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Landiolol is an ultra-short-acting, selective β1-adrenergic receptor blocker that was originally approved in Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1-selectivity, potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half-life (around 4 min); moreover, it may have a potential therapeutic effects for sepsis and pediatric patients. Landiolol seems to be superior to other short-acting and selective beta-blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting β1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data. [ABSTRACT FROM AUTHOR]

Background: Esophagectomy is a high-risk procedure that can involve serious postoperative complications. There has been an increase in the number of minimally invasive esophagectomies (MIEs) being performed. However, the relationship between intraoperative management and postoperative complications in MIE remains unclear. Methods: After the institutional review board approval, we enrolled 300 patients who underwent MIE at Tohoku University Hospital between April 2016 and March 2021. The relationships among patient characteristics, intraoperative and perioperative factors, and postoperative complications were retrospectively analyzed. The primary outcome was the relationship between intraoperative fluid volume and anastomotic leakage, and the secondary outcomes included the associations between other perioperative factors and postoperative complications. Results: Among 300 patients, 28 were excluded because of missing data; accordingly, 272 patients were included in the final analysis. The median [interquartile range] operative duration was 599 [545–682] minutes; total intraoperative infusion volume was 3,747 [3,038–4,399] mL; total infusion volume per body weight per hour was 5.48 [4.42–6.73] mL/kg/h; and fluid balance was + 2,648 [2,015–3,263] mL. The postoperative complications included anastomotic leakage in 68 (25%) patients, recurrent nerve palsy in 91 (33%) patients, pneumonia in 62 (23%) patients, cardiac arrhythmia in 13 (5%) patients, acute kidney injury in 5 (2%) patients, and heart failure in 5 (2%) patients. The Cochrane-Armitage trend test indicated significantly increased anastomotic leakage among patients with a relatively high total infusion volume (P = 0.0085). Moreover, anastomotic leakage was associated with male sex but not with peak serum lactate levels. Patients with a longer anesthesia duration or recurrent nerve palsy had a significantly higher incidence of postoperative pneumonia than those without. Further, the incidence of postoperative pneumonia was not associated with the operative duration, total infusion volume, or fluid balance. The operative duration and blood loss were related to the total infusion volume. Acute kidney injury was not associated with the total infusion volume or serum lactate levels. Conclusions: Among patients who underwent MIE, the total infusion volume was positively correlated with the incidence of anastomotic leakage. Further, postoperative pneumonia was associated with recurrent nerve palsy but not total infusion volume or fluid balance. [ABSTRACT FROM AUTHOR]

Introduction: Posterior wall isolation (PWI) combined with pulmonary vein isolation (PVI) has proven effective for persistent atrial fibrillation (AF). However, when performing PWI, creating transmural lesions with subendocardial ablation is sometimes difficult. Endocardial unipolar voltage amplitude had a higher sensitivity than bipolar voltage mapping for identifying intramural viable myocardium in the atria. In this study, we aimed to retrospectively investigate the correlation between the residual potential in the posterior wall (PW) following PWI for persistent AF and atrial arrhythmia recurrence using endocardial unipolar voltage. Methods: This was a single‐center observational study. Patients who underwent PVI and PWI for persistent AF in the first procedure between March 2018 and December 2021 at the Tokyo Metropolitan Hiroo Hospital were included in this study. The patients were divided into two groups based on the presence of residual unipolar PW potentials after PWI with a cutoff of 1.08 mV and the recurrence of atrial arrhythmias was compared. Results: In total, 109 patients were included in the analysis. Forty‐three patients had residual unipolar potentials after PWI and 66 patients had no residual unipolar potentials. The atrial arrhythmia recurrence rate was significantly higher in the group with residual unipolar potential (41.8% vs. 17.9%, p = 0.003). The residual unipolar potential was an independent predictor of recurrence (odds ratio: 4.53; confidence interval: 1.67–12.3, p = 0.003). Conclusion: Residual unipolar potential after PWI for persistent AF is associated with recurrent atrial arrhythmias. [ABSTRACT FROM AUTHOR]

To compare the characteristics and clinical course of patients with coronavirus disease (COVID-19) according to the healthcare level of the admitted hospital, to provide an insight into determining the appropriate level of care for each patient. This retrospective, observational study utilized data from the COVID-19 Registry Japan (COVIREGI-JP), the largest Japanese registry of hospitalized patients with COVID-19. Datasets were obtained from reports filed as of May 31, 2022. A total of 59,707 patients (2004 in the primary care group, 41,420 in the secondary care group, and 16,283 in the tertiary care group) from 585 facilities were included in the analysis. Patients with established risk factors for severe disease, such as old age and the presence of comorbidities, were treated at higher care facilities and had poorer initial conditions and in-hospital clinical course, as well as higher mortality. Analysis of the fatality rates for each complication suggested that patients with complications requiring procedures (e.g. pleural effusions, myocardial ischemia, and arrhythmia) may have better survival rates in facilities with specialist availability. The number of deaths and severe COVID-19 cases in this study were notably less than those reported overseas. Our results showed that more difficult COVID-19 cases with poor outcomes were treated at higher care level facilities in Japan. Attending to possible complications may be useful for selecting an appropriate treatment hospital. Healthcare providers need to maintain a broad perspective on the distribution of medical resources. [ABSTRACT FROM AUTHOR]

Background: Although postoperative bleeding is a common and serious complication in breast cancer surgery, the risk factors remain unclear. Therefore, we examined the risk factors using a Japanese nationwide database. Methods: Patients who underwent breast cancer surgery between July 2010 and March 2020 were identified from a Japanese nationwide database. Multivariable analyses for 47 candidate risk factors (4 patient characteristics, 32 comorbidities, 5 tumor characteristics, 3 preoperative drug uses, and 3 surgical procedures) were conducted to investigate risk factors associated with postoperative bleeding requiring reoperation. Two sensitivity analyses were conducted: an analysis for postoperative bleeding with or without reoperation and an analysis for patients who underwent total mastectomy without breast reconstruction. Results: Among the 477,108 patients included, 7048 (1.5%) developed postoperative bleeding and 2357 (0.5%) underwent reoperation for postoperative bleeding. Male sex, old age, body mass index ≥ 25.0 kg/m2, several comorbidities (deficiency anemia, cardiac arrhythmias, hypertension, liver disease, psychoses, and valvular disease), preoperative heparin use, and several procedures were identified as risk factors. Deficiency anemia showed the highest odds ratio among the risk factors (4.41 [95% confidence interval, 3.63–5.36]). High odds ratios were also observed in total mastectomy (2.32 [2.10–2.56]), flap reconstruction (1.93 [1.55–2.40]), and preoperative heparin use (1.64 [1.26–2.14]). The results corresponded with the sensitivity analyses. Conclusions: This study identified several risk factors for postoperative bleeding in breast cancer surgery, such as high body mass index, anemia, cardiovascular diseases, liver diseases, psychoses, preoperative heparin use, and surgical procedures. [ABSTRACT FROM AUTHOR]

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence.Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis.Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion (<40%) on admission, and ventricular tachycardia or fibrillation on admission day were associated with worse 90-day survival. Severe histologic damage (damaged cardiomyocytes comprising ≥50% of the total cardiomyocytes) was associated with a worse 90-day prognosis in patients with lymphocytic myocarditis.Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP.Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000039763. [ABSTRACT FROM AUTHOR]

About three million people die from sudden cardiac arrest (SCA) or infarction each year. It is the biggest killer on the planet and it can happen to anyone, anywhere, and anytime. Early and effective diagnosis from ECG signals can help save a large part of these SCAs. Premature ventricular contraction (PVC) detection and classification was performed with different methods. A new method of automatic classification of PVC based on a three‐bit linear interpolation error signal (LIES) is proposed in this paper. We start by a QRS detection, a nonlinear transformation and then a sliding window. This method was tested on normal and abnormal beats obtained from MIT‐BIH and AHA databases. The proposed algorithm with a sensitivity 94.8% and a specificity was 98.6%. is accurate. This algorithm is also automatic, robust, and fast. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Perioperative anaphylaxis is a severe adverse event during anesthesia that requires prompt diagnosis and treatment by physicians, including anesthesiologists. Muscle relaxants and antibiotics are the most common drugs that cause perioperative anaphylaxis in Japan, as in many countries. In addition, sugammadex appears to be a primary causative agent. Obtaining previous anesthesia records is necessary in a patient with a history of allergic reactions during anesthesia, whenever possible, to avoid recurrence of anaphylaxis. Although medical staff are likely to notice abnormal vital signs because of complete monitoring during anesthesia, surgical drapes make it difficult to notice the appearance of skin symptoms. Even if there are no skin symptoms, anaphylaxis should be suspected, especially when hypotension resistant to inotropes and vasopressors persists. For improving the diagnostic accuracy of anaphylaxis, it is helpful to collect blood samples to measure histamine/tryptase concentrations immediately after the events and at baseline. The first-line treatment for anaphylaxis is adrenaline. In the perioperative setting, adrenaline should be administered through the intravenous route, which has a faster effect onset and is secured in most cases. Adrenaline can cause serious complications including severe arrhythmias if the appropriate dose is not selected according to the severity of symptoms. The anesthesiologist should identify the causative agent after adverse events. The gold standard for identifying the causative agent is the skin test, but in vitro tests including specific IgE antibody measurements and basophil activation tests are also beneficial. The Working Group of the Japanese Society of Anesthesiologists has developed this practical guide to help appropriate prevention, early diagnosis and treatment, and postoperative diagnosis of anaphylaxis during anesthesia. Grade of recommendations and levels of evidence Anaphylaxis is a relatively rare condition with few controlled trials, and thus a so-called evidence-based scrutiny is difficult. Therefore, rather than showing evidence levels and indicating the level of recommendation, this practical guideline only describes the results of research available to date. The JSA will continue to investigate anaphylaxis during anesthesia, and the results may lead to an amendment of this practical guideline. [ABSTRACT FROM AUTHOR]

Background: Telethonin (TCAP) is a Z‐disk protein that maintains cytoskeletal integrity and various signaling pathways in cardiomyocytes. TCAP is shown to modulate α‐subunit of the human cardiac sodium channel (hNav1.5) by direct interactions. Several TCAP variants are found in cardiomyopathies. We sought to investigate whether TCAP variants are associated with arrhythmia syndromes. Methods: Mutational analyses for TCAP were performed in 303 Japanese patients with Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and J‐wave pattern ECG. Using patch‐clamp techniques, electrophysiological characteristics of hNav1.5 were studied in HEK‐293 cells stably expressing hNav1.5 and transiently transfected with wild‐type (WT) or variant TCAP. Results: We identified two TCAP variants, c.145G>A:p.E49K and c.458G>A:p.R153H, in four individuals. p.E49K was found in two patients with ARVC or BrS. p.R153H was found in two patients with BrS or J‐wave pattern ECG. No patient had variant hNav1.5. Patch‐clamp experiments demonstrated that peak sodium currents were significantly reduced in cells expressing p.R153H and p.E49K compared with WT‐TCAP (66%, p.R153H; 72%, p.E49K). Voltage dependency of peak IV curve was rightward‐shifted by 5 mV in cells expressing p.E49K compared with WT‐TCAP. Voltage dependency of activation was not leftward‐shifted by p.R153H, while voltage dependency of steady‐state inactivation was leftward‐shifted by p.E49K. Conclusions: We found two TCAP variants in the patients with BrS, J‐wave pattern ECG, and ARVC that can cause loss‐of‐function of the hNav1.5 in heterologous expression systems. Our observation suggests that these variants might impair INa and be associated with the patients' electrophysiological phenotypes. Further studies linking our experimental data to clinical phenotypes are warranted. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Sulfonylurea‐related hypoglycemia increases the risk of cardiovascular sequela, such as cardiac arrhythmia. This study aimed to clarify the relationship between the level of glycated hemoglobin (HbA1c) and the duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas. Materials and Methods: Glucose levels in the enrolled patients (n = 300) were investigated with a professional continuous glucose monitoring device in the outpatient setting at six diabetes centers in Japan. Results: A total of 269 participants completed the study. The duration of hypoglycemia with glucose values of <54 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4% than in those with an HbA1c level of ≥8.0%, and that of hypoglycemia with glucose values of <70 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4%, 6.5–6.9% or 7.0–7.4% than in those with an HbA1c level of ≥8.0%. Patients with an HbA1c level of ≤6.4% were exposed to glucose values of <70 mg/dL for >10% of the time in daily life (6.8 ± 5.6 min/h). The duration of hypoglycemia with glucose values of <70 mg/dL was longer at night than during the daytime, and the nadir of glucose values occurred between 03.00 and 05.00 hours irrespective of HbA1c level. The duration of hypoglycemia was associated with the duration of diabetes and sulfonylurea dose. Conclusions: The duration of hypoglycemia was inversely correlated with HbA1c level and was longer during the night‐time than daytime in type 2 diabetes patients treated with sulfonylureas. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by right ventricular enlargement, right heart failure (HF), and ventricular arrhythmias which lead to sudden death especially in young adults. Current recommendations for management of patients with ARVC are antiarrhythmic medications, catheter ablation, and implantable cardioverter defibrillator therapy to prevent sudden cardiac death. However, despite these treatments, few patients suffer from recurrent ventricular arrhythmias or HF unresponsive to conventional management. Heart transplantation (HTx) is a preferred treatment for these cases, but because of a persistent donor heart shortage in Japan, ventricular assist device (VAD) support has become an important option for a management of the end‐stage ARVC. Previous articles reported 4 cases of a successful management by left ventricular assist device (LVAD), but the longest interval of LVAD support was only 333 days. We present 3 cases of ARVC patients who were successfully managed by LVAD implantation for more than a year. These 3 cases are unconventional examples of ARVC patients, considering the nature of the disease. The novelty of these cases should be taken in the context of the extremely long waiting period for HTx in Japan. [ABSTRACT FROM AUTHOR]

Objectives. Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website discloses adverse drug-event data that have been obtained from medical personnel reports investigated by the Pharmaceutical and Medical Devices Agency. Using these data, we investigated adverse events associated with ethical Kampo formulations. Methods. Reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data were obtained from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analyzed. Results. There were 4,232 reported adverse events associated with ethical Kampo formulations. The numbers of events by category were as follows: events related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix. The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba. Conclusion. Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety. [ABSTRACT FROM AUTHOR]

Aim: To investigate the influence of reproductive medicine in maternal death cases in Japan. Methods: This retrospective study investigated the incidence of maternal deaths related to reproductive medicine in Japan from 2013 to 2015, and the relationship between fertility treatment and maternal death. Results: Fifteen out of 134 women (11.2%) involved in this study who underwent treatment for infertility died. Four experienced pregnancy with severe maternal complications (26.6%). The complications were active systemic lupus erythematosus, exacerbated depression, uncontrolled arrhythmia and uncontrolled type 2 diabetes mellitus. At least three of these four died due to these complications. Conclusion: The maternal death rate of women who have undergone fertility treatment is similar to the birth rate due to assisted reproductive technology in Japan. Some maternal death cases involve severe uncontrolled complications. Therefore, medical histories should be evaluated before fertility treatment. [ABSTRACT FROM AUTHOR]

This study aimed to describe the characteristics of cases of out-of-hospital cardiac arrest (OHCA) with an initial asystole rhythm in which extracorporeal cardiopulmonary resuscitation (ECPR) was introduced and discuss the clinical indications for ECPR in such patients. This was a secondary analysis of the SAVE-J II study, a retrospective, multicentre, registry study involving 36 participating institutions in Japan. Patients with an initial asystole rhythm were selected. Favourable neurological outcomes (cerebral performance categories 1–2) constituted the primary outcome. In total, 202 patients met the inclusion criteria, with favourable neurological outcomes at hospital discharge in 12 patients (5.9%). Causes of cardiac arrest with favourable neurological outcomes were hypothermia (7 cases), acute coronary syndrome (2 cases), arrhythmia (2 cases), and pulmonary embolism (1 case). Among patients with non-hypothermia (temperature ≥32 °C) on hospital arrival with the cardiac rhythm of asystole or pulseless electrical activity (PEA) on arrival, all 107 patients (66 asystole, 41 PEA) who lacked one or more of the requirements (witness; bystander CPR; signs of life or pupil < 5 mm) had unfavourable neurological outcomes. All 5 cases with favourable neurological outcomes, except for 1 case with a short duration of no-flow time that was highly suspected based on the patient's history, met all the requirements on hospital arrival. A total of 202 ECPR cases with an initial asystole rhythm, including 12 patients with favourable neurological outcomes, were described. Even if the initial cardiac rhythm is asystole, ECPR could be considered if certain conditions are met. [ABSTRACT FROM AUTHOR]

Background: Long-acting β2-adrenoceptor agonists have been shown to increase the risk of atrial arrhythmias in patients with stable chronic obstructive pulmonary disease. The aim of this study was to investigate whether perioperative long-acting β2-adrenoceptor agonists treatment would increase the risk of postoperative atrial arrhythmias after lung cancer surgery in chronic obstructive pulmonary disease patients.Methods: We retrospectively analyzed 174 consecutive chronic obstructive pulmonary disease patients with non-small-cell lung cancer who underwent lobectomy or segmentectomy. The subjects were divided into those with or without perioperative long-acting β2-adrenoceptor agonists treatment. Postoperative cardiopulmonary complications were compared between the two groups.Results: There were no statistically significant differences between the perioperative long-acting β2-adrenoceptor agonists treatment group and the control group in the incidence of postoperative atrial arrhythmias (P = 0.629). In 134 propensity-score-matched pairs, including variables such as age, gender, comorbidities, smoking history, operation procedure, lung-cancer staging, and respiratory function, there were no significant differences between the two groups in the incidence of postoperative cardiopulmonary complications, including atrial arrhythmias.Conclusions: Perioperative administration of long-acting β2-adrenoceptor agonists might not increase the incidence of postoperative atrial arrhythmias after surgical resection for non-small-cell lung cancer in chronic obstructive pulmonary disease patients. [ABSTRACT FROM AUTHOR]

Background Our aim in this study was to estimate entrance skin doses (ESDs) to patients who underwent catheter ablation procedures, by using a reference air-kerma (RAK) displayed on the monitor of an angiography system (displayed RAK). Methods The displayed RAK was calibrated with use of an air-kerma value measured on a 20-cm-thick acrylic plate at the interventional reference point for the inclusion of backscattered x-rays (calibrated RAK). The ESD evaluated from the calibrated RAK (evaluated ESD) was verified through direct ESD measurements on an anthropomorphic phantom. The values of the evaluated ESD agreed with those of the measured ESD within a statistical error of 10% for both fluoroscopy and digital cine. The patient population included 356 consecutive patients (108 female and 248 male) who underwent catheter ablation procedures in the catheter laboratory of the Nagoya Daini Red-Cross Hospital from January 2013 to February 2014, where ablation procedures were performed for seven types of arrhythmias, i.e., atrial fibrillation (AF), atrial flutter (AFL), atrial tachycardia (AT), atrioventricular nodal reentrant tachycardia (AVNRT), ventricular premature contraction (VPC), ventricular tachycardia (VT), and Wolff-Parkinson-White syndrome (WPW). Results Patients who had arrhythmias that received the highest evaluated ESD were those for AF, followed by those for VPC, AT, WPW, AFL, VT, and AVNRT. Conclusions Despite extremely long fluoroscopy times of up to 66.6 minutes in left anterior oblique projection, only one patient was considered to exceed a threshold dose of 2 Gy for the onset of radiation-induced skin injuries. [ABSTRACT FROM AUTHOR]

Background: The association between QT interval and heart rate (HR), QT dynamics, has been reported to vary greatly between individuals. We investigated QT dynamics using fully automated QT interval measurement with a commercially available multifunctional electrocardiogram (ECG) recorder. Methods: The study group included 17 otherwise healthy subjects (mean age, 12.7 years; 11 girls, 6 boys), who were undergoing exercise test for arrhythmia evaluation. The subjects had single premature ventricular contraction. Results: Mean corrected QT interval (Fridericia) at rest was 412 ± 19ms (male, 408 ± 20ms; female, 414 ± 19ms), manually measured with a digitizer, using the tangent method. We assessed QT interval/HR slope during the whole exercise test, the exercise phase, and the recovery from exercise phase; the slopes were calculated offline after excluding wide QRS complex and were -1.15± 0.26 (r2=0.65), -1.18± 0.30 (r²=0.62), and -1.11± 0.25 (r² = 0.70), respectively. Estimated QT interval at HR 60 beats/min (QT60) was calculated using the regression line formula and was 383 ± 24 ms, 387 ± 28 ms, and 375 ± 21 ms, respectively. QT60 of the total exercise test correlated with the corrected QT interval at rest (P=0.04, r²=0.25). Conclusions: Assessment of QT dynamics is feasible on fully automated QT intervalmeasurement with this ECG recorder. Further studies are required in larger populations to confirm the accuracy and precision of QT measurement and QT dynamics using this new multifunctional ECG. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. Background: Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. Methods: The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. Results: Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. Conclusions: We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients. [Copyright &y& Elsevier]

Introduction: An increased incidence of sudden death has been observed among patients treated with antidepressants. A prolonged QTc interval is a known prognostic factor for fatal arrhythmia, and several studies have shown that the use of antidepressants can cause a prolonged QTc interval. However, few studies, especially in Japan, have compared the effects of multiple drugs on QTc interval or examined dose relationships in a clinical setting. Methods: We compared the effects of antidepressants on QT interval, corrected to QTc by Bazett's formula, in 729 Japanese patients who were diagnosed with mood disorder. Results: Using stepwise multiple linear regression analysis, we found that the use of tricyclic antidepressants (P < 0.01) and concomitant use of antipsychotics (P < 0.05), as well as advanced age and being female (known factors for prolonged QTc interval; both P < 0.01), significantly prolonged the QTc interval. Analysis of individual antidepressants also revealed that the use of clomipramine (P < 0.01) and amitriptyline (P < 0.05) significantly prolonged the QTc interval. Conclusion: Our results reveal that tricyclic antidepressants, especially clomipramine and amitriptyline, confer a risk of prolonged QTc interval in a dose-dependent manner. The selective serotonin reuptake inhibitors investigated (fluvoxamine, paroxetine, sertraline) were not indicated as risk factors for QTc prolongation. [ABSTRACT FROM AUTHOR]

. (J Cardiovasc Electrophysiol, Vol. 22, pp. 669-676, June 2011) [ABSTRACT FROM AUTHOR]

VT Associated with HCM. Objective: To assess the incidence, characteristics, and prognosis of ventricular tachyarrhythmia in hypertrophic cardiomyopathy (HCM). Patients: The study consisted of 66 consecutive patients with HCM who were admitted to Niigata University Hospital between 1992 and 2005. Their clinical characteristics and ECG morphology were investigated according to the type of HCM. Results: The type of HCM was asymmetric hypertrophy (ASH) in 34 patients (51%), obstructive HCM (HOCM) in 9 (14%), apical HCM (ApHCM) in 14 (21%), and midventricular obstruction (MVO) in 9 (14%). The cause of admission was ventricular tachyarrhythmia in 25 patients (38%), unexplained syncope in 11 (17%), and heart failure in 30 (45%). Sustained monomorphic ventricular tachycardia (SMVT) occurred in 19 patients and ventricular fibrillation in 6. In the 19 patients with SMVT, 12 had MVO and 3 of these had previous apHCM. Six of the 19 patients with SMVT had ASH, and 3 had abnormal apical wall motion. In 14 patients, the SMVT appeared to originate from the apical aneurysm based on the morphology of the tachycardia. Ventricular tachyarrhythmia recurred in 14 of the 25 patients (56%), and 4 of the 18 patients with an ICD had electrical storm. ASH with abnormal wall motion of the LV apex or MVO was recognized in the 4 patients with electrical storm; they commonly had abnormal Q waves and ST elevation in leads V4–V6. Conclusion: Ventricular tachyarrhythmia was responsible for 38% of hospitalizations in HCM, and SMVT occurred in patients with MVO and/or with abnormal wall motion of the LV apex. Electrical storm was more common in patients with ST elevation in precordial leads V4–V6. (J Cardiovasc Electrophysiol, Vol. 21, pp. 991-999, September 2010) [ABSTRACT FROM AUTHOR]

Objectives: This study describes a novel heterozygous gain-of-function mutation in the cardiac sodium (Na+) channel gene, SCN5A, identified in a Japanese family with lone atrial fibrillation (AF). Background: SCN5A mutations have been associated with a variety of inherited arrhythmias, but the gain-of-function type modulation in SCN5A is associated with only 1 phenotype, long-QT syndrome type 3 (LQTS3). Methods: We studied a Japanese family with autosomal dominant hereditary AF, multiple members of which showed an onset of AF or frequent premature atrial contractions at a young age. Results: The 31-year-old proband received radiofrequency catheter ablation, during which time numerous ectopic firings and increased excitability throughout the right atrium were documented. Mutational analysis identified a novel missense mutation, M1875T, in SCN5A. Further investigations revealed the familial aggregation of this mutation in all of the affected individuals. Functional assays of the M1875T Na+ channels using a whole-cell patch-clamp demonstrated a distinct gain-of-function type modulation; a pronounced depolarized shift (+16.4 mV) in V1/2 of the voltage dependence of steady-state inactivation; and no persistent Na+ current, which is a defining mechanism of LQTS3. These biophysical features of the mutant channels are potentially associated with increased atrial excitability and normal QT interval in all of the affected individuals. Conclusions: We identified a novel SCN5A mutation associated with familial AF. The mutant channels displayed a gain-of-function type modulation of cardiac Na+ channels, which is a novel mechanism predisposing to increased atrial excitability and familial AF. This is a new phenotype resulting from the SCN5A gain-of-function mutations and is distinct from LQTS3. [Copyright &y& Elsevier]

Abstract: Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+–Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects. [Copyright &y& Elsevier]

Malignant arrhythmia triggers critical attack on the heart and it can lead cardiac patients to death. We propose an arrhythmia detection algorithm based on recurrent neural network encoder–decoder (RED). Collecting arrhythmia data is practically possible, but it is costly because of arrhythmia has varying types. We ease the cost of labeling for constructing dataset using RED because it can be trained with normal data only. Also, collecting many kinds of arrhythmia data requires lots of cost. Also, for more efficient training, we use the Lyapunov exponent (LE) to extract features from electrocardiography. LE helps training RED with only a few data from normal people. RED determines the arrhythmia according to the restoration error. We assessed our algorithm with the MIT‐BIH Arrhythmia Database with a cutting‐edge performance on arrhythmia detection. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Inherited arrhythmias in Japan. The clinical and genetic characteristics of inherited arrhythmic disorders in Japan are briefly summarized. The incidence of hereditary long QT syndrome (LQTS) in Japan seems comparable to that in western countries. The genotypes are mainly LQT1 and LQT2; LQT3 and other types are rare. Mutations found in Japanese LQTS families are mostly novel compared to mutations reported in other countries and in different ethnic populations. Functional assays of the mutants in heterologous expression systems have disclosed novel mechanisms of current suppression in LQT1 and LQT2, and of gain of function in LQT3. Mutations in KCNJ2 may provide a new genotype (LQT7) of LQTS. In addition, mutations or single nucleotide polymorphisms in the channel genes responsible for LQTS (KvLQT1, HERG, and SCN5A) may predispose to drug-induced LQTS. A relatively high prevalence of Brugada syndrome is suspected in the Japanese population, and 1 of ∼2,000 asymptomatic individuals present Brugada-type ECG changes upon annual examination. Genetic screening of the symptomatic Brugada syndrome and suspected cases has revealed SCN5A mutations in only ∼12%. Therefore, the genetic basis of the majority of cases is not known. The expressed Na[sup +] current of SCN5A mutant channels showed the phenotype of decreased channel function commonly seen in Brugada mutations. A case of idiopathic ventricular fibrillation was found to have a novel mutation in SCN5A, in which the expressed current showed marked suppression of channel function.(J Cardiovasc Electrophysiol, Vol. 14, pp. 431-434, April 2003). [ABSTRACT FROM AUTHOR]

Abstract We report here 20 single-nucleotide polymorphisms (SNPs), including 15 novel ones, in six genes that are considered to be candidates for long QT syndrome (LQTS): 2 SNPs in KCNB1, 3 in KCND3, 3 in KCNJ11, 7 in ABCC9, 3 in ADRB1, and 2 in SLC18A2. We also examined their allelic frequencies in a Japanese sample population of LQTS-affected and nonaffected individuals. These data will be useful for genetic association studies designed to investigate acquired arrhythmias. [ABSTRACT FROM AUTHOR]

Excessive intake of caffeine, otherwise known to be a safe and mild central nervous system stimulant, causes nausea, vomiting, convulsions, tachycardia, and eventually fatal arrhythmias and death. Caffeine intoxication, a global problem, has been increasing in Japan since 2013. Thus, there is a need for rapid and accurate diagnosis of caffeine poisoning in forensic and clinical toxicology investigations. Herein, we demonstrate rapid and accurate caffeine quantitation by liquid chromatography tandem mass spectrometry using the standard addition method in a fatal case. Biological samples were diluted 500–100,000-fold and subjected to a simple pretreatment (adding caffeine standard and internal standard and passing through a lipid removal cartridge). The multiple reaction monitoring transitions were 195 → 138 for quantitation, 195 → 110 for the qualifier ion, and 204 → 144 for the internal standard (caffeine-d9). The standard plots were linear over 0–900 ng/mL (r 2 = 0.9994–0.9999) for biological samples, and the reproducibility (%RSD) of the method was 1.53–6.97% (intraday) and 1.59–10.4% (interday). Fatal levels of caffeine (332 μg/mL) and toxic to fatal levels of olanzapine (625 ng/mL), along with other pharmaceuticals were detected in the external iliac venous blood. The cause of death was determined to be multi-drug poisoning, predominantly caused by caffeine. Our method is useful for not only forensic cases but also the rapid diagnosis of caffeine overdose in emergency clinical settings. [ABSTRACT FROM AUTHOR]

• Wild-type ATTR amyloidosis is one of the typical diseases of systemic amyloidosis. • We investigated the prevalence rate of wild-type ATTR amyloidosis in Japan among 556 forensic autopsy cases. • The morbidity rate for this study was 12.3% for individuals >80 years and 34.9% for those >90 years. • ATTR-wt may be a risk factor for unexpected death among elderly individuals. Wild-type ATTR amyloidosis (ATTR-wt) is characterized by the accumulation of amyloid in the heart, leading to fatal heart failure and arrhythmia. In this study, we investigated the amyloid deposits in the heart from 556 forensic autopsy cases over 60 years of age. The prevalence of ATTR-wt was 5.8% (32 of the 556), with the prevalence increasing as a function of age. We identified an ATTR-wt-specific morbidity rate of 12.3% for patients over 80 years of age, while the prevalence among individuals over 90 years of age was 34.9%. In none of these 32 cases had a clinical diagnosis of ATTR-wt been made. In 29 of the 32 cases found to be ATTR-wt positive, an obvious extraneous cause of death was identified and included burning, drowning, hypothermia, suicide, and traffic accident. On the other hand, heart failure due to ATTR-wt was confirmed as the cause of death in 3 of the 32 cases. It is suggested that ATTR-wt may be associated with unexpected death among the elderly. [ABSTRACT FROM AUTHOR]

The article reports that according to research studies no association has been found between cardiac ion channel variants and sudden infant death. Recent molecular autopsy studies have although identified arrhythmia and inherited metabolic disease as possible cause of SUD and that small number of cases were due to disease-causing gene variants.

Introduction: Arrhythmia is a major complication in the acute phase of Takotsubo syndrome (TTS). However, the prevalence and impact of arrhythmias on short-term prognosis remains to be elucidated in a large cohort. Hypothesis: TTS patients with arrhythmia had a poorer short-term prognosis than those without arrhythmia. Methods: Using the Diagnosis Procedure Combination database 2010-2014 in Japan, we retrospectively identified eligible patients with TTS who underwent coronary angiography within two days after admission. We divided the patients into those who developed serious arrhythmia (arrhythmia group) and those who did not (non-arrhythmia group). Serious arrhythmia was defined as ventricular tachycardia or fibrillation (VT/VF), 2nd or 3rd atrioventricular block (AVB), sick sinus syndrome (SSS) or other arrhythmias requiring temporary pacing. We compared the patient characteristics and in-hospital outcomes between the groups. Results: Of 4,028 eligible patients (mean age 73.6 years; females 79.9%), 235 (5.8%) developed serious arrhythmia (87 VT/VF, 87 AVB, 33 SSS, 10 multiple arrhythmias, 18 other arrhythmias requiring temporary pacing). Patients in the arrhythmia group were more likely to have impaired consciousness and fewer comorbidities than patients in the non-arrhythmia group. Crude in-hospital mortality was significantly higher in the arrhythmia group (8.1% vs. 4.3%; p = 0.013). However, multivariable logistic regression analysis failed to show a significant association between the presence of arrhythmia and in-hospital mortality (adjusted odds ratio 1.60; 95% confidence interval 0.93-2.73) whereas older age, male sex, impaired consciousness, and a higher Charlson comorbidity index were significantly associated with higher in-hospital mortality. In the arrhythmia group, 52 (22.1%) patients received a permanent pacemaker (37 AVB; 10 SSS; 5 multiple arrhythmias) and eight (3.4%) received an implantable cardioverter defibrillator for secondary prevention of VT/VF. Conclusions: The prevalence of arrhythmia was 5.8% among patients with TTS. Although patients with arrhythmia were at higher risk of mortality, patient background rather than the arrhythmia itself may be associated with higher in-hospital mortality. [ABSTRACT FROM AUTHOR]

Abstract We report here 20 single nucleotide polymorphisms (SNPs), including 10 novel ones, and their allelic frequencies detected in four genes that are known to be responsible for familial long QT syndrome in the Japanese population; 7 polymorphisms are in the KCNQ1 gene, 6 in the KCNH2 gene, 5 in the SCN5A gene, and 2 in the KCNE1 gene. These data will be of use for genetic association studies of acquired cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

An abstract of the article "Nocturnal Difference in Ultra-Low Frequency Band of the Heart Rate Variability of Patients Stratified by Kampo Medicine Prescription" by Mosaburo Kainuma, Norihiro Furusyo, Shin-ichi Ando, Haru Mukae, Eiichi Ogawa, Kazuhiro Toyoda and Masayuki Murata is presented.

Highlights the genetic factors in cardiovascular disease. Discussion of how low-density lipoprotein, sitrosterolemia, deficient lipoprotein transport, and familial hypercholesterolemia can be factors in coronary heart disease; Discussion of monogenic cardiac disorders affecting blood pressure or causing arrhythmias; Identification of DNA variants that underly complex cardiovascular traits; Research in Japan by Yamada and colleagues examining polymorphisms and myocardial infarction.