Jotaro Iwamoto

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.

Tranilast Prevents Atrial Remodeling and Development of Atrial Fibrillation in a Canine Model of Atrial Tachycardia and Left Ventricular Dysfunction

OBJECTIVES This study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model. BACKGROUND Tranilast inhibits transforming growth factor (TGF)-β1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear. METHODS Beagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses. RESULTS Atrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-β1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-β1, 1.28 ± 0.20, p < 0.05 vs. control). CONCLUSIONS Tranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-β1 and Rac1 overexpression may contribute to its antiremodeling effects.

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.

Early repolarization in Wolff-Parkinson-White syndrome: prevalence and clinical significance.

AIMS Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. METHODS AND RESULTS One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P < 0.005 and 42 ± 11 vs. 34 ± 9 ms, P < 0.001, respectively). CONCLUSION In patients with WPW syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.

Recurrent syncope in two patients with a sigmoid-shaped interventricular septum and no left ventricular hypertrophy.

Sigmoid‐shaped interventricular septum (SIS) is not uncommon in elderly patients and is considered a normal part of the aging process. However, several patients have been reported to have clinical symptoms due to the narrowing of the left ventricular outflow tract (LVOT). Two patients with SIS presented with recurrent episodes of syncope after drinking or taking sublingual nitroglycerin (NG). In both patients, a head‐up tilt test involving provocation with alcohol, NG, or isoproterenol induced the vasovagal reflex along with an increase in the pressure gradient between the apex and LVOT. The patients experienced no further episodes of syncope after initiating bisoprolol treatment. In patients with SIS, induction of the vasovagal reflex via an increase in left ventricular (LV) pressure due to LVOT obstruction concomitant with increased LV construction is a potentially important cause of syncope, which may be effectively prevented by beta‐blockers.

N-(3,4-DIMETHOXYCINNAMOYL) ANTHRANILIC ACID PREVENTS CANINE ATRIAL FIBRILLATION ASSOCIATED WITH TACHYCARDIA-INDUCED CARDIOMYOPATHY

Results: In CTL dogs, 4 weeks of ATP increased the duration of AF (from 0.3±0.2 to 40±6 sec, P<0.01), and decreased atrial effective refractory period (ERP, from 161±7 to 95±6 ms at basic cycle length 300 ms, P<0.01). Tranilast therapy attenuated ATP effects on the duration of AF (3.0±0.4 sec , P<0.01), without affecting ERP (106±4 ms, NS). ATP impaired hemodynamic parameters in CTL dogs (left ventricular ejection fraction: from 58±5 to 24±2%, P<0.01, left atrial area: from 311±17 to 456±39 mm2, P<0.01), and increased atrial fibrosis (CTL 10.2±2.8 vs. Sham 0.6±0.1%, P<0.01). Tranilast suppressed ATP-induced atrial fibrosis (1.7±0.6%, P<0.01) without affecting left ventricular ejection fraction (29±3%, NS) and left atrial area (394±19 mm2, NS). Conclusions: Tranilast suppresses AF perpetuation in a canine model of AF by preventing atrial structural remodeling. Anti-inflammatory effects of tranilast may play an important role in the prevention of atrial structual remodeling.