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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. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Targeting HTT in pigs: Huntington's disease (HD) is a genetic neurodegenerative disorder caused by mutated huntingtin (HTT) gene. Reducing the expression of the aberrant HTT has been shown to be effective in preclinical models. Now, Vallès et al. evaluated the effects of an adeno-associated viral vector (AAV)–mediated strategy delivering microRNA (miRNA) targeting human mutant HTT (mHTT) in a pig model of HD that closely resembles the human condition. Intracerebral delivery of the miRNA into the striatum resulted in widespread distribution and reduced mHTT for up to a year after injection. The results suggest that the approach could be effective in patients with HD. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Damage to the esophagus during radiofrequency ablation of atrial fibrillation can result in fatal atrioesophageal fistula. Our aim is to describe the relationship of the left atrium (LA) and esophagus with a focus on contact of the posterior wall (PW) of the LA and the esophagus. Methods. From 9/2011 to 8/2012, CT of the heart was performed in 56 patients undergoing catheter ablation of atrial fibrillation using CT GE Lightspeed VCT 64 by nongated standard protocol. Positions of the esophagus to the LA, width of the esophagus and contact with the PW of the LA were determined. Results. The most frequent position of the esophagus was behind the left side of the LA. The average width of the esophagus was 16.0 ± 4.1 mm, and the average distance between the PW and esophagus was 4.8 ± 1.6 mm. On average, 50 ± 4.11 mm of the PW was in close contact with the esophagus. The average length of the fat pad between the esophagus and LA was 9.1 ± 5.5 mm in the upper part of the LA and 15.8 ± 7.3 mm at the bottom. Significantly longer contact occurred behind the right part of the LA. Conclusions. The most common esophageal position is behind the left side of the LA. The esophagus is located in close contact by approximately 2/3 of the length and 1/4 of the width of the PW of the LA. The esophagus is more adjacent to the upper part of PW of the LA. [ABSTRACT FROM AUTHOR]

Background. Three-dimensional rotational angiography (3DRA) of the heart is an imaging technique that displays the left atrium and adjacent structures during catheter ablation of atrial fibrillation. The aim is to evaluate the feasibility and safety of 3DRA for imaging the right and left ventricles of patients undergoing catheter ablation of ventricular arrhythmias. Methods. From 8/2010 to 6/2015, 35 patients underwent 3DRA of the right (20 patients) or left ventricle (15 patients) with a Philips Allura FD 10 X-ray system using a direct protocol. The success rate of the 3D model, as well as the procedure times and complications of 3DRA, was evaluated, and the 3DRA model was compared with ventricular computer tomography (CT). Results. The overall 3D model success rate was 91.4%. The 3D models were graded as excellent for 65.7% of patients and as useful for 25.7% of patients. The imaging success rate was slightly higher for the right ventricle than for the left ventricle (95%, 86.7%, respectively). The times required to perform 3DRA of the right and left ventricle were 12.5 +/- 2.1 min and 14.7 +/- 2.8 min, respectively. There were no significant differences between 3DRA and ventricular CT. Conclusion. Ventricular 3DRA allows the easy and safe creation of 3D models of the cardiac ventricles. The success rate is comparable to the success rate of the 3DRA for imaging the left atrium. There was no difference in imaging quality between the two ventricles. 3DRA models of the ventricles are comparable with CT models of the ventricles. [ABSTRACT FROM AUTHOR]

Background. Catheter ablation of complex atrial arrhythmias guided by 3D models of a left atrium (LA) derived from CT/MRI or 3D rotational angiography of the heart (3DRA) is currently a common practice. Our aim is to compare radiation dose, consumption of a contrast agent and cost of these methods. Methods. From 10/2012 to 10/2015, either 3DRA (157 patients using the X-ray system Philips Allura FD 10) or computer tomography (CT) (157 patients using 64-slice CT GE Lightspeed VCT) of the LA was performed in patients undergoing complex atrial arrhythmias ablation. All procedures were monitored for average effective radiation dose, dose of the contrast agent and analysis of a financial expenditures. Results. The average effective radiation dose for 3DRA was 2.11±0.392 mSv compared to 10.52±2.093 mSv for CT. The contrast agent consumption was 22.2 mg and 48.2 mg of iodine for 3DRA and CT, respectively. Total price per procedure is 123€ for 3DRA and 161€ for CT. Conclusion. Consumption of the contrast agent and radiation burden for LA 3DRA is significantly lower in comparison to most currently used CT scan methods. Cost of both methods is comparable, however, 3DRA is slightly less expensive than CT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [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.)

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.)

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.)

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: 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.)

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.)