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Aims: Several algorithms can differentiate inferior axis premature ventricular contractions (PVCs) originating from the right side and left side on 12-lead electrocardiograms (ECGs). However, it is unclear whether distinguishing the origin should rely solely on PVC or incorporate sinus rhythm (SR). We compared the dual-rhythm model (incorporating both SR and PVC) to the PVC model (using PVC alone) and quantified the contribution of each ECG lead in predicting the PVC origin for each cardiac rotation., Methods and Results: This multicentre study enrolled 593 patients from 11 centres-493 from Japan and Germany, and 100 from Belgium, which were used as the external validation data set. Using a hybrid approach combining a Resnet50-based convolutional neural network and a transformer model, we developed two variants-the PVC and dual-rhythm models-to predict PVC origin. In the external validation data set, the dual-rhythm model outperformed the PVC model in accuracy (0.84 vs. 0.74, respectively; P < 0.01), precision (0.73 vs. 0.55, respectively; P < 0.01), specificity (0.87 vs. 0.68, respectively; P < 0.01), area under the receiver operating characteristic curve (0.91 vs. 0.86, respectively; P = 0.03), and F1-score (0.77 vs. 0.68, respectively; P = 0.03). The contributions to PVC origin prediction were 77.3% for PVC and 22.7% for the SR. However, in patients with counterclockwise rotation, SR had a greater contribution in predicting the origin of right-sided PVC., Conclusion: Our deep learning-based model, incorporating both PVC and SR morphologies, resulted in a higher prediction accuracy for PVC origin, considering SR is particularly important for predicting right-sided origin in patients with counterclockwise rotation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

We presented a detailed time course of RFCA-associated PV calcification process. Because RFCA-associated PV calcification may progress over time even with a single ablation, long-term caution should be paid in cases of especially extensive ablation and/or patients with stiff LA syndrome., Competing Interests: Authors declare no conflict of interests for this article., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: The effect of cardiac rehabilitation (CR) on patients undergoing device implantation (DI) for arrhythmias has been reported; however, the implementation status of these patients has not been clarified. This study aimed to verify the implementation status of CR for patients with heart disease who have undergone DI using real-world data., Methods: This was an observational study using a nationwide administrative database associated with the diagnosis procedure combination (DPC) system in Japan (2014-2018). Subjects were patients with heart disease (70 667 cases) who underwent DI during the above scheduled hospitalization period. The overall rate of CR and the background factors of the subjects were verified., Results: The CR rate for patients with heart disease who underwent DI during hospitalization was 23%, and the CR rate for patients with comorbid heart failure who underwent DI was only 32%. It was confirmed that progressing age was associated with a higher CR implementation rate. The lower the Barthel index score at the time of admission, the higher the CR implementation rate., Conclusions: CR was performed for only one-quarter of all the patients during admission for DI and just one-third of the patients for DI with heart failure. Most of these patients were elderly and had a decreased ability to perform activities of daily living. The DPC data are subject to various limitations, and further research is necessary., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: The number of employees with physical diseases is increasing, and there is a need for support to help them return and continue to work. To provide effective support, it is important to identify barriers and facilitators for individuals in returning and continuing to work. Previous studies have reported barriers and facilitators for specific diseases. However, few reports have dealt with these issues across various diseases. To identify a range of barriers and facilitators that may apply to different physical diseases, we conducted a qualitative analysis by interviewing patients with diverse characteristics being treated for diseases., Methods: We conducted semi-structured interviews based on the criteria for qualitative research. We investigated three disease groups to obtain details of barriers and facilitators: impairments that were visible to other people (mainly stroke); impairments invisible to others (mainly heart disease); and impairments that changed over time (mainly cancer). Interview transcripts were analyzed and the results reported using systematic text condensation., Results: We extracted 769 meaning units from 28 patient interviews. We categorized barriers and facilitators that were generalizable to various diseases into three themes (personal factors, workplace factors, and inter-sectoral collaboration and social resources) and 10 sub-themes (work ability, psychological impacts, health literacy, social status, family background, workplace structure, workplace system, workplace support, inter-sectoral collaboration, and social resources)., Conclusions: This study identified 10 sub-themes that can be applied for workers with physical diseases; those sub-themes may be used as a basis for communicating with those individuals about returning and continuing to work. Our results suggest that various barriers and facilitators for workers with physical diseases should be understood and addressed at medical institutions, workplaces, and support sites., (© 2022. The Author(s).)

Background: The prognosis associated with right ventricular (RV) free-wall pacing is worse than that of septal pacing. Identification of the pacing site using a 12‑lead electrocardiogram (ECG) is controversial and may be influenced by ECG changes within the same septal or free-wall area. The relationship between the diagnostic capabilities of ECG and pacing sites has previously been qualitatively evaluated. However, in this study, this relationship was analyzed quantitatively, and accurate evaluation of the pacing site was determined using computed tomography (CT)., Methods: Of 779 consecutive outpatients, 65 who underwent pacemaker implantation and thoracic CT were prospectively included and classified into the following groups according to the lead tip position: free-wall, septal, or septum/free-wall boundary (hinge) group. The hinge was used as an anatomical marker, and the distance from the hinge to the lead tip was measured. Under RV pacing, a 12‑lead ECG was obtained. ECG findings were evaluated using three criteria (including lead I, II, and aV L and precordial leads V 5 and V 6 ) previously reported to be useful in differentiating pacing sites., Results: The lead tips were anchored at the free-wall in 10 patients, the septal wall in 19 patients, and the hinge in 32 patients. Paced QRS duration correlated with the distance from the hinge to the lead tip for the free-wall and septum (r = 0.47 and - 0.68, respectively). Estimation of the lead tip implantation site using the ECG algorithm was useful; however, the algorithm's accuracy decreased around the hinge., Conclusions: ECG is useful in differentiating pacing sites but is less accurate around the hinge, which may be the reason that the identification of the RV pacing site using ECG remains controversial., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We reported a case of early S-ICD shock due to the carryover of previously charged energy. Depending on the interval with the preceding event, an early shock may occur for the subsequent event. Especially, in cases where non-sustained VTs occur frequently, the indication for S-ICD surgery should be considered carefully., Competing Interests: The authors declare no conflict of interests for this article., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: The displacement of cardiac implantable electronic devices (CIEDs) toward the caudal side during standing after CIED implantation could cause lead dislodgement. This study investigated the relationship between supine pocket position and standing CIEDs' displacement distance after the implantation., Methods: After CIED surgeries performed at 2 hospitals between 2012 and 2020, 134 patients underwent postoperative chest x-rays in the supine and standing positions during hospitalization. To measure the displacement distance of CIEDs from the supine to the standing position, we identified the first thoracic vertebrae (Th1) in the supine position using the first rib as an index, drew a horizontal line at the lower edge of the Th1, and calculated the distance from that point to the upper edge of the CIED. The difference between measures for the two positions was compared. At the position of the pocket in the thorax in the supine position, the ratio of the distance between the thorax and the device is defined as the device thorax ratio (DTR). We examined the relationship between DTR and CIED displacement distance., Results: In this study, we included 134 patients (53% men; median age, 79 years, body mass index, 22.3 ± 3.4; pacemaker 93%, left implantation 96%). We found that the more lateral the position of the CIED pocket, the more the CIED fell when standing (confidence interval = 0.34-0.60, P < .001)., Conclusions: The farther the CIED was implanted outside the thorax in the supine position, the more significantly the CIED was displaced in the standing position., (© 2022 Wiley Periodicals LLC.)

A 74-year-old man experienced complete atrioventricular (AV) block 2 days after catheter ablation for right atrial (RA) macroreentrant tachycardia. We performed DDD pacemaker implantation with atrial septal pacing because other sites of pacing threshold were not acceptable. The maximum left ventricular outflow tract velocity time integral was 15.8 cm with sensed AV delay (40 ms) and 15.0 cm with paced AV delay (220 ms); however, this exceeded the pacemaker's maximum difference of 100 ms. We herein report the case of a large discrepancy in optimal AV delay intervals between sensed and paced atrial events, requiring consideration of proper pacemaker settings., (© 2021 Wiley Periodicals LLC.)

An 84-year-old woman with type B Wolff-Parkinson-White (WPW) with Ebstein anomaly was admitted with heart failure. She had rapid wide QRS tachycardia due to accessory pathway (AP) conduction associated with atrial fibrillation (AF). Since transesophageal echocardiography before catheter ablation showed a left atrial thrombus, ablation was performed using a 3D mapping system under AF. After marking the functional tricuspid anulus with intra-cardiac echocardiography, 3D intra-cardiac electrogram visualization (ripple map) during AF enabled clear identification of location of the AP. After ablation, there was no complication of cerebral infarction, and the heart failure improved., (© 2021 Wiley Periodicals LLC.)

In terms of the pulmonary vein (PV), atrial fibrillation (AF) patients have a shorter effective refractory period (ERP) than those without AF and a large dispersion of the ERP. Although the frequency of AF from the superior vena cava (SVC) was the highest among non-PV foci, the characteristics of the ERP in the SVC (SVC-ERP) were unclear. The purpose of this study was to elucidate the relationship between SVC-ERP and the inducibility of AF after PV isolation (PVI).Consecutive 28 patients who underwent PVI were included. After successful PVI, the SVC-ERP was measured at three positions in SVC. Rapid electrical stimuli were delivered at the shortest SVC-ERP to induce AF. Patients in whom AF was induced were assigned to the SVC-induced group (SIG), and the remaining patients were the non-SVC-induced group (non-SIG). The size of the SVC sleeve was evaluated via three-dimensional electroanatomic mapping.The SIG had a significantly shorter average SVC-ERP (236.0 ± 25.2 versus 294.8 ± 36.8 ms, P < 0.001), whereas SVC-ERP dispersion was not significantly different (30.0 ± 25.4 versus 33.3 ± 20.1 ms, P = 0.56). Although the longer SVC diameter was significantly longer in the SIG (27.4 ± 4.3 versus 22.9 ± 4.6 mm, P = 0.03), the SVC-ERP was significantly associated with pacing inducibility of AF after adjustment for the longer SVC diameter (odds ratio: 0.96 [1 ms increments], P = 0.01).The SIG had a shorter SVC-ERP, whereas the dispersion was not significantly different between the two groups. The SVC-ERP can be one of the mechanisms of arrhythmogenicity for AF originating from the SVC.

Objectives: The prevention and improvement of the prognosis of out-of-hospital cardiac arrests (OHCAs) are important issues especially with respect to their social and economic significance in working populations. The age distribution of the working population in Japan is expected to change continually due to its ageing society and extension of retirement; however, few reports have examined the long-term condition of OHCA in the working population, defined by age. The aim of this study was to determine the incidence of OHCAs and the survival rates after 1 month, among the Japanese working population, defined by age, considering the changing age distribution., Design and Setting: We analysed the All-Japan Utstein registry, a prospective, nationwide, population-based, observational registry (2005-2016)., Participants: From the registry, 212 961 patients with OHCA from the Japanese working population (defined aged 20-69 years), with only cardiogenic aetiology participated in this study. These patients were further divided into four groups according to the type of citizen bystander (family, friends, work-colleagues and passers-by)., Primary and Secondary Outcome Measures: The main outcomes were 1-month survival with favourable neurological outcomes., Results: The incidence of OHCAs, in any age group, was almost constant during the 12-year period. The work-colleagues had the best prognosis despite having significantly longer times to initial defibrillations compared with the passers-by (13 vs 12 min, respectively, p<0.001) that was associated independently with 1-month survival with favourable neurological outcomes (adjusted OR: 0.94 (1 min increments), p<0.001)., Conclusions: In the 12-year period, the incidence of OHCAs in any age group remained almost constant, whereas the prognosis improved each year. Reducing the time to initial defibrillation may further improve the prognosis of OHCAs with a work-colleague bystander., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability., Methods: We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti-tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated., Results: Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively., Conclusions: ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible., Competing Interests: This study was financially supported by Medtronic Japan. Dr Satoshi Higa is a consultant to Japan Life Line and Johnson & Johnson and received speaker's honoraria from Japan Life Line, Medtronic, Abbott, Bayer, Biotronik, Boehringer‐Ingelheim, Bristol‐Myers, Daiichi‐Sankyo Pharmaceutical Company, and Pfizer., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

We generated a transgenic rat line that expresses oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos-like immunoreactivity (co-expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN- and PEG-treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Introduction: One cause of cerebral infarction during cryoballoon ablation is the entry of air into a sheath due to the use of inappropriate catheters. It is known that the left atrial pressure of patients with obstructive sleep apnea syndrome can be negative. However, the effects of catheter selection and negative pressure changes in the sheath on air intrusion are not yet well understood. The aim of this study was to evaluate how catheter selection and negative pressure changes affect air intrusion and to perform countermeasures for air intrusion., Methods and Results: This experiment used siphon principle to create negative pressure in the sheath. Noncryoablation catheters (not designed exclusively for cryoballoon ablation) and cryoballoon catheters were investigated. Catheters were inserted into the sheath and then removed. Thereafter, the amount of air in the sheath was measured. For catheters producing significantly larger amounts of air intrusion, the catheters were inserted via a long sheath in the sheath (sheath-in-sheath technique) and the same procedures were repeated. We found that the amount of air intrusion through most of the noncryoablation catheters was significantly larger than that through cryoablation catheters. An increase in the magnitude of negative pressure in the sheath resulted in a proportional increase in air intrusion, but the sheath-in-sheath technique significantly reduced air intrusion., Conclusion: The amount of air intrusion increased when using catheters with complicated tip shapes and thin outer diameters and when the magnitude of negative pressure in the sheath increased. The sheath-in-sheath technique may be an effective countermeasure., (© 2019 Wiley Periodicals, Inc.)

Background: Although fluoroscopy-guided right ventricular (RV) lead placement in the ventricular septum is a widely performed procedure, variation in true RV lead tip position confirmed via computed tomography (CT) and its prognostic implications in patients with atrioventricular block (AVB) are not well understood., Objective: The purpose of this study was to evaluate the prognostic impact of CT-confirmed RV lead tip position., Methods: We retrospectively enrolled 228 consecutive patients (age 77 ± 10 years; 125 men) with AVB who underwent fluoroscopy-guided RV septal lead implantation and thoracic CT after pacemaker implantation. Patients were classified into septal and free-wall groups according to RV lead tip position. The primary endpoint was the composite outcome of cardiac death and heart failure hospitalization., Results: The RV lead tip was located at the free wall in 18 patients (8%). The primary endpoint occurred in 37 patients (16%) over median follow-up of 41 months. Electrocardiographic analysis found that R amplitude >0.53 mV in lead I was significantly predictive of free-wall pacing, with sensitivity of 70% and specificity of 77%. Multivariate Cox regression analysis demonstrated that the lead tip in the free wall (hazard ratio 2.93; 95% confidence interval 1.21-7.11; P = .018) was an independent predictor of the primary endpoint., Conclusion: Fluoroscopy-guided RV lead placement carries potential risk of unexpected RV free-wall pacing and may increase the risk of cardiac death and heart failure-related hospitalization in patients undergoing RV septal pacing due to AVB and receiving thoracic CT for medical reasons., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Dual-antiplatelet therapy (DAPT) after second-generation drug-eluting stent (2nd-DES) implantation reduces the risk of stent thrombosis and subsequent ischemic events, with an increase in bleeding risk. Although chronic kidney disease patients have both high ischemic and bleeding events, little is known about both risks during DAPT in hemodialysis (HD) patients., Methods: From July 2009 to March 2017, we retrospectively analyzed bleeding events and major adverse cardiac and cerebrovascular events (MACCE) in 644 consecutive patients who underwent successful percutaneous coronary intervention (PCI) with 2nd-DES implantation in our institution. We divided the patients into 2 groups [102 HD and 518 non-HD patients] after excluding 24 patients. The primary endpoint was bleeding events of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5. The secondary endpoint was MACCE. We also investigated potential bleeding risk factors in those patients., Results: At a median follow-up of 49 months, bleeding events occurred in 76 (12.3%) patients. Critical bleeding events of BARC type 3 or 5 occurred more frequently in HD (HD vs. non-HD: 16.7% vs. 7.1%; p=0.004). Most events tended to occur within 6 months post PCI. Multivariate analysis demonstrated that HD [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.03-3.16; p=0.04], body mass index (BMI) (HR 0.91, 95%CI 0.87-0.99, p=0.02), and serum albumin (HR 0.35, 95%CI 0.34-0.96, p=0.03) were independent predictors of bleeding events. MACCE also occurred more frequently in HD (HD vs. non-HD: 53.9% vs. 29.3%; p<0.001). Multivariate analysis demonstrated that pre-dialysis systolic blood pressure (HR 1.03, 95%CI 1.00-1.06, p=0.02) and high-sensitive C-reactive protein level (HR 1.76, 95%CI 1.06-2.72, p=0.03) were independent predictors of bleeding events in HD., Conclusions: HD displayed more adverse bleeding and ischemic events compared with non-HD. Therefore, practitioners should reconsider the current regimen of DAPT in this patient cohort to prevent critical bleeding complications and spates of ischemic events., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.

Intravascular ultrasound (IVUS)-derived minimum lumen cross-sectional area (MLA) is useful to predict myocardial ischemia using fractional flow reserve (FFR). Recent studies reported an increase in the intraluminal ultrasonic integrated backscatter (IB) value using IVUS across the coronary artery stenosis (CAS) was significantly correlated with FFR. However, these details have not been fully understood. We evaluated the utility of intraluminal IB analysis for predicting myocardial ischemia based on FFR measurements by comparing that with conventional IVUS-derived MLA. A total of 65 patients with 75 intermediate lesions underwent both FFR and IB-IVUS simultaneously were analyzed. We measured IVUS-derived MLA and intraluminal IB value at the coronary ostial site, 5 mm distal site to the CAS, and far distal site, which is the same as the position of the pressure wire sensor. The increase in IB values was calculated as the distal IB value - the ostial IB value (focal ∆IB) and the far distal IB value - the ostial IB value (total ∆IB). MLA did not show a significant correlation with FFR (p = 0.13); however, focal ∆IB and total ∆IB showed significant correlations with FFR (p = 0.008 and p < 0.001, respectively). The receiver operating characteristic curve analysis shows that the best cut-off value of focal ∆IB and total ∆IB was 8 and 14, respectively. Although the diagnostic abilities to predict FFR ≤ 0.75 among IVUS-derived MLA ≤ 3.0 mm 2 , focal ∆IB ≥ 8, and total ∆IB ≥ 14 were similar, a multivariate analysis showed that total ∆IB was the most useful index (p < 0.001). In conclusion, total ∆IB, which is measured at the same as the position of FFR measurement, might be useful for functional assessment of intermediate CAS.

Background: Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality. Methods and Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0-35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1-422.3; P=0.0016)., Conclusions: Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality.

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation was an independent predictor of clinical outcome; however, the relationship between IP and the presence of subsequent in-stent neoatherosclerosis remains unclear. This study aimed to assess the relationship between IP and in-stent neoatheroscrerosis formation using OCT. We evaluated 83 patients (101 lesions) who underwent second-generation DES implantation and 8-month follow-up (8M-FU) using OCT. Lesions were divided into two groups in presence of IP (IP: n = 43, non-IP: n = 58). At prepercutaneous coronary intervention (pre-PCI), lipid-rich plaque, lesions with positive remodeling, and in-stent thrombus formation were more frequent in IP than in non-IP. On multivariate analysis, the thrombus at pre-PCI and the lesions with positive remodeling were independent predictors of IP. At 8M-FU, heterogeneous neointima, microvessel, lipid-laden neointima, and thin-cap fibro-atheroma like neointima were more frequent in IP than in non-IP (respectively, P < 0.05). On multivariate analysis, IP was associated with heterogeneous neointima. Binary restenosis was more frequent and late lumen loss tended to be larger in IP than in non-IP (19% versus 5%, P = 0.04; 1.25 ± 1.24 mm versus 0.91 ± 0.63 mm, P = 0.09); however, the target lesion revascularization rate was similar in both groups at 8M-FU. In conclusion, our study suggested that poststent IP was associated with subsequent neoatherosclerosis formation at 8M-FU after the second-generation DES implantation.

Background: Mutations in LMNA ( lamin A/C ), which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, cardiac conduction disturbance, atrial fibrillation, and malignant ventricular arrhythmias. Although the type of LMNA mutations have been reported to be associated with susceptibility to malignant ventricular arrhythmias, the gene-based risk stratification for cardiac complications remains unexplored., Methods and Results: The multicenter cohort included 77 LMNA mutation carriers from 45 families; cardiac disorders were retrospectively analyzed. The mean age of patients when they underwent genetic testing was 45±17, and they were followed for a median 49 months. Of the 77 carriers, 71 (92%) were phenotypically affected and showed cardiac conduction disturbance (81%), low left ventricular ejection fraction (<50%; 45%), atrial arrhythmias (58%), and malignant ventricular arrhythmias (26%). During the follow-up period, 9 (12%) died, either from end-stage heart failure (n=7) or suddenly (n=2). Genetic analysis showed truncation mutations in 58 patients from 31 families and missense mutations in 19 patients from 14 families. The onset of cardiac disorders indicated that subjects with truncation mutations had an earlier occurrence of cardiac conduction disturbance and low left ventricular ejection fraction, than those with missense mutations. In addition, the truncation mutation was found to be a risk factor for the early onset of cardiac conduction disturbance and the occurrence of atrial arrhythmias and low left ventricular ejection fraction, as estimated using multivariable analyses., Conclusions: The truncation mutations were associated with manifestation of cardiac phenotypes in LMNA -related cardiomyopathy, suggesting that genetic analysis might be useful for diagnosis and risk stratification., (© 2017 American Heart Association, Inc.)

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.

Background: Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent., Methods: Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180μg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase., Results: In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001)., Conclusion: Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Segmental and global mitral valve prolapse (MVP) comprise 2 representative phenotypes in this syndrome. While mitral regurgitation (MR) severity is a major factor causing left atrial (LA) remodeling in MVP, prominent mitral valve (MV) annulus dilatation in global MVP may specifically cause inferiorly predominant LA remodeling. We compared MV annulus and LA geometry in patients with segmental and global MVP.Methods and Results:LA volume as well as inferior, middle, and superior LA cross-sectional areas (CSA) were measured on 3-D echocardiography in 20 controls, in 40 patients with segmental MVP, and in 18 with global MVP. On multivariate analysis, MR severity was primarily associated with LA dilatation in segmental MVP (P<0.001), while MV annular dilatation was primarily associated with LA dilatation in global MVP (P<0.001). Although there was no regional predominance in LA dilatation in segmental MVP, inferior predominance of LA dilatation was significant in global MVP (increase in inferior, middle, and superior LA-CSA relative to mean of the controls: +220±70% vs. +171±55% vs. +137±37%, P<0.001)., Conclusions: LA remodeling in segmental and global MVP is considerably different regarding its association with MR volume or MV annular dilatation and its regional predominance. While MR volume may mainly contribute to LA remodeling in segmental MVP, MV annular dilatation seems to have an important role in LA remodeling in global MVP. (Circ J 2016; 80: 2533-2540).

Background: Whether pacing from the right ventricular (RV) septum improves prognosis is unclear. Furthermore, the clinical characteristics of patients who develop atrial fibrillation (AF) and cardiovascular events during long-term RV septal pacing have not been described.Methods and Results:We retrospectively evaluated the incidence of AF and cardiovascular events, including cardiac death, heart failure requiring hospitalization, or stroke, for a median of 4.0 years in 123 recipients of dual-chamber pacemakers implanted for atrioventricular block with preserved left ventricular function, who were free from AF before device implantation. AF developed in 30 patients (24%), and multivariable analysis suggested that the cumulative percentage of RV pacing was the only independent predictor of newly developed AF (hazard ratio: 1.19 for each 10% increment; 95% confidence interval: 1.04-1.41; P=0.01). Furthermore, older age, newly developed AF and a paced QRS duration ≥155 ms at pacemaker implantation were significant predictors of cardiovascular events., Conclusions: RV septum pacing may induce AF in up to one-quarter of patients paced for atrioventricular block, according to the frequency of pacing. More importantly, in such patients, AF induced by RV pacing and a paced QRS duration ≥155 ms at pacemaker implantation are significantly associated with poor prognosis. Therefore, we recommend pacing from sites producing a paced QRS duration <155 ms and avoiding unnecessary RV pacing. (Circ J 2016; 80: 2302-2309).

Background: The most common form of idiopathic Purkinje-related ventricular tachycardia (VT) is the reentrant type. We describe the clinical and electrophysiological characteristics of focal non-reentrant fascicular tachycardia., Methods and Results: Among 530 idiopathic VT patients who were referred for ablation, we identified 15 (2.8%) with non-reentrant fascicular tachycardia (11 men, 45±21 years). Sinus rhythm ECG showed normal conduction intervals with a His-ventricular interval of 41±4 ms. All patients had monomorphic VT (cycle length: 337±88 ms) with a relatively narrow QRS (123±12 ms), and they did not respond to verapamil during the initial presentation. VT exhibited right bundle-branch block/superior axis configuration in 11 patients (73%) and inferior axis in 3 (20%). In 1 patient (7%), VT exhibited left bundle-branch block/superior axis configuration. During ablation, spontaneous VT occurred in 3 patients (20%) and nonentraintable VT or identical premature ventricular complex was induced in 9 (60%). A high-frequency presystolic Purkinje potential was recorded during VT/premature ventricular complex, preceding the QRS by 25±16 ms. VT recurrence was observed in 4 patients (27%), and among them, 3 underwent pacemap-guided ablation during the first session. A second ablation with activation mapping guidance eliminated the VT during the 88±8-month follow-up., Conclusions: Among idiopathic VT cases referred for ablation, 2.8% were focal non-reentrant fascicular tachycardia, which had distinct clinical characteristics and usually originated from the left posterior fascicle, and less commonly from the left anterior fascicle and right ventricular Purkinje network. Catheter ablation is effective, whereas pacemap-guided approach is less efficacious., (© 2016 American Heart Association, Inc.)

Background: Prominent mitral valve (MV) annular dilatation with only modest left ventricular (LV) dilatation in patients with MV prolapse (MVP) suggests predominant dilatation in adjacent basal LV, which may augment regional wall tension and attenuate contraction by Laplace's law. We hypothesized that MV annular dilatation in patients with MVP is associated with the basal predominance of LV dilatation and attenuated contraction, which can be altered by surgical MV plasty with annulus reduction., Methods and Results: Echocardiography with speckle-tracking analysis to assess regional cross-sectional short-axis area and longitudinal contraction (strain) of basal, middle, and apical LV was performed in 30 controls and 130 patients with MVP. The basal value/averaged middle and apical values (B/M·A ratio) of LV cross-sectional area and strain were obtained. Patients with MVP showed significantly greater MV annular area (6.4±1.6 versus 3.7±0.6 cm 2 /m 2 ), increased B/M·A LV area ratio (2.4±0.5 versus 1.8±0.2), and reduced B/M·A LV strain ratio (0.83±0.14 versus 0.96±0.09) than controls (P<0.001). Multivariable analyses identified that MV annular dilatation was independently associated with increased B/M·A LV area ratio (β=0.60, P<0.001), which was associated with reduced B/M·A LV strain ratio (β=-0.32, P<0.001). In 35 patients with MVP, B/M·A LV area and strain ratio significantly altered after surgical MV plasty with annulus reduction (2.5±0.5-1.8±0.3 and 0.73±0.10-0.89±0.17, P<0.001, respectively)., Conclusions: In patients with MVP, MV annular dilatation was associated with the basal predominance of LV dilatation and reduced contraction, which can be altered by surgical MV plasty with annulus reduction, suggesting unfavorable influence from MV annular dilatation on basal LV., (© 2016 American Heart Association, Inc.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: 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., Methods: Data from a total of 205 ICD recipients with structural heart disease (median age, 63 years) in two Japanese university hospitals were reviewed. Patients with bradycardia with a pacing indication and permanent atrial fibrillation at implantation were excluded., Results: Single- and dual-chamber ICDs were implanted in 36 (18%) and 169 (82%) patients, respectively. Non-ischemic cardiomyopathy dominated both groups. Seventeen dual-chamber patients developed atrial pacing-dependency over 4.5 years, and it developed immediately after implantation in 14. Although preoperative testing showed no sign of bradycardia in these patients, their pacing rate was set higher than it was in patients who were pacing-independent (61 vs. 46 paces per min, p<0.01). Two single-chamber patients (5%) underwent atrial lead insertion. While inappropriate shock equally occurred in both groups (7 vs. 21 patients, single- vs. dual-chamber, P=0.285), device-related infection occurred only in dual-chamber patients (0 vs. 9 patients, P=0.155). No differences in death or heart failure hospitalization were observed between groups., Conclusions: Dual-chamber ICDs were four-fold more common in Japanese patients without a pacing indication. No benefit over single-chamber ICD was observed. Newly developed atrial pacing-dependency seemed to be limited and could have been overestimated due to higher pacing rate settings in dual-chamber patients.

Background: Heart failure (HF) can be caused by left ventricular (LV) pump failure as well as by bradyarrhythmias. Hemodynamic differences between HF by LV pump failure and that by bradyarrhythmia have not been fully investigated. We hypothesized that HF by LV pump failure could be associated with both reduced cardiac output (CO) and increased LV filling pressure due to associated LV diastolic dysfunction, whereas HF by bradyarrhythmia could be associated with reduced CO but only modestly increased LV filling pressure due to the absence of LV diastolic dysfunction., Methods: In 39 patients with HF by LV pump failure (LV ejection fraction <35%), 24 with HF by bradyarrhythmia, and 22 normal controls, LV volume, ejection fraction, stroke volume, left atrial volume, and early diastolic mitral valve flow to tissue annular velocity ratio (E/E') were measured by echocardiography., Results: Compared to patients with HF by LV pump failure, those with HF by bradyarrhythmia had significantly lower heart rates, less LV dilatation, preserved LV ejection fraction, preserved stroke volume, similarly reduced cardiac index (1.8 ± 0.4 vs. 1.6 ± 0.4 L/min/m(2), n.s.), preserved LV diastolic function (E') (4.4 ± 2.1 vs. 7.1 ± 2.9 cm/s, p < 0.001), less dilated end-systolic LA volume, and preserved E/E' (24 ± 10 vs. 13 ± 7, p < 0.001)., Conclusions: HF by LV pump failure is characterized by both significantly reduced CO and increased LV filling pressure, whereas HF by bradyarrhythmia is characterized by a similar reduction in CO but only modestly increased LV filling pressure.

Background: Short QT syndrome (SQTS) is a rare inheritable arrhythmia, associated with atrial and ventricular fibrillations, caused by mutations in six cardiac ion channel genes with high penetrance. However, genotype-specific clinical differences between SQTS patients remain to be elucidated., Methods and Results: We screened five unrelated Japanese SQTS families, and identified three mutations in KCNH2 and KCNQ1. A novel mutation KCNH2-I560T, when expressed in COS-7 cells, showed a 2.5-fold increase in peak current density, and a positive shift (+14 mV) of the inactivation curve compared with wild type. Computer simulations recapitulated the action potential shortening and created an arrhythmogenic substrate for ventricular fibrillation. In another family carrying the mutation KCNQ1-V141M, affected members showed earlier onset of manifestation and frequent complications of bradyarrhythmia. To determine genotype-specific phenotypes in SQT1 (KCNH2), SQT2 (KCNQ1), and other subtypes SQT3-6, we analyzed clinical variables in 65 mutation-positive patients among all the 132 SQTS cases previously reported. The age of manifestation was significantly later in SQT1 (SQT1: 35 ± 19 years, n = 30; SQT2: 17 ± 25 years, n = 8, SQT3-6: 19 ± 15 years, n = 15; p = 0.011). SQT2 exhibited a higher prevalence of bradyarrhythmia (SQT2: 6/8, 75%; non-SQT2: 5/57, 9%; p < 0.001) and atrial fibrillation (SQT2: 5/8, 63%; non-SQT2: 12/57, 21%; p = 0.012). Of 51 mutation-positive individuals from 16 SQTS families, nine did not manifest short QT, but exhibited other ECG abnormalities such as atrial fibrillation. The resulting penetrance, 82%, was lower than previously recognized., Conclusion: We propose that SQTS patients may exhibit different clinical manifestations depending upon their genotype., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Unnecessary ventricular pacing in sinus node disease (SND) must be avoided. To test the hypothesis that in SND, with or without 1st degree atrioventricular (AV) block, cumulative percent ventricular pacing (cum%VP) can be limited by low right atrial septal (LRAS) instead of right atrial appendage (RAA) pacing., Methods: We studied 102 dual-chamber pacemaker recipients with SND. The PQ interval on 12-lead electrocardiogram and the atrial paced to ventricular sensed interval (Ap-Vs) during LRAS and RAA pacing were measured and compared at implantation, 3 months and 1 year of follow-up. Group 1 included 62 patients with baseline PQ interval <200 milliseconds during LRAS (n = 28) versus RAA (n = 34) pacing. Group 2 included 40 patients with baseline PQ ≥200 milliseconds during LRAS (n = 20) versus RAA (n = 20) pacing. cum%VP were measured at 3 months and 1 year., Results: The characteristics and AV conduction properties were similar and the Ap-Vs interval was significantly shorter in the LRAS than in the RAA pacing group up to 1 year (193 ± 32 milliseconds vs. 220 ± 27 milliseconds in Group 1; P = 0.003, 222 ± 41 milliseconds vs. 281 ± 30 milliseconds in Group 2; P < 0.001). While cumulative percent atrial pacing was consistently similar, cum%VP was significantly smaller during LRAS than RAA pacing (1 ± 1% vs. 8 ± 18% in Group 1; P = 0.03, 7 ± 10% vs. 48 ± 38% in Group 2; P < 0.001). Similar observations were made with or without left atrial (LA) enlargement., Conclusion: Compared with RAA, LRAS pacing showed shorter AV interval in SND patients with or without 1st degree AV block and LA enlargement. This beneficial effect persisted through 1-year follow-up, and decreased cum%VP significantly., (© 2014 Wiley Periodicals, Inc.)

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., (© 2014 American Heart Association, Inc.)

Background: Active fixation pacing leads with silicon cylinder tips have been used for their safety and flexibility. Measurement of baseline sensing/pacing characteristics before fixation of helix helps to identify the optimal pacing site, but we encountered difficulties in making these measurements despite multiple attempts with the model LPA 1200M lead. To identify the cause and overcome this complication, we compared 4 different retractable active fixation lead models, which enabled baseline sensing/pacing measurements before extension of helix. METHODS AND RESULTS: We immersed 4 different lead tips and rings in a 0.18% saline solution, and measured the lead impedance before and after flushing of air bubble visible inside the lead tip. Before evacuation of the air bubble, the impedance of the model LPA 1200M lead was >4,000 Ω in 8 out of 10 measurements, although that of the other leads was within the measurable range. After evacuation of the air bubble, the lead impedance returned to within the measurable range. There was no prominent change in the impedance of the metal cylinder tip lead., Conclusions: Air bubbles may interfere with the measurement of baseline sensing/pacing characteristics before active fixation of pacing leads with cylindrical silicon tips. In the case of high impedance beyond the measurable range before extension of helix, the measurement should be repeated after fixation into the myocardium before suspecting lead dysfunction.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)