Ritsuko Kohno

Differential modulation of late sodium current by protein kinase A in R1623Q mutant of LQT3

AIMS In the type 3 long QT syndrome (LQT3), shortening of the QT interval by overdrive pacing is used to prevent life-threatening arrhythmias. However, it is unclear whether accelerated heart rate induced by beta-adrenergic agents produces similar effects on the late sodium current (I(Na)) to those by overdrive pacing therapy. We analyzed the beta-adrenergic-like effects of protein kinase A and fluoride on I(Na) in R1623Q mutant channels. MAIN METHODS cDNA encoding either wild-type (WT) or R1623Q mutant of hNa(v)1.5 was stably transfected into HEK293 cells. I(Na) was recorded using a whole-cell patch-clamp technique at 23 degrees C. KEY FINDINGS In R1623Q channels, 2 mM pCPT-AMP and 120 mM fluoride significantly delayed macroscopic current decay and increased relative amplitude of the late I(Na) in a time-dependent manner. Modulations of peak I(Na) gating kinetics (activation, inactivation, recovery from inactivation) by fluoride were similar in WT and R1623Q channels. The effects of fluoride were almost completely abolished by concomitant dialysis with a protein kinase inhibitor. We also compared the effect of pacing with that of beta-adrenergic stimulation by analyzing the frequency-dependence of the late I(Na). Fluoride augmented frequency-dependent reduction of the late I(Na), which was due to preferential delay of recovery of late I(Na). However, the increase in late I(Na) by fluoride at steady-state was more potent than the frequency-dependent reduction of late I(Na). SIGNIFICANCE Different basic mechanisms participate in the QT interval shortening by pacing and beta-adrenergic stimulation in the LQT3.

Characteristics of Syncope in Japan and the Pacific Rim

As is true in the Western world, syncope of cardiac and non-cardiac origin is one of the common clinical presentations in daily medical practice in Japan and Asia. However, the underlying disorders and social backgrounds associated with syncope may differ, from those encountered in Western countries, particularly in Japan. While non-cardiac causes, neurally-mediated reflex faints in particular, are highly prevalent, out-of-hospital deaths by drowning due to syncope occurring during bathing at home are not rare in Japan, particularly in the elderly. Other underlying cardiac or non-cardiac disorders are also noteworthy, particularly Brugada syndrome and coronary vasospasm, which may present as isolated syncope. In addition, the characteristic clinical presentation of micturition and defecation syncope is not uncommon. This review is focused on these specific underlying diseases in the light of the guidelines issued by the Japanese Circulation Society regarding the diagnosis and treatment of syncope.

Reflex syncope during a hot bath as a specific cause of drowning in Japan

Out-of-hospital cardiac arrest is a leading cause of death in Japan and other industrialized countries [1,2]. In 2005, the Fire and Disaster Management Agency of Japan launched the All-Japan Utstein Registry—a prospective, nationwide, population-based study of out-of-hospital cardiac arrest [3]. The annual incidence of out-of-hospital cardiac arrest and the number of events with cardiac causes increased gradually from 56,412 in 2005 to 63,296 in 2008. The incidence of out-of-hospital cardiac arrest was highest in the elderly, reaching 71% in individuals 470 years of age, and more than half of the overall population was male. There was a significantly higher incidence of out-of-hospital cardiac arrests in the winter season, particularly in January and December, than in other months of the year. This finding was consistent from year to year and at all ages. The Fire and Disaster Management Agency of Japan indicates that the incidence of outof-hospital cardiac arrest is as follows: (a) more common on Sundays and Mondays than on other days of the week, and (b) more common during early morning and evening hours than at other times of the day. The monthly and weekly distributions of the incidence of out-of-hospital cardiac arrest in populations of individuals o69 years of age (individuals of working age) are similar to those of all-age populations. In contrast, the daily distributions of the incidence of out-of-hospital cardiac arrest in the working population show a single peak in the early morning hours. One of the possible explanations for this difference in the daily distributions between working populations and elderly Japanese might be syncope during bathing in Japan. Between 1989 and 1993, approximately 10% of sudden deaths in Japan confirmed by the Tokyo Medical Examiner’s Office occurred at home during hot baths in a deep bathtub. The reported risk of sudden death is 10-fold higher during bathing than during sleep in the elderly Japanese people [4]. One of the causes of drowning during immersion in hot water may be syncope due to a precipitous decrease in blood pressure [4,5]. A low external temperature in the winter season increases sympathetic nerve tone and catecholamine release, which increase heart rate, vascular resistance, ventricular contractility, and blood pressure [6,7]. A rapid increase in body temperature by bathing causes a precipitous fall in blood pressure and syncope within the bathtub. Most Japanese individuals take a deep hot bath each evening because most homes are not as well insulated as those in Western

Right ventricular outflow tract endocardial pacing complicated by intercostal muscle twitching.

A recipient of a dual‐chamber pacing system, with a bipolar endocardial lead screwed into the right ventricular outflow tract (RVOT), developed intercostal muscle twitching. No lead perforation was identified. This observation suggests that meticulous attention should be paid to this potential complication when choosing the RVOT as a site of permanent endocardial pacing.

Ambulatory electrocardiogram monitoring devices for evaluating transient loss of consciousness or other related symptoms

Capturing electrocardiograms (ECGs) during spontaneous events is the most powerful available tool to identify or exclude an arrhythmic cause of symptoms, and often can elucidate the definite diagnosis for different conditions, such as transient loss of consciousness (T‐LOC), lightheadedness, or palpitations. Current ambulatory ECG monitoring technologies include 24‐hour Holter, wearable event recorder, external loop recorder (ELR), and insertable cardiac monitoring (ICM). Of them, Holter ECG is most frequently used in daily practice in Japan, while ELR and ICM are less frequently used. However, the appropriate monitor choice should be based on the expected frequency of symptoms. Frequent events may be adequately detected by Holter ECG, but less frequent symptoms are more effectively assessed by longer‐term monitoring (i.e., ELR or ICM). In this report, based on our clinical experience, we review the usefulness of ambulatory ECG monitoring devices, especially of ELR, for evaluating T‐LOC and other potentially arrhythmia‐related symptoms. Specifically, we focus on the use of ELR and ICM for evaluating Japanese patients with T‐LOC.

Identifying atrial arrhythmias versus pacing-induced rhythm disorders with state-of-the-art cardiac implanted devices

Repetitive non‐reentrant ventriculo‐atrial synchrony (RNRVAS) is a pacemaker‐induced arrhythmia that must be distinguished from atrial fibrillation (AF). Pacemaker‐induced arrhythmias are commonly detected as atrial high rate episodes (AHRE) by implanted cardiac devices. Two main types of atrial oversensing are recognized: far‐field R‐wave (FFRW) oversensing and pacemaker‐induced arrhythmias, which include pacemaker‐mediated tachycardia and RNRVAS. The presence of ventriculo‐atrial conduction is required for both types of pacemaker‐induced arrhythmias. The incidence of RNRVAS can increase with the use of various device settings and functions, such as long atrioventricular (AV) interval programming, the rate‐adaptive mode, and the atrial overdrive pacing algorithm. The negative aspects of pacemaker‐induced arrhythmias, especially RNRVAS, include (1) loss of optimal AV delay, (2) inappropriate increase in ventricular pacing, (3) induction of atrial arrhythmias, and (4) inaccurate diagnosis of AHRE. We review the incidence of arrhythmias, electrophysiological mechanisms, and the clinical diagnosis of RNRVAS identified by using dual‐chamber implantable cardiac devices.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm ― Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial ―

BACKGROUND Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology®(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

Outcomes of single- or dual-chamber implantable cardioverter defibrillator systems in Japanese patients

There are no criteria for selecting single‐ or dual‐chamber implantable cardioverter defibrillators (ICDs) in patients without a pacing indication. Recent reports showed no benefit of the dual‐chamber system despite its preference in the United States. As data on ICD selection and respective outcomes in Japanese patients are scarce, we investigated trends regarding single‐ and dual‐chamber ICD usage in Japan.

Effects of right ventricular pacing sites on blood pressure variation in upright posture: a comparison of septal vs. apical pacing sites

AIMS Large variations in blood pressure (BP) in the upright position are a major cause of pacemaker syndrome, observed in up to 80% of patients paced non-physiologically at the right ventricular (RV) apex. We hypothesized that the magnitude of BP variations might be influenced by the RV pacing site. To assess this, we compared haemodynamic findings during supine and upright posture with RV apical vs. septal pacing. METHODS AND RESULTS The study population comprised a retrospective cohort of 24 dual-chamber pacemaker patients with advanced or complete atrioventricular block, in which 11 were randomly chosen from those with RV apical pacing, and 13 randomly chosen from those with septal pacing. Studies were performed during fixed rate VVI and DDD pacing modes with patients in both supine and passive head-up tilt positions. Continuous BP, stroke volume, cardiac index, and total peripheral resistance index were measured non-invasively. During RV apical pacing, there were significant differences of beat-to-beat BP variation after movement from supine to upright posture for both VVI and DDD pacing modes (P < 0.05); however, this was not the case for either mode during RV septal pacing. Further, comparing RV apical to RV septal pacing in the supine position, there were no BP variation differences for either DDD or VVI modes. Conversely, in the upright position BP variation was significantly greater during RV apical vs. RV septal VVI pacing (P = 0.017) but not during DDD pacing. CONCLUSION During VVI pacing, RV septal pacing exhibited lesser BP variation during upright posture compared with RV apical pacing.

Effects of pacing modes on cardiac baroreflex function in permanently paced patients with sinus node dysfunction

Objectives: We compared, in patients with sick sinus syndrome, the effects of various pacing modes on baroreceptor (BR)‐stroke volume (SV) reflex sensitivity, a method we have closely correlated with BR‐heart rate (HR) reflex sensitivity.