: MUNI/A/1462/2021 Background Cardiac magnetic resonance feature tracking (CMR-FT) allows a quantitative analysis of regional heart deformation and understanding several diseases' underlying mechanisms. Paroxysmal atrial fibrillation (PAF), defined as recurrent arrhythmic episodes that terminate spontaneously, may induce early changes in the left atrial (LA) wall, which CMR-FT can detect. Thus, the LA function assessment may help early identification of PAF via imaging markers. Purpose Evaluate the left atrial volumetric change rate in PAF patients during the reservoir and contractile LA phases. Methods The local Ethics Committee approved the study following the Declaration of Helsinki (2000) of the World Medical Association. A group of 50 subjects (27 PAF patients and 23 controls (CG)) were examined with CMR. The analyses were performed using CMR-FT commercial software (2D CPA MR, TomTec v4.6.4.40, Germany). Left ventricle (LV) and left atrial (LA) volume curves were obtained from analyzing long-axis cine images (50 frames per cardiac cycle). Corresponding slopes in the reservoir-LV emptying (LVemp) and LA filling (LAfill) volume rate-and contractile-LV filling (LVfill) and LA emptying (LAemp) volume rate-phases were calculated. Negative slope values imply blood volume decreasing with time. The LA longitudinal strain (LS) was also assessed. All statistical data analyses were done in RStudio (R, v4.0.3). Results PAF patients have a significatively higher LAfill and lower LAemp than controls in the reservoir and contractile phases (LAfill 129.1±32.6 ml/s vs 101.4±22.8 ml/s, P<0.001 and LAemp -154.1±54.0 ml/s  vs -116.2±40.4 ml/s, P=0.007). In contrast, the LV volumetric rates were similar in both phases (LVemp -311.3±79.2 ml/s vs -280.3±62.1 ml/s, P=0.128 and LVfill 199.4±75.6 ml/s vs 190.0±62.8 ml/s, P=0.631, respectively). The volumetric rates significantly correlated for PAF patients (reservoir (LVemp and LAfill) r = -0.54, P = 0.003 and contractile (LVfill and LAemp) r = -0.64, P < 0.001), but not for controls. The LS was also impaired in PAF patients vs controls (reservoir 26.1% (21.5% to 30.5%) vs 32.7% (28.1% to 39.1%), P = 0.001 and contractile 10.5% (8.8% to 13.3%) vs 14.9% (12.1% to 19.7%), P = 0.003). Conclusion The LA volumetric rates suggest a possible compensation mechanism that allows the LA to deform faster or slower enough to receive or release blood volume during the LA phases; PAF patients' LA receives more blood in a fixed time interval. Their LA cavity could experience pressure or volume overload, allowing LA enlargement. Likewise, the LA emptying (contractile) was slower in PAF patients, which means they release less blood than controls in a given time. Consequently, the PAF patient's LA holds a higher blood volume during the whole cardiac cycle. However, other explanatory factors should be independently assessed. The volumetric rates assessment through CMR-FT could help identify early changes in the LA deformation in PAF patients. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Conflict of interest: A.D.C. has received speaking honoraria from Abbott Medical and Biosense Webster. T.R.B. has received research funding and honoraria from Abbott for speaking, education, and consulting. D.G. is a consultant for Abbott, Boston Scientific, Biotronik, and Zoll. L.Z.V., B.H., and J.L. are employees of Abbott. P.S. is an advisory board member for Abbott, Biosense Webster, Boston Scientific, and Medtronic. All remaining authors have declared no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Conflict of interest: N.S. and L.G. reports consulting fees from Abbott, not related to the present study., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

(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.

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 Ca 2+ 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Klimovic, Scurek, Pesl, Beckerova, Jelinkova, Urban, Kabanov, Starek, Bebarova, Pribyl, Rotrekl and Brat.)

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., Competing Interests: Dr Wojakowski received a lecture honorarium from Biosense Webster, a Johnson & Johnson company. The other authors declare no conflict., (Copyright: © 2021 Termedia Sp. z o. o.)

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 × 10 13 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., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

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)., Competing Interests: Funding Support And Author Disclosures This study was sponsored by Epix Therapeutics, Inc., which was acquired by Medtronic, Inc. in March 2019. Dr. Kautzner has received consultancy services from Biosense Webster, Medtronic, and Merit Medical; and has received speaker honoraria from Abbott, Biosense Webster, Biotronik, and Medtronic. Dr. Albenque has received consultancy services from Biosense Webster and Abbott. Dr. Natale has received consultancy services from Biosense Webster, Boston Scientific, Medtronic, Biotronik, Abbott, and Baylis. Dr. Maddox has received consultancy services from Abbott, ACT, Biosense Webster, Boston Scientific, and Medtronic; and has received speaker honoraria fees from Biosense Webster and Boston Scientific. Dr. Cuoco has received consultancy services from Medtronic. Mr. Getman and Ms. Liu are employed by and are stockholders of Medtronic. Dr. Dukkipati has received research grants from Biosense Webster. Dr. Colley reports no relationships with industry beyond that of the funding in support of this study from Epix Therapeutics. Dr. Al-Ahmad has received honoraria from Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr. Sidney has provided consultancy services for Janssen (J&J), Abbott, and Boston Scientific. Dr. McElderry has provided consultancy and has financial interest in Farapulse; and has provided consultancy and research in Medtronic/EPIX, Biosense Webster, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: SH was employed by BIOTRONIK SE & Co. KG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Caluori, Odehnalova, Jadczyk, Pesl, Pavlova, Valikova, Holzinger, Novotna, Rotrekl, Hampl, Crha, Cervinka and Starek.)

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/cm 2 , 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.

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., (© 2020 Wiley Periodicals, Inc.)

Nanotechnology and stem cells are one of the most promising strategies for clinical medicine applications. The article provides an up-to-date view on advances in the field of regenerative and targeted vascular therapies describing a molecular design (propulsion mechanism, composition, target identification) and applications of nanorobots. Stem cell paragraph presents current clinical application of various cell types involved in vascular biology including mesenchymal stem cells, very small embryonic-like stem cells, induced pluripotent stem cells, mononuclear stem cells, amniotic fluid-derived stem cells and endothelial progenitor cells. A possible bridging between the two fields is also envisioned, where bio-inspired, safe, long-lasting nanorobots can fully target the cellular specific cues and even drive vascular process in a timely manner., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review., (© 2019 The authors.)

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.

Objectives: The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN)., Background: Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies., Methods: WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy., Results: In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months' follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group., Conclusion: Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

Background: Arrhythmia management is a complex process involving both pharmacological and non-pharmacological approaches. Radiofrequency ablation is the pillar of nonpharmacological arrhythmia treatment. Unipolar ablation is considered to be the gold standard in the treatment of the majority of arrhythmias; however, its efficacy is limited to specific cases. In particular, the creation of deep or transmural lesions to eliminate intramurally originating arrhythmias remains inadequate. Bipolar ablation is proposed as an alternative to overcome unipolar ablation boundaries., Results: Despite promising results gained from in vitro and animal studies showing that bipolar ablation is superior in creating transmural lesions, the use of bipolar ablation in daily clinical practice is limited. Several studies have been published showing that bipolar ablation is effective in the treatment of clinical arrhythmias after failed unipolar ablation, however, there is inconsistency regarding the safety of bipolar ablation within the available research papers. According to research evidence, the most common indications for bipolar ablation use are ventricular originating rhythmic disorders in patients with structural heart disease resistant to standard radiofrequency ablation., Conclusion: To allow wider clinical application the efficiency and safety of bipolar ablation need to be verified in future studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina., Methods: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment., Results: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period., Conclusions: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

Aims: Three-dimensional rotational angiography (3DRA) of the left atrium (LA) and the esophagus is a simple and safe method for analyzing the relationship between the esophagus and the LA during catheter ablation of atrial fibrillation. The purpose of this study is to describe the location of the esophagus relative to the LA and mobility of the esophagus during ablation procedure., Methods: From 3/2011 to 9/2015, 3DRA of the LA and esophagus was performed in 326 patients before catheter ablation of atrial fibrillation. 3DRAwas performed with visualization of the esophagus via peroral administration of a contrast agent. The positions of the esophagus were determined at the beginning of the procedure, for part of patients also at the end of procedure with contrast esophagography., Results: The most frequent position is behind the center of the LA (91 pts., 31.9%) The least frequent position is behind the right pulmonary veins (27 pts., 9.4%). The average shift of the esophagus position was 3.36±2.15mm, 3.59±2.37mm and 3.67±3.23mm for superior, middle and inferior segment resp., Conclusions: The position of the esophagus to the LA is highly variable. The most common position of the esophagus relative to the LA is behind the middle and left part of the posterior wall of the LA. The least frequently observed position is behind the right pulmonary veins. No significant position change of esophagus motion from before to after the ablation procedure in the majority (≥95%) of the patients was observed., (Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Aims: The objective of this study was to evaluate the mobility of the oesophagus and the stability of the three-dimensional (3D) model of the oesophagus using 3D rotational angiography (3DRA) of the left atrium (LA) and the oesophagus, fused with live fluoroscopy during catheter ablation for atrial fibrillation., Methods and Results: From March 2015 to September 2015, 3DRA of the LA and the oesophagus was performed in 33 patients before catheter ablation for atrial fibrillation. Control contrast oesophagography was performed every 30 min. The positions of the oesophagograms and the 3D model of the LA and the oesophagus were repeatedly measured and compared with the spine. The average shift of the oesophagus ranged from 2.7 ± 2.2 to 5.0 ± 3.5 mm. The average real-time oesophageal shift ranged from 2.7 ± 2.2 to 3.8 ± 3.4 mm. No significant shift was detected until the 90th minute of the procedure. The average shift of the 3D model of the LA and the oesophagus ranged from 1.4 ± 1.8 to 3.3 ± 3.0 mm (right-left direction) and from 0.9 ± 1.2 to 2.2 ± 1.3 mm (craniocaudal direction). During the 2 h procedure, there were no significant shifts of the model., Conclusion: During catheter ablation for atrial fibrillation, there is no significant change in the position of the oesophagus until the 90th minute of the procedure and no significant shift in the 3D model of the LA and the oesophagus. The 3D model of the oesophagus reliably depicts the position of the oesophagus during the entire procedure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Patients with atrial fibrillation (AF) have an increased risk of diastolic dysfunction and heart failure. The purpose of this study was to identify independent predictors of early (ie, only exercise-induced) heart failure with preserved ejection fraction (HFpEF) and to describe the prevalence of early HFpEF among patients with paroxysmal AF., Methods and Results: One hundred patients with paroxysmal AF and preserved left ventricular ejection fraction (LVEF) underwent catheterization for left atrial pressure (LAP) measurements at rest and at the peak of arm exercise (LAP-exe). Based on resting and exercise LAP values, the patients were divided into 3 groups. Sixty-one patients had no evidence of HFpEF (LAP at rest ≤15 mm Hg, LAP-exe <25 mm Hg). Twenty-five subjects had early HFpEF (LAP at rest ≤15 mm Hg, LAP-exe ≥25 mm Hg, prevalence 25%). Fourteen patients already had HFpEF at rest (LAP at rest >15 mm Hg). Multivariate exact logistic regression analysis identified age ≥58 years, LAP at rest ≥11 mm Hg, and peak systolic mitral annular velocity ≤9.3 cm/s to be independent predictors of early HFpEF., Conclusions: In patients with paroxysmal AF and preserved LVEF, there appears to be a clinically significant prevalence of early HFpEF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Stem cell-derived cardiomyocytes (CMs) hold great hopes for myocardium regeneration because of their ability to produce functional cardiac cells in large quantities. They also hold promise in dissecting the molecular principles involved in heart diseases and also in drug development, owing to their ability to model the diseases using patient-specific human pluripotent stem cell (hPSC)-derived CMs. The CM properties essential for the desired applications are frequently evaluated through morphologic and genotypic screenings. Even though these characterizations are necessary, they cannot in principle guarantee the CM functionality and their drug response. The CM functional characteristics can be quantified by phenotype assays, including electrophysiological, optical, and/or mechanical approaches implemented in the past decades, especially when used to investigate responses of the CMs to known stimuli (eg, adrenergic stimulation). Such methods can be used to indirectly determine the electrochemomechanics of the cardiac excitation-contraction coupling, which determines important functional properties of the hPSC-derived CMs, such as their differentiation efficacy, their maturation level, and their functionality. In this work, we aim to systematically review the techniques and methodologies implemented in the phenotype characterization of hPSC-derived CMs. Further, we introduce a novel approach combining atomic force microscopy, fluorescent microscopy, and external electrophysiology through microelectrode arrays. We demonstrate that this novel method can be used to gain unique information on the complex excitation-contraction coupling dynamics of the hPSC-derived CMs., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Noninvasive diagnosis of exercise-induced elevation of left ventricular filling pressure is difficult and remains unsatisfactory. The aim of this study was to assess the accuracy of the ratio of early diastolic transmitral (E) to mitral annular (e') velocity and to determine new parameters or parameter combinations with the ability to predict exercise-induced left atrial pressure (LAP) elevation., Methods and Results: Eighty patients with paroxysmal atrial fibrillation (AF) referred for catheter AF ablation underwent simultaneous exercise echocardiography and direct invasive LAP measurements, as well as a resting and postexercise biomarker analysis. Exercise E/e' ≥8.85 predicted exercise LAP ≥20 mm Hg with 61.5% sensitivity and 88.9% specificity (area under the curve [AUC], 0.76). Of all of the individual parameters tested, the best prediction was achieved with exercise E/s' (s'=peak systolic mitral annular velocity) ≥8.75 (sensitivity, 88.5%; specificity, 64.8%; positive predictive value, 54.8%; negative predictive value, 92.1%; AUC, 0.84). However, the combination of exercise E/A (A = late diastolic transmitral flow velocity) ≥1.22 + exercise E/e' ≥8.85 + exercise s'≤11.05 cm/s provided the most precise prediction of exercise LAP elevation (sensitivity, 84.6%; specificity, 79.6%; positive predictive value, 66.7%; negative predictive value, 91.5%; AUC, 0.90)., Conclusions: Exercise E/e', when used as a sole parameter, was not sufficiently reliable to predict exercise-induced elevation of LAP. The application of a multivariate-adjusted combination of parameters appeared to be the preferable approach for the noninvasive prediction of exercise LAP elevation., (© 2016, Wiley Periodicals, Inc.)

A new method in creating 3D models of the left atrium (LA) and esophagus before catheter ablation of atrial arrhythmias is 3D rotational angiography (3DRA) of the LA. The purpose of this retrospective study was to test various acquisition protocols of the 3DRA and attempt to define the parameters influencing the success of the protocols. From August 2010 to November 2014, 3DRA of the LA using the Philips Allura FD 10 X-ray system was performed in 547 consecutive patients using right atrial and left atrial protocols. Visualization of the esophagus was performed after oral administration of a contrast agent. Patients were monitored for success (creation of a useful 3D models) and evaluated for a number of parameters affecting the success of 3DRA. The success of the RA protocol was 88.89 % with and 91.91 % without esophagus imaging. The success of the LA protocol was 97.42 % with and 94.54 % without esophagus imaging. The only factor reducing the success of the RA protocol was BMI; the LA protocol was not influenced by any factor. Ventricular fibrillation induced in two patients was successfully treated with defibrillation. 3DRA of the LA is a reliable method that supports catheter ablation of complex atrial arrhythmias. The LA protocol with esophagus imaging was significantly more reliable than the RA protocol; the other protocols were comparable. The RA protocol may be negatively affected by high BMI. Simultaneous imaging of the esophagus is safe and feasible, and the LA protocol can be recommended.

Objectives: The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device., Background: Renal denervation has emerged as a potential treatment approach for resistant hypertension., Methods: Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast., Results: All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5)., Conclusions: Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further randomized, sham-controlled trials will be needed to validate this unique approach., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Catheter ablation in the left atrium has become a common therapeutic strategy in the management of atrial fibrillation (AF). The high degree of success and safety profile of this procedure is dependent on precise knowledge of the true anatomy in the chamber. This information is imported mostly from cardiac computed tomography. A novel method for imaging the left atrial anatomy is three-dimensional rotational angiography (3DRA)., Methods: The aim of our study was to the compare clinical outcome and safety of catheter ablation for atrial fibrillation guided by 3DRA vs. conventional CT scan. One hundred and twenty-five patients referred for AF catheter ablation at St. Anne's University Hospital Brno were included in the retrospective analysis of clinical outcome within the first year after the procedure., Results: There was a close correlation in overall procedural parameters between the groups. The frequency of recurrent episodes of AF (24% in CT-guided group vs. 27% in 3DRA-guided group, P=0.721) as well as the onset of atypical atrial flutter after the procedure (10% vs. 8%, respectively, P=0.731) were similar in both groups. No difference in the number of patients necessitating repeat ablation (5% vs. 5%, P=0.984) was found. Procedural complications of ablations guided by 3DRA were comparable with those guided by CT (2% vs. 3%, respectively, P=0.568)., Conclusion: 3DRA has proven to be a safe and simple method for imaging the left atrium and guiding catheter ablation for AF. This approach is anticipated to become a new standard in 3D reconstruction of the left atrium.

Three-dimensional rotational angiography (3 DRA) is a novel imaging method introduced to guide complex catheter ablations of the left atrium. Our aim was to investigate the feasibility of the method in visualization of left ventricular anatomy and to develop a corresponding protocol for guidance of ventricular tachycardia ablation. We performed 3D rotational angiography in 13 patients using a direct left atrial protocol for data acquisition and the 3D reconstruction of the left ventricle was achieved in all patients. Clinical data comparison has proved lower use of radiation and contrast medium during 3 DRA-guided ablations as compared to CT-guided procedures.

Atrial fibrillation is the most common sustained arrhythmia. Because of the sub-optimal outcomes and associated risks of medical therapy as well as the recent advances in non-pharmacologic strategies, a multitude of combined (hybrid) algorithms have been introduced that improve efficacy of standalone therapies while maintaining a high safety profile. Antiarrhythmic administration enhances success rate of electrical cardioversion. Catheter ablation of antiarrhythmic drug-induced typical atrial flutter may prevent recurrent atrial fibrillation. Through simple ablation in the right atrium, suppression of atrial fibrillation may be achieved in patients with previously ineffective antiarrhythmic therapy. Efficacy of complex catheter ablation in the left atrium is improved with antiarrhythmic drugs. Catheter ablation followed by permanent pacemaker implantation is an effective and safe treatment option for selected patients. Additional strategies include pacing therapies such as atrial pacing with permanent pacemakers, preventive pacing algorithms, and/or implantable dual-chamber defibrillators are available. Modern hybrid strategies combining both epicardial and endocardial approaches in order to create a complex set of radiofrequency lesions in the left atrium have demonstrated a high rate of success and warrant further research. Hybrid therapy for atrial fibrillation reviews history of development of non-pharmacological treatment strategies and outlines avenues of ongoing research in this field.