Types Of Ventricular Arrhythmias Research Articles

Evaluation of cardiac pro-arrhythmic risks using the artificial neural network with ToR-ORd in silico model output.

Torsades de pointes (TdP) is a type of ventricular arrhythmia that can lead to sudden cardiac death. Drug-induced TdP has been an important concern for researchers and international regulatory boards. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative was proposed that integrates in vitro testing and computational models of cardiac ion channels and human cardiomyocyte cells to evaluate the proarrhythmic risk of drugs. The TdP risk classification performance using only a single TdP metric may require some improvements because of information limitations and the instability of generalizing results. This study evaluates the performance of TdP metrics from the in silico simulations of the Tomek-O'Hara Rudy (ToR-ORd) ventricular cell model for classifying the TdP risk of drugs. We utilized these metrics as an input to an artificial neural network (ANN)-based classifier. The ANN model was optimized through hyperparameter tuning using the grid search (GS) method to find the optimal model. The study outcomes show an area under the curve (AUC) value of 0.979 for the high-risk category, 0.791 for the intermediate-risk category, and 0.937 for the low-risk category. Therefore, this study successfully demonstrates the capability of the ToR-ORd ventricular cell model in classifying the TdP risk into three risk categories, providing new insights into TdP risk prediction methods.

Design of hardware-efficient PVC recognition and classification system for early detection of sudden cardiac arrests

Sudden cardiac arrest (SCA) is a critical cardiovascular condition that needs greater emphasis on its early detection because it occurs unexpectedly and is fatal within minutes. Nowadays, wearable healthcare technologies are preferred for continuous monitoring of a wide range of cardiovascular diseases. Additionally, the recognition of cardiac arrhythmias such as premature ventricular contraction (PVC) and non-sustained ventricular tachycardia (NSVT) by wearable healthcare devices can help in the early detection of SCAs. The biggest challenge in this regard for compactly sized wearable healthcare devices is to design a hardware-efficient yet highly accurate PVC detection and classification system. In this work, a novel and hardware-efficient PVC recognition and classification system capable of categorizing PVCs into five types of ventricular arrhythmias, including NSVT, for the early detection of SCAs is proposed. For PVC detection, lifting-based discrete wavelet transform (LDWT) is used to perform pre-processing and extract morphological electrocardiogram (ECG) features and the Teager energy operator. When compared to the state-of-the-art ventricular arrhythmias and PVC detection systems, the proposed system performs PVC beat recognition and classification with an improved accuracy and sensitivity of 98.29% and 98.64%, respectively, while utilizing only 4.36% of the total resources when implemented on the Nexys 4 DDR FPGA board.

Perioperative ventricular arrhythmias are increased with hemoperitoneum and are associated with increased mortality in dogs undergoing splenectomy for splenic masses.

To identify risk factors for intra- and postoperative ventricular arrhythmias (VAs) and in-hospital mortality in dogs undergoing splenectomy for splenic masses. 308 dogs. Records from 2010 through 2018 were reviewed for dogs undergoing splenectomy for a splenic mass. Clinical and laboratory findings on admission, diagnostic imaging, anesthesia, surgery and pathology reports, treatment records, and in-hospital mortality were evaluated with logistic regression. VAs occurred in 138 (44.8%) dogs (126/308 [40.9%] postoperative, 51/308 [16.6%] intraoperative, 26/308 [8.4%] preoperative), with 50/308 (16.2%) dogs having more than one type of VA. Increasing heart rate and body weight, decreasing PCV and platelet count, hemoperitoneum, receipt of a transfusion, and diagnosis of hemangiosarcoma were associated with the presence of intra- and postoperative VAs on univariable analysis (all P < .001). On multivariable analysis, hemoperitoneum (P < .001 , < .001), increasing body weight (P = .026, < .001), and increasing heart rate (P = .028, < .001) were significant for intra- and postoperative VAs, respectively. Twenty dogs died (20/308 [6.5%]; 14/138 [10.1%] with VAs, 6/170 [3.5%] without VAs). Intra- and postoperative VAs were associated with in-hospital mortality (P = .009, .025, respectively). Perioperative VAs were common and odds of VAs were increased with hemoperitoneum, increasing heart rate, and increasing body weight. Presence of VAs increased the odds of in-hospital mortality. Despite this, the overall in-hospital mortality rate was low (6.5%), indicating a good prognosis for survival of surgery in dogs with splenic masses, regardless of the presence of VAs or hemoperitoneum.

Electrical storm management in structural heart disease.

Electrical storm (ES) is a life-threatening condition characterized by at least three separate episodes of ventricular arrhythmias (VAs) over 24 h, each requiring therapeutic intervention, including implantable cardioverter defibrillator (ICD) therapies. Patients with ICDs in secondary prevention are at higher risk of ES and the most common presentation is that of scar-related monomorphic VAs. Electrical storm represents a major unfavourable prognostic marker in the history of patients with structural heart disease, with an associated two- to five-fold increase in mortality, heart transplant, and heart failure hospitalization. Early recognition and prompt treatment are crucial to improve the outcome. Yet, ES management is complex and requires a multidisciplinary approach and well-defined protocols and networks to guarantee a proper patient care. Acute phase stabilization should include a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, and acute sympathetic modulation, while the sub-acute/chronic phase requires a comprehensive heart team evaluation to define the better treatment option according to the haemodynamic and overall patient's condition and the type of VAs. Advanced anti-arrhythmic strategies, not mutually exclusive, include invasive ablation, cardiac sympathetic denervation, and, for very selected cases, stereotactic ablation. Each of these aspects, as well as the new European Society of Cardiology guidelines recommendations, will be discussed in the present review.

Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: A substudy of VALIDATE-SWEDEHEART trial

Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia. We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry. Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality. VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance.

Electrophysiological features of repetitive focal Purkinje ventricular arrhythmias originating from the proximal cardiac conduction system.

Focal Purkinje ventricular arrhythmias (VAs) might originate from the vicinity of the proximal portion of the cardiac conducting system. This study aimed to clarify the features associated with focal Purkinje VAs originating from the proximal conduction system. A total of 18 patients with focal Purkinje VAs undergoing radiofrequency catheter ablation (RFCA) were retrospectively examined and divided into the proximal type or the non-proximal type. The proximal type was defined as having the origin at the proximal half of the interventricular septum, or the proximal half and the septal side of the anterior wall. The 12-lead electrocardiogram and electrophysiological findings were investigated. Seven patients met criteria for proximal type of focal Purkinje VA. Out of the 7, 4 patients with proximal VAs had multiple QRS morphologies of VAs clinically, whereas out of 11 patients with non-proximal VAs, only 1 had multiple morphologies (p=.047). VA QRS duration was shorter in the proximal type than in the non-proximal type (111.2 ± 19.8ms vs. 135.7 ± 17.7ms; p= .003). The absolute axis difference between sinus rhythm and VA was smaller in the proximal type (80.4 ± 46.1°vs. 138.8 ± 59.6°; p= .014). The absolute axis difference ≤134° was useful in distinguishing the two types. Recurrence of VA was recorded in 3 proximal type patients and 3 non-proximal type patients. No procedure-related conduction block was observed. A VA of absolute axis difference ≤134°, and multiple QRS morphologies of clinical VAs indicate a proximal origin. Focal Purkinje VAs from proximal origins can be suppressed by RFCA without severe conduction disturbance.

The Association of Clustered Ventricular Arrhythmia and Cycle Length With ScarBurden in Cardiomyopathy.

Patients with≥2 ventricular arrhythmia (VA) events within 3months (clustered VA) have increased risk for mortality. The aim of this study was to examine the association of risk factors including scar characteristics on cardiovascular magnetic resonance imaging with clustered VA and VA cycle length in nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM). Data from 329 primary prevention implantable cardioverter-defibrillator recipients (mean age 57 years, 26% women) were analyzed from the Left Ventricular Structural Predictors of Sudden Cardiac Death study. Twenty-one patients developed clustered VA (median time 2.7 years after implantable cardioverter-defibrillator placement). Men had the greatest risk for recurrent VA. Patients with NICM and scar had the highest incidence rate of clustered VA. In patients with NICM, each 1-g increase in core scar correlated with greater clustered VA risk (HR: 1.19; 95%CI: 1.07-1.32). Gray scar was similar among subgroups. Patients with NICM with clustered VA had the longest mean VA cycle length (297 ± 40 milliseconds). Higher core scar burden correlated with longer VA cycle length inpatients with NICM (P = 0.002), and higher body mass index correlated with shorter VA cycle length in those with ICM (P = 0.02). Type of VA was similar between cardiomyopathy subgroups, and no scar pattern predominated. Clustered VA was most common in patients with NICM and scar, with greatest risk among those with larger core scar. Core scar correlated with slower VA in patients with NICM, and higher body mass index correlated with faster VA in those with ICM. Type of VA was similar by cardiomyopathy etiology, and no dominant scar pattern was associated with clustered VA.

Caffeine Induces Spontaneous Ventricular Tachyarrhythmias and Bidirectional Ventricular Tachycardia: Increased Vulnerability with Aging

IntroductionCaffeine is generally suspected to trigger or exacerbate cardiac arrhythmias in patients, but so far clinical data have been conflicting. We have demonstrated previously that caffeine plus dobutamine challenge can induce ventricular tachyarrhythmias in normal rats (Heart Rhythm O2 2020;1:359‐367). However, whether caffeine alone can induce cardiac arrhythmias has not been investigated. We hypothesize that caffeine alone could trigger spontaneous cardiac arrhythmias, which may be affected by aging and sexes. In this study we have investigated the effect of caffeine on spontaneous cardiac arrhythmias in younger and older adult rats of both sexes.MethodsThis study used Sprague‐Dawley rats. Younger (5‐month‐old) and older (1‐year‐old) adult rats of both sexes were enrolled. The study consisted of the following groups: 5‐month‐old male rats (younger male, n=8) and 1‐year‐old male rats (older male, n=9), 5‐month‐old female rats (younger female, n=6) and 1‐year‐old female rats (older female, n=5). These rats received caffeine (80mg/kg, IP) injection. In addition, a group of 5‐month‐old rats (both sexes, n=8) receiving saline injection without caffeine served as the control group. Surface electrocardiogram (ECG, standard Lead II) was continuously monitored and recorded during the experiments.ResultsNo arrhythmia was induced in the control group with saline injection. Caffeine injection induced ventricular tachyarrhythmias in 8/9 older male rats, while only in 2/8 younger male rats (younger versus older male rats, p=0.0152, Fisher's exact test). Similarly, ventricular arrhythmias were induced in 5/5 older female rats, and only in 1/6 younger female rats (older versus younger female rats, p=0.0152). There were no significant differences in male versus female rats in both age groups. Induced ventricular arrhythmias include various premature ventricular contractions (PVC, Figure‐Panel A) in all rats, monomorphic ventricular tachycardia (VT, Panel B) in 3 rats and polymorphic VT and bidirectional VT (Panel C) in all rats. No atrial arrhythmia was observed.ConclusionCaffeine can induce spontaneous ventricular arrhythmias in normal rats, and the younger rats are more resistant to arrhythmia induction. Arrhythmia inducibility increases significantly in older rats. There is no sex difference in caffeine induced ventricular arrhythmias. Although different types of ventricular arrhythmias are induced, the characteristic bidirectional VT is highly prevalent among the caffeine induced arrhythmias and no atrial arrhythmia was observed.

Prediction and classification of ventricular arrhythmia based on phase-space reconstruction and fuzzy c-means clustering

Background and objectivePrediction and classification of Ventricular Arrhythmias (VA) may allow clinicians sufficient time to intervene for stopping its escalation to Sudden Cardiac Death (SCD). This paper proposes a novel method for predicting VA and classifying its type, in particular, the fatal VA even before the event occurs. MethodsA statistical index J based on the combination of phase-space reconstruction (PSR) and box counting has been used to predict VA. The fuzzy c-means (FCM) clustering technique is applied for the classification of impending VA. Results32 healthy and 32 arrhythmic subjects from two open databases - PTB Diagnostic database (PTBDB) and CU Ventricular Tachyarrhythmia (CUDB) database respectively; were used to validate our proposed method. Our method showed average prediction time of approximately 5 min (4.97 min) for impending VA in the tested dataset while classifying four types of VA (VA without ventricular premature beats (VPBs), ventricular fibrillation (VF), ventricular tachycardia (VT), and VT followed by VF) with an average 4 min (approximately) before the VA onset, i.e., after 1 min of the prediction time point with average accuracy of 98.4%, a sensitivity of 97.5% and specificity of 99.1%. ConclusionsThe results obtained can be used in clinical practice after rigorous clinical trial to advance technologies such as implantable cardioverter defibrillator (ICD) that can help to preempt the occurrence of fatal ventricular arrhythmia - a main cause of SCD.

B-PO05-174 CORE SCAR BURDEN ON CARDIAC MAGNETIC RESONANCE IMAGING IS ASSOCIATED WITH CLUSTERED VENTRICULAR ARRHYTHMIA AND LONGER CYCLE LENGTH IN NONISCHEMIC CARDIOMYOPATHY

Patients with ≥2 ventricular arrhythmia (VA) events within three months (clustered VA) have higher mortality than patients without frequent VA. However, the association between myocardial scar and clustered VA in nonischemic (NICM) and ischemic cardiomyopathy (ICM) is unknown. The type of VA (MMVT, PMVT, VF) and relationship of scar burden and VA cycle length has also not been well characterized in these subgroups. To study the association of core and gray zone scar on cardiac magnetic resonance imaging (CMR) with clustered VA and VA cycle length in NICM and ICM, and characterize the type of VA present. We retrospectively analyzed data from 331 primary prevention ICD recipients (mean age 57 years, 26% female, 29% black) in the LV Structural Predictors of Sudden Cardiac Death study (NCT01076660). VA was defined as an adjudicated appropriate ICD shock for VT or VF. After stratifying by cardiomyopathy etiology (47% NICM, 53% ICM), we performed Fine and Gray competing risk and multinomial logistic regression analysis to evaluate the association of core and heterogeneous gray zone scar by CMR with the occurrence of clustered vs. unclustered VA. We further examined the association of VA cycle length with myocardial scar burden in stratified multivariate regression analysis. 69 participants developed ≥1 VA event (48 unclustered, 21 clustered). Time to clustered VA was 3.6±3.1 years. While accounting for competing risk of death, each 1-gram increase in core scar was associated with greater clustered VA in NICM (HR 1.19; 95% CI: 1.07-1.32). Gray scar did not increase the likelihood of clustered VA in NICM or ICM. The NICM and clustered VA subgroup had the highest overall mean VA cycle length (297±40 ms). In regression analysis, higher core scar burden was associated with longer VA cycle length in NICM (p=0.002). Higher BMI was associated with shorter VA cycle length in ICM (p=0.02). Type of VA was similar between cardiomyopathy subgroups and MMVT was more common in the clustered VA subgroups. In patients with NICM, CMR imaging may help identify those at risk for clustered VA and slower VA. BMI may be inversely associated with VA cycle length in ICM.

Catheter Ablation of Life-Threatening Ventricular Arrhythmias in Athletes.

A recent surveillance analysis indicates that cardiac arrest/death occurs in ≈1:50,000 professional or semi-professional athletes, and the most common cause is attributable to life-threatening ventricular arrhythmias (VAs). It is critically important to diagnose any inherited/acquired cardiac disease, including coronary artery disease, since it frequently represents the arrhythmogenic substrate in a substantial part of the athletes presenting with major VAs. New insights indicate that athletes develop a specific electro-anatomical remodeling, with peculiar anatomic distribution and VAs patterns. However, because of the scarcity of clinical data concerning the natural history of VAs in sports performers, there are no dedicated recommendations for VA ablation. The treatment remains at the mercy of several individual factors, including the type of VA, the athlete’s age, and the operator’s expertise. With the present review, we aimed to illustrate the prevalence, electrocardiographic (ECG) features, and imaging correlations of the most common VAs in athletes, focusing on etiology, outcomes, and sports eligibility after catheter ablation.

Practical Approaches to Catheter Ablation of Idiopathic Ventricular Arrhythmias

In this review, we provide a practical approach to the catheter ablation of idiopathic focal ventricular arrhythmias (VAs) by summarizing the electrocardiographic (ECG) characteristics, mapping strategies, and ablation techniques for each of the major types of idiopathic VAs. We identify special considerations to be taken when treating specific forms of idiopathic VAs with catheter ablation that can increase success rates and reduce complications. Insights on ECG morphologies of VAs have led to novel criteria that can aid in accurate identification and localization of VA sites of origin. Advancements in mapping catheters and software as well as the use of intracardiac echocardiography have allowed for more precise mapping and ablation of arrhythmias arising from complex cardiac structures. Idiopathic VAs occurring in patients without overt structural heart disease can be categorized into four groups on the basis of anatomic location: (1) outflow tract VAs (which include the right ventricular outflow tract, left ventricular outflow tract, and left ventricular summit; (2) fascicular VAs; (3) papillary muscle VAs; and (4) annular VAs. Knowledge of the ECG characteristics of idiopathic VAs and the three-dimensional anatomy surrounding their sites of origin can guide pre-procedure planning, prioritization of cardiac regions for mapping, and approach for ablation.

Role of Oxidative Stress in the Genesis of Ventricular Arrhythmias.

Ventricular arrhythmias, mainly lethal arrhythmias, such as ventricular tachycardia and fibrillation, may lead to sudden cardiac death. These are triggered as a result of cardiac injury due to chronic ischemia, acute myocardial infarction and various stressful conditions associated with increased levels of circulating catecholamines and angiotensin II. Several mechanisms have been proposed to underlie electrical instability of the heart promoting ventricular arrhythmias; however, oxidative stress which adversely affects ion homeostasis due to changes in the ion channel structure and function, seems to play a critical role in eliciting different types of ventricular arrhythmias. Prevention or mitigation of the severity of ventricular arrhythmias due to antioxidants has been indicated as the fundamental contribution in the field of preventive cardiology; however, novel interventions have to be developed for greater effectiveness and specificity in attenuating the adverse effects of oxidative stress. In this review, we have attempted to discuss proarrhythmic effects of oxidative stress differing in time and concentration dependence and highlight a molecular and cellular concept how it alters cardiac cell automaticity and conduction velocity sensitizing the probability of ventricular arrhythmias with resultant sudden cardiac death due to ischemic heart disease and other stressful situations. It is concluded that pharmacological approaches targeting multiple mechanisms besides oxidative stress might be more effective in the treatment of ventricular arrhythmias than current antiarrhythmic therapy.

Ventricular Arrhythmias

Ventricular arrhythmias are common in all forms of heart disease and are an important cause of cardiac arrest and sudden death. Many ventricular arrhythmias are benign but may serve as a marker for underlying disease or its severity. Others are life threatening. The significance of an arrhythmia is determined by the specific characteristics of the arrhythmia and the associated heart disease, and these features guide evaluation and therapy. This review discusses various mechanisms and types of ventricular arrhythmias and management based on clinical presentation (including patients with symptomatic arrhythmia and increased risk of sudden death without arrhythmia symptoms). Genetic arrhythmia syndromes, such as abnormalities of repolarization and the QT interval, catecholaminergic polymorphic ventricular tachycardia (VT), and inherited cardiomyopathies, are discussed in depth. Under the rubric of management of ventricular arrhythmias, drug therapy for ventricular arrhythmias, implantable cardioverter-defibrillators (ICDs), and catheter ablation for VT are also covered. Tables chart out guideline recommendations for ICD therapy, drugs for the management of ventricular arrhythmias, and indications and contraindications for catheter ablation of ventricular arrhythmias. Electrocardiograms are provided, as well as management algorithms for ventricular arrhythmias based on patient presentation, and an algorithm for identifying patients with systolic heart failure and left ventricular ejection less than or equal to 35% who are candidates for consideration of an ICD for primary prevention of sudden cardiac death. This review contains 5 figures, 8 tables, and 61 references. Keywords: Ventricular arrhythmias, implanted cardioverter-defibrillator (ICD), Ventricular tachycardia (VT), Premature Ventricular Contractions (PVC), Myocardial Infarction (MI), Brugada syndrome, Arrhythmogenic right ventricular cardiomyopathy (ARVC), electrocardiographic (ECG)

Ventricular Arrhythmias

Ventricular arrhythmias are common in all forms of heart disease and are an important cause of cardiac arrest and sudden death. Many ventricular arrhythmias are benign but may serve as a marker for underlying disease or its severity. Others are life threatening. The significance of an arrhythmia is determined by the specific characteristics of the arrhythmia and the associated heart disease, and these features guide evaluation and therapy. This review discusses various mechanisms and types of ventricular arrhythmias and management based on clinical presentation (including patients with symptomatic arrhythmia and increased risk of sudden death without arrhythmia symptoms). Genetic arrhythmia syndromes, such as abnormalities of repolarization and the QT interval, catecholaminergic polymorphic ventricular tachycardia (VT), and inherited cardiomyopathies, are discussed in depth. Under the rubric of management of ventricular arrhythmias, drug therapy for ventricular arrhythmias, implantable cardioverter-defibrillators (ICDs), and catheter ablation for VT are also covered. Tables chart out guideline recommendations for ICD therapy, drugs for the management of ventricular arrhythmias, and indications and contraindications for catheter ablation of ventricular arrhythmias. Electrocardiograms are provided, as well as management algorithms for ventricular arrhythmias based on patient presentation, and an algorithm for identifying patients with systolic heart failure and left ventricular ejection less than or equal to 35% who are candidates for consideration of an ICD for primary prevention of sudden cardiac death. This review contains 5 figures, 8 tables, and 61 references. Keywords: Ventricular arrhythmias, implanted cardioverter-defibrillator (ICD), Ventricular tachycardia (VT), Premature Ventricular Contractions (PVC), Myocardial Infarction (MI), Brugada syndrome, Arrhythmogenic right ventricular cardiomyopathy (ARVC), electrocardiographic (ECG)

Blinded In Silico Drug Trial Reveals the Minimum Set of Ion Channels for Torsades de Pointes Risk Assessment.

Torsades de Pointes (TdP) is a type of ventricular arrhythmia which could be observed as an unwanted drug-induced cardiac side effect, and it is associated with repolarization abnormalities in single cells. The pharmacological evaluations of TdP risk in previous years mainly focused on the hERG channel due to its vital role in the repolarization of cardiomyocytes. However, only considering drug effects on hERG led to false positive predictions since the drug action on other ion channels can also have crucial regulatory effects on repolarization. To address the limitation of only evaluating hERG, the Comprehensive in Vitro Proarrhythmia Assay initiative has proposed to systematically integrate drug effects on multiple ion channels into in silico drug trial to improve TdP risk assessment. It is not clear how many ion channels are sufficient for reliable TdP risk predictions, and whether differences in IC50 and Hill coefficient values from independent sources can lead to divergent in silico prediction outcomes. The rationale of this work is to investigate the above two questions using a computationally efficient population of human ventricular cells optimized to favor repolarization abnormality. Our blinded results based on two independent data sources confirm that simulations with the optimized population of human ventricular cell models enable efficient in silico drug screening, and also provide direct observation and mechanistic analysis of repolarization abnormality. Our results show that 1) the minimum set of ion channels required for reliable TdP risk predictions are Nav1.5 (peak), Cav1.2, and hERG; 2) for drugs with multiple ion channel blockage effects, moderate IC50 variations combined with variable Hill coefficients can affect the accuracy of in silico predictions.

Epicardial approach for cardiac electrophysiology procedures.

Since its introduction over two decades ago, percutaneous epicardial procedures have become well-adopted by cardiac electrophysiologists, most commonly for catheter ablation of cardiac arrhythmias as well as left atrial appendage closure. The percutaneous epicardial approach has also been utilized for cardiac pacing and drug delivery. But still, its most common usage is for the treatment of intramural and subepicardial substrates that give rise to ventricular tachycardia, particularly in patients with nonischemic cardiomyopathy. In fact, subxiphoid, percutaneous epicardial mapping and ablation have emerged as an important adjunct and in some cases the preferred strategy for characterizing and treating certain types of ventricular arrhythmias. Herein, we will review the indications and rationale for various epicardial procedures. Additionally, we will explore the anatomy of the pericardium as well as the frequently-used epicardial access techniques. We will further examine the optimal approaches and methodologies for epicardial mapping and ablation and the impact of epicardial fat. We will also discuss the epicardial technique for left atrial appendage closure for the purpose of embolic stroke risk reduction. Finally, we will consider the potential for various complications in the setting of epicardial procedures along with their risk factors and discuss strategies to mitigate such adverse events.

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model.

Background: Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance. Methods: Human bone marrow derived CD271+ mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2−/− γc−/− mouse strain subjected to myocardial “infarction-reinfarction”. The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 min with a subsequent second permanent LAD ligation after seven days from the first infarct. Results: This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271+ MSC after the first MI significantly reduced VA induced after the second MI. Conclusions: In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271+ stem cells in vivo.

Role of Imaging in the Management of Ventricular Arrhythmias.

The management of ventricular arrhythmias (VA) has evolved over time to an advanced discipline, incorporating many technologies in the diagnosis and treatment of the myriad types of VA. The first application of imaging is in the assessment for structural heart disease, as this has the greatest impact on prognosis. Advanced imaging has its greatest utility in the planning and execution of ablation for VA. The following review outlines the application of different imaging modalities, such as ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography, for the treatment of VA.

P919Ventricular arrhythmias in patients with mitral valve prolapse and severe mitral regurgitation

Abstract Background Mitral valve prolapse (MVP) is known to be associated with ventricular arrhythmias (VA), from symptomatic premature ventricular contractions (PVCs) to malignant ventricular tachycardia (VT) and sudden cardiac death (SCD). Previous studies identified risk factors for VA in these patients such as young woman, bileaflet prolapse and inverted T-waves, but they included only specific cohort of patients who experienced SCD or who had only trivial or mild mitral regurgitation (MR). The prevalence of VA and their potential risk factors in a population of MVP patients with severe MR are unknown. Purpose The aim of our study was to describe the prevalence of VA in patients who underwent mitral valve surgery for moderate to severe MR due to MVP and to identify clinical, electrocardiographic and echocardiographic parameters associated with VA. Methods 797 patients (65±12 years, 65% male) who underwent surgery for MVP were included from 2000 until 2018. The presence of VA was defined as symptomatic and frequent PVCs (Lown grade ≥2), non-sustained ventricular tachycardia (nsVT), VT or ventricular fibrillation (VF) documented before surgery and without an ischemic cause. The echocardiogram and electrocardiogram (ECG) prior to operation were used for the specific analysis. ECGs were checked for rhythm, conduction times, QRS morphology and inferior T-wave inversion. The origin of the PVCs was derived from a 12-lead ECG when available and divided in 5 groups; mitral annulus, papillary muscle (PM), left ventricle (LV, including outflow tract), right ventricle (including outflow tract) and other. By echocardiography, several parameters such as LV thickness and volumes, LV ejection fraction (EF), global longitudinal strain (GLS) and MR grade were obtained. Results A total of 99 (12%) patients showed VA; 70% (69/99) of the patients had symptomatic PVCs, 36% (36/99) had nsVT, 12% (12/99) VT and 3% (3/99) VF. 21 patients had more than one type of VA, of which the combination PVCs and nsVT was the most common (19/99, 19%). In addition, 6 patients experienced an out of hospital cardiac arrest of a non-ischemic cause. When comparing the clinical characteristics (Table), patients with VA were significantly younger (and with better renal function), more frequently diagnosed with Barlow's disease and experienced more palpitations as compared to patients without VA. The ECG analysis showed that patients with VA more often had inferior T-wave inversions and that the PVCs predominantly originated from the PM whereas in patients without VA the PVCs originated from different regions. Echocardiography showed that patients with VA had a thinner posterior wall, reduced LV EF and worse GLS; more severe MR was not associated with VA. Conclusion In MVP patients with moderate to severe MR undergoing surgery, Barlow's disease, inferior T-wave inversions, thinner posterior wall and LV systolic dysfunction are associated with the presence and development of VA.