Origin Of Arrhythmias Research Articles

Ablation strategies for intramural ventricular arrhythmias

Intramural origin of ventricular arrhythmias is one of the reasons for failure of catheter ablation, especially in nonischemic substrates. Conventional unipolar ablation has limited efficacy for the creation of deep transmural lesions in the ventricular myocardium, and alternative ablation strategies have been developed to overcome this problem. These novel approaches include simultaneous unipolar ablation, bipolar ablation, use of low-ionic irrigant solution, needle ablation, and ethanol ablation. This review provides an overview of each one of these techniques, including their main advantages and limitations.

Evaluation of ECG Imaging to Map Hemodynamically Stable and Unstable Ventricular Arrhythmias.

ECG imaging (ECGI) has been used to guide treatment of ventricular ectopy and arrhythmias. However, the accuracy of ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia (VT) in structurally abnormal hearts remains to be fully validated. During catheter ablation of VT, simultaneous mapping was performed using electroanatomical mapping (CARTO, Biosense-Webster) and ECGI (CardioInsight, Medtronic) in 18 patients. Sites of entrainment, pace-mapping, and termination during ablation were used to define the VT site of origin (SoO). Distance between SoO and the site of earliest activation on ECGI were measured using co-registered geometries from both systems. The accuracy of ECGI versus a 12-lead surface ECG algorithm was compared. A total of 29 VTs were available for comparison. Distance between SoO and sites of earliest activation in ECGI was 22.6, 13.9 to 36.2 mm (median, first to third quartile). ECGI mapped VT sites of origin onto the correct AHA segment with higher accuracy than a validated 12-lead ECG algorithm (83.3% versus 38.9%; P=0.015). This simultaneous assessment demonstrates that CardioInsight localizes VT circuits with sufficient accuracy to provide a region of interest for targeting mapping for ablation. Resolution is not sufficient to guide discrete radiofrequency lesion delivery via catheter ablation without concomitant use of an electroanatomical mapping system but may be sufficient for segmental ablation with radiotherapy.

Altered microtubule structure, hemichannel localization and beating activity in cardiomyocytes expressing pathologic nuclear lamin A/C

Given the clinical effect of laminopathies, understanding lamin mechanical properties will benefit the treatment of heart failure. Here we report a mechano-dynamic study of LMNA mutations in neonatal rat ventricular myocytes (NRVM) using single cell spectroscopy with Atomic Force Microscopy (AFM) and measured changes in beating force, frequency and contractile amplitude of selected mutant-expressing cells within cell clusters. Furthermore, since beat-to-beat variations can provide clues on the origin of arrhythmias, we analyzed the beating rate variability using a time-domain method which provides a Poincaré plot. Data were further correlated to cell phenotypes. Immunofluorescence and calcium imaging analysis showed that mutant lamin changed NRVMs beating force and frequency. Additionally, we noted an altered microtubule network organization with shorter filament length, and defective hemichannel membrane localization (Connexin 43). These data highlight the interconnection between nucleoskeleton, cytoskeleton and sarcolemmal structures, and the transcellular consequences of mutant lamin protein in the pathogenesis of the cardiac laminopathies.

P3750Efficiency of electrocardiographic algorithms in management of idiopathic outflow tract ventricular arrhythmias in children

Abstract Introduction Ablation of idiopathic ventricular arrhythmias (IVA) originating in left ventricle outflow tract (LVOT) are more challenging as compared to right ventricle outflow tract (RVOT). In recent years, several ECG algorithms predicting the site of origin (SOO) of arrhythmia for adult population have been published. There is a sparse information on their diagnostic performance in children. Purpose The aim of this study was to validate two algorithms: 1) Novel TZ index, 2) V2S/V3R and their combined application in children for predicting the appropriate SOO of IVA. Methods Two groups of children without structural heart disease, thorax anomalies and normal QRS complexes during sinus rhythm were included in the study: 1) patients with IVA with inferior axis who underwent successful RFCA using the 3D-electroanatomical system, 2) patients with paced or mechanically-induced QRS complexes from LVOT or RVOT during other procedures. ECGs were analyzed in a specially developed software for analyzing the amplitude of the QRS complex waves. Semi-automated measurements of amplitudes of QRS complexes and calculations were carried out for 2 published algorithms: 1) Novel TZ index, 2) V2S/V3R. The results of their separate and combined use were compared with SOO of acute successful RFCA and mapping or spot of pacing. Results 108 PVC morphologies (68 from the RVOT and 40 from LVOT) from 74 pediatric patients (age: 14.0±2.9, 39 female) were included into the study. The algorithm V2S/V3R predicted left-sided SOO with a sensitivity and specificity of 94%. Novel TZ-index showed sensitivity of 89% and specificity of 84%. Combined use of Novel TZ-index+V2S/V3R showed high sensitivity (92%) and very height specificity (97%) of the LVOT SOO prediction Conclusion Both algorithms allowed accurate, simple and precise identification of SOO of RVOT/LVOT IVA in children. The combined use of those algorithms may facilitate additional pharmacologic treatment, omitting RVOT mapping with direct mapping LVOT, performance of the procedure by experienced operator.

Right ventricular outflow tract low-voltage areas identify the site of origin of idiopathic ventricular arrhythmias: A high-density mapping study.

Electronatomical mapping allows direct and accurate visualization of myocardial abnormalities. This study investigated whether high-density endocardial bipolar voltage mapping of the right ventricular outflow tract (RVOT) during sinus rhythm may guide catheter ablation of idiopathic ventricular arrhythmias (VAs). Forty-four patients (18 males, mean age: 38.1 ± 13.8 years) with idiopathic RVOT VAs and negative cardiac magnetic resonance imaging underwent a stepwise mapping approach for the identification of the site of origin (SOO). High-density electronatomical mapping (1096.6 ± 322.3 points) was performed during sinus rhythm and identified at least two low bipolar voltage areas less than 1 mV (mean amplitude of 0.20 ± 0.10 mV) in 39 of 44 patients. The mean low-voltage surface area was 1.4 ± 0.8 cm2 . Group 1 consisted of 28 patients exhibiting low-voltage areas and high-arrhythmia burden during the procedure. Pace match to the clinical VAs was produced in one of these low-voltage areas. Activation mapping established the SOO at these sites in 27 of 28 cases. Group 2 comprised 11 patients exhibiting abnormal electroanatomical mapping, but very low-arrhythmia burden during the procedure. Pace mapping produced a near-perfect or perfect match to the clinical VAs in one of these areas in 9 of 11 patients which was marked as potential SOO and targeted for ablation. During the follow-up period, 25 of 28 patients from group 1 (89%) and 7 of 9 patients from group 2 (78%) were free from VAs. Small but detectable very low-voltage areas during mapping in sinus rhythm characterize the arrhythmogenic substrate of idiopathic RVOT VAs and may guide successful catheter ablation.

Twelve-lead electrocardiographic localization of idiopathic premature ventricular contraction origins.

The major sites of origins of idiopathic ventricular arrhythmias have been elucidated. Idiopathic ventricular arrhythmias most often present as premature ventricular contractions (PVCs) with a focal mechanism, and commonly occur without structural heart disease. Idiopathic ventricular arrhythmias usually originate from specific anatomical structures, commonly endocardial but sometimes epicardial and exhibit characteristic electrocardiograms (ECGs) based on their anatomical background. There are general and specific ECG characteristics that can localize the site of idiopathic PVC origins. The general ECG characteristics include the bundle branch block pattern, axis, QRS polarity in lead V6, QRS duration, precordial transition, maximal deflection index, and so forth. They can roughly localize the site of idiopathic PVC origins. Several major sites of idiopathic PVC origins are located close to each other, and specific ECG characteristics are helpful for localizing the site of origins more accurately in those PVCs. Twelve-lead surface ECG algorithms usually can localize the site of idiopathic PVC origins with a high accuracy, but their accuracy can be limited by the patients' physique, heart rotation, specific conduction properties, presence of structural heart disease, and so forth. This review describes an overview of the approaches to the 12-lead surface ECG localization of idiopathic PVCs, and also discusses their caveats and limitations.

The V1-V3 transition index as a novel electrocardiographic criterion for differentiating left from right ventricular outflow tract ventricular arrhythmias.

The aim of this study was to develop a new electrocardiographic criterion for differentiating the origin of outflow tract ventricular arrhythmias (OT-VAs) with precordial transition in lead V3. A total of 147 consecutive patients with OT-VAs displaying precordial transition in lead V3 who underwent successful catheter ablation in the right ventricular outflow tract (RVOT) (n = 118) or left ventricular outflow tract (LVOT) (n = 29) were included in this study. The V1-V3 transition index was defined as the sum of S-wave amplitude in lead V1 and V2 during premature ventricular contractions (PVCs) divided by the S-wave amplitude during sinus rhythm (SR), respectively, minus the sum of R-wave amplitude in lead V1, V2, and V3 during PVCs divided by the R-wave amplitude during SR, respectively, i.e., [(SPVC/SSR)V1 + (SPVC/SSR)V2] - [(RPVC/RSR) V1 + (RPVC/RSR)V2 + (RPVC/RSR)V3]. The V1-V3 transition index was significantly higher for RVOT origins than for LVOT origins (1.25 ± 2.48 vs. - 3.94 ± 3.11; P < 0.001). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.931 for the V1-V3 transition index, and a cutoff value of > - 1.60 predicted a RVOT origin with a 93% sensitivity and 86% specificity. With respect to AUC and accuracy, the V1-V3 transition index was superior to any previously proposed ECG indices for differentiating left from right OT-VAs. In 37 prospective cases, the new index was able to predict the site of a RVOT origin with 95% accuracy (35 of 37 cases). The V1-V3 transition index is a useful novel ECG criterion for distinguishing left from right OT-VAs with precordial transition in lead V3.

Accuracy of cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm to identify sites of origin of cardiac electrical activation.

We have developed a system that could potentially be used to identify the site of origin of ventricular tachycardia (VT) and to guide a catheter to that site to deliver radio-frequency ablation therapy. This system employs the Inverse Solution Guidance Algorithm based upon Single Equivalent Moving Dipole (SEMD) localization method. The system was evaluated in in vivo swine experiments. Arrays consisting of 9 or 16 bipolar epicardial electrodes and an additional mid-myocardial pacing lead were sutured to each ventricle. Focal tachycardia was simulated by applying pacing pulses to each epicardial electrode at multiple pacing rates during breath hold at the end-expiration phase. Surface potentials were recorded from 64 surface electrodes and then analyzed using the SEMD method to localize the position of the pacing electrodes. We found a close correlation between the locations of the pacing electrodes as measured in computational and real spaces. The reproducibility error of the SEMD estimation of electrode location was 0.21 ± 0.07cm. The vectors between every pair of bipolar electrodes were computed in computational and real spaces. At 120bpm, the lengths of the vectors in the computational and real space had a 95% correlation. Computational space vectors were used in catheter guidance simulations which showed that this method could reduce the distance between the real space locations of the emulated catheter tip and the emulated arrhythmia origin site by approximately 72% with each movement. We have demonstrated the feasibility of using our system to guide a catheter to the site of the emulated VT origin.

Eccentric Activation Patterns in the Left Ventricular Outflow Tract during Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Summit: A Pitfall for Predicting the Sites of Ventricular Arrhythmia Origins.

Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular summit (LVS) can be ablated from the great cardiac vein and remote endocardial sites. The ablation sites are determined by mapping in the great cardiac vein and left ventricular outflow tract. This study investigated whether that mapping could accurately predict the sites of LVS-VA origins. We studied 26 consecutive patients with idiopathic LVS-VA origins that were identified in the basal and apical LVS in 15 and 11 patients, respectively. Radiofrequency catheter ablation of the apical LVS-VAs was successful in the great cardiac vein in 9 patients and in the apical LV outflow tract in 2. That of the basal LVS-VAs was successful in the aortomitral continuity in 9 patients, at the junction of the left and right coronary cusps in 4, and in the left coronary cusp in 2. Three apical LVS-VAs exhibited an eccentric endocardial activation pattern that was from the basal to apical LV outflow tract. In 11 basal LVS-VAs, the activation pattern was eccentric because the ventricular activation within the great cardiac vein in the apical LVS was earlier than that in the basal LV outflow tract. In 2 basal LVS-VAs, the activation pattern was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site. Eccentric activation patterns often occurred during idiopathic LVS-VAs, which could mislead the catheter ablation of those VAs. Understanding such eccentric activation patterns was suggested to be able to improve the outcomes of the catheter ablation of those VAs by the anatomic approach.

Challenging Cases of Wide Complex Tachycardias: Use and Limits of Algorithms.

Electrocardiographic algorithms are particularly useful to differentiate, in the presence of a wide complex tachycardia, between supraventricular aberrancy and ventricular tachycardias (VT). There are numerous limitations to the sensitivity and specificity of these algorithms including the presence of accessory pathways, use of antiarrhythmic drugs, congenital heart diseases, electrolytes impairments, and artificial pacing. Once the diagnosis of VT has been reached, other algorithms can help in localizing the origin of the ventricular arrhythmia. These approaches are also limited by the anatomic structure of where the arrhythmia originates. This article illustrates the difficulties in applying common algorithms in many clinical circumstances.

How to use the 12-lead ECG to predict the site of origin of idiopathic ventricular arrhythmias

Idiopathic ventricular arrhythmias may arise from anywhere in the heart, and the majority of them can be effectively treated with catheter ablation. The 12-lead electrocardiogram (ECG) is the initial mapping tool to predict the most likely site of origin and is valuable to choose the appropriate ablation strategy. Crucial to ECG interpretation is understanding the attitudinal orientation of the heart within the chest and the relationship between the different cardiac structures. In this review, we provide a stepwise anatomical approach for the localization of idiopathic ventricular arrhythmias based on sequential analysis of the most relevant ECG features.

Cardiomyocyte mitochondrial dysfunction in diabetes and its contribution in cardiac arrhythmogenesis

Cardiovascular disease is the leading cause of diabetes-related morbidity and mortality. It is widely accepted that heart failure risk is increased in diabetic patients even after adjusting for coronary artery disease and hypertension. Mitochondria are the center of fatty acid (FA) and glucose metabolism and thus are likely to be impacted by impaired metabolism associated with diabetes. Although the cause of this increased heart failure risk is multifactorial, increasing evidence points toward a crucial role for cardiomyocyte mitochondria dysfunction. Altered energy metabolism, defects in mitochondrial dynamics, increased oxidative stress, impaired calcium (Ca2+) handling and mitochondria-induced cell death are observed in mitochondria of diabetic myocardium. In addition, mitochondrial dysfunction appears to contribute substantially to the origin of arrhythmias in diabetic hearts. The current review will describe these mitochondrial abnormalities in cardiomyocytes attempting to provide an overview of underlying mechanisms. Finally, we briefly discuss the potential link between mitochondrial malfunction and arrhythmogenesis.

NON-INVASIVE ELECTROANATOMICAL MAPPING FOR PREDICTING SITE OF ORIGIN OF OUTFLOW TRACT VENTRICULAR TACHCYARDIAS

Prediction of site of origin of ventricular arrhythmias (VA) prior to ablation is important for procedural prognostication, risk assessment and preparation. We used noninvasive electrocardiographic mapping (ECM) to identify the origin of outflow tract VAs (OTVA). We included patients with OTVA

MAN VERSUS MACHINE: COMPARISON OF MANUAL VERSUS NOVEL 12-LEAD ECG ALGORITHM TO PREDICT THE VENTRICULAR ARRHYTHMIA ORIGIN TO GUIDE ABLATION PROCEDURE

Catheter ablation of frequent idiopathic ventricular arrhythmias (VA) is increasingly performed. Preprocedural prediction of the arrhythmia origin from the 12-lead ECG is critical to reduce invasive mapping procedure time. Preprocedural prediction, however, is limited by inter-individual variation

Role of the Purkinje system in heritable arrhythmias

Much has been written about arrhythmias in structurally normal hearts. In this review, we focus on rapid ventricular arrhythmias that occur in hearts having a pathogenic genetic variant that has been found in families in which arrhythmias occur. We discuss these mutations in terms of their effect on cardiac cell electrical function and initiation of arrhythmias. We also focus on Purkinje cells, their anatomic networks, and their molecular signatures as the sites of origin of arrhythmias. We discuss therapeutic options for treatment of these potentially life-threatening arrhythmias. Although all Purkinje-based arrhythmias are not included (eg, conduction block rhythms), syndromes discussed include idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, Andersen-Tawil syndrome, and Brugada syndrome.

Ablation of ventricular arrhythmias with predominant monophasic "R" waves in precordial leads from the left sinus of Valsalva: Electrocardiographic and electrophysiologic characteristics.

While the left sinus of Valsalva (LSV) is a frequent origin of ventricular arrhythmias (VAs). Uncommonly, VAs with right bundle branch block (RBBB) morphology may be successfully terminated from the LSV. We aimed to investigate the electrocardiographic and electrophysiologic characteristics of VAs with RBBB which were successfully eliminated from the LSV. We identified patients with VAs successfully ablated from the LSV from January 2014 to December 2017 and compared electrophysiologic characteristics and ablation sites of those VAs with RBBB versus a control group of patients with left bundle branch block morphology. We identified 18 patients with RBBB and predominant "R" waves in the precordial leads. In 12 (66.7%) patients, a small "s" wave in lead V2 and positive "R" in the remaining pericardial leads could be seen. Overall, a single "V" potential was seen in 72.2% of patients in the study group, while discrete potentials were recorded in 80% of the patients in the control group. The majority (88.9%) of the VAs could only be terminated at the nadir of the LSV in the study group. After mean follow-up of 33 ± 14 months, 93.8% and 92% were free of VAs after initial ablation in study and control group, respectively (P = 0.99). Some VAs with predominant monophasic "R" wave in precordial leads could be terminated from LSV, especially a small "s" wave in lead V2 was recorded. The nadir of LSV is highly successful for RBBB VAs and single electrogram was recorded at the target for most of the cases.

Localization of Activation Origin on Patient-Specific Endocardial Surface by the Equivalent Double Layer (EDL) Source Model With Sparse Bayesian Learning.

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). 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. 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 etal. Simulation experiments localized the source dipoles ( n=48) from forward-simulated potentials with the error of 9.4 ± 4.5mm (mean ± SD). 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. The proposed approach to localizing endocardial sources may have important applications in pre-procedure assessment of arrhythmias and in guiding their ablation treatment.

Computational Model of Calcium Signaling in Cardiac Atrial Cells at the Submicron Scale.

In cardiac cells, calcium is the mediator of excitation-contraction coupling. Dysfunctions in calcium handling have been identified as the origin of some cardiac arrhythmias. In the particular case of atrial myocytes, recent available experimental data has found links between these dysfunctions and structural changes in the calcium handling machinery (ryanodine cluster size and distribution, t-tubular network, etc). To address this issue, we have developed a computational model of an atrial myocyte that takes into account the detailed intracellular structure. The homogenized macroscopic behavior is described with a two-concentration field model, using effective diffusion coefficients of calcium in the sarcoplasmic reticulum (SR) and in the cytoplasm. The model reproduces the right calcium transients and dependence with pacing frequency. Under basal conditions, the calcium rise is mostly restricted to the periphery of the cell, with a large concentration ratio between the periphery and the interior. We have then studied the dependence of the speed of the calcium wave on cytosolic and SR diffusion coefficients, finding an almost linear relation with the former, in agreement with a diffusive and fire mechanism of propagation, and little dependence on the latter. Finally, we have studied the effect of a change in RyR cluster microstructure. We find that, under resting conditions, the spark frequency decreases slightly with RyR cluster spatial dispersion, but markedly increases when the RyRs are distributed in clusters of larger size, stressing the importance of RyR cluster organization to understand atrial arrhythmias, as recent experimental results suggest (Macquaide et al., 2015).

Ventricular Arrhythmias in the Patient with a Structurally Normal Heart.

Ventricular arrhythmias (VAs) are among the most common cardiac rhythm disturbances encountered in clinical practice. Patients presenting with frequent ventricular ectopy or sustained ventricular tachycardia represent a challenging and worrisome clinical scenario for many practitioners because of concerning symptoms, frequent associated acute hemodynamic compromise, and the adverse prognostic implications inherent to these cases. While an underlying structural or functional cardiac abnormality, metabolic derangement, or medication toxicity is often readily apparent, many patients have no obvious underlying condition, despite a comprehensive diagnostic evaluation. Such patients are diagnosed as having an idiopathic VA, which is a label with specific implications regarding arrhythmia origin, prognosis, and potential for pharmacologic and invasive management. Further, a subset of patients with otherwise benign idiopathic ventricular ectopy can present with polymorphic ventricular tachycardia and ventricular fibrillation, adding a layer of complexity to a clinical syndrome previously felt to have a benign clinical course. Thus, this review seeks to highlight the most common types of idiopathic VAs with a focus on their prognostic implications, underlying electrophysiologic mechanisms, unique electrocardiographic signatures, and considerations for invasive electrophysiologic study and catheter ablation. We further address some of the data regarding idiopathic ventricular fibrillation with respect to the heterogeneous nature of this diagnosis.

Localization of Activation Origin on Patient-Specific Epicardial Surface by Empirical Bayesian Method

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 by using a novel Bayesian approach. The inverse problem of electrocardiography was solved by reconstructing epicardial potentials from 120 body-surface electrocardiograms and from patient-specific geometry of the heart and torso for four patients suffering from scar-related ventricular tachycardia who underwent epicardial catheter mapping, which included pace-mapping. Simulations using dipole sources in patient-specific geometry were also performed. The proposed method, using dynamic spatio-temporal apriori constraints of the solution, was compared with classical Tikhonov methods based on fixed constraints. The mean localization error of the proposed method for all available pacing sites (n=78) was significantly smaller than that achieved by Tikhonov methods; specifically, the localization accuracy for pacing in the normal tissue (n=17) was [Formula: see text]mm (mean ± SD) versus [Formula: see text]mm reported in the previous study using the same clinical data and Tikhonov regularization. Simulation experiments further supported these clinical findings. The promising results of invivo and in silico experiments presented in this study provide a strong incentive to pursuing further investigation of data-driven Bayesian methods in solving the electrocardiographic inverse problem. The proposed approach to localizing origin of ventricular activation sequence may have important applications in pre-procedure assessment of arrhythmias and in guiding their ablation treatment.