Takayuki Tsuneda

Vagal Activity Modulates Spontaneous Augmentation of ST Elevation in the Daily Life of Patients with Brugada Syndrome

Introduction: In Brugada syndrome, ventricular fibrillation (VF) occurs mainly during sleep, and Brugada ECG signs are intensified by parasympathomimetic drugs; therefore, vagal activity could be a precipitating factor of VF. The aim of the present study was to elucidate the relation between spontaneous augmentation of ST elevation and changes in autonomic nervous activities in the daily life of patients with Brugada syndrome.

Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm.

The aim of this study was to investigate the efficacy and safety of bepridil (a multichannel blocker including several potassium channels) for conversion of long-lasting atrial fibrillation (AF). Bepridil restored sinus rhythm alone or in combination with aprindine in 69% of 32 patients with persistent AF lasting > or = 3 months. The time to conversion after starting bepridil was 30 +/- 12 days. An increase in fibrillation cycle length with bepridil was greater in responders (31 +/- 10%), but an increase in QTc did not differ between responders and nonresponders. Bepridil is effective and safe for terminating long-lasting persistent AF.

Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction

Effects of enalapril on a canine model of atrial pacing-induced atrial fibrillation (AF) with rapid ventricular responses were determined. Methods: Four weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial effective refractory period (ERP), P-wave width, duration of AF, and left ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length was determined by spectral analyses of fibrillation waves. Quantitative analysis of histology was added. Results: After 4 weeks of pacing, P-wave width was longer in Group I than in Group II, and the duration of induced AF was significantly longer in Group I (59.6 ± 66.3 seconds) than in Group II (3.6 ± 3.4 seconds, P < 0.05). AF cycle length was longer in Group I than in Group II despite similar shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was not different between the two groups. LVEF similarly decreased in both groups. Interstitial fibrosis and expression of connexin43 was greater in Group I than in Group II (interstitial fibrosis, 9.2 ± 8.4 versus 1.9 ± 2.1%, P < 0.05; connexin43, 5.3 ± 2.2 versus 1.1 ± 1.1%, P < 0.05). Conclusions: Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis, connexin43 over-expression and conduction delay.

Repolarization dynamics in patients with idiopathic ventricular fibrillation : Pharmacological therapy with bepridil and disopyramide

The electrocardiographic parameters relating occurrence of ventricular fibrillation (VF) episodes in patients with idiopathic VF (IVF) are still unknown. The aim of this study was to clarify efficacy of pharmacological therapy in patients with IVF with respect to repolarization dynamics. The study group consisted of 8 men (age 43.6 ± 9.1 years) with IVF (Brugada type 5 patients, prominent J wave in the inferior leads 3 patients) who had documented spontaneous episodes of VF, 7 of whom had implantable cardioverter defibrillators. The relation between QT and RR interval was analyzed from 24-hour Holter ECG using an automatic analyzing system before and after pharmacological therapy (bepridil 5 and disopyramide 3). From QT-RR linear regression lines, QT intervals were determined at RR intervals of 0.6 second [QT(0.6)], 1.0 second [QT(1.0)], and 1.2 seconds [QT(1.2)]. Pharmacological therapy increased the slope of QT-RR regression line from 0.105 ± 0.020 to 0.144 ± 0.037 (P < 0.05). Accordingly, QT(1.0) and QT(1.2) became longer after drug therapy [QT(1.0), 0.382 ± 0.016 seconds vs 0.414 ± 0.016 seconds (P < 0.01); QT(1.2), 0.403 ± 0.017 seconds vs 0.442 ± 0.021 seconds (P < 0.01)]. However, QT(0.6) did not change after drug administration. Before drug therapy the average episodes of VF were 5.5 ± 5.8 (range 1 to17) during the observation period of 19.3 ± 17.6 months (range 6 to 60 months). After drug therapy, 6 patients had no episode of VF for 24 to 120 months (66.0 ± 38.5 months). Two patients had a single episode of VF for 12- and 96-month follow-ups. Pharmacological therapy decreased the frequency of VF episodes in association with prolongation of QT intervals at slower heart rates. Not only J wave and ST elevation but also shorter QT intervals at slower heart rates may represent an electrophysiological substrate for development of VF episodes in these specific IVF patients.

Vagal activity modulates spontaneous augmentation of J-wave elevation in patients with idiopathic ventricular fibrillation

BACKGROUND Although J-wave elevation in the inferolateral leads could be related to idiopathic ventricular fibrillation (IVF), little is known about the pathophysiologic characteristics of J-wave elevation in patients with IVF. OBJECTIVE This study aimed to determine the relationship between augmentation of J-wave elevation and changes in RR interval or autonomic nervous activities in patients with IVF. METHODS Eight patients with IVF and 22 controls with J-wave elevation (≥0.1 mV) in lead V5 were studied. The J-wave amplitude was automatically measured in lead CM5 of a digital Holter electrocardiogram, and the J-RR relationship was determined. Based on the analysis of heart rate variability, the relationship between the J-wave amplitude and the natural logarithm of high-frequency (HF) components (J-ln HF relationship) or the ratio of low frequency (LF) components to HF components (J-LF/HF relationship) was also determined. RESULTS The J-RR slope (mm/s) was greater in patients with IVF than in controls (3.5 ± 0.7 vs 2.4 ± 0.8; P <.01), as was J-wave amplitude (mm) at an RR interval of 1.2 seconds (2.8 ± 0.9 vs 2.0 ± 0.6; P <.05). The J-wave amplitude was correlated positively with ln HF and negatively with LF/HF, and the slopes of both J-ln HF and J-LF/HF regression lines were greater in patients with IVF than in controls. During an entire 24-hour period, there was no difference between the 2 groups in either HF or LF/HF. Nine of the total 11 episodes (82%) of spontaneous ventricular fibrillation occurred between 18:00 and 6:00. CONCLUSIONS In patients with IVF as compared with control subjects, J-wave elevation was more strongly augmented during bradycardia and was associated with an increase in vagal activity. This could be related to the occurrence of ventricular fibrillation predominantly at night in patients with IVF.

Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.

Introduction: We evaluated the characteristics of QT‐RR and QaT (apex of T wave)‐RR relationships in patients with idiopathic ventricular fibrillation (IVF) compared with control subjects. We hypothesized that IVF patients have unique repolarization dynamics related to a reduced fast Na current and a prominent transient outward current.

Canine Model of Brugada Syndrome Using Regional Epicardial Cooling of the Right Ventricular Outflow Tract

Introduction: Myocardial cooling can induce J point elevation (Osborn wave) as seen on ECG of the Brugada syndrome by activating transient outward current (Ito) and causing a spike‐and‐dome configuration of the monophasic action potential (MAP) in the ventricular epicardium in isolated canine ventricular wedge preparations. We determined the effect of regional epicardial cooling of the right ventricular outflow tract (RVOT) on surface ECG and ventricular vulnerability in the dog.

Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.

Postprandial augmentation of bradycardia-dependent ST elevation in patients with Brugada syndrome.

Introduction : In patients with Brugada syndrome, the circadian variation of ST elevation could be modulated by the autonomic nervous activity and RR interval. Recently, glucose‐induced insulin secretion was also reported to contribute to fluctuation of ST elevation. Therefore, we assessed the effects of taking meals on the ST‐RR relationship in the daily life of patients with Brugada syndrome.

New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome

Objectives: To introduce a nomogram of the normal QT interval at various heart rates measured from 24 hour Holter ECG recordings in healthy subjects with respect to age and sex and to use the nomogram to characterise dynamic changes in QT interval in patients with idiopathic ventricular fibrillation (IVF) and the long QT syndrome (LQT). Methods: The study group consisted of 422 subjects: 249 healthy men ranging in age from 21–88 years (mean (SD) 47 (20) years) and 173 healthy women ranging in age from 21–85 years (47 (19) years). In addition, seven men with IVF ranging in age from 33–53 years (43 (9) years) and five women with LQT ranging in age from 20–55 years (37 (14) years) were studied. For each subject, QT interval and heart rate were determined automatically from 24 hour Holter ECG digital data—namely, QT interval was measured from signal averaged ECG waves obtained by averaging consecutive sinus beats during each 15 second period over 24 hours. Data were grouped and averaged at an interval of 5 beats/min for heart rates ranging from 46–120 beats/min. Results: In healthy subjects aged < 50 years and ⩾ 50 years QT intervals were longer in women than in men. QT intervals were longer in both men and women aged ⩾ 50 years than in ages < 50 years. From these findings a nomogram of QT interval at varying heart rates adjusted for age (younger group aged < 50 years or older group aged ⩾ 50 years) and sex was determined. In patients with IVF, QT intervals were significantly shorter at slower heart rates than normal values obtained from the nomogram. In patients with LQT, QT intervals were significantly longer at both faster and slower heart rates than normal values. Conclusions: The nomogram of QT interval at varying heart rates adjusted for sex and age could be used to assess dynamic changes of QT interval of various pathological conditions. For example, patients with IVF had shorter QT interval at slower heart rates, a finding suggestive of arrhythmogenicity of this specific syndrome at night. Patients with LQT had prolonged QT interval at specific heart rate ranges depending on their genotype.