Satoki Fukae

Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization

Background— Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. Methods and Results— This study included 50 patients (44 men; age, 45±17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. Conclusions— We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

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 identification 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 identified 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 significantly 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.

Ventricular Fibrillation in a Patient with Prominent J Wave in the Inferior and Lateral Electrocardiographic Leads After Gastrostomy

We describe the case of a 39‐year‐old man who experienced a ventricular fibrillation storm related to a prominent J wave in the inferior and lateral electrocardiographic leads on the day after gastrostomy. The J wave slowly decreased after amiodarone therapy (400 mg/day) was started, and ventricular fibrillation disappeared.

A Patient with LQTS in Whom Verapamil Administration and Permanent Pacemaker Implantation Were Useful for Preventing Torsade de Pointes

A 21‐year‐old woman with long QT syndrome and missense mutation in HERG (T613M), suffered from repeated attacks of pause dependent torsade de pointes, even though she was given β‐blockers and underwent stellate ganglion block twice at the age of eight. After she received permanent pacemaker implantation and administration of verapamil, no premature beats or pause dependent torsade de pointes was observed. (PACE 2004; 27:123–124)

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC.

Effects of Intravenous Nifekalant, A Class III Antiarrhythmic Drug, on Atrial Vulnerability Parameters in Patients with Paroxysmal Atrial Fibrillation

Nifekalant, a class III antiarrhythmic drug, has been shown to suppress ventricular tachyarrhythmias, but its effects on AF are unclear. The aim of this study was to clarify the effects of nifekalant on the atrial vulnerability parameters in patients with paroxysmal AF. The study included 18 patients with paroxysmal AF who underwent electrophysiological study before and after intravenous infusion of nifekalant. The atrial electrophysiological parameters including the atrial effective refractory period (AERP), maximum intraatrial conduction delay, and wavelength index, calculated as the ratio of AERP to the maximum conduction delay, were quantitatively measured at baseline and during nifekalant infusion. The mean AERP was significantly prolonged from 214 ± 27 ms at baseline to 242 ± 39 ms after nifekalant (P < 0.001). Although earlier studies have shown that nifekalant does not affect the atrial conduction time, the mean maximum conduction delay of the study patients was significantly prolonged from 59 ± 19 ms at baseline to 72 ± 28 ms after nifekalant (P = 0.015). There was no significant difference in the wavelength index at baseline (4.1 ± 1.7) and after nifekalant (4.1 ± 2.5). However, when the differences of AERP and wavelength index were defined as each parameter during nifekalant infusion minus that at baseline, the difference of AERP showed a direct positive correlation with that of the wavelength index (P = 0.013). In conclusion, nifekalant may be effective in the prevention of AF due to prolongation of the AERP. However, in those patients who have a lesser degree of prolongation of the AERP by nifekalant, the wavelength index tended to be decreased, suggesting that the drug might augment the propensity for AF. (PACE 2004; 27:212–217)

Rivaroxaban therapy resulting in the resolution of right atrial thrombosis resistant to ordinary control with warfarin in a patient with atrial fibrillation.

A 72-year-old man with non-valvular atrial fibrillation and metastatic liver and lung cancer after surgery for colon cancer developed thrombosis in the right atrium one month after decreasing the dose of warfarin due to the introduction of double anti-platelet therapy for coronary stent implantation. Restoring the warfarin dose with ordinary control for two months did not result in any changes in the size of the thrombus; however, the subsequent substitution of rivaroxaban (oral treatment with a direct Factor Xa inhibitor) for warfarin ultimately resolved the thrombosis.

Angiotensin‐Converting Enzyme Inhibitor Suppresses the Incidence of Prolonged and Fractionated Right Atrial Electrograms

Introduction: Although prolonged and fractionated right atrial electrograms have been reported as predictors of the development of chronic atrial fibrillation in patients with paroxysmal atrial fibrillation (PAF), the effects of angiotensin‐converting enzyme inhibitor (ACEI) on these electrophysiologic abnormalities remain unknown. The purpose of this study was to evaluate whether ACEI influences these electrophysiologic abnormalities of atrial muscle in patients with PAF.

Postural Orthostatic Tachycardia in a Patient with Type 2 Diabetes with Diabetic Neuropathy

A 24-year-old Japanese man with type 2 diabetes mellitus and diabetic neuropathy was admitted to our ward to evaluate the cause of orthostatic intolerance. During a head-up tilt test, his heart rate increased from 105 to 155 beats/minute within 3 minutes, and chest discomfort began. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), and orthostatic intolerance disappeared after β-blocker treatment. Scintigraphy using 123I-metaiodobenzylguanidine showed decreased cardiac uptake. Power spectral analysis of heart rate variability for 24 hours in Holter electrocardiography demonstrated decreases in both sympathetic and parasympathetic nervous system activities, with a greater decrease in parasympathetic activity than sympathetic activity. The relative sympathetic hyperactivity in the present patient with diabetic neuropathy seemed to be related to POTS.

Successful treatment for various arrhythmias in an older patient treated with pilsicainide for paroxysmal supraventricular tachycardia

Yuishin Izumi, Hiroyuki Morino, Ryosuke Miyamoto, Yukiko Matsuda, Ryosuke Ohsawa, Takashi Kurashige, Yoshimitsu Shimatani, Ryuji Kaji and Hideshi Kawakami Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan Department of Epidemiology, Research Institute for Radiation Biology & Medicine, Hiroshima University, Hiroshima, Japan Department of Neurology, National Hospital Organization Kure Medical Center, Hiroshima, Japan Department of Neurology, Tokushima Prefectural Central Hospital, Tokushima, Japan References