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Background: Transmural propagation and endoepicardial delays in activation observed in patients with atrial fibrillation are hypothesized to be associated with structural remodeling and endoepicardial dissociation. We aim to explore in a computational model how the distribution of delays and the rate of endo- and epicardial breakthrough activation patterns are affected by fibrosis and heterogeneous layer dissociation., Methods: A bilayer interconnected cable model of the left atrium was used to simulate a total of 4,800 episodes of atrial fibrillation on 960 different arrhythmogenic substrates with up to 30% epicardium-only diffuse fibrosis. Endoepicardial connections were heterogeneously distributed following random spatial patterns (characteristic length scale from 1.6 to 11.4 mm). Intermediate nodes were introduced in the transmural connections to enable the simulation of weaker coupling. This heterogeneous interlayer dissociation divided the atrial bilayer into connected and disconnected regions (from 27 to 48,000 connected regions). Activation time series were extracted in both layers to compute endoepicardial delays and detect breakthrough patterns., Results: Because of epicardial fibrosis, fibrillatory waves were driven by the endocardium, which generated endoepicardial delays. The delays in the connected regions (up to 10 ms, but generally < 5 ms) were prolonged by higher fibrosis density and weaker coupling. Disconnected regions allowed longer delays (> 15 ms) and promoted the occurrence of breakthroughs. These breakthroughs had short lifespan (< 10-20 ms) and were more prevalent with higher fibrosis density and heterogeneous dissociation (larger disconnected regions). Severe remodeling (< 500 connected regions) was needed to produce clinically reported rates (> 0.1 breakthrough/cycle/cm2)., Conclusion: Heterogeneous endoepicardial dissociation aggravates activation delays and increases the prevalence of epicardial breakthroughs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zakeri Zafarghandi, Jacquemet. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Catheter ablation (CA) of idiopathic ventricular arrhythmias (VAs) from the epicardial left ventricular summit is challenging. The endocardial approach targets two sites: the endocardial closest site (ECS) to the epicardial earliest activation site (epi-EAS) and the endocardial earliest activation site (endo-EAS). We aimed to differentiate between cases where CA at the ECS was effective and where CA at the endo-EAS yielded success., Methods and Results: Fifty-eight patients (47 men; age 60 ± 13 years) were analysed with VAs in which the EAS was observed in the coronary venous system (CVS). Overall, VAs were successfully eliminated in 42 (72%) patients: 8 in the CVS, 8 where the ECS matched with the endo-EAS, 11 at the ECS, and 15 at the endo-EAS. A successful ECS ablation was associated with a shorter epi-EAS-ECS distance (10.2 ± 4.7 vs. 18.8 ± 5.3 mm; P < 0.001) and shorter epi-EAS-left main coronary trunk (LMT) ostial distance (20.3 ± 7.6 vs. 30.3 ± 8.4 mm; P = 0.005), with optimal cut-off values of ≤12.6 and ≤24.0 mm, respectively. A successful endo-EAS ablation was associated with an earlier electrogram at the endo-EAS [23 (8, 36) vs. 15 (0, 19) ms preceding the QRS; P < 0.001] and shorter epi-EAS-endo-EAS interval [6 (1, 8) vs. 22 (12, 25) ms; P < 0.001], with optimal cut-off values of ≥18 and ≤9 ms, respectively., Conclusion: Shorter anatomical distances between the epi-EAS and ECS, and between the epi-EAS and LMT ostium, predict a successful ECS ablation. The prematurity of the endo-EAS electrogram and a shorter interval between the epi-EAS and endo-EAS predicted a successful endo-EAS ablation., Competing Interests: Conflict of interest: K.N. received speaker honoraria from Johnson & Johnson, Medtronic Japan, Boston Scientific Japan, Abbott Japan, and Daiichi-Sankyo. S.T. received honoraria from Medtronic Japan, Daiichi-Sankyo, Johnson & Johnson, Boston Scientific Japan, Abbott Japan, Bayer Yakuhin, and Japan Lifeline and is affiliated with the endowed research courses supported by Medtronic Japan, Japan Lifeline, Boston Scientific Japan, Abbott Japan, and Biotronik Japan. Y.O. received research grants unrelated to this study from Johnson & Johnson KK and Biosense Webster, Inc., scholarship funds from Nippon Boehringer Ingelheim, and remuneration from Daiichi-Sankyo, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, and Johnson & Johnson KK and additionally belongs to the endowed departments of Boston Scientific Japan, Biotronik Japan, Abbott Medical Japan, Japan Lifeline, and Medtronic Japan. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Drs Santangeli and Wazni have received research grants and consultancy fees from Biosense Webster, Abbott, Boston Scientific, and Medtronic. Dr Obeng-Gyimah received consulting fees from Biosense and InHeart. Dr Hubert Cochet is a founder for In Heart.

Background: Endocardial electrogram (EGM) characteristics in nonischemic cardiomyopathy (NICM) have not been explored adequately for prognostication., Objective: We aimed to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM., Methods: Electroanatomic mapping of the left ventricle was performed. EGM characteristics were correlated with LVEF. Differences between groups with and without VT and predictors of VT were studied., Results: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r = +0.36), peak negative unipolar voltage (r = -0.42), peak positive unipolar voltage (r = +0.38), and percentage area of unipolar low-voltage zone (LVZ; r = -0.41). Global mean unipolar voltage (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), extent of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3), and percentage area of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had an area under the curve of 0.82 (95% CI, 0.69-0.95; P < .001), and percentage area of unipolar LVZ had an area under the curve of 0.83 (95% CI, 0.71-0.96; P = .01). Cutoff of >3 segments for extent of unipolar LVZ had the best diagnostic accuracy (sensitivity, 90%; specificity, 67%) and cutoff of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity, 95%; specificity, 60%) for VT., Conclusion: In NICM, extent and percentage area of unipolar LVZs are significant predictors of VT. Cutoffs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ have good diagnostic accuracies for association with VT., Competing Interests: Disclosures Dr Sanders reports having served on the advisory boards of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate and that the University of Adelaide has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, and Boston Scientific. Dr Pathak reports having served on the advisory boards of Medtronic, Abbott Medical, and Boston Scientific and that Canberra Heart Rhythm Foundation has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to analyze the ability of subendocardial viability ratio (SEVR) to predict the degree of coronary artery stenosis and the relationship between SEVR and the incidence of short-term cardiovascular endpoint events., Method: The indexes of 243 patients with chest pain were collected.. Binary logistic regression analyses were performed using the dichotomous outcome of high and non-high SYNTAX scores. Receiver operating characteristic curves were employed to comparatively analyze the diagnostic efficiencies of the indices and models. A survival analysis combined with the Cox regression analysis was performed using the Kaplan-Meier method to understand the relationship between the SEVR and the incidence of cardiovascular events within 1 year in patients with coronary heart disease (CHD)., Results: SEVR was significantly lower ( P  < 0.05) in the high-stenosis group than control and low-stenosis groups. The diagnostic efficacy of SEVR [area under the curve (AUC) = 0.861] was better than those of age (AUC = 0.745), ABI (AUC = 0.739), and AIx@HR75 (AUC = 0.659). The cutoff SEVR was 1.105. In patients with confirmed CHD who had been discharged from the hospital for 1 year, only SEVR affected survival outcomes (hazard ratio = 0.010; 95% confidence interval: 0.001-0.418; P  = 0.016)., Conclusion: A significant decrease in SEVR predicted severe coronary artery stenosis, with a cutoff value of 1.105 and an accuracy of 0.861. In patients with CHD, the lower the SEVR, the higher was the rate of cardiovascular events at 1 year after hospital discharge., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Patients with viral myocarditis can present with challenging life-threatening arrhythmias. Catheter ablation can be a life-saving procedure in some patients with recurrent drug-refractory ventricular arrhythmias., Methods and Results: A patient with three prior ablations targeting two different monomorphic ventricular tachycardias (MMVTs) presented with recurrent ventricular tachycardia (VT). Consequently, he underwent epicardial mapping with adjuvant AI-enabled CT images with the creation of a three-dimensional model, which demonstrated a midmyocardial scar. Fractionated potentials were noted during mapping in this region, and entrainment suggested an inner loop. Interestingly, pacing showed two different QRS morphologies identical to his previously ablated VTs with a long stim-QRS at this region. Epicardial ablation carried on during the VT successfully terminated it, but the VT remained inducible and required endocardial ablation to make it noninducible., Conclusion: This case emphasizes the importance of recognizing possible three-dimensional VT circuits in some patients and the need to understand and target mid-myocardial substrate from both the endocardium and epicardium to achieve the elimination of the VT circuits., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Assessment of origin of ventricular tachycardias (VTs) arising from epicardial vs endocardial sites are largely challenged by the available criteria and etiology of cardiomyopathy. Current electrocardiographic (ECG) criteria based on 12-lead ECG have varying sensitivity and specificity based on site of origin and etiology of cardiomyopathy., Objectives: This study sought to test the hypothesis that epicardial VT has a slower initial rate of depolarization than endocardial VT., Methods: We developed a method that takes advantage of the fact that electrical conduction is faster through the cardiac conduction system than the myocardium, and that the conduction system is primarily an endocardial structure. The technique calculated the rate of change in the initial VT depolarization from a signal-averaged 12-lead ECG. We hypothesized that the rate of change of depolarization in endocardial VT would be faster than epicardial. We assessed by applying this technique among 26 patients with VT in nonischemic cardiomyopathy patients., Results: When comparing patients with VTs ablated using epicardial and endocardial approaches, the rate of change of depolarization was found to be significantly slower in epicardial (6.3 ± 3.1 mV/s vs 11.4 ± 3.7 mV/s; P < 0.05). Statistical significance was found when averaging all 12 ECG leads and the limb leads, but not the precordial leads. Follow up analysis by calculation of a receiver-operating characteristic curve demonstrated that this analysis provides a strong prediction if a VT is epicardial in origin (AUC range 0.72-0.88). Slower rate of change of depolarization had high sensitivity and specificity for prediction of epicardial VT., Conclusions: This study demonstrates that depolarization rate analysis is a potential technique to predict if a VT is epicardial in nature., Competing Interests: Funding Support and Author Disclosures This work was supported in part by the University of Minnesota’s Medical School Academic Investment Education Program grant and the Institute for Engineering in Medicine. Dr Prisco is funded by the National Institutes of Health T32 HL144472. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Background: Pulsed Field Ablation (PFA) has recently been proposed as a non-thermal energy to treat atrial fibrillation by selective ablation of ganglionated plexi (GP) embedded in epicardial fat. While some of PFA-technologies use an endocardial approach, others use epicardial access with promising pre-clinical results. However, as each technology uses a different and sometimes proprietary pulse application protocol, the comparation between endocardial vs. epicardial approach is almost impossible in experimental terms. For this reason, our study, based on a computational model, allows a direct comparison of electric field distribution and thermal-side effects of both approaches under equal conditions in terms of electrode design, pulse protocol and anatomical characteristics of the tissues involved., Methods: 2D computational models with axial symmetry were built for endocardial and epicardial approaches. Atrial (1.5-2.5 mm) and fat (1-5 mm) thicknesses were varied to simulate a representative sample of what happens during PFA ablation for different applied voltage values (1000, 1500 and 2000 V) and number of pulses (30 and 50)., Results: The epicardial approach was superior for capturing greater volumes of fat when the applied voltage was increased: 231 mm 3 /kV with the epicardial approach vs. 182 mm 3 /kV with the endocardial approach. In relation to collateral damage to the myocardium, the epicardial approach considerably spares the myocardium, unlike what happens with the endocardial approach. Although the epicardial approach caused much more thermal damage in the fat, there is not a significant difference between the approaches in terms of size of thermal damage in the myocardium., Conclusions: Our results suggest that epicardial PFA ablation of GPs is more effective than an endocardial approach. The proximity and directionality of the electric field deposited using an epicardial approach are key to ensuring that higher electric field strengths and increased temperatures are obtained within the epicardial fat, thus contributing to selective ablation of the GPs with minimal myocardial damage., Competing Interests: Declaration of competing interest Barry O'Brien is employee of AtriAN Medical, Galway, Ireland. The rest of the authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients., Methods: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps., Results: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively)., Conclusion: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1., (© 2024 Wiley Periodicals LLC.)

We have previously reported that atrial endocardial remodeling is induced by atrial fibrillation (AF), and the endocardial dysfunction may be partly responsible for the thrombus formation in the left atrium associated with AF. However, the relationship between the endocardial dysfunction and the epidemiologically determined risk factors of AF-related strokes, including aging, hypertension, and diabetes mellitus, is yet to be elucidated.To test the hypothesis that aging, hypertension, and diabetes mellitus individually impair the atrial endocardial function in conjunction with AF, we have analyzed the expression of the tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) in the atrial endocardium in 30-week-old Wister-Kyoto (WKY), 60-week-old WKY, 30-week-old spontaneously hypertensive rats (SHR), and 30-week Goto-Kakizaki (GK) rats during normal sinus rhythm and after rapid atrial pacing at 1200 bpm for 8 hours, using Western blotting and immunohistochemical analysis. Even during sinus rhythm, the TFPI and TM expressions were noted to be remarkably downregulated in the atrial endocardium among 60-week-old WKY rats. In contrast, in SHR rats, only the TFPI expression has significantly decreased, while TM was preserved to the same level of control 30-week-old WKY rats. Rapid atrial pacing significantly reduced the TM and TFPI expression similarly in each model, thereby augmenting the endocardial dysfunction during normal sinus rhythm individually induced by the risk factors themselves prior to AF.Aging and hypertension, both of which are epidemiologically well-known risk factors for strokes in AF, have been associated with a specific atrial endocardial impairment prior to AF that could additionally disturb the antithrombotic function of the atrial endocardium.

Pulmonary hypertension (PH) is a chronic progressive disease diagnosed when the pressure in the main pulmonary artery, assessed by right heart catheterization (RHC), is greater than 25 mmHg. Changes in the pulmonary vasculature due to the high pressure yield an increase in the right ventricle (RV) afterload. This starts a remodeling process during which the ventricle exhibits changes in shape and eventually fails. RV models were obtained from the segmentation of cardiac magnetic resonance images at baseline and 1-year follow-up for a pilot study that involved 12 PH and 7 control subjects. The models were used to create surface meshes of the geometry and to compute the principal, mean, and Gaussian curvatures. Ten global curvature indices were calculated for each of the RV endocardial wall reconstructions at the end-diastolic volume (EDV) and end-systolic volume (ESV) phases of the cardiac cycle. Statistical analysis of the data was performed to discern if there are significant differences in the curvature indices between controls and the PH group, as well as between the baseline and follow-up phases for the PH subjects. Six curvature indices, namely, the Gaussian curvature at ESV, the mean curvature at EDV and ESV, the L2-norm of the mean curvature at ESV, and the L2-norm of the major principal curvature at EDV and ESV, were found to be significantly different between controls and PH subjects (p < 0.05). We infer that these geometry measures could be used as indicators of RV endocardial wall morphology changes. Two global parameters, the Gaussian and mean curvatures at ESV, showed significant changes at the one-year follow-up for the PH subjects (p < 0.05). The aforementioned geometry measures to assess changes in RV shape could be used as part of a noninvasive computational tool to aid clinicians in PH diagnostic and progression assessment, and to evaluate the effectiveness of treatment., (Copyright © 2021 by ASME.)

Background: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL., Methods: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed., Results: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence., Conclusions: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally., (© 2021 Wiley Periodicals LLC.)

The ability of zebrafish to heal their heart after injury makes them an attractive model for investigating the mechanisms governing the regenerative process. In this study, we show that the gene cellular communication network factor 2a ( ccn2a ), previously known as ctgfa , is induced in endocardial cells in the injured tissue and regulates CM proliferation and repopulation of the damaged tissue. We find that, whereas in wild-type animals, CMs track along the newly formed blood vessels that revascularize the injured tissue, in ccn2a mutants CM proliferation and repopulation are disrupted, despite apparently unaffected revascularization. In addition, we find that ccn2a overexpression enhances CM proliferation and improves the resolution of transient collagen deposition. Through loss- and gain-of-function as well as pharmacological approaches, we provide evidence that Ccn2a is necessary for and promotes heart regeneration by enhancing the expression of pro-regenerative extracellular matrix genes, and by inhibiting the chemokine receptor gene cxcr3.1 through a mechanism involving Tgfβ/pSmad3 signaling. Thus, Ccn2a positively modulates the innate regenerative response of the adult zebrafish heart., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Background: Endocardial pacing may be beneficial in patients who fail to improve following conventional epicardial cardiac resynchronization therapy (CRT). The potential to pace anywhere inside the left ventricle thus avoiding myocardial scar and targeting the latest activating segments may be particularly important. The WiSE-CRT system (EBR systems, Sunnyvale, CA) reliably produces wireless, endocardial left ventricular (LV) pacing. The purpose of this analysis was to determine whether this system improved symptoms or led to LV remodeling in patients who were nonresponders to conventional CRT., Method: An international, multicenter registry of patients who were nonresponders to conventional CRT and underwent implantation with the WiSE-CRT system was collected., Results: Twenty-two patients were included; 20 patients underwent successful implantation with confirmation of endocardial biventricular pacing and in 2 patients, there was a failure of electrode capture. Eighteen patients proceeded to 6-month follow-up; endocardial pacing resulted in a significant reduction in QRS duration compared with intrinsic QRS duration (26.6 ± 24.4 ms; P = .002) and improvement in left ventricular ejection fraction (LVEF) (4.7 ± 7.9%; P = .021). The mean reduction in left ventricular end-diastolic volume was 8.3 ± 42.3 cm 3 (P = .458) and left ventricular end-systolic volume (LVESV) was 13.1 ± 44.3 cm 3 (P = .271), which were statistically nonsignificant. Overall, 55.6% of patients had improvement in their clinical composite score and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%., Conclusion: Nonresponders to conventional CRT have few remaining treatment options. We have shown in this high-risk patient group that the WiSE-CRT system results in improvement in their clinical composite scores and leads to LV remodeling., (© 2020 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA. Areas of CB were defined as conduction delays of ≥12 ms, EEA as activation time differences of opposite electrodes of ≥15 ms and transmural CB as CB at similar endo-epicardial sites. CB was more pronounced at the endocardium (all locations P <0.025). Amount, extensiveness and severity of CB was higher at the superior RA. Transmural CB at the inferior RA was associated with a higher incidence of post-operative AF ( P =0.03). EEA occurred up to 84 ms and was more pronounced at the superior RA (superior: 27 ms [interquartile range, 18.3-39.3], versus mid-RA: 20.3 ms [interquartile range, 0-29.9], and inferior RA: 0 ms [interquartile range, 0-21], P <0.001). Hypertension ( P =0.009), diabetes mellitus ( P =0.018), and hypercholesterolemia ( P =0.015) were associated with a higher degree of EEA. CB ( P =0.007) and EEA ( P =0.037) were more pronounced in patients with a history of persistent AF compared with patients without AF history. Conclusions This study provides important insights into complex atrial endo-epicardial excitation. Significant differences in conduction disorders between the endo- and epicardium and a significant degree of EEA are already present during sinus rhythm and are more pronounced in patients with cardiovascular risk factors or a history of persistent AF.

Background: Endocardial-epicardial dissociation and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study, we used simultaneous endo-epi phase mapping to characterize endo-epi activation patterns on long segments of human persistent AF., Methods: Simultaneous intraoperative mapping of endo- and epicardial lateral right atrium wall was performed in patients with persistent AF using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms of continuous 2-minute AF recordings and electrodes locations were exported for phase analyses. We defined endocardial-epicardial dissociation as phase difference of ≥20 ms between paired endo-epi electrodes. Wavefronts were classified as rotations, single wavefronts, focal waves, or disorganized activity as per standard criteria. Endo-Epi wavefront patterns were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with ≥5 directional changes occupying at least 70% of sample duration., Results: Fourteen patients with persistent AF undergoing cardiac surgery were included. Endocardial-epicardial dissociation was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (Endo: 41.3% versus Epi: 46.8%, P =0.0194) and single wavefronts (Endo: 31.3% versus Epi: 28.1%, P =0.129) were the dominant patterns. Transient rotations (Endo: 22% versus Epi: 19.2%, P =0.169; mean duration: 590±140 ms) and nonsustained focal waves (Endo: 1.2% versus Epi: 1.6%, P =0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. Electrogram fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P <0.0001)., Conclusions: Simultaneous endo-epi phase mapping of prolonged human persistent AF recordings shows significant Endocardial-epicardial dissociation marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insight into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Graphic Abstract: A graphic abstract is available for this article.

Left atrial appendage closure (LAAC) is a safe and effective therapy for the prevention of stroke in patients with nonvalvular atrial fibrillation and high bleeding risk with oral anticoagulants. Multimodality imaging with transesophageal echocardiography and computed tomography angiography to define the anatomy and its implications on endocardial exclusion is becoming increasingly important. The only LAAC device currently approved for clinical use in the United States is the WATCHMAN device. Systematic assessment of the transseptal crossing site, left atrial appendage anatomy, adequate device size selection, and device postdeployment evaluation is essential for the safety and efficacy of the procedure., Competing Interests: Disclosure statement Dr C.E. Sanchez: consulting for Boston Scientific. Dr S.J. Yakubov: medical advisory board for Boston Scientific. Dr A. Amin: medical advisory board for Boston Scientific. Dr A. Arshi: no disclosures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The Convergent procedure is a hybrid, multidisciplinary treatment for symptomatic atrial fibrillation (AF) consisting of minimally invasive surgical epicardial ablation and percutaneous/catheter endocardial ablation. We investigated outcomes following introduction of the Convergent procedure at our institution., Methods: Retrospective study examining single-center outcomes. Demographic, procedural, and post-procedural variables were collected with follow-up data obtained at 3, 6, and 12 months., Results: In all, 36 patients with paroxysmal (11%) or persistent/long-standing persistent (89%) AF underwent the Convergent procedure. 36% also underwent concomitant left atrial appendage (LAA) exclusion by thoracoscopic placement of an epicardial clip. Mean age 60.6 ± 8.0 years with mean arrhythmia burden of 3.9 ± 2.7 years. All patients had failed prior attempts at medical management, 81% had failed prior cardioversion, and 17% had failed prior catheter ablation. Convergent was performed successfully in all patients with no peri-procedural deaths or major complications. At 3 and 12 months, 77.8% and 77.3% of patients, respectively, were free from symptomatic arrhythmia. 65.8% were off anti-arrhythmic medication at 12 months., Conclusions: The Convergent procedure is safe and has good short- and intermediate-term clinical success rates. This unique hybrid approach combines strengths of surgical and catheter ablation and should be part of any comprehensive AF treatment program.

Cardiac pathologies associated with arrhythmic activity are often accompanied by inflammation. The contribution of inflammatory cells to the electrophysiological properties of injured myocardium is unknown. Myocardial scar cell types and intercellular contacts were analyzed using a three-dimensional reconstruction from serial blockface scanning electron microscopy data. Three distinct cell populations were identified: inflammatory, fibroblastic and endocardial cells. While individual fibroblastic cells interface with a greater number of cells, inflammatory cells have the largest contact area suggesting a role in establishing intercellular electrical connections in scar tissue. Optical mapping was used to study the electrophysiological properties of scars in fetal liver chimeric mice generated using connexin43 knockout donors (bmpKO). Voltage changes were elicited in response to applied current pulses. Isopotential maps showed a steeper pattern of decay with distance from the electrode in scars compared with uninjured regions, suggesting reduced electrical coupling. The tissue decay constant, defined as the distance voltage reaches 37% of the amplitude at the edge of the scar, was 0.48 ± 0.04 mm (n = 11) in the scar of the bmpCTL group and decreased 37.5% in the bmpKO group (n = 10). Together these data demonstrate inflammatory cells significantly contribute to scar electrophysiology through coupling mediated at least partially by connexin43 expression.

Differentiation between epicardial and endocardial ventricular activation remains a challenge despite the latest technologies available. The aim of the present study was to develop a new tool method, based on electromechanical wave imaging (EWI), to improve arrhythmogenic substrate activation analysis. Experiments were conducted on left ventricles (LVs) of four isolated working mode swine hearts. The protocol aimed at demonstrating that different patterns of mechanical activation could be observed whether the ventricle was in sinus rhythm, paced from the epicardium or from the endocardium. A total of 72 EWI acquisitions were recorded on the anterior, lateral and posterior segments of the LV. A total of 54 loop records were blindly assigned to two readers. EWI sequences interpretations were correct in 89% of cases. The overall agreement rate between the two readers was 83%. When in a paced ventricle, the origin of the wave front was focal and originated from the endocardium or the epicardium. In sinus rhythm, wave front was global and activated within the entire endocardium toward the epicardium at a speed of 1.7 ± 0.28 m·s -1 . Wave front speeds were respectively measured when the endocardium or the epicardium were paced at a speed of 1.1 ± 0.35 m·s -1 versus 1.3 ± 0.34 m·s -1 (p = NS). EWI activation mapping allows activation localization within the LV wall and calculation of the wave front propagation speed through the muscle. In the future, this technology could help localize activation within the LV thickness during complex ablation procedures., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon., Methods: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. A standard (USCI) temporary bipolar endocardial catheter positioned at the apex of the right ventricle (RV) and bipolar chest leads from two precordial leads V1 and V4 were used to record the tracings during TdP., Results: The presence of a wide spectrum of fragmentations was noted on endocardial electrograms (EGMs), which were invisible on the surface electrocardiogram (ECG) tracing. Endocardial signals indicated that TdP started in the proximity of the RV apex, since the local EGM began prior to the QRS complex on the surface ECG. Early afterdepolarizations (EADs) were observed in 2 out of 5 cases confirming a common opinion about the mechanism of TdP. However, this phenomenon was not observed in 3 other patients suggesting that the arrhythmia was the result of a different mechanism originating in proximity to the RV apex., Conclusions: This work demonstrated early endocardial signals in the RV apex during TdP associated with high-degree AVB in humans, and exhibits a spectrum of fragmented signals in this area occurring on a single or multiple beats. These fragmentations indicate areas of poor conduction and various degrees of intramyocardial block, and therefore a new mechanism of TdP tachycardia in some patients with spontaneous high-degree AVB.

Introduction: Recurrent ventricular tachycardia (VT) after percutaneous ablation is associated with a high morbidity and mortality. We assessed the feasibility of open chest extracorporeal circulation (ECC)-supported 3D multielectrode mapping and targeted VT substrate ablation in patients with previously failed percutaneous endocardial and epicardial VT ablations., Methods: In patients with previously failed percutaneous endocardial and epicardial VT ablations and a high risk of hemodynamic collapse during the procedure, open chest ECC-supported mapping and ablation were performed in a hybrid EP lab setting. Electro-anatomic maps (3D) were acquired during sinus rhythm and VT using a multielectrode mapping catheter (HD grid; Abbott or Pentaray, Biosense Webster). Irrigated radiofrequency ablations of all inducible VT were performed with a contact force ablation catheter., Results: Hybrid VT ablation was performed in 5 patients with structural heart disease (i.e., 3 with previous old myocardial infarction and 2 with nonischemic cardiomy-opathy) and recurrent VT. Acute procedural success was achieved in all patients. Four patients were successfully weaned off the ECC. In 1 patient with a severely reduced LVEF (16%), damage to the venous graft occurred after sternotomy and that patient died after 1 month. Four patients (80%) remained VT free after a median follow-up of 6 (IQR 4-10) months., Conclusion: In high-risk patients with previously failed percutaneous endocardial and epicardial VT ablations, open chest ECC-supported multielectrode epicardial mapping revealed a VT substrate in all of the patients, and targeted epicardial ablation abolished VT substrate in these patients., (© 2019 S. Karger AG, Basel.)

Introduction: Isolation of the left atrial appendage (LAA) is often performed in persistent atrial fibrillation (AF). Propagation patterns in the LAA during AF remain to be elucidated. We sought to characterize propagation patterns in the LAA during AF in persistent AF., Methods: Persistent AF patients undergoing catheter ablation were studied. Pulmonary vein isolation (PVI) was performed during continuous AF. If AF was not terminated by PVI, bi-atrial mapping was performed using a multi-electrode catheter during AF. Maps were collected at each site for 30 seconds and analyzed offline with a novel software, CARTOFINDER. This software made automatic determinations of whether activation was focal or rotational. The left atrium (LA) was divided into five regions, of which the LAA was one, and the right atrium (RA) into three., Results: Eighty patients were studied (62 ± 10 years, 65 males). On average, 9.6 ± 2.2 and 4.1 ± 1.2 maps were created in the LA and RA, respectively. The LAA was mapped in 70 patients, resulting in 85 maps. In the LAA, activation was identified as focal more often than rotational (64 [91%] vs 10 [14%] patients, P < .001), seven patients displayed both. The number of focal activation events was greatest in the LAA (28.5 events/30 seconds [interquartile range, 15-54]) of the eight atrial regions. During focal activation, sites designated as earliest activation frequently covered a wide area, rather than being localized to a discrete site (5.4 ± 3.1 electrodes)., Conclusions: The results of this study suggest that focal activation is a major mechanism underlying the arrhythmogenicity of the LAA in persistent AF., (© 2019 Wiley Periodicals, Inc.)

In vitro human ether-à-go-go related gene (hERG) inhibition assay alone might provide insufficient information to discriminate "safe" from "dangerous" drugs. Here, effects of multichannel inhibition on cardiac electrophysiology were investigated using a family of cardiac cell models (Purkinje (P), endocardial (Endo), mid-myocardial (M) and epicardial (Epi)). We found that: (1) QT prolongation alone might not necessarily lead to early afterdepolarization (EAD) events, and it might be insufficient to predict arrhythmogenic liability; (2) the occurrence and onset of EAD events could be a candidate biomarker of drug-induced arrhythmogenicity; (3) M cells are more vulnerable to drug-induced arrhythmias, and can develop early afterdepolarization (EAD) at slower pacing rates; (4) the application of quinidine can cause EADs in all cell types, while I NaL is the major depolarizing current during the generation of drug-induced EAD in P cells, I CaL is mostly responsible in other cell types; (5) drug-induced action potential (AP) alternans with beat-to-beat variations occur at high pacing rates in P cells. These results suggested that quantitative profiling of transmural and rate-dependent properties can be essential to evaluate drug-induced arrhythmogenic risks, and may provide mechanistic insights into drug-induced arrhythmias.

Background: Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited., Methods: Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated., Results: A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, P =0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8-25.6) mm (median and [first-third] quartile). Distances were not significantly different across cardiac chambers., Conclusions: The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.

Background: Cardiovascular disease has its origins in adolescents. Endothelial dysfunction, arterial stiffness, and decreased endocardial oxygen supply: demand ratios are early functional markers of cardiovascular risk. The goal of this study was to determine the relationships of these markers to physical, inflammatory, and metabolic markers in healthy non-Hispanic, white adolescents., Methods: Thirty-four of the 75 subjects were female. Mean age was 15.0 ± 1.7 years and mean body mass index (BMI) was 22.0 ± 5.8 kg/m 2 (mean ± SD). Reactive hyperemia was measured using venous occlusion plethysmography. Arterial tonometry was used to measure the augmentation index (AIx 75 ) and the Buckberg subendocardial viability ratio. Blood samples were taken to measure inflammatory and lipid markers and oral glucose tolerance test was used to assess insulin sensitivity., Results: Reactive hyperemia decreased as body mass and fat mass increased. It also decreased with increasing neutrophil count. The Buckberg index was higher in males and was positively related to insulin sensitivity even when accounting for age, sex, and resting heart rate. AIx 75 was not related to any of the other variables., Conclusions: These results demonstrate that increased fat mass and decreased insulin sensitivity are related to poorer vascular function and cardiac risk in adolescents before the development of actual cardiovascular disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS)., Methods: We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers., Results: Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences ( P <0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences., Conclusions: There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.

Objectives: This study sought to evaluate the value of combined electrogram (EGM) information provided by simultaneous mapping using micro- and conventional electrodes in the identification of post-myocardial infarction ventricular tachycardia substrate., Background: Ventricular tachycardias after myocardial infarction are related to scars with complex geometry. Scar delineation and ventricular tachycardia substrate identification relies on bipolar voltages (BV) and EGM characteristics. Early reperfusion therapy results in small, nontransmural scars, the details of which may not be delineated using 3.5 mm tip catheters., Methods: Nine swine with early reperfusion myocardial infarction were mapped using Biosense Webster's QDOT Micro catheter, incorporating 3 microelectrodes at the tip of the standard 3.5 mm electrode. Analysis of EGM during sinus rhythm, right ventricular pacing, and short-coupled right ventricular extrastimuli was performed. The swine were sacrificed and mapping data were projected onto the heart. Transmural biopsies (n = 196) corresponding to mapping points were obtained, allowing a head-to-head comparison of EGM recorded by micro- and conventional electrodes with histology., Results: To identify scar areas using standard electrodes, unique cutoff values of unipolar voltage <5.44 mV, BV <1.27 mV (conventional), and BV <2.84 mV (microelectrode) were identified. Combining the information provided by unipolar voltage and BV mapping, the sensitivity of scar identification was increased to 93%. Micro-EGM were better able to distinguish small near-fields corresponding to a layer of viable subendocardium than conventional EGM were., Conclusions: The combined information provided by multisize electrode mapping increases the sensitivity with which areas of scar are identified. EGM from microelectrodes, with narrower spacing, allow identification of near-fields arising from thin subendocardial layer and layers activated with short delay obscured in EGM from conventional mapping catheter., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic arrhythmias commonly arise from the septal right ventricular outflow tract (RVOT), sinuses of Valsalva (SoV), and great cardiac vein (GCV). Predicting the exact site of origin is important for preparation for catheter ablation., Objective: The purpose of this study was to examine the diagnostic value of noninvasive electroanatomic mapping (NIEAM) to differentiate between septal RVOT, SoV, and GCV origin and compare it to that of 12-lead electrocardiography (ECG)., Methods: NIEAM maps (CardioInsight, Medtronic) were generated during spontaneous ventricular premature depolarizations (VPDs) and threshold pacing from septal RVOT, SoV, and GCV. Origin prediction using NIEAM was compared to algorithmic ECG criteria (maximal deflection index; V 2 transition ratio) and subjective ECG evaluation., Results: Sixty NIEAMs (18 spontaneous VPDs and 42 pace-maps) from 31 patients (age 56 ± 16 years) were analyzed. NIEAM showed distinct conduction patterns, best visualized at the base of the heart: septal RVOT VPDs propagate toward the tricuspid annulus, depolarizing the septum from inferior to superior; SoV VPDs engage the superior septum early; and GCV VPDs move laterally along the mitral annulus, depolarizing the heart from left to right. Activation of the lateral mitral annulus >60.50 ms and the superior basal septum <22.5 ms from onset predicts RVOT and SoV origin, respectively, in 100% of cases. NIEAM was superior to maximum deflection index in predicting GCV origin (100% vs 42.2% accuracy) and superior to V 2 transition ratio in predicting SoV origin (100% vs 75.9% accuracy)., Conclusion: Arrhythmias arising from the outflow tracts follow distinct propagation patterns depending on the origin. A 2-step algorithm using activation timing by NIEAM yields 100% diagnostic accuracy in predicting origin., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In infarct-related ventricular tachycardia (VT), the circuit often corresponds to a location characterized by activation slowing during sinus rhythm (SR). However, the relationship between activation slowing during SR and vulnerability for reentry and correlation to components of the VT circuit are unknown. This study examined the relationship between activation slowing during SR and vulnerability for reentry and correlated these areas with components of the circuit., Methods: In a porcine model of healed infarction, the spatial distribution of endocardial activation velocity was compared between SR and VT. Isthmus sites were defined using activation and entrainment mapping as areas exhibiting diastolic activity within the circuit while bystanders were defined as areas displaying diastolic activity outside the circuit., Results: Of 15 swine, 9 had inducible VT (5.2±3.0 per animal) while in 6 swine VT could not be induced despite stimulation from 4 RV and LV sites at 2 drive trains with 6 extra-stimuli down to refractoriness. Infarcts with VT had a greater magnitude of activation slowing during SR. A minimal endocardial activation velocity cutoff ≤0.1 m/s differentiated inducible from noninducible infarctions ( P =0.015). Regions of maximal endocardial slowing during SR corresponded to the VT isthmus (area under curve=0.84 95% CI, 0.78-0.90) while bystander sites exhibited near-normal activation during SR. VT circuits were complex with 41.7% exhibiting discontinuous propagation with intramural bridges of slow conduction and delayed quasi-simultaneous endocardial activation. Regions forming the VT isthmus borders had faster activation during SR while regions forming the inner isthmus were activated faster during VT., Conclusions: Endocardial activation slowing during SR may differentiate infarctions vulnerable for VT from those less vulnerable for VT. Sites of slow activation during SR correspond to sites forming the VT isthmus but not to bystander sites.

Introduction: In patients with early repolarization patterns on ECG, many researchers have studied to find predictors of fatal arrhythmia. However, there are no satisfying clinical predictors. We evaluated the value of the T peak -T end interval on pseudo-ECG in canine myocardial wedge preparation models of early repolarization syndrome., Methods and Results: Transmural pseudo-ECG and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n = 34). The I to agonist NS5806 (8-10 µM), the calcium channel blocker verapamil (3 µM) and acetylcholine (2-3 µM) were used to mimic the disease model. A ventricular arrhythmia induction test was performed. QT peak , QT end , T peak -T end , and T peak -T end /QT end were measured at 15 to 20 minutes after the provocative agent infusion. Polymorphic ventricular tachycardias (pVT) developed in 23 of the 34 preparations (67%). The maximal values of T peak -T end and T peak -T end /QT end were recorded just before pVT induction. At baseline, without the provocative agents, T peak -T end and T peak -T end /QT end were not different between pVT-induced and pVT-noninduced preparations. The T peak -T end of the pVT-induced preparations was longer than that of non-induced preparations (58 ± 26.8 msec vs 33 ± 6.8 msec, P < .001). The T peak -T end /QT end of pVT- induced preparations was larger than that of noninduced preparations (0.220 ± 0.1017 vs 0.128 ± 0.0312, P < .001). The transmural and epicardial dispersion of repolarization of pVT-induced preparations were larger than those of pVT-noninduced preparations. The transmural dispersion of repolarization showed a positive correlation with T peak -T end ., Conclusion: T peak -T end predicted malignant ventricular arrhythmias in early repolarization syndrome models. T peak -T end reflects the repolarization heterogeneity of ventricular myocardium., (© 2019 Wiley Periodicals, Inc.)

Objectives: This study sought to determine new reference cutoffs for normal unipolar voltage (UV) and bipolar voltage (BV) that would be adjusted for the LV remodeling., Background: The definition of "normal" left ventricular (LV) endocardial voltage in patients with post-infarct scar is still lacking. The reference voltage of the noninfarcted myocardium (NIM) may differ between patients depending on LV structural remodeling and the ensuing interstitial fibrosis., Methods: Electroanatomic voltage mapping was integrated with isotropic late gadolinium-enhanced cardiac magnetic resonance in 15 patients with nonremodeled LV and 12 patients with remodeled LV (end-systolic volume index >50 ml/m 2 with ejection fraction <47% assessed by cardiac magnetic resonance). Reference voltages (fifth percentile values) were determined from pooled NIM segments without late gadolinium enhancement., Results: The cutoffs for normal BV and UV were ≥3.0 and ≥6.7 mV for nonremodeled LV and ≥2.1 and ≥6.4 mV for remodeled LV. Endocardial low-voltage area (LVA) defined by the adjusted cutoffs corresponded better to late gadolinium enhancement-detected scar than did LVA defined by uniform cutoffs. In 15 patients who underwent successful ablation of ventricular tachycardia, the LVA contained >97% of targeted evoked delayed potentials. Insights from whole-heart T1 mapping revealed more fibrotic NIM in patients with remodeled LV compared with nonremodeled LV., Conclusions: This study found substantial differences in endocardial voltage of NIM in post-infarct patients with remodeled versus nonremodeled LV. The new adjusted cutoffs for "normal" BV and UV enable a patient-tailored approach to electroanatomic voltage mapping of LV., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The efficacy of endocardial catheter ablation for ventricular tachycardia (VT) can be limited by intramural or epicardial substrates. Adding epicardial mapping and ablation may improve arrhythmia outcomes compared with an endocardial-only approach., Methods: We performed a systematic review and meta-analysis of studies comparing a strategy of endo-epicardial catheter ablation to an endocardial-only approach for VT. Subanalyses were performed for ischemic and nonischemic cardiomyopathies., Results: A total of 22 studies including 1138 patients were included in the meta-analysis. Of those, 44% underwent an endo-epicardial approach. During intermediate to long-term follow-up (average 7 to 70 months), recurrent VT or appropriate implantable cardioverter defibrillator (ICD) therapies were significantly lower with the endo-epicardial strategy (OR, 0.52; P < .01). All-cause mortality was also lower in this group (OR, 0.50; P = .03). No difference between endo-epicardial and endocardial-only ablation was noted in nonischemic cardiomyopathies. Among 323 patients with ischemic cardiomyopathy, recurrent VT or appropriate ICD therapies was less frequent in the endo-epicardial group (OR, 0.39; P = .01), as was all-cause mortality (OR, 0.38; P = .05). In patients with arrhythmogenic right ventricular cardiomyopathy, recurrent VT or appropriate ICD therapy was also lower in the endo-epicardial group (OR, 0.42; P = .04)., Conclusion: These results suggest that a strategy of combined endo- and epicardial access for mapping and ablation of VT may provide superior efficacy to an endocardial-only approach in selected patients. Randomized trials are warranted to further investigate this question., (© 2019 Wiley Periodicals, Inc.)

Anti-ischemic activity of fabomotizole hydrochloride was studied on the model of subendocardial ischemia in rats with endothelial dysfunction. Endothelial dysfunction was modeled by intragastric administration of methionine (3 g/kg, once a day for 7 days). Acute subendocardial ischemia was induced in narcotized rats by intraperitoneal injection of isoproterenol (20 μg/kg/min over 5 min). Fabomotizole hydrochloride (intraperitoneally, 15 mg/kg) significantly reduced isoproterenol-induced ST segment depression in animals with endothelial dysfunction and with intact vasculature.

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by an epicardial (EPI) to endocardial (ENDO) fibrofatty infiltration of the RV predisposing to both EPI and ENDO ventricular tachycardia (VT). The relative timing between the VT QRS onset on the far-field ventricular electrogram (VEGM) to the local activation time recorded at the RV apex on the near-field VEGM from stored implantable cardioverter-defibrillator (ICD) events of VT can be helpful to discriminate ENDO from EPI VT in ARVC., Methods and Results: We analyzed consecutive ARVC patients undergoing catheter ablation between 2006 and 2018. Only patients with retrievable ICD VEGMs of clinical VTs which could be matched with VTs induced at the time of ablation were included. A total of 26 VT events (16 ENDO, 10 EPI) from 19 ARVC patients were examined, yielding a mean far-field to near-field interval of 33 ± 15 ms for ENDO VTs and 52 ± 20 ms for EPI VTs (P = .020). At receiver-operating characteristic analysis, a far-field to a near-field interval of 60 ms or more ruled out ENDO VTs in 16 (100%) cases and identified EPI VTs with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 73%. An interval of less than or equal to 30 ms ruled out EPI VTs in eight (80%) cases and diagnosed ENDO VTs with a PPV of 80% and an NPV of 50%., Conclusion: Far-field to near-field ICD VEGM timing may be used to predict ENDO vs EPI VT in ARVC before ablation, indicating an ENDO origin if the timing is less than or equal to 30 ms and an EPI origin if greater than or equal to 60 ms., (© 2019 Wiley Periodicals, Inc.)

The present study aimed to investigate whether layer-specific regional peak-systolic longitudinal strain (LS) measurement on transthoracic echocardiogram (TTE) with exercise stress can be useful for the detection of functionally significant coronary artery disease as confirmed by invasive fractional flow reserve (FFR) in stable patients. This is a prospective analysis of 88 coronary arteries in 30 stable patients undergoing invasive FFR measurement and ergometer exercise stress TTE. Regional LS in the mid, endocardial and epicardial layers was calculated at rest, peak stress and early and late recovery phases after the exercise stress test. The endocardial-to-epicardial LS ratio was calculated as an indicator of endocardial-layer dependency of the left ventricular myocardium. Ischemic FFR defined as FFR ≤ 0.80 was observed in 33 of 88 coronary arteries. The mid-, endocardial- and epicardial-layer LS at early recovery (- 15.4 ± 5.2 vs. -  13.0 ± 4.4%, P = 0.040;  - 15.7 ± 5.1 vs.  - 13.2 ± 4.5%, P = 0.029;  - 14.6 ± 5.1 vs.  - 12.4 ± 4.0%, P = 0.038, respectively) and the percent change in the endocardial-to-epicardial LS ratio from baseline to peak stress, early recovery, and late recovery phases (1.5 ± 11.2% vs. 6.6 ± 10.5%, P = 0.009; 2.8 ± 8.9% vs. 7.1 ± 12.6%, P = 0.002; 5.2 ± 8.8% vs. 8.5 ± 13.7%, P = 0.026; respectively) were significantly more impaired in the ischemic territories (FFR ≤ 0.80) compared with the non-ischemic territories (FFR > 0.80). According to the receiver operating characteristic curve analysis, a combination of endocardial LS and percent change in the endocardial-to-epicardial LS ratio at early recovery phase plus visual evaluation of LV wall motion had incremental diagnostic value for the detection of the ischemic territory compared with visual evaluation alone (area under the curve = 0.752 and 0.618, P = 0.006). The results of this study suggested that assessing layer-specific LS and the endocardial-to-epicardial LS ratio after exercise stress on speckle-tracking TTE may have potential for objective and quantitative evaluation in the assessment of myocardial ischemia. Further studies in a larger population are needed to confirm these findings.

Objective: Ablation treatment of ventricular arrhythmias can be facilitated by pre-procedure planning aided by electrocardiographic inverse solution, which can help to localize the origin of arrhythmia. Our aim was to improve localization accuracy of the inverse solution for activation originating on the left-ventricular endocardial surface, by using a sparse Bayesian learning (SBL)., Methods: The inverse problem of electrocardiography was solved by reconstructing endocardial potentials from time integrals of body-surface electrocardiograms and from patient-specific geometry of the heart and torso for three patients with structurally normal ventricular myocardium, who underwent endocardial catheter mapping that included pace mapping. Complementary simulations using dipole sources in patient-specific geometry were also performed. The proposed method is using sparse property of the equivalent-double-layer (EDL) model of cardiac sources; it employs the SBL and makes use of the spatio-temporal features of the cardiac action potentials., Results: The mean localization error of the proposed method for pooled pacing sites ( n=52) was significantly smaller ( p=0.0039) than that achieved for the same patients in the study of Erem et al. Simulation experiments localized the source dipoles ( n=48) from forward-simulated potentials with the error of 9.4 ± 4.5 mm (mean ± SD)., Conclusion: The results of our clinical and simulation experiments demonstrate that localization of left-ventricular endocardial activation by means of the Bayesian approach, based on sparse representation of sources by EDL, is feasible and accurate., Significance: The proposed approach to localizing endocardial sources may have important applications in pre-procedure assessment of arrhythmias and in guiding their ablation treatment.

Background: Ablation of the pulmonary venous carina is occasionally required for pulmonary vein isolation (PVI) despite its nonessential role in ipsilateral PVI from the anatomical (endocardial) viewpoint. Although the Bachmann bundle (BB) is a common and main interatrial band, local variations in small tongues of muscular fibers were frequently found in autopsy studies., Objective: We sought to clarify the effect of the electrical conduction pattern from the right atrium (RA) to the left atrium (LA) during sinus rhythm on the necessity of performing right-sided pulmonary venous carina ablation to achieve PVI., Methods: Study subjects comprised 37 consecutive patients undergoing initial catheter ablation of lone atrial fibrillation. During sinus rhythm, RA and LA activation maps were acquired using an electroanatomical mapping system. LA breakthroughs were classified into 3 sites: BB, fossa ovalis (FO), and right-sided pulmonary venous carina. Patients were divided into the carina-ABL (ablation) or non-carina-ABL group on the basis of the necessity of pulmonary venous carina ablation to achieve PVI., Results: Patients were classified in the non-carina-ABL group (n = 26 [70%]) and carina-ABL group (n = 8 [22%]) after excluding 3 patients (8%) because of their complex ablation lesion sets. Breakthrough occurred in the BB (n = 21 patients [62%]), FO (n = 7 [21%]), carina (n = 1 [3%]), carina and BB (n = 3 [9%]), and carina and FO (n = 2 [6%]). Carina breakthrough occurred in 6 patients (75%) in the carina-ABL group but in no patients in the non-carina-ABL group (P < .0001)., Conclusion: PVI was not achievable without carina ablation in one-fifth of patients, probably because of epicardial connections present between the right-sided pulmonary venous carina and the RA., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Differences of action potential duration (APD) in regions of myocardial scar and their borderzones are poorly defined in the intact human heart. Heterogeneities in APD may play an important role in the generation of ventricular tachycardia (VT) by creating regions of functional block. We aimed to investigate the transmural and planar differences of APD in patients admitted for VT ablation., Methods and Results: Six patients (median age 53 years, five male); (median ejection fraction 35%), were studied. Endocardial (Endo) and epicardial (Epi) 3D electroanatomic mapping was performed. A bipolar voltage of <0.5 mV was defined as dense scar, 0.5-1.5 mV as scar borderzone, and >1.5 mV as normal. Decapolar catheters were positioned transmurally across the scar borderzone to assess differences of APD and repolarization time (RT) during restitution pacing from Endo and Epi. Epi APD was 173 ms in normal tissue vs. 187 ms at scar borderzone and 210 ms in dense scar (P < 0.001). Endocardial APD was 210 ms in normal tissue vs. 222 ms in the scar borderzone and 238 ms in dense scar (P < 0.01). This resulted in significant transmural RT dispersion (ΔRT 22 ms across dense transmural scar vs. 5 ms in normal transmural tissue, P < 0.001), dependent on the scar characteristics in the Endo and Epi, and the pacing site., Conclusion: Areas of myocardial scar have prolonged APD compared with normal tissue. Heterogeneity of regional transmural and planar APD result in localized dispersion of repolarization, which may play an important role in initiating VT., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Noninvasive electrocardiographic mapping of ventricular tachycardia (VT) and ablation using stereotactic radiotherapy was recently reported. This strategy does not directly evaluate the critical diastolic components and assumes that the epicardial exit site of VT subtends closely over the endocardial mid-diastolic isthmus., Objective: To determine if the epicardial exit site of VT spatially corresponds to the critical diastolic components of ischemic scar-related VT., Materials and Methods: Intraoperative simultaneous endocardial and epicardial mapping were performed during VT using a 112-bipole endocardial balloon and 112-bipole epicardial sock array. In eight patients, nine VTs having entire diastolic circuit mapped were included in the study. The diastolic path and VT-exit sites (epicardial and endocardial) were determined., Results: The diastolic path was mapped in the endocardium for all nine VTs (median length, 50; interquartile range [IQR], 28 mm). The tachycardia cycle length ranged from 210-500 ms. The VT-exit site was early in the endocardium for six VTs and on the epicardium for three VTs. The mid-diastolic isthmus and endocardial exit site of the six endocardial VTs were spatially distant from their epicardial exit site by a median distance of 32 and 27 mm, respectively. For the three VTs with an early epicardial exit, the isthmus and endocardial exit sites were distant from the epicardial exit site by a median distance of 34 and 38 mm, respectively., Conclusion: The epicardial exit site and the mid-diastolic isthmus sites were spatially distant and discrepant. Surface electrocardiography (ECG)-derived strategy in identifying epicardial exit site to select noninvasive ablation targets is prone to identify epicardial exit sites and may not identify critical targets in ischemic scar VT., (© 2019 Wiley Periodicals, Inc.)

Background: Spatial resolution in cardiac activation maps based on voltage measurement is limited by far-field interference. Precise characterization of electrical sources would resolve this limitation; however, practical charge-based cardiac mapping has not been achieved., Methods: A prototype algorithm, developed from first principles of electrostatic field theory, derives charge density (CD) as a spatial representation of the true sources of the cardiac field. The algorithm processes multiple, simultaneous, noncontact voltage measurements within the cardiac chamber to inversely derive the global distribution of CD sources across the endocardial surface., Results: Comparison of CD to an established computer-simulated model of atrial conduction demonstrated feasibility in terms of spatial, temporal, and morphologic metrics. Inverse reconstruction matched simulation with median spatial errors of 1.73 mm and 2.41 mm for CD and voltage, respectively. Median temporal error was less than 0.96 ms and morphologic correlation was greater than 0.90 for both CD and voltage. Activation patterns observed in human atrial flutter reproduced those established through contact maps, with a 4-fold improvement in resolution noted for CD over voltage. Global activation maps (charge density-based) are reported in atrial fibrillation with confirmed reduction of far-field interference. Arrhythmia cycle-length slowing and termination achieved through ablation of critical points demonstrated in the maps indicates both mechanistic and pathophysiological relevance., Conclusion: Global maps of cardiac activation based on CD enable classification of conduction patterns and localized nonpulmonary vein therapeutic targets in atrial fibrillation. The measurement capabilities of the approach have roles spanning deep phenotyping to therapeutic application., Trial Registration: ClinicalTrials.gov NCT01875614., Funding: The National Institute for Health Research (NIHR) Translational Research Program at Royal Papworth Hospital and Acutus Medical.