Takao Katoh

Long-term treatment with antipsychotic drugs in conventional doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease.

AbstractObjective: The aim of this study was to examine the hypothesis that long-term treatment with antipsychotic drugs in conventional doses prolongs QTc dispersion and increases ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. Methods: We measured QTc and QTc dispersion and ventricular tachyarrhythmias in 64 patients with schizophrenia, including 59 patients who received psychiatric medications, and five patients who did not receive psychiatric medications, and 45 healthy volunteers. None of the subjects had a history of cardiac disease or showed any abnormality in chest radiograph and transthoracic echocardiographic studies. None of the subjects had electrolyte abnormality. None of the subjects were taking drugs known to influence the QT interval, other than psychiatric medications. Results: QTc and QTc dispersion were significantly (P < 0.017) increased in patients who received psychiatric medications compared with patients who did not receive psychiatric medications, or with healthy volunteers [QTc: 0.442 (0.029), 0.418 (0.029), 0.417 (0.028) s, QTc dispersion: 0.054 (0.013), 0.038 (0.017), 0.038 (0.009) s]. Daily ventricular premature beats were 183 (689), 77 (23), and 86 (149), respectively. No ventricular tachycardia was observed. There were no correlation between QTc and QTc dispersion and ventricular premature beats. Conclusion: Long-term treatment with antipsychotic drugs in conventional doses prolonged both QTc and QTc dispersion in patients with schizophrenia, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. However, despite the negative findings, ventricular tachyarrhythmias may occur as a rare side-effect of antipsychotic drugs, particularly if a patient has additional risk factors.

Bortezomib therapy‐related lung disease in Japanese patients with multiple myeloma: Incidence, mortality and clinical characterization

Because of the potentially high mortality rate (6.5%) associated with bortezomib‐induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health‐care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular‐targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population.

Prediction of atrial fibrillation after ischemic stroke using P-wave signal averaged electrocardiography

BACKGROUND Atrial fibrillation (AF) is highly prevalent in patients with ischemic stroke, but the diagnosis is often difficult. METHODS This study consisted of 68 stroke patients in sinus rhythm without history of AF. All patients underwent P-wave signal-averaged electrocardiography (P-SAECG), echocardiography, 24-h Holter monitoring, and measurement of plasma B-type natriuretic peptide (BNP) concentrations at admission. RESULTS An abnormal P-SAECG was found in 34 of 68 stroke patients. In the follow-up period of 11 ± 4 months, AF developed in 17 patients (AF group). The remaining 51 patients were classified as the non-AF group. The prevalence of atrial late potentials (ALP) on P-SAECG, and the number of premature atrial contractions (PACs) were significantly higher in the AF group than those in the non-AF group (88.2% vs 37.3%; p<0.001, 149 ± 120 vs 79 ± 69; p=0.030, respectively). However, there were no significant differences in age, left atrial dimension, or BNP concentrations between both groups. Cox proportional hazards analysis revealed that the presence of ALP (risk ratio 11.15; p=0.002) and frequent PACs (more than 100/24h) (risk ratio 4.53; p=0.007) had significant correlation to the occurrence of AF. CONCLUSIONS ALP may be a novel predictor of AF in stroke patients. P-SAECG should be considered in stroke of undetermined etiology.

Efficacy and Safety of Intravenous Amiodarone Infusion in Japanese Patients with Hemodynamically Compromised Ventricular Tachycardia or Ventricular Fibrillation

Introduction: Amiodarone infusion has been recommended for life‐threatening ventricular arrhythmias. However its effectiveness in Japanese patients has not yet been determined.

The cellular electrophysiologic mechanism of the dual actions of disopyramide on rabbit sinus node function.

To determine the contribution of disopyramides suggested opposing direct depressant and indirect acceleratory actions on sinus node function, we studied the effects of disopyramide, 1 x 10‐7 to 1 X 10‐4 M, on isolated rabbit sinus node preparations using standard microelectrode techniques. Transmembrane potentials were recorded simultaneously from the sinus node and adjoining crista terminalis area. Disopyramide, as much as 1 x 10‐5 M, had no effects on the sinus cycle length. At a concentration of 1 x 10-4 M, sinus cycle length was significantly prolonged due to prolongation of the sinus nodal action potential duration. During cholinergic blockade with atropine, 1 x 10-6M, disopyramide, x 10-7to 1 x i0-4 M, significantly prolonged sinus cycle length as a result of a prolongation of the sinus nodal action potential duration and a decrease of the slope of phase 4 depolarization. During cholinergic stimulation with carbamyl choline, 1 x 10-9 M, disopyramide, 1 x 10- to 1 x 10-6M, tended to reverse carbamyl choline-induced prolongation of the sinus cycle length (NS). This acceleratory action of disopyramide was caused by a significant increase of the slope of phase 4 depolarization. Disopyramide, 1 x 0-7 to 1 x 10-4 M, had no significant effects on corrected sinus node recovery time or on sinoatrial conduction time under any conditions studied. We conclude that disopyramide has a direct depressant action on normal sinus node cells at the upper therapeutic and toxic levels, which is enhanced during cholinergic blockade, and that disopyramides acceleratory action appears only at much lower concentrations and only during cholinergic stimulation.

Electrocardiographic and Electrophysiological Characteristics of Atrial Fibrillation Organized Into Atrial Flutter by Oral Administration of Class I Antiarrhythmic Agents

OHMURA, K., et al. Electrocardiographic and Electrophysiological Characteristics of Atrial Fibrillation Organized Into Atrial Flutter by Oral Administration of Class I Antiarrhythmic Agents. The aim of this study was to evaluate the electrocardiographic (ECG) and electrophysiological characteristics of atrial fibrillation (AF) that organized into atrial flutter during oral administration of class I antiarrhythmic agents. The former clinical study included 72 consecutive patients (58 paroxysmal AF, 14 persistent AF) in whom class I antiarrhythmic agents were orally administered in the outpatient clinic for termination or prophylaxis of AF. The clinical background and ECG variables were compared between the patients with and without atrial flutter during class I antiarrhythmic agents therapy. An electrophysiological study was performed in ten patients with paroxysmal AF (five with [group A] and five without atrial flutter [group B] during oral class I antiarrhythmic agents therapy. Local electrograms from five different atrial sites (high and low right free wall, high and low septum, and distal coronary sinus) were analyzed during induced AF. The activation pattern of the right free wall during AF was also analyzed using a Halo catheter. Atrial flutter was documented during class I antiarrhythmic agents therapy in 14 (24%) patients with paroxysmal AF, whereas in none with persistent AF. The mean cycle length (f‐f interval) and amplitude of the fibrillation waves in leads II and V1 from the surface ECG were significantly greater in the patients with than in those without atrial flutter. In the electrophysiological study, the mean cycle lengths for the low and high right free wall were significantly longer in group A than in group B, whereas those for the low septums and distal coronary sinus did not differ between the two groups. During the induced AF, the ratio of time exhibiting a consistent activation pattern (cranio‐caudal, caudo‐cranial, or undetermined) along the right free wall was significantly greater in group A than in group B. Atrial flutter newly developed during class I antiarrhythmic agents therapy in patients with coarse AF on the surface ECG and a relatively organized activation in the right atrial free wall. The observation of these findings may facilitate the identification of candidates for hybrid pharmacologic and ablative therapies. (PACE 2003; 26:692–702)

Wavelet transform system makes one-beat analysis possible in late potential evaluation.

High-frequency components of the QRS complex, including late potentials, can be analyzed by signal averaging (SA). However, this method may fail to detect transient changes as a result of cancellation. The wavelet transform, which has a superior time-frequency resolution, was used to analyze beat-to-beat changes of the QRS components in 50 normal subjects and 50 patients who showed positive late potentials. The transformed data, displayed in three dimensions and in color, were highly reproducible in each patient. Measurement of high-power duration at a frequency of 50 Hz (WD50) showed a significant correlation between WD50 and filtered QRS duration in both groups. When the mean +/- SD of WD50 in normal subjects was defined as normal, 96% of patients with late potentials were out of the normal range. The wavelet signals in patients with late potentials were more inhomogeneous than those of normal subjects. It is concluded that this newly developed color display, three-dimensional wavelet transform system showed extremely good time-frequency resolution in analyzing every beat without signal averaging.

Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone.

BACKGROUND Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. METHODSANDRESULTS IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. CONCLUSIONS IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation.

Anatomic and Electrophysiologic Evaluation of a Right Lateral Atrioventricular Mahaim Fiber

We report a patient who underwent an electrophysiologic study and radiofrequency catheter ablation for a right lateral Mahaim fiber. During sinus rhythm with overt preexcitation, propagation mapping was performed in the right ventricle using a three‐dimensional electro‐anatomical mapping system (CARTO). Small discrete potentials, which reflected the excitation of the Mahaim fiber, could be recorded along the line from the vicinity of the parental tricuspid annulus to approximately one‐third of distal site from the base to the apex. The relationship of the timing of its potential to the anatomical location could be disclosed on recordings of the local electrogram and anatomical map.

Radiofrequency Catheter Ablation of a Coronary Sinus‐Ventricular Accessory Connection in Dextrocardia with Complete Situs Inversus and an Anomalous Inferior Vena Cava

An anomalous inferior vena cava (IVC) is often associated with patients with dextrocardia. However, radiofrequency catheter ablation in such a case with that combination has not been reported. We encountered a case of Wolff‐Parkinson‐White syndrome with dextrocardia associated with complete situs inversus and an azygos continuation of the IVC. A steep angulation at the junction of the azygos vein and superior vena cava precluded the precise mapping of the anatomical right cavity with a femoral vein approach. Successful catheter ablation of an accessory connection between the coronary sinus and left ventricle could be achieved with a right cubital vein approach.