Origin Of Arrhythmias Research Articles

On-chip spatiotemporal electrophysiological analysis of human stem cell derived cardiomyocytes enables quantitative assessment of proarrhythmia in drug development

We examined a simultaneous combined spatiotemporal field potential duration (FPD) and cell-to-cell conduction time (CT) in lined-up shaped human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using an on-chip multielectrode array (MEA) system to evaluate two origins of lethal arrhythmia, repolarization and depolarization. The repolarization index, FPD, was prolonged by E-4031 and astemizole, and shortened by verapamil, flecainide and terfenadine at 10 times higher than therapeutic plasma concentrations of each drug, but it did not change after lidocaine treatment up to 100 μM. CT was increased by astemizol, flecainide, terfenadine, and lidocaine at equivalent concentrations of Nav1.5 IC50, suggesting that CT may be an index of cardiac depolarization because the increase in CT (i.e., decrease in cell-to-cell conduction speed) was relevant to Nav1.5 inhibition. Fluctuations (short-term variability; STV) of FPD and CT, STVFPD and STVCT also discriminated between torsadogenic and non-torsadogenic compounds with significant increases in their fluctuation values, enabling precise prediction of arrhythmogenic risk as potential new indices.

The anatomic substrates for outflow tract arrhythmias

Much has been learned regarding the cellular and molecular mechanisms involved in producing idiopathic ventricular tachycardias originating from the ventricular outflow tract. Questions remain, however, regarding their genesis. In part, this reflects the uncertainty regarding the anatomic arrangement of their myocardial components. This is exacerbated by the lack of consensus regarding the appropriate terms to describe their components, as shown by the current use of "cusp," used interchangeably to describe either the valvar sinuses or the leaflets of the arterial valves. Such uncertainty can be resolved only by providing precise definitions of leaflets, sinuses, and the sinutubular junction. Further problems are created when the arterial roots are described in an attitudinally incorrect manner. Current techniques reveal the location of the cardiac components as they are positioned within the thorax. In this review, we discuss these potential difficulties, putting them into the context of the anatomy of the ventricular outflow tracts as revealed by virtual dissection of computed tomographic datasets. We provide a brief account of cardiac development, suggesting that such evidence can provide vital clues to the potential origins of arrhythmias originating from the myocardial components of the ventricular outflow tracts.

P4849Man vs. machine: comparison of manual vs. automated 12-lead ECG prediction of the origin of idiopathic ventricular arrhythmias to guide catheter ablation

P4849Man vs. machine: comparison of manual vs. automated 12-lead ECG prediction of the origin of idiopathic ventricular arrhythmias to guide catheter ablation

Electrocardiographic morphology of multiple ventricular arrhythmias originating from the right ventricular outflow tract: inverse correlation of the amplitude in the inferior leads and anatomic height of the origin

It is unclear whether the electrocardiogram amplitude in the inferior leads (Amp-I) can always predict the height of the origin of right ventricular outflow tract arrhythmias (RVOT-VAs). We analyzed patients who received catheter ablation of multiple RVOT-VAs in the same session in our hospital from 2011 to 2016. Two distinguished RVOT-VAs, those with anatomically higher origins (HOs) and lower origins (LOs), were identified and compared to measure the longitudinal distance. Amp-I was uniquely determined for each OTVA as the highest amplitude in leads II, III, and aVF and compared between the HO-VAs and LO-VAs. In total, out of 187 patients who underwent catheter ablation of RVOT-VAs, 9 (4.8%) had multiple right OTVAs successfully treated. Four cases (Group A) had HO-VAs (10.8 ± 5.3mm from an LO) with a lower Amp-I (1.28 ± 0.46mV) than the LO-VAs (1.81 ± 0.59mV), whereas the other 4 patients (Group B) had HO-VAs with a higher Amp-I (1.91 ± 0.23mV) than the LO-VAs (1.26 ± 0.35mV). In Group A, all HO-VAs originated from the lateral free wall and had notched R waves in the inferior leads, whereas all LOs with higher Amp-Is were located on the septum. In one patient, the HO and LO were at almost the same height, while a VA from a lateral origin had lower notched R waves in the inferior leads. A divided excitation from high lateral origins may result in not only QRS notching, but also a reduction in the QRS amplitude. In patients harboring multiple RVOT-VAs, VAs arising from the high lateral free wall could have lower Amp-Is than VAs from low septal origins.

Analysis on the factors related to the immediate success rate of radiofrequency catheter ablation on patients with idiopathic right ventricular outflow tract ventricular arrhythmia

Objective: To analyze the clinical characteristics of patients with idiopathic right ventricular outflow tract (RVOT) ventricular arrhythmias (VA) and factors related to the immediate success rate of radiofrequency ablation. Methods: Patients diagnosed as idiopathic RVOT arrhythmia in Fuwai Hospital from February 2009 to January 2013 were retrospectively screened. Patients with structural heart disease or inherited arrhythmia were excluded. All patients underwent endocardial electrophysiological study and radiofrequency catheter ablation. Baseline clinical and operation records were collected and analyzed. Immediate success rate was defined as no inducible ventricular arrhythmia by isoprinosine and electrophysiological induction at the end of ablation. The origins of idiopathic RVOT were classified as septal, anterior, posterior, free wall site, epicardial and RVOT-aorta root site. Results: A total of 468 patients were finally included, and the age was (40.4±13.3) years old and 60.5%(283/468) patients were female. Immediate radiofrequency success rate was 89.3%(418/468). Patients were divided into ablation success group (n=418) and ablation failure group (n=50). Percent of female patients and patients with interventricular septal origin was significantly higher in the ablation success group than in ablation failure group (261(62.4%) vs. 22 (44.0%) , P=0.01, and 233(55.7%) vs. 18(36.0%), P=0.005), while percent of patients with epicardial origin was significantly lower in the ablation success group than in ablation failure group (17(4.1%) vs. 11(22.0%), P<0.001). Immediate success rate was the highest for patients with the septal origin and the lowest for patients with epicardial origin (92.8%(233/251) vs. 60.7%(17/28), P<0.05). Multivariate analysis showed that the origin site of VAs was the most important independent factor related to the success rate of ablation. Compared with the septal origin patients, patients with RVOT-aorta root and epicardial origin VAs faced with 1.82-fold and 8.26-fold increased risk of failed ablation, respectively (OR=2.82, 95%CI 1.05-7.57, and OR=9.26, 95%CI 3.60-23.86). Sex category was not the independent risk factor for failed ablation(OR=1.76, 95%CI 0.93-3.33, P=0.08) . Conclusions: The immediate success rate of radiofrequency catheter ablation for idiopathic RVOT ventricular arrhythmia is relative high, however, immediate success rate of radiofrequency catheter ablation is relatively low for patients with epicardial and RVOT-aorta root origin arrhythmia and VAs origin is an independent risk factor of immediate ablation success rate.

Multiparametric Approach to Arrhythmogenic Cardiomyopathy: Clinical, Instrumental, and Lifestyle Indications

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder with an autosomal dominant inheritance and incomplete penetrance. It predominantly affects the right ventricle (RV), predisposing to the origin of ventricular arrhythmias and sudden death (SD). The structural basis of the disease consists of the progressive loss of myocardium with fibro-adipose replacement. ARVC is a “desmosomes” disease involving mutations of proteins such as placoglobin, desmoplachine, placophylline, desmoglein, and desmocollin. In the “classical” form, the disease mainly implicates the RV chamber, while the left ventricle (LV) is involved in advanced stages. Genotype-phenotype correlation studies have identified some phenotypic variants characterized by an early participation of the LV, which can proceed in parallel toward the two ventricles (“biventricular” variant) or prevails over the RV (variant to “left dominance”). These data led to the evolution of the initial definition of ARVC, which is currently considered a genetic disease of both ventricles and, therefore, deserves the denomination “arrhythmogenic cardiomyopathy”. Many aspects of diagnosis, treatment, and indications for a correct lifestyle are important in sports medicine. This paper will discuss the clinical management of ARVC, with particular reference to diagnosis, risk stratification, therapy, and indications for physical activity.

An electrocardiographic diagnostic model for differentiating left from right ventricular outflow tract tachycardia origin.

Although several electrocardiographic (ECG) algorithms have been proposed for differentiating the origins of outflow tract ventricular arrhythmias, the most optimal one has not been agreed on. The purpose of this study was to establish an ECG diagnostic model based on the previous ECG algorithms. The following ECG diagnostic model, Y=-1.15×( TZ )-0.494×(V2S/V3R), was developed by standard 12-lead ECG algorithms in 488 patients with idiopathic premature ventricular contractions or ventricular tachycardia with a left bundle branch block pattern and inferior axis QRS morphology. Binary logistic regression analysis was performed to establish the ECG diagnostic model. The ECG diagnostic model consisted of two ECG algorithms-the transition zone (TZ) index and V2S/V3R index. The area under the curve by receiver operating characteristic curve analysis for the ECG diagnostic model was 0.88, with a cut-off value of ≥ -0.76 predicting a left ventricular outflow tract (LVOT) origin with a sensitivity of 82% and a specificity of 86%, which was higher than other ECG algorithms in this study. The predictive accuracy of the ECG diagnostic model was also the best among all ECG algorithms in patients with a lead V3 precordial transition. This model was tested prospectively in 207 patients with a sensitivity of 90%, a specificity of 87%, and Youden index of 0.77. A highly accurate ECG diagnostic model for correctly differentiating LVOT origin from right ventricular outflow tract origin was developed.

CORRELATION OF EKG BASED SITE OF ORIGIN OF VENTRICULAR ARRHYTHMIAS WITH SITE OF INFLAMMATION ON FDG-PET SCAN IN PATIENTS WITH ARRHYTHMOGENIC INFLAMMATORY CARDIOMYOPATHY

Patients presenting with frequent ventricular arrhythmias can have underlying myocardial inflammation as an inciting factor. We seek to determine whether the site of origin (SOO) of ventricular arrhythmias on 12 lead EKG correlate with areas of inflammation on FDG PET cardiac imaging in patients

P773Centrifugal wave-front propagation speed for localizing the origin of ventricular arrhythmias: Investigation using a new ultra-high-resolution mapping system

P773Centrifugal wave-front propagation speed for localizing the origin of ventricular arrhythmias: Investigation using a new ultra-high-resolution mapping system

P780Clinical evaluation of an automatic activation mapping algorithm for identifying the site of origin of idiopathic ventricular arrhythmias

P780Clinical evaluation of an automatic activation mapping algorithm for identifying the site of origin of idiopathic ventricular arrhythmias

Cardiac Electrophysiology Studies Based on Image and Machine Learning

Cardiac Electrophysiology study is the origin and treatment of arrhythmia, which is an abnormality in the rate, regularity or sequence of cardiac activation. There has been considerable recent development in this field, where computational methods such as Imaging and Machine Learning for Cardiac Electrophysiology, provide the framework for cardiac re-modeling. In this research, we review various recent strategies currently available for the meeting the goal of structurally and functionally integrated models of cardiac function that combine data intensive cellular systems models with compute-intensive anatomically detailed multiscale simulations.

Mitral Prolapse: An Old Mysterious Entity - The Incremental Role of Multimodality Imaging in Sports Eligibility.

Mitral valve prolapse is generally a benign condition characterized by fibromyxomatous changes of the mitral leaflet with displacement into the left atrium and late-systolic regurgitation. Although it is an old clinical entity, it still arouses perplexity in diagnosis and clinical management. Complications, such as mitral regurgitation (MR), atrial fibrillation, congestive heart failure, endocarditis, ventricular arrhythmias, and sudden cardiac death (SCD), have been reported. A large proportion of the overall causes of SCD in young competitive athletes is explained by mitral valve prolapse. Recent studies have shown the fibrosis of the papillary muscles and inferobasal left ventricular wall in mitral valve prolapse, suggesting a possible origin of ventricular fatal arrhythmias. Athletes with mitral valve prolapse and MR should undergo annual evaluations including physical examination, echocardiogram, and exercise stress testing to evaluate the cardiovascular risks of competitive sports and obtain the eligibility. In this setting, multimodality imaging techniques – echocardiography, cardiac magnetic resonance, and cardiac computed tomography – should provide a broad spectrum of information, from diagnosis to clinical management of the major clinical profiles of the disease.

Centrifugal Wave Front Propagation Speed for Localizing the Origin of Ventricular Arrhythmias: Investigation Using a New Ultra-High-Resolution MappingSystem.

The aim of this study was to assess the use of wave front propagation speed on a right ventricular map for determining the earliest activation site as the origin of outflow tract ventricular arrhythmias (VAs). VAs with centrifugal right ventricular outflow tract (RVOT) activation can be from an RVOT focus or a focus outside the RVOT. This prospective observational study included 23 patients with idiopathic outflow tract VAs. Mapping of theRVOT was performed using a new ultra-high-resolution electroanatomic mapping system. The wave front propagation speed was estimated from the area surrounded by a propagated wave front at 5, 10, 15, and 20 ms after the earliest activation. VAs disappeared following ablations in the RVOT in 15 patients (RVOT origin). The remaining 8 patients hadVAs of non-RVOT origin determined by ablation success at another site or ablation failure. The areas surrounded by apropagated wave front were significantly smaller in VAs of RVOT origin than non-RVOT VAs at 5 ms (1.0 [0.7 to 1.1]cm2vs. 2.2 [1.6 to 4.4] cm2), 10 ms (1.9 [1.4 to 2.2] cm2 vs. 4.5 [3.2 to 5.8] cm2), 15 ms (3.2 [2.3 to 4.4] cm2 vs. 7.1[6.3to 9.8] cm2), and 20 ms (5.0 [3.0 to 6.6] cm2 vs. 9.8 [9.3 to 14.8] cm2). A propagated area of<5.0 cm2 at 15 ms predicted RVOT VAs with 87% sensitivity, 100% specificity, and 91% predictive accuracy. VAs with slow wave front propagation speed on the right ventricular map indicate an RVOT origin.

A preliminary study on the relationship between idiopathic arrhythmia and cardiac magnetic resonance imaging defined cardiac features in patients with straight back syndrome

Objective: To retrospectively analyze the potential correlation between cardiac magnetic resonance (CMR) imaging and clinical features and idiopathic arrhythmia in patients with straight back syndrome (SBS). Methods: Patients receiving CMR imaging examination from April 2015 to March 2016 at our department (n=1 432) were screened, 76 patients met the diagnosis criteria of flat chest (anteroposterior diameter/transthoracic diameter (APD/TTD) ratio<0.37 at the T8 vertebra). After excluding 33 patients with structural heart disease, 43 SBS patients were divided into two groups: SBS without obvious morphological change in the heart (group A, n=19) and SBS with morphological change of the heart (group B, n=24). CMR images were analyzed, focusing the heart morphological changes induced by SBS. The clinical data were collected to comprehensively analyze the medical history, electrocardiogram and electrophysiological examination in order to observe the relationship between SBS induced heart morphological change and the arrhythmia type and origin. Results: There were 21 male patients in this cohort, mean age was (28.5±11.5) years (13-58 years). APD/TTD ratio was similar between the two groups (0.30±0.03 vs. 0.29±0.04, P>0.05). LVEF tended to be lower in group B than in group A ((47.48±12.77)%vs. (59.31±9.04)%, P>0.05) . In group B, there were 15 patients with left ventricular enlargement, 2 with left ventricular wall thickening, 5 with uncoordinated ventricular wall motion, 5 with tricuspid regurgitation, 3 with mitral regurgitation, 2 with myocardial fibrosis, 5 with increased trabecular and 16 with decreased left ventricular function. Direct compression sign of right ventricle (disappeared precordial fat tissue space, secondary right atria enlargement and tricuspid regurgitation) and left atria (with or without secondary left ventricular enlargement and mitral regurgitation) were evidenced in patients of group B. CMR revealed that the arrhythmia origin corresponded the compression site of the heart in 8 cases (42.1%) in group A and 13 cases (54.2%) in group B, not corresponded to the compression site in 6 patients (31.6%) in group A and in 7 patients (29.2%) in group B, not attributable in 5 patients (26.3%) in group A and 4 patients (16.7%) in group B. The percent of arrhythmia origin corresponded the compression site of the heart tended to be higher in group B as compared to group A (P>0.05). Conclusion: SBS can induce changes of cardiac morphology and cardiac function. SBS induced cardiac compression is linked with the development of arrhythmias and might be one of the reasons of arrhythmias in these patients.

Imaging characteristics of papillary muscle site of origin of ventricular arrhythmias in patients with mitral valve prolapse.

Mitral valve prolapse has been associated with increased risk of ventricular arrhythmias. We aimed to examine whether certain cardiac imaging characteristics are associated with papillary muscle origin of ventricular arrhythmias in these patients. We screened electronic medical records of all patients documented to have mitral valve prolapse on either transthoracic echocardiogram (TTE) or cardiac magnetic resonance imaging (CMR) in our center, who also underwent an electrophysiologic study (EPS) between 2007 and 2016. Anterior and posterior mitral leaflet thickness and prolapsed distance were measured on TTE and late gadolinium enhancement (LGE) was assessed on CMR. Patients were categorized as papillary muscle positive (pap (+)) or negative (pap (-)) using EPS. Eighteen patients were included in this study. Of the 15 patients who underwent TTE, a significantly higher proportion of patients in the pap (+) group had an anterior to posterior leaflet prolapse ratio of>0.45 indicating more symmetric leaflet prolapse. There were no differences in anterior or posterior leaflet thickness or prolapse distance between the groups. Patients in the pap (+) group were more likely to be women. Of the 7 patients who underwent CMR, those who were pap (+) were more likely to have LGE in the region of the papillary muscles than those who were pap (-). Female gender, more symmetric bileaflet prolapse on TTE, and the presence of papillary muscle LGE on CMR may be associated with papillary muscle origin of ventricular arrhythmias in patients with mitral valve prolapse.

Predicting the Origin of Ventricular Arrhythmia Using Acoustic Cardiography

This study aimed to examine the relationship between measurements related to heart sounds and the origin of ventricular arrhythmia. We retrospectively evaluated 45 patients undergoing catheter ablation with contemporaneous digital acoustic cardiography of the first heart sound (S1) and the second heart sound (S2). The patients with baseline wide QRS morphology (>120 ms or aberrant conduction), heart failure, valvular heart disease, chronic pulmonary disease, and obesity were excluded. Ventricular arrhythmias from the left ventricle had an increased S1 complexity score and S1 duration in comparison to adjacent sinus beats. On the other hand, ventricular arrhythmia from right ventricle had decreased S1 complexity score and S1 duration in comparison to adjacent sinus beats. The difference of S1 (ΔS1) parameters between premature ventricular complex and sinus beat was significantly smaller in right ventricular arrhythmia group compared with and left ventricular arrhythmia group. For predicting the origin of ventricular arrhythmia, the ΔS1 duration provide better predictive accuracy (sensitivity: 100%, specificity: 100%, cutoff value: −1.28 ms) in comparison to ΔS1 complexity score (sensitivity 71.4%, specificity 75.0%, cutoff value: −0.13). The change of S1 complexity and duration determined from acoustic cardiography could accurately predict the ventricular arrhythmia origin.

Three-Dimensional Noninvasive Imaging of Ventricular Arrhythmias in Patients With Premature Ventricular Contractions.

Noninvasive imaging of cardiac electrical activity promises to provide important information regarding the underlying arrhythmic substrates for successful ablation intervention and further understanding of the mechanism of such lethal disease. The aim of this study is to evaluate the performance of a novel 3-D cardiac activation imaging technique to noninvasively localize and image origins of focal ventricular arrhythmias in patients undergoing radio frequency ablation. Preprocedural ECG gated contrast enhanced cardiac CT images and body surface potential maps were collected from 13 patients within a week prior to the ablation. The electrical activation images were estimated over the 3-D myocardium using a cardiac electric sparse imaging technique, and compared with CARTO activation maps and the ablation sites in the same patients. Noninvasively-imaged activation sequences were consistent with the CARTO mapping results with an average correlation coefficient of 0.79, average relative error of 0.19, and average relative resolution error of 0.017. The imaged initiation sites of premature ventricular contractions (PVCs) were, on average, within 8 mm of the last successful ablation site and within 3 mm of the nearest ablation site. The present results demonstrate the excellent performance of the 3-D cardiac activation imaging technique in imaging the activation sequence associated with PVC, and localizing the initial sites of focal ventricular arrhythmias in patients. These promising results suggest that the 3-D cardiac activation imaging technique may become a useful tool for aiding clinical diagnosis and management of ventricular arrhythmias.

Localization of Origins of Premature Ventricular Contraction by Means of Convolutional Neural Network From 12-Lead ECG.

This paper proposes a novel method to localize origins of premature ventricular contractions (PVCs) from 12-lead electrocardiography (ECG) using convolutional neural network (CNN) and a realistic computer heart model. The proposed method consists of two CNNs (Segment CNN and Epi-Endo CNN) to classify among ventricular sources from 25 segments and from epicardium (Epi) or endocardium (Endo). The inputs are the full time courses and the first half of QRS complexes of 12-lead ECG, respectively. After registering the ventricle computer model with an individual patient's heart, the training datasets were generated by multiplying ventricular current dipoles derived from single pacing at various locations with patient-specific lead field. The origins of PVC are localized by calculating the weighted center of gravity of classification returned by the CNNs. A number of computer simulations were conducted to evaluate the proposed method under a variety of noise levels and heart registration errors. Furthermore, the proposed method was evaluated on 90 PVC beats from nine human patients with PVCs and compared against ablation outcome in the same patients. The computer simulation evaluation returned relatively high accuracies for Segment CNN (∼78%) and Epi-Endo CNN (∼90%). Clinical testing in nine PVC patients resulted an averaged localization error of 11mm. Our simulation and clinical evaluation results demonstrate the capability and merits of the proposed CNN-based method for localization of PVC. This paper suggests a new approach for cardiac source localization of origin of arrhythmias using only the 12-lead ECG by means of CNN, and may have important applications for future real-time monitoring and localizing origins of cardiac arrhythmias guiding ablation treatment.

P793Non-invasive three-dimensional electro-anatomical imaging of the site of origin of outflow tract ventricular arrhythmias with magnetocardiographic mapping

P793Non-invasive three-dimensional electro-anatomical imaging of the site of origin of outflow tract ventricular arrhythmias with magnetocardiographic mapping

Asymmetric sympathetic output: The dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias.

The autonomic response to emotional stress, while involving several target organs, includes an important increase in sympathetic drive to the heart. There is ample evidence that cardiac sympathetic innervation is lateralized, and asymmetric autonomic output to the heart during stress is postulated to be a causal factor that precipitates cardiac arrhythmias. Recent animal studies provided a new picture of the central pathways involved in the cardiac sympathetic response evoked by emotional stress, pointing out a key role for the region of dorsomedial hypothalamus. However, how much of this information can be extrapolated to humans? Analysis of human functional imaging data at rest or during emotional stress shows some consistency with the components that integrate these pathways, and attention must be given to the asymmetric activation of subcortical sites. In this short review, we will discuss related findings in humans and animals, aiming to understand the neurogenic background for the origin of emotional stress-induced cardiac arrhythmias.