What Is the Real Identity of the Mysterious Potential P1, and What Is the Most Important Segment of the Fascicular Ventricular Tachycardia Circuit?

In 1845, Johannes Evangelista Purkinje (Purkyně) discovered gelatinous fibers in the ventricular subendocardium. Later, they were called Purkinje fibers.1 However, he could not determine the function of that strange tissue and thought it was muscular. In 1906, Sunao Tawara finally described its function as the conducting system (Figure).2 In the last 3 decades, there has been rapid progress in the treatment of ventricular arrhythmias, and the Purkinje system has been found to be responsible for the mechanism of some ventricular tachyarrhythmias. These ventricular tachyarrhythmias can be called Purkinje-related arrhythmias and are manifested as monomorphic ventricular tachycardia (VT) and polymorphic VT, including ventricular fibrillation

Purkinje Arrhythmia Origin Made Easy

Tachycardia originating from the fascicles or His-Purkinje 1 system includes a wide spectrum of arrhythmias such as ventricular fibrillation (VF) and ventricular tachycardia (VT) which could be monomorphic or polymorphic with various substrates, locations and mechanisms.1 The most common type of reentrant fascicular tachycardia is left posterior fascicular VT (LPF-VT) which was recognized as an electrocardiographic entity by Zipes et al.2 who defined its diagnostic triad as following: (1) induction with atrial pacing, (2) right bundle branch block (RBBB) and a left-axis configuration, and (3) manifestation in patients without structural heart disease. In 1981, Belhassen et al.3 reported verapamil sensitivity, as a fourth identifying feature of this tachycardia

Kaplan–Meier survival analysis and Cox regression analyses regarding right ventricular septal pacing: Data from Japanese pacemaker cohort

AbstractThe presented data were obtained from 982 consecutive patients receiving their first pacemaker implantation with right ventricular (RV) lead placement between January 2008 and December 2013 at two centers in Japan. Patients were divided into RV apical and septal pacing groups. Data of Kaplan–Meier survival analysis and Cox regression analysis are presented. Refer to the research article “Implications of right ventricular septal pacing for medium-term prognosis: propensity-matched analysis” (Mizukami et al., in press) [1] for further interpretation and discussion

National survey of catheter ablation for atrial fibrillation: The Japanese catheter ablation registry of atrial fibrillation (J-CARAF)

AbstractTo assess the current status of atrial fibrillation (AF) ablation in Japan, the Japanese Heart Rhythm Society (JHRS) instituted a national registry, the Japanese Catheter Ablation Registry of AF (J-CARAF).MethodsUsing an online questionnaire, the JHRS invited electrophysiology centers in Japan to voluntarily and retrospectively register data regarding the AF ablation procedures performed in September, 2011.ResultsA total of 128 centers submitted data regarding AF ablation procedures in 932 patients (age 62.1±10.4 years; male 76.8%; paroxysmal AF 65.7%, CHADS2 score 1.0±1.0). The majority received oral anticoagulant therapy during and following the procedure (68.9% and 97.5%, respectively). Pulmonary vein isolation (PVI) was performed in 97.5% of the patients; ipsilateral encircling PVI was the preferred technique (79.7%). Three-dimensional (3D) mapping systems and irrigated-tip catheters were used in 94.8% and 87.7% of the procedures, respectively. Ablation methods other than PVI were performed in 78.8% of all the patients and 73.5% of the patients with paroxysmal AF. Acute complications were reported in 6.2% of the patients, but no early deaths were recorded.ConclusionsIpsilateral encircling PVI, using 3D mapping and irrigated-tip catheters, is the standard AF ablation method in Japan. However, adjunctive ablations were performed frequently, even in patients with paroxysmal AF

Thoracic Epidural Anesthesia Can Be Effective for the Short‐Term Management of Ventricular Tachycardia Storm

Background Novel therapies aimed at modulating the autonomic nervous system, including thoracic epidural anesthesia (TEA), have been shown in small case series to be beneficial in treating medically refractory ventricular tachycardia (VT) storm. However, it is not clear when these options should be considered. We reviewed a multicenter experience with TEA in the management of VT storm to determine its optimal therapeutic use.Methods and Results Data for 11 patients in whom TEA was instituted for VT storm between July 2005 and March 2016 were reviewed to determine the clinical characteristics, outcomes, and role in management. The clinical presentation was incessant VT in 7 (64%), with polymorphic VT in 3 (27%) and monomorphic VT in 8 (73%). The underlying conditions were nonischemic cardiomyopathy in 5 (45%), ischemic cardiomyopathy in 3 (27%), and hypertrophic cardiomyopathy, Brugada syndrome, and cardiac lipoma in 1 (9%) each. Five (45%) had a complete and 1 (9%) had a partial response to TEA; 4 of the complete responders had incessant VT. All 4 patients with a documented response to deep sedation demonstrated a complete response to TEA.Conclusions More than half of the patients with VT storm in our series responded to TEA. TEA may be effective and should be considered as a therapeutic option in patients with VT storm, especially incessant VT, who are refractory to initial management. Improvement in VT burden with deep sedation may suggest that sympathoexcitation plays a key role in perpetuating VT and predict a positive response to TEA

Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism

Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process

Sodium Channelopathy Underlying Familial Sick Sinus Syndrome With Early Onset and Predominantly Male Characteristics

Background-Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identifcation of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity. Methods and Results-We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identifed 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was signifcantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P<0.001) or nonfamilial SSS (74.3±0.4 years; n=538; P<0.001). Meta-analysis of SSS probands carrying SCN5A mutations (n=29) indicated profound male predominance (79.3%) resembling Brugada syndrome but with a considerably earlier age of onset (20.9±3.4 years). Conclusions-The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations

Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome.

BACKGROUND: The right ventricular outflow tract (RVOT) is acknowledged to be responsible for arrhythmogenesis in Brugada syndrome (BrS), but the pathophysiology remains controversial. OBJECTIVES: This study assessed the substrate underlying BrS at post-mortem and in vivo, and the role for open thoracotomy ablation. METHODS: Six whole hearts from male post-mortem cases of unexplained sudden death (mean age 23.2 years) with negative specialist cardiac autopsy and familial BrS were used and matched to 6 homograft control hearts by sex and age (within 3 years) by random risk set sampling. Cardiac autopsy sections from cases and control hearts were stained with picrosirius red for collagen. The RVOT was evaluated in detail, including immunofluorescent stain for connexin-43 (Cx43). Collagen and Cx43 were quantified digitally and compared. An in vivo study was undertaken on 6 consecutive BrS patients (mean age 39.8 years, all men) during epicardial RVOT ablation for arrhythmia via thoracotomy. Abnormal late and fractionated potentials indicative of slowed conduction were identified, and biopsies were taken before ablation. RESULTS: Collagen was increased in BrS autopsy cases compared with control hearts (odds ratio [OR]: 1.42; p = 0.026). Fibrosis was greatest in the RVOT (OR: 1.98; p = 0.003) and the epicardium (OR: 2.00; p = 0.001). The Cx43 signal was reduced in BrS RVOT (OR: 0.59; p = 0.001). Autopsy and in vivo RVOT samples identified epicardial and interstitial fibrosis. This was collocated with abnormal potentials in vivo that, when ablated, abolished the type 1 Brugada electrocardiogram without ventricular arrhythmia over 24.6 ± 9.7 months. CONCLUSIONS: BrS is associated with epicardial surface and interstitial fibrosis and reduced gap junction expression in the RVOT. This collocates to abnormal potentials, and their ablation abolishes the BrS phenotype and life-threatening arrhythmias. BrS is also associated with increased collagen throughout the heart. Abnormal myocardial structure and conduction are therefore responsible for BrS