Idiopathic Ventricular Tachycardia Research Articles

The genetic variation rs12143842 in NOS1AP increases idiopathic ventricular tachycardia risk in Chinese Han populations

Genome-wide association studies identified that the common T of rs12143842 in NOS1AP is associated with a QT/QTc interval in European populations. In this study, we test the association between the variation rs12143842 in NOS1AP and idiopathic ventricular tachycardia (IVT). A case-control association study examining rs12143842 was performed in two independent cohorts. The Northern cohort enrolled 277 IVT patients and 728 controls from a Chinese Gene ID population. The Central cohort enrolled 301 IVT patients and 803 matched controls. Genotyping was performed using high-resolution melt analysis. The minor T allele of the rs12143842 SNP was significantly associated with decreased IVT risk in the Northern cohort (adjusted P = 0.024, OR 0.71(0.52~0.96)), and this association was replicated in an independent Central Gene ID cohort (adjusted P = 0.029, OR 0.78 (0.62~0.97)). The association was more significant in the combined population (adjusted P = 0.001, OR 0.76 (0.64~0.90)). The P values for the genotypic association were significant for the dominant (P < 0.001) and additive (P = 0.001) models. The minor T allele for the SNP rs12143842 in NOS1AP is significantly associated with IVT. NOS1AP might be a novel gene affecting IVT, and further functional studies should be performed.

Primary ventricular tachycardia in paediatric population in a tertiary centre

ObjectiveTo delineate the outcome of ventricular tachycardia (VT) in the paediatric population.MethodsPatients who developed sustained VT between the ages of 0 and 18 years in a referral centre from 1991...

Inferior lead discordance in ventricular arrhythmias: A specific marker for certain arrhythmia locations.

Most idiopathic ventricular arrhythmias (VAs) originate from the outflow tracts and are characterized by an inferior axis on the 12-lead ECG. A group of patients will exhibit inferior lead discordance (ILD), demonstrating a positive QRS in lead II with negative QRS in III or the opposite finding. We identified patients undergoing ablation of idiopathic premature ventricular contractions (PVCs) or ventricular tachycardia (VT) between 2013 and 2015. The site of earliest activation was determined using electroanatomic mapping and intracardiac echocardiography. Out of 281 patients, 25 (8.9%) exhibited ILD. In patients with positive/negative discordance (n = 18), the source was mapped to the parahisian region in 14 cases and to the right ventricular (RV) moderator band (MB) or papillary muscles (PMs) in 4, while all those with negative/positive discordance (n = 7) were mapped to the anterolateral PM (ALPM). In the group with positive/negative discordance, a later precordial transition (>V4), wider QRS duration, and the presence of notch in the inferior leads pointed toward a RV MB/PM origin. Complete PVC/VT suppression was achieved in 72%. In 2 patients with parahisian PVCs, ablation was not attempted due to risk of heart block. The presence of ILD is associated with particular anatomical locations, namely, the parahisian region, RV MB/PM, and ALPM. The outcomes of ablation are more modest compared to other idiopathic VAs, reflecting the technical difficulties associated with these anatomical locations, such as the proximity to the conduction system in parahisian VAs or stability issues when ablating the PMs or MB.

A novel noninvasive surface ECG analysis using interlead QRS dispersion in arrhythmogenic right ventricular cardiomyopathy.

BackgroundThis study investigated the feasibility of using the precordial surface ECG lead interlead QRS dispersion (IQRSD) in the identification of abnormal ventricular substrate in arrhythmogenic right ventricular cardiomyopathy (ARVC).MethodsSeventy-one consecutive patients were enrolled and reclassified into 4 groups: definite ARVC with epicardial ablation (Group 1), ARVC with ventricular tachycardia (VT, Group 2), idiopathic right ventricular outflow tract VT without ARVC (Group 3), and controls without VT (Group 4). IQRSD was quantified by the angular difference between the reconstruction vectors obtained from the QRS-loop decomposition, based on a principal component analysis (PCA). Electroanatomic mapping and simulated ECGs were used to investigate the relationship between QRS dispersion and abnormal substrate.ResultsThe percentage of the QRS loop area in the Group 1–2 was smaller than the controls (P = 0.01). The IQRSD between V1-V2 could differentiate all VTs from control (P<0.01). Group 1–2 had a greater IQRSD than the Group 3–4 (V4-V5,P = 0.001), and Group 1 had a greater IQRSD than Group 3–4 (V6-Lead I, P<0.001). Both real and simulated data had a positive correlation between the maximal IQRSD (γ = 0.62) and the extent of corresponding abnormal substrate (γ = 0.71, both P<0.001).ConclusionsThe IQRSD of the surface ECG precordial leads successfully differentiated ARVC from controls, and could be used as a noninvasive marker to identify the abnormal substrate and the status of ARVC patients who can benefit from epicardial ablation.

De Novo FGF12 (Fibroblast Growth Factor 12) Functional Variation Is Potentially Associated With Idiopathic Ventricular Tachycardia.

BackgroundIdiopathic ventricular tachycardia (VT) is a type of cardiac arrhythmia occurring in structurally normal hearts. The heritability of idiopathic VT remains to be clarified, and numerous genetic factors responsible for development of idiopathic VT are as yet unclear. Variations in FGF12 (fibroblast growth factor 12), which is expressed in the human ventricle and modulates the cardiac Na+ channel NaV1.5, may play an important role in the genetic pathogenesis of VT.Methods and ResultsWe tested the hypothesis that genetic variations in FGF12 are associated with VT in 2 independent Chinese cohorts and resequenced all the exons and exon–intron boundaries and the 5′ and 3′ untranslated regions of FGF12 in 320 unrelated participants with idiopathic VT. For population‐based case–control association studies, we chose 3 single‐nucleotide polymorphisms—rs1460922, rs4687326, and rs2686464—which included all the exons of FGF12. The results showed that the single‐nucleotide polymorphism rs1460922 in FGF12 was significantly associated with VT after adjusting for covariates of sex and age in 2 independent Chinese populations: adjusted P=0.015 (odds ratio: 1.54 [95% CI, 1.09–2.19]) in the discovery sample, adjusted P=0.018 (odds ratio: 1.64 [95% CI, 1.09–2.48]) in the replication sample, and adjusted P=2.52E‐04 (odds ratio: 1.59 [95% CI, 1.24–2.03]) in the combined sample. After resequencing all amino acid coding regions and untranslated regions of FGF12, 5 rare variations were identified. The result of western blotting revealed that a de novo functional variation, p.P211Q (1.84% of 163 patients with right ventricular outflow tract VT), could downregulate FGF12 expression significantly.ConclusionsIn this study, we observed that rs1460922 of FGF12 was significantly associated with VT and identified that a de novo variation of FGF12 may be an important genetic risk factor for the pathogenesis of VT.

P812Clinical validation of automatic local activation time annotation during idiopathic ventricular tachycardia ablation procedures

P812Clinical validation of automatic local activation time annotation during idiopathic ventricular tachycardia ablation procedures

MiR-320a as a Potential Novel Circulating Biomarker of Arrhythmogenic CardioMyopathy

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53 ± 0.04 fold expression difference in ACM vs. HC (p < 0.01). A similar trend was observed when comparing ACM (n = 13) and HC (n = 17) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78 ± 0.05 fold expression change vs. IVT (p = 0.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation.

Pulmonary artery: A pivotal site for catheter ablation in idiopathic RVOT ventricular arrhythmias.

In patients without associated myocardial diseases, characterized by left bundle branch block and inferior axis morphologies, repetitive idiopathic right ventricular tachycardias and ventricular premature contractions typically arise from right ventricular outflow tract (RVOT). Accumulated evidences have shown that radiofrequency catheter ablation is a useful treatment for patients with RVOT ventricular arrhythmias (VAs). Interestingly, several medical centers have shown that pulmonary artery (PA) is a potential novel site for catheter ablation in RVOT-like VAs, particularly in patients where termination of RVOT VAs at the usual site fails. In this review, we comprehensively demonstrated that RVOT VAs were successfully terminated at the site of PA, analyzed the characteristics of surface electrocardiogram and endocardial potentials, and explored the underlying mechanisms for these cases.

Years of palpitations and a heart rate of 213 beats per minute.

Key Clinical MessageBelhassen tachycardia is the most common idiopathic ventricular tachycardia arising from the left ventricle, classically characterized by a right bundle branch block and left axis deviation. Vigilance for Belhassen tachycardia is essential as intravenous verapamil has proven to be highly efficacious for treating symptomatic patients with this underlying arrhythmia.

Idiopathic left ventricular tachycardia following atrioventricular conduction block by rapid atrial tachycardia

Key Clinical MessageThe present case demonstrated a rare situation alternating between a repetitive atrial tachycardia (AT) and ventricular tachycardia (VT). A unique induction mechanism was noted in which the VT was induced after Wenckebach AV node conduction block following the repetitive rapid AT.

1154Clinical validation of automatic local activation time annotation during idiopathic ventricular tachycardia ablation procedures

1154Clinical validation of automatic local activation time annotation during idiopathic ventricular tachycardia ablation procedures

Conventional mapping and ablation of focal ventricular tachycardias in the healthy heart.

Ventricular tachycardias (VT) in the healthy heart, also known as idiopathic VTs, often have afocal origin. Triggered activity due to delayed after-depolarization is the most likely mechanism of focal VTs. Localization of the site of origin of focal VTs is based on activation mapping with or without combination with pace mapping. The characteristic anatomic site of origin of idiopathic VTs is the right and left outflow tract. Other sites include the tricuspid and mitral annulus, the papillary muscles, and Purkinje fibers. Catheter ablation is indicated for monomorphic symptomatic VT and can be an alternative to antiarrhythmic drugs. Success rates are high, but mapping and ablation can be challenging. We review the main electrophysiological findings and the important clues for ablation of focal VTs. Specific considerations for each location are considered.

Utility of Conventional Electrocardiographic Criteria in Patients With Idiopathic VentricularTachycardia.

This study sought to determine the ability of conventional electrocardiographic (ECG) criteria to correctly differentiate idiopathic ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrancy. Previously reported VT ECG criteria were developed from cohorts of patients with structural heart disease and have not been applied to patients with idiopathic VT. ECGs of 115 idiopathic VTs, 101 post-myocardial infarction (MI) VTs, and 111 wide QRS SVTs were analyzed using standard criteria. VT was diagnosed in patients when at least 1 criterion was met, SVT when no criteria were met, and indeterminate when there were conflicting criteria. Standard ECG criteria more frequently diagnosed VT in the post-MI group than the idiopathic group (95% vs. 82%, respectively; p< 0.01). Diagnosis in only 12 of the 111 SVT patients (11%) met the criteria for VT. All patients in the idiopathic VT group with right branch bundle block morphology who did not meet VT criteria demonstrated an rsR' pattern in V1 (consistent with SVT). Among idiopathic VT patients, Purkinje-associated VT had the lowest sensitivity for correct VT diagnosis in 13 of 23 patients (57%), septal sites of origin were correctly diagnosed in only 56 of 76 patients (74%), whereas nonseptal sites had a high sensitivity in 35 of 35 patients (100%; p< 0.005). Conventional ECG criteria have reduced sensitivity to distinguish VT from SVT with aberrancy in patients with idiopathic VT. This is most pronounced in VT originating from septal sites, particularly Purkinje sites and the septal outflow tract regions. Clinicians should be aware that application of conventional ECG criteria in idiopathic VT may underdiagnose VT.

The use of a novel signal analysis to identify the origin of idiopathic right ventricular outflow tract ventricular tachycardia during sinus rhythm: Simultaneous amplitude frequency electrogram transformation mapping.

IntroductionThe signal characteristics of intracardiac bipolar electrograms at the origin of idiopathic RVOT-VT during sinus rhythm remain unclear.ObjectiveThe study sought to develop a novel real-time/online technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to quantify and localize the diseased ventricular substrate in idiopathic RVOT-VT.MethodsWe retrospectively investigated the intracardiac bipolar recordings in 70 consecutive patients (26% male, mean age 42±12 years) who underwent successful radiofrequency catheter ablation of idiopathic RVOT-VT. We quantified the extent of the frequency fraction of ventricular potentials during sinus rhythm or ventricular pacing using a novel formula, the product of instantaneous amplitude and frequency, and showed that in a 3D geometry as an online SAFE-T map.ResultsThe characteristics of the HHT spectra of electrograms derived from VT origins demonstrated high frequency components (>70 Hz), which were independent of the rhythm. The density of the abnormal potentials at the VT origins were higher (VT origins, 7.5±2.3 sites/cm2 vs. surrounding myocardium, 1.5±1.3 sites/cm2, p<0.001), and were significantly decreased after ablation (0.7±0.6 sites/cm2, p<0.001). A small region of abnormal potentials were observed in the VT origins (mean area of 1.5±0.8 cm2). The SAFE-T maps predicted the VT origins with 92% sensitivity, 78% specificity with optimal cut-off value of >3.0 Hz·mV.ConclusionThe online SAFE-T map was feasible for quantifying the diseased ventricular substrate, irrespective of the rhythm of activation, and can be used to identify the optimal ablation targets for idiopathic RVOT-VT. We found a limited region of abnormal potentials where the RVOT-VT origins were successfully ablated.

Incidence of Idiopathic Ventricular Arrhythmias: A Population-Based Study.

Ventricular tachycardia and premature ventricular complexes (PVCs) most frequently occur in the context of structural heart disease. However, the burden of idiopathic ventricular arrhythmias (IVA) in the general population is unknown. We identified incident cases of IVA between 2005 and 2013 from Olmsted County, Minnesota, using the Rochester Epidemiology Project database. For PVC cohorts, we included those with frequent (defined as ≥100 PVC/24 hours) symptomatic PVCs. We defined IVA-associated cardiomyopathy as a drop in ejection fraction of ≥10% from baseline. Between 2005 and 2013, we identified 614 individuals with incident IVA (229 [37.3%] were male; average age was 52.1±17.2 years). Of these, 177 (28.8%) had idiopathic ventricular tachycardia, 408 (66.5%) had symptomatic PVCs, and 29 (4.7%) had IVA-associated cardiomyopathy. The age- and sex-adjusted incidence rates in 2005 to 2007, 2008 to 2010, and 2011 to 2013 were 44.9 per 100 000 (95% confidence interval [CI], 38.0-51.8), 47.6 per 100 000 (95% CI, 40.8-54.5), and 62.0 per 100 000 (95% CI, 54.4-69.6), respectively. In idiopathic ventricular tachycardia, there was an increase in incidence rate with ages (P<0.001) but not between sexes (P=0.12). The age-adjusted incidence of symptomatic PVC was higher in females than in males (46.2 per 100 000 [95% CI, 40.9-51.6] versus 20.5 per 100 000 [95% CI, 16.8-24.3]; P<0.001). The small number of individuals with IVA-associated cardiomyopathy precluded any formal testing. The incidence of IVA is increasing. Furthermore, overall incidence increases with age. Although the rate of idiopathic ventricular tachycardia is similar across sexes, women have a higher incidence of symptomatic PVC.

A De Novo Loss-of-Function Mutation in KCNJ6 Associated with Idiopathic Ventricular Tachycardia

A De Novo Loss-of-Function Mutation in KCNJ6 Associated with Idiopathic Ventricular Tachycardia

Fascicular Ventricular Arrhythmias: Pathophysiologic Mechanisms, Anatomical Constructs, and Advances in Approaches to Management.

Ventricular arrhythmias involving the fascicular system may be seen in both structurally normal and abnormal hearts. Idiopathic fascicular ventricular tachycardia represents almost 10% to 15% of idiopathic ventricular tachycardia related to the left ventricle.1,2 Cohen et al3 and subsequently Zipes et al4 first described these arrhythmias in the 1970s as relatively narrow right bundle left axis arrhythmias that arose close to the posterior fascicle and could be induced with atrial pacing. Belhassen et al5 later described the responsiveness of these arrhythmias to verapamil. Although initial studies focused on arrhythmias related to the left posterior fascicle, it is possible for arrhythmias to arise from any portion of the fascicular system and in both structurally normal and abnormal hearts. Furthermore, when approaching the patient presenting with arrhythmias arising from the His-Purkinje system, it is important to consider the unique complexities related to mapping and ablation. In this review, we will focus on the mechanisms of such arrhythmias, relevant embryology, anatomy and physiology, and approaches to management in both the presence and absence of other structural heart disease. Broadly, fascicular ventricular tachycardia in the absence of other structural heart disease will be termed idiopathic fascicular ventricular tachycardia (IFVT), whereas that related to structural disease will be discussed in the context of the relevant disease state. Generally, IFVT is separated into 3 types—left posterior fascicular with a right bundle branch block pattern and left axis deviation, left anterior with a right bundle branch block and right axis deviation pattern, and left upper septal fascicular with a narrow QRS and normal axis but often with a right bundle branch block morphology. There are rare reported cases of left bundle branch block pattern, V3–V4 transition IFVT with a normal axis arising from the right bundle branch. In …

Idiopathic Polymorphic Ventricular Tachycardia: a "Benign Disease" with a Touch of Bad Luck?

Ventricular extrasystole originating from the right ventricular outflow tract or the left ventricular outflow tract are the most commonly encountered ventricular arrhythmias recorded in ostensibly healthy individuals with no evidence of heart disease. These ventricular arrhythmias have a distinctive electrocardiographic morphology. The morphology is so distinctive that it is common practice to accept the diagnosis of “idiopathic benign ventricular arrhythmias from the outflow tract” based on this unique morphology when the electrocardiogram during sinus rhythm and the echocardiogram are normal, sometimes removing the need to perform invasive tests in patients. Even if the outflow ventricular extrasystole ultimately triggers sustained ventricular arrhythmia, the resulting ventricular tachycardia (VT) will be a monomorphic VT originating from the outflow tract, which is known to be hemodynamically well tolerated. Thus, idiopathic ventricular arrhythmias originating from outflow tracts are universally considered benign. In 2005, we described a rare form of malignant polymorphic VT resulting in syncope or cardiac arrest. Here, we review the literature on this topic since the emergence of initial descriptions of this intriguing phenomenon.

Bundle Branch Re-Entrant VentricularTachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia.

This study sought to investigate for an underlying genetic etiology in cases of apparent idiopathic bundlebranch re-entrant ventricular tachycardia (BBRVT). BBRVT is a life-threatening arrhythmia occurring secondary to macro-re-entry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated,unexplained conduction system disease. Cases of BBRVT with normal biventricular size and function were recruited from 6 North American centers. Enrollment required a clinically documented wide complex tachycardia and BBRVT proven during invasive electrophysiology study. Study participants were screened for mutations within genes associated with cardiac conductionsystem disease. Pathogenicity of identified mutations was evaluated using in silico phylogenetic and physicochemical analyses and invitro biophysical studies. Among 6 cases of idiopathic BBRVT, each presented with hemodynamic compromise and 2 suffered cardiac arrests requiring resuscitation. Putative culprit mutations were identified in 3 of 6 cases, including 2 in SCN5A (Ala1905Gly [novel] and c.4719C>T [splice site mutation]) and 1 in LMNA (Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly Nav1.5 channels in tsA201 cells revealed significantly reduced peak current density and positive shiftsin the voltage-dependence of activation, consistent with a loss-of-function. The SCN5A c.4719C>T splice sitemutation has previously been reported as disease-causing in 3 cases of Brugada syndrome, whereas the novel LMNA Leu327Val mutation was associated with a classic laminopathy phenotype. Following catheter ablation, BBRVT was noninducible in all cases and none experienced a clinical recurrence during follow-up. Our investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening arrhythmia, providing further insight into its underlying pathophysiology and emphasizing a potentialrole for genetic testing in this condition. Our findings also highlight BBRVT as a novel genetic etiology ofunexplainedsudden cardiac death that can be cured with catheter ablation.

The Role of Intravenous Dopamine on Hemodynamic Support during Radiofrequency Catheter Ablation of Poorly Tolerated Idiopathic Ventricular Tachycardia.

Background and ObjectivesHemodynamically unstable idiopathic ventricular tachycardias (VTs) are a challenge for activation or entrainment mapping technique. Mechanical circulatory support is an option, but is not always readily available. In this study, we investigated the safety and efficacy of hemodynamic support using intravenous (IV) dopamine solely during radiofrequency catheter ablation (RFCA) of hemodynamically unstable VT.Subjects and MethodsSeven out of 86 patients with hemodynamically unstable idiopathic VT underwent de novo RFCA using dopamine in our single center. They were included in the study and reviewed retrospectively to investigate the procedural characteristics and outcomes.ResultsAll patients were male, and the mean age was 50.7±5.3 years. One patient had implantable cardioverter-defibrillator for the secondary prevention. No evidence of myocardial ischemia was found in all patients. During the procedure, the mean blood pressure during VT without dopamine was 52.3±4.1 mmHg and increased to 82.6±3.8 mmHg after administering dopamine (Δ28.8±3.2 mmHg; total average dopamine dosage was 1266.1±389.6 mcg/kg). In all patients, activation mapping was safely applied, and VTs were terminated during energy delivery. Non-inducibility of clinical VT was achieved in all cases. There was no evidence of deterioration due to hypoperfusion during the peri-procedural period. No recurrence of ventricular tachyarrhythmias was observed in any of the patients, during a median follow-up of 23.0±6.1 months.ConclusionHemodynamic support using IV dopamine during RFCA of hemodynamically unstable idiopathic VT facilitated detailed mapping to guide successful ablation.