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Brugada syndrome (BrS), which is characterized by J-point elevation in right precordial leads of a 12-lead electrocardiogram, is associated with the occurrence of ventricular fibrillation (VF). However, risk stratification of VF in patients with BrS remains challenging.The aim of this study was to identify a risk predictor of VF in patients with BrS using pharmacological tests.Twenty-one consecutive patients with BrS and a history of documented spontaneous VF (n = 16) or syncope presumed to be caused by lethal ventricular arrhythmia (n = 5) were enrolled. J-wave changes in response to intravenous verapamil, propranolol, and pilsicainide were separately assessed.During the median follow-up period of 86.0 months, 8 patients had VF recurrence (recurrence group) and 13 patients did not have VF recurrence (non-recurrence group). Intravenous propranolol injection induced significant J-wave augmentation (i.e., increase in amplitude0.1 mV) in the inferior and/or lateral leads in the recurrence group compared to the non-recurrence group (p = .048 and p = .015, respectively). Kaplan-Meier analysis revealed that VF recurrence is significantly higher in patients with BrS and J-wave augmentation due to intravenous propranolol than in patients without J-wave augmentation (p = .014).The study results show that propranolol-induced J-wave augmentation is involved in the risk of VF in patients with BrS. The results suggest that early repolarization patterns in response to pharmacological tests may be useful for risk stratification of VF in patients with symptomatic BrS.

This study aimed to determine possible associations between sarcopenia and poor cardiovascular outcomes in patients with chronic heart failure after cardiac resynchronization therapy.This retrospective study evaluated 120 patients who underwent cardiac resynchronization therapy between March 2004 and June 2018. In total, 58 patients who underwent computed tomography within 30 days of cardiac resynchronization therapy implantation were eligible for inclusion, and their data were analyzed (25 women; 33 men; mean age 71.6 ± 8.7 years). Skeletal muscle area was measured at the third lumbar vertebra, and skeletal muscle index was calculated. Major adverse cardiovascular events included cardiovascular death, hospitalization due to heart failure, cerebral infarction, acute myocardial infarction and cardiac arrest.During the follow-up period (mean 868 ± 617 days), major adverse cardiovascular events occurred in 22 of 58 patients (38%). The patients were allocated to two groups according to sex-based tertiles of skeletal muscle index. The lowest tertile was defined as the low skeletal muscle index group. Kaplan-Meier survival analysis showed that the low skeletal muscle index group had a higher incidence of major adverse cardiovascular events (log-rank 4.38; P = 0.036). Cox proportional hazards regression analysis also showed that low skeletal muscle index values were significantly associated with major adverse cardiovascular events (hazard ratio 3.08; 95% confidence interval 1.26-7.66, P = 0.014).Decreases in skeletal mass index on computed tomography might predict the occurrence of major adverse cardiovascular events in patients with chronic heart failure who underwent cardiac resynchronization therapy. Geriatr Gerontol Int 2022; 22: 1013-1018.

Background: Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40 mm Hg and stroke volume index [SVI] < 35 ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI., Materials and methods: A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40 mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF., Results: According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25 ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60–17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis., Conclusions: Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25 ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

The outcome of catheter ablation could probably differ among patients with atrial fibrillation (AF), depending on age and AF type. We aimed to investigate the difference in predictors of outcome after catheter ablation for AF among the patient categories divided by age and AF type.A total of 396 patients with AF (mean age 65.69 ± 11.05 years, 111 women [28.0%]) who underwent catheter ablation from January 2018 to December 2019 were retrospectively analyzed. We divided the patients into four categories: patients with paroxysmal AF (PAF) or persistent AF (PeAF) who were 75 years or younger (≤75 years) or older than 75 years (75 years). Kaplan-Meier survival analysis demonstrated that patients with PAF aged ≤75 years had the lowest AF recurrence among the four groups (log-rank test, p = .0103). In the patients with PAF aged ≤75 years (N = 186, 46.7%), significant factors associated with recurrence were female sex (p = .008) and diabetes (p = .042). In the patients with PeAF aged ≤75 years (N = 142, 35.9%), the only significant factor associated with no recurrence was medication with a renin-angiotensin system inhibitor (p = .044). In the patients with PAF aged75 years (N = 53, 14.4%), diabetes was significantly associated with AF recurrence (p = .021). No significant parameters were found in the patients with PeAF aged75 years (N = 15, 4.1%).Our findings indicate that the risk factors for AF recurrence after catheter ablation differed by age and AF type.

Mobile cloud electrocardiography (C-ECG) can reduce the door-to-balloon time of acute coronary syndrome (ACS) patients, so we hypothesized it would also assist in transporting ACS-suspected patients to the optimal institutes.Methods and Results: Initially, 10 fire departments in Oita had 10 ambulances equipped with C-ECG. Ambulance crews recorded a 12-lead ECG from the patient at the first point of contact and transmitted them to 18 hospitals (13 institutions (PCII) with 24-h availability for percutaneous coronary intervention (PCI) and 5 regional core hospitals (RCH) without 24-h PCI) for analysis by a cardiologist. During 41 months, 476 ECGs suspected to be ACS were transmitted and analyzed. Of these, 24 ECGs transmitted to PCII were judged as not requiring PCI, and the patients were directly transported to a RCH (PCII-RCH); 35 ECGs sent to a RCH were judged as requiring PCI, and the patients were directly transported to a PCII (RCH-PCII). The prevalence of cardiovascular disease was significantly higher in the RCH-PCII group than in the PCII-RCH group (P0.01). There was no significant difference in the door-to-balloon time between the RCH-PCII and the group in which the C-ECG was sent to a PCII and the patients were transported directly to PCII (PCII-PCII) (49±14 vs. 59±20 min, P=0.14).Prehospital 12-lead ECG can assist in transporting ACS-suspect patients to the optimal treatment facility.

Background It is common to develop heart failure (HF) events even in respondents to cardiac resynchronization therapy (CRT) during a long‐term observation period. We investigated the predictors for long‐term outcome in responders in comparison with nonresponders in patients diagnosed with HF along with implanted CRT. Methods We enrolled 133 consecutive patients (mean age, 70 ± 10 years; 72 males) implanted with CRT from April 2010 to July 2019. Accurate follow‐up information (mean follow‐up period, 983 ± 801 days) was obtained from 66 responders and 53 nonresponders. Results Kaplan‐Meier event‐free curves showed that major adverse cerebral and cardiovascular event (MACCE)‐free ratio was significantly lower as the stage of renal function progresses (log rank, 19.5; P 44 mL/min/1.73 m2) group than in the depressed group (log rank, 20.29; P, Our results suggest that the factors for MACCE during long follow‐up period were distinctively different between responders and nonresponders. Patients with depressed e‐GFR are suggested to have poor prognosis even if they are responders to CRT.

Implantable cardioverter-defibrillators (ICDs) are the main therapy to prevent sudden cardiac death in patients with Brugada syndrome (BrS). The subcutaneous ICD (S-ICD) can eliminate lead-associated complications compared with transvenous ICD (TV-ICD). However, S-ICD is susceptible to T-wave oversensing (TWOS) and may result in more frequent inappropriate shocks in patients with BrS. This study aimed to compare inappropriate shocks between TV-ICD and S-ICD in patients with BrS. We enrolled 32 patients with BrS (including one woman; mean age 52 ± 18 years) who were implanted with ICD (23 TV-ICDs and 9 S-ICDs) between January 2002 and November 2018 in Oita University Hospital. We carried out a standard surface electrocardiogram (ECG) screening tests in both supine and standing positions prior to S-ICD implantation. The patients received routine clinical review every month and device monitoring every 4 months. The period of follow-up was 129 ± 51 months. Six patients with BrS and TV-ICDs experienced inappropriate shocks (26%) with their ICD therapy. In contrast, two patients with BrS and S-ICDs experienced inappropriate shocks (22%). There was no significant difference between the two groups (P = 0.82). Although one case in the S-ICD group experienced TWOS-induced inappropriate shock, SMART Pass (new high-pass filter) prevented the subsequent recurrence of inappropriate shocks during ICD therapy. Our results suggest that S-ICD is not inferior to TV-ICD in the incidence of inappropriate shocks. SMART Pass may be a useful tool to prevent inappropriate ICD shocks by TWOS in patients with BrS.

The properties of glucose changes in patients with chronic heart failure remain elusive. In the present study, we investigated the sequential changes of interstitial glucose concentrations in patients with chronic heart failure and heart disease who were not undergoing antidiabetic therapy.A glucose monitoring device (FreeStyle Libre Pro) was attached to the backside of an upper arm and the interstitial glucose concentration was monitored every 15 minutes for 1 week. Eleven patients with chronic heart failure (Heart failure (+) ) and 7 patients with chronic heart diseases but not with heart failure (Heart failure (-) ) were enrolled. The average level and peak value of interstitial glucose concentrations, and the duration of hyperglycemia (≥ 140 mg/dL) were not significantly different between Heart failure (+) and Heart failure (-). The duration of hypoglycemia (< 80 mg/dL) was significantly longer and the trough value was significantly lower in Heart failure (+) compared with Heart failure (-). Most of the patients in Heart failure (+) were exposed to a long duration of hypoglycemia from midnight to morning. Importantly, none of the patients who showed hypoglycemia complained of any subjective symptoms during hypoglycemia. Malabsorption may be one of the mechanisms of hypoglycemia.In summary, patients with chronic heart failure are at risk of developing hypoglycemia even if they do not undergo any antidiabetic therapy.

Aims Cardiac hypertrophy is a compensatory response to pressure overload, leading to heart failure. Recent studies have demonstrated that Rho is immediately activated in left ventricles after pressure overload and that Rho signalling plays crucial regulatory roles in actin cytoskeleton rearrangement during cardiac hypertrophic responses. However, the mechanisms by which Rho and its downstream proteins control actin dynamics during hypertrophic responses remain not fully understood. In this study, we identified the pivotal roles of mammalian homologue of Drosophila diaphanous (mDia) 1, a Rho-effector molecule, in pressure overload-induced ventricular hypertrophy. Methods and results Male wild-type (WT) and mDia1-knockout (mDia1KO) mice (10–12 weeks old) were subjected to a transverse aortic constriction (TAC) or sham operation. The heart weight/tibia length ratio, cardiomyocyte cross-sectional area, left ventricular wall thickness, and expression of hypertrophy-specific genes were significantly decreased in mDia1KO mice 3 weeks after TAC, and the mortality rate was higher at 12 weeks. Echocardiography indicated that mDia1 deletion increased the severity of heart failure 8 weeks after TAC. Importantly, we could not observe apparent defects in cardiac hypertrophic responses in mDia3-knockout mice. Microarray analysis revealed that mDia1 was involved in the induction of hypertrophy-related genes, including immediate early genes, in pressure overloaded hearts. Loss of mDia1 attenuated activation of the mechanotransduction pathway in TAC-operated mice hearts. We also found that mDia1 was involved in stretch-induced activation of the mechanotransduction pathway and gene expression of c-fos in neonatal rat ventricular cardiomyocytes (NRVMs). mDia1 regulated the filamentous/globular (F/G)-actin ratio in response to pressure overload in mice. Additionally, increases in nuclear myocardin-related transcription factors and serum response factor were perturbed in response to pressure overload in mDia1KO mice and to mechanical stretch in mDia1 depleted NRVMs. Conclusion mDia1, through actin dynamics, is involved in compensatory cardiac hypertrophy in response to pressure overload.

Background: The onset of acute myocardial infarction (AMI) is related to weather conditions, but the impact of age on gender differences in the AMI onset–weather association has not been elucidated. Methods and Results: We analyzed the Oita AMI Registry and obtained data for 403 enrolled patients. To examine the impact of age, we categorized the patients into 4 groups: young (age ≤65 years) women (n=20); young men (n=123); elderly (age >65 years) women (n=84); and elderly men (n=176). The analyzed meteorological factors were maximum and minimum temperature, intraday temperature difference, average humidity, and average atmospheric pressure. The young women group had a higher minimum temperature (17.7±5.7℃ vs. 13.8±8.2℃, P=0.04), lower intraday temperature difference (7.0±2.6℃ vs. 8.4±2.9℃, P=0.03), higher average humidity (74.5±12.1% vs. 68.1±12.0%, P=0.03), and lower average atmospheric pressure (1,009.5±5.0 hPa vs. 1,012.9±5.8 hPa, P=0.01) than the young men group on the onset day. In the elderly groups, there was no significant difference in meteorological variables except for the intraday temperature difference 2 days before AMI onset. Conclusions: AMI onset appears to be more sensitive to weather conditions (i.e., minimum temperature, average atmospheric pressure, and average humidity) in young patients than in elderly patients. In particular, young women had AMI on days with low intraday temperature difference and high humidity relative to men.

Hyponatraemia is defined as a serum sodium concentration of

Background: The mobile cloud electrocardiography (C-ECG) system is useful for reducing door-to-balloon (DTB) time in patients with acute coronary syndrome (ACS), but few studies have reported the usefulness of the C-ECG system across a wide provincial prefecture, such as Oita, in Japan. Methods and Results: On 17 April 2017, the C-ECG system was integrated into the Oita remote image transmission system, in 10 ambulances of 10 respective fire departments in Oita Prefecture. During 6 months, 162 ECG indicating suspected ACS were transmitted to 18 hospitals using the C-ECG system. Of 162 patients, 17 who received emergency percutaneous coronary intervention (PCI) were assigned to the cloud group (mean age, 71±11 years). The control group consisted of 29 consecutive ACS patients who were transported to Oita University Hospital without using the C-ECG system (mean age, 66±12 years). Another 40 consecutive patients were diagnosed with ACS before transportation to Oita University Hospital, and were assigned to the diagnosed group (mean age, 70±14 years). DTB time (70±26 min vs. 96±24 min, P

Background: Fibrotic remodeling of epicardial adipose tissue (EAT) is crucial for proinflammatory atrial myocardial fibrosis, which leads to atrial fibrillation (AF). Objectives: We tested the hypothesis that the ratio of central to marginal adipocyte diameter in EAT represents its fibrotic remodeling. Based on a similar concept, we also tested whether the percent (%) change in EAT fat attenuation determined using computed tomographic (CT) images can detect this remodeling. Methods: Left atrial appendages were obtained from 76 consecutive AF patients during cardiovascular surgery. EAT in the central area (central EAT: C-EAT) and that adjacent to the atrial myocardium (Marginal EAT: M-EAT) were evaluated histologically. CT images for all of the 76 patients were also analyzed. Results: The adipocyte diameter was smaller, fibrotic remodeling of EAT (EAT fibrosis) was more severe, and infiltration of macrophages and myofibroblasts was more extensive in M-EAT than in C-EAT. EAT fibrosis was positively correlated with adipocyte diameter in C-EAT and negatively correlated in M-EAT, resulting in a positive correlation between EAT fibrosis and the ratio of central to marginal adipocyte diameter (C/M diameter ratio; r = 0.73, P < .01). The C/M diameter ratio was greater in patients with persistent AF than in those with paroxysmal AF. CT images demonstrated that the %change in EAT fat attenuation was positively correlated with EAT fibrosis. Conclusion: Our results suggest that the central-to-marginal adipocyte diameter ratio is tightly associated with fibrotic remodeling of EAT. In addition, the %change in EAT fat attenuation determined using CT imaging can detect remodeling noninvasively.

Reducing complications at the puncture site after percutaneous coronary intervention (PCI) is important. The diameter of a 6.5-French (Fr) sheathless guiding catheter (GC) is smaller by approximately 2-Fr compared to a 6-Fr conventional sheath. In the present study, we investigated the post-PCI puncture site complications of a transradial approach in each gender while using a 6.5-Fr sheathless GC.Our study consisted of 332 patients who underwent transradial coronary intervention (TRI) between August 2017 and July 2019. We classified the patients into either the 6.5-Fr sheathless GC (Asahi, Intecc, Aichi, Japan) Group (Sheathless group: n = 182 males, 58 females) or the 6-Fr sheathed GC Group (Sheathed group: n = 150 males, 36 females). We determined the complications at the puncture site: oozing, subcutaneous hemorrhage, formation of hematoma, pseudoaneurysms, and peripheral neuropathy. The body mass index of the patients was greater in the sheathless GC group compared to the sheathed GC group (24.5 ± 3.5 kg/mThe use of the 6.5-Fr sheathless GC system in a transradial approach reduced the complications at the puncture site in female patients. The 6.5-Fr sheathless GC system may be a safe option for them compared to the conventional sheath system.

Background The Shanghai Score System, which weighs electrocardiogram (ECG) findings reflecting repolarization abnormalities, has been proposed for diagnosis of early repolarization syndrome (ERS). However, recent studies have suggested the involvement of depolarization abnormalities in some ERS patients. The aim of this study was to validate the Shanghai Score System in predicting the recurrence of ventricular fibrillation (VF) in ERS patients. The predictive value of fragmented QRS (fQRS) was also investigated. Methods Fifteen consecutive ERS patients (14 males, median age of 47 years) with a history of VF were retrospectively reviewed. The Shanghai Score System points were calculated, and the presence of fQRS was evaluated. Results During the median follow‐up period of 79.2 months, five patients experienced VF recurrence. In the VF recurrence group, two patients showed augmented amplitude of J waves with horizontal ST‐segment, while the other three patients had dynamic changes in J‐wave amplitude. The Shanghai Score System points in the VF recurrence group were higher than those in the VF non‐recurrence group (6.5 [range: 5.8–6.8] vs. 4.5 [range: 4.0–4.5], p = 0.002). The presence of fQRS on standard 12‐lead ECG was more frequently observed in the VF recurrence group compared with the non‐recurrence group (100% vs. 10%, p = 0.002). Conclusions The present study demonstrated that the Shanghai Score System could effectively identify ERS patients at high risk for VF recurrence. The results also suggested that the presence of fQRS, a marker of depolarization abnormalities, may be useful for predicting VF recurrence in ERS patients.

Background It has been reported that atrial fibrillation (AF) may contribute to impairment of baroreflex sensitivity (BRS). However, the difference of BRS between patients with persistent AF (PeAF) and those with paroxysmal AF (PAF) is unknown. We tested the hypothesis that patients with PeAF have a more impaired BRS compared with those with PAF. Methods and Results From October 2015 onwards, a total of 67 patients (14 women [20.9%]; mean age 65.2±10.1 years) with PAF (n=46, 68.7%) and PeAF (n=21, 31.3%), who underwent catheter ablation, were prospectively enrolled. The baseline BRS was evaluated during sinus rhythm. The baseline BRS in patients with PeAF was significantly lower than those with PAF (2.97 [0.52–6.62] ms/mm Hg versus 4.70 [2.36–8.37] ms/mm Hg, P =0.047). The BRS was significantly depressed after catheter ablation in all the patients (4.66 [1.80–7.37] ms/mm Hg versus 0.55 [−0.15 to 1.22] ms/mm Hg, P P Conclusions Our findings demonstrated that the baseline BRS was more depressed in patients with PeAF compared with PAF. Catheter ablation depressed BRS irrespective of the type of AF, with a greater effect in patients with PAF than PeAF.

Background Rikkunshito (RKT), a traditional herbal medicine, has been demonstrated to exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in several organs. This study tested the hypothesis that RKT can suppress angiotensin II (AngII)-induced inflammatory atrial fibrosis and ameliorate enhanced vulnerability to atrial fibrillation (AF). Methods Eight-week-old male C57BL/6 mice were subcutaneously infused with either vehicle or AngII (2.0 mg/kg/day) for 2 weeks. Water or RKT at a dose of 1000 mg/kg/day were orally administered once daily for 2 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced either by transesophageal burst pacing in vivo or by burst/extrastimuli in isolated perfused hearts using a Langendorff apparatus. Results RKT at a dose of 1000 mg/kg/day for 2 weeks attenuated atrial interstitial fibrosis and profibrotic and proinflammatory signals induced by continuous infusion of AngII. RKT attenuated AngII-induced enhanced vulnerability to AF in in vivo experiments and in isolated perfused hearts. Atractylodin, an active component of RKT, exhibited antifibrotic activity comparable to that of RKT. RKT reversed AngII-induced suppression of sirtuin 1 (Sirt1) translocation to the nuclei. RKT suppressed AngII-induced phosphorylation of IκB, overexpression of p53, and cellular apoptotic signals and apoptosis. All of the antagonizing effects of RKT against AngII were attenuated by a concomitant treatment with a growth hormone secretagogue receptor (GHSR)-inhibitor. Conclusion Our results demonstrated that RKT prevented atrial fibrosis and attenuated enhanced vulnerability to AF induced by AngII. The results also suggested that potentiating the GHSR-Sirt1 pathway is involved in these processes.

The onset of acute myocardial infarction (AMI) has been reportedly related to weather conditions. The aim of this study was to investigate the impact of weather conditions on AMI onset. Our study population consisted of 274 patients enrolled in the Oita AMI Registry who were admitted with AMI between June 2012 and May 2013. We divided the 365 days of the year into the four seasons: spring (March, April, May), summer (June, July, August), autumn (September, October, November), and winter (December, January, February). We classified each day as a day of onset of AMI (onset day) or a day of non-onset of AMI (non-onset day). Information on maximum temperature, minimum temperature, mean humidity, and mean atmospheric pressure was obtained from the Japan Meteorological Agency. In summer, the temperatures and intraday temperature differences were significantly lower on onset days than on non-onset days. Receiver operating characteristic analysis for predicting AMI onset in each season showed that the maximum temperature 2 days before AMI onset in summer had the largest area under the curve (AUC = 0.72, p = 0.0005). Our analysis demonstrated that there exist specific weather conditions that influence AMI onset in each season in Oita prefecture. AMI onset in summer was particularly associated with the maximum temperature 2 days before AMI onset.

Background Variant angina (VA) is caused by reversible coronary artery spasm, which is characterized by chest pain with ST segment elevations on a standard 12-lead electrocardiogram (ECG) at rest. VA attack often causes lethal ventricular arrhythmia. The early repolarization (ER) pattern is associated with ventricular fibrillation (VF). However, whether the ER pattern is involved in VF in patients with VA is not known. We investigated the association between the ER pattern and VF in patients with VA. Methods Fifty patients underwent induction of ST elevation on 12-lead ECGs with total or nearly total occlusion by provocation test (VA patients). Twelve of these patients underwent induction of VF or had documented VF before hospital admission (VF occurrence group). The J-wave morphology was characterized as exhibiting notching or slurring. The amplitude of each J wave was measured manually with amplified waveforms. Results ER patterns were observed significantly more often in the VF occurrence group than in the non-VF occurrence group (P = 0.007). The J-wave amplitude was significantly higher in the VF occurrence group compared with the non-VF occurrence group (P = 0.02). Univariate analyses suggested that age, smoking, and ER patterns were associated with VF. Upon multivariate analyses, age (odds ratio [OR] = 0.880; 95% confidence interval [CI]: 0.794-0.975; P = 0.014) and ER patterns (OR = 8.937; 95% CI:1.661-48.06; P = 0.011) predicted VF independently. Conclusions These data suggest that an ER pattern in VA patients is a risk factor for VF. The ER pattern may be one of the useful factors for adaptation of implantation of implantable cardioverter-defibrillator in patients with coronary spasm-induced VF.

Hyperleptinemia and Atrial FibrillationBackground Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. Methods and Results Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P < 0.01). In WT-HFD mice, hyperleptinemia was observed as expected. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob-HFD mice (P < 0.01). In isolated perfused hearts, the interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (P < 0.05). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT-HFD mice, which was not observed in Ob-HFD mice (P < 0.05). Upregulation of collagen1, collagen3, α-smooth muscle actin, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA levels was noted in WT-HFD mice LA, but attenuated in Ob-HFD mice LA. Conclusions Our findings suggest that hyperleptinemia exacerbates HFD-mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF.

Background We have recently reported that peri-left atrial epicardial adipose tissue (EAT) is associated with atrial myocardial fibrosis, in which angiopoietin-like protein 2 (Angptl2) protein content in EAT is associated with atrial myocardial fibrosis. Objective This study aimed to examine whether Angptl2 contained in peri-left atrial EAT can induce atrial myocardial fibrosis. Methods Human peri-left atrial EAT and abdominal subcutaneous adipose tissue (SAT) were collected from 9 autopsy cases. EAT- or SAT-conditioned medium was dropped onto the rat left atrial epicardial surface using an organo-culture system. Conditioned medium, recombinant Angptl2, and its antibody effects on organo-cultured rat atrial myocardial fibrosis were evaluated. Angptl2 effects on cultured neonatal rat fibroblasts were also investigated. Results EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium with a progressive increase in the number of myofibroblasts. The profibrotic effect of EAT was greater than that of SAT. EAT in patients with atrial fibrillation induced a more significant atrial fibrosis than in those without. Treatment with human recombinant Angptl2 induced fibrosis in organo-cultured rat atrium, which was suppressed by the concomitant treatment with Angptl2 antibody. In cultured fibroblasts, Angptl2 upregulated the expression of α-smooth muscle actin, transforming growth factor-β1, phospho-extracellular signal-regulated kinase,phospho-inhibitor of κBα, and phospho-p38 mitogen-activated protein kinase. Conclusion This study demonstrated that Angptl2 contained in EAT played a crucial role in EAT-induced inflammatory atrial fibrosis. The results also suggested that antagonizing the expression of Angptl2 in EAT can be a novel therapeutic approach to prevent atrial fibrillation.

Background Using excised human left atrial appendage samples, we previously demonstrated that epicardial adipose tissue (EAT) are highly associated with atrial myocardial fibrosis as a substrate of atrial fibrillation (AF). We also reported the relationship between Angptl2 in EAT and atrial fibrosis. However, the mechanism is not clear. The purpose is to clarify the mechanisms underlying the effect of EAT on the atrial myocardium. Methods Human peri-left atrial EAT and abdominal subcutaneous adipose tissue (SAT) samples were obtained from 6 cases (2 females, 70.2±13.2 years). 50 mg of EAT and SAT were quickly washed with PBS and centrifuged 1min at 1200rpm. After 3 times this procedures, adipose tissues were cultured in DMEM F12 medium with Fetal bovine Serum (FBS) overnight. After pre-incubation, EAT and SAT tissues were washed and centrifuge d three times and cultured in medium without FBS for 24hours. Finally, we collected oozed medium (conditioned medium) and used for experiments. Concentrations of Angptl2 in conditioned medium were measured by ELISA. To study the effects of conditioned medium, we used “organo-culture” system. Isolated atrium from 8week old male Sprague-Dawley rats were placed on the porous membrane with the endothelial face toward the membrane. After that, loading medium (conditioned medium:culture medium = 1:4), culture medium (control), or recombinant Angptl2 were dropped onto the epicardial face of the atrium once a day and incubated for 7 days (37°C, 5% CO2). Then, histological and immunohistochemical analysis were performed. We also performed quantitative reverse transcription–polymerase chain reaction (RT–PCR) analysis. Next, we isolated and cultured neonatal rat fibroblast and loaded Angptl2 for 24 hours.After collected these cells, we performed western blotting analysis. Results Atria organo-culture incubated for 7 days with conditioned medium showed global fibrosis. At epicardial side, fibrotic area of EAT group was significantly greater compared to that of SAT and control group (P mRNA of Col1a1, col3a1 and TGFβ1 were significantly increased in EAT group compared with the SAT and control group. And, the concentration of conditioned medium created from EAT was significant higher than that from SAT (P Then, we dropped 500 ng/ml of recombinant Angptl2 onto the rat atria. Fibrotic area of Angptl22 group significantly greater than that of control with increasing number of α-SMA positive cells, and mRNA of col3a1 and TGFβ1 were significantly increased in Angptl2 group compared with control group. In cultured fibroblasts, α-SMA and p-ERK expression were increased in Angptl2 group measured by western blotting analysis. Conclusions Our results demonstrated that EAT rather than SAT induces atrial myocardial fibrosis. There is a possibility that Angptl2 effused from EAT plays a part in atrial fibrosis thought EAT paracrine effect. Acknowledgement/Funding ONO PHARMACEUTICAL CO

Background Cardiac sarcoidosis is a cause of epicarditis and sustained life-threatening ventricular arrhythmias. These arrhythmias occasionally arise from epicardial. Positron emission tomogramphy-comututed tomography (PET-CT) is useful for diagnosis with sarcoidosis. However, the usefulness for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis is unknown. Objective We hypothesized that the evaluation of pericardial fat inflammation could identify high-risk sarcoidosis patients for ventricular arrhythmias. Methods We enrolled 20 consecutive patients with cardiac sarcoidosis performed PET-CT between August 2016 and December 2018. In each case, we measured the maximum standardized uptake value (SUVmax) of pericardial fat around the left atrium, both ventricules, atrioventricular groove, and left main coronary. Results Seven patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). VT/VF patients had significantly more complete right bundle branch block (P=0.035), larger left atrial dimension (P=0.021), larger left ventricular end-diastolic dimension (P=0.005), lower ejection fraction (P=0.007), and higher E/e' (P=0.004). SUVmax of pericardial fat in the roof of left atrium (LA) and left ventricular (LV) with VT/VF patients were significantly higher than non-VT/VF patients (LA: 1.63 vs 1.32, P=0.0311; LV: 1.84 vs 1.26, P=0.045). The cut-off values of SUVmax derived from the ROC curve in the roof of LA and LV are 1.47 and 1.59 respectively. The Kaplan Meire estimator showed that high SUVmax patients in the roof of LA had significantly more detection of NSVT. Conclusions Our results suggest the relationship between SUVmax and VT/VF occurrence in patients with cardiac sarcoidosis. The evaluateon of SUVmax may be useful for VT/VF risk stratification.

The present case report describes a 59-year-old female with manifest Wolff–Parkinson–White syndrome and severe left ventricular (LV) dysfunction, however, there was no indication of heart palpitations. The polarity of delta is consistent with the features of the right anteroseptal accessory pathways (APs). The echocardiography showed a remarkable dyssynchrony of the LV wall motion. To circumvent the cardiac dysfunctions, radiofrequency catheter ablation (RFCA) was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and the clinical reports observed 6 months following RFCA showed that the LV ejection fraction had been improved from 13% up to 48%, in addition to the improvement in other parameters. The RFCA prevented her from receiving a cardiac resynchronization therapy defibrillator as well as a heart transplantation.

Cardiac Sarcoidosis and CRT OutcomeIntroduction Cardiac resynchronization therapy (CRT) has been shown to be effective for patients with chronic heart failure; however, the efficacy of CRT in patients with cardiac sarcoidosis (CS) has not been established. Methods We compared the outcomes of patients with CS who received CRT to patients with dilated cardiomyopathy (DCM). The incidence of major adverse cerebral and cardiovascular events (MACCE) in 11 consecutive CS patients (8 females; mean age, 66 ± 8.0 years) who received CRT were compared with 29 DCM patients (9 females; mean age, 70 ± 8.9 years). Results Females and patients with previous right ventricular pacing were largely included in the comparison of CS and DCM patients (P

BACKGROUND AND OBJECTIVES Recently, it was reported that mast cells (MCs) could underlie the mechanisms of several cardiovascular diseases. However, the role of MCs in diabetes-induced atrial fibrillation (AF) has not been notably investigated. We tested the hypothesis that MC deficiency attenuates hyperglycemia-induced AF in mice. METHODS AND RESULTS Mast cell-deficient W/W(v) mice, and congenic +/+ littermates (WT) were divided into either the vehicle (VEH)-injection group or the streptozotocin (STZ)-injection group (MCKO-VEH, MCKO-STZ, WT-VEH, and WT-STZ groups). On day 28 of our studies, we observed that (1) STZ-induced hyperglycemia increased MC infiltration in the left atrium (LA) in WT mice (P < 0.01), (2) atrium isolated from the WT-STZ group showed inhomogeneous interstitial fibrosis, abundant infiltration of macrophages, and enhanced apoptosis compared to the WT-VEH group (P < 0.01, P < 0.01, P < 0.05, respectively). However, the changes observed in the WT-STZ group were significantly attenuated in the MCKO-STZ mice. In addition, we observed that (3) messenger RNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, transforming growth factor-β, and collagen-1 in the LA were increased in the WT-STZ group, but not in the MCKO-STZ group, (4) STZ-induced hyperglycemia increased AF induction and prolonged interatrial conduction time in the WT mice, which were not observed in the MCKO mice, and that (5) hyperglycemia-enhanced atrial production of reactive oxygen species (ROS) was equally observed in the WT and MCKO mice. CONCLUSIONS Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.

Pulmonary vein antrum isolation (PVAI) by radiofrequency catheter ablation (RFCA) could unexpectedly transect the sites where the major atrial ganglionated plexi are located, which affects the cardiac autonomic function [(1)][1]. The evaluation of baroreflex sensitivity (BRS) is an established tool

Although J-waves have been known to be associated with vulnerability to ventricular fibrillation, their electrophysiologic mechanism remains to be elucidated. The papillary muscles (PMs) of the left ventricle (LV) have been recognized as the target site of radiofrequency ablation for ventricular arrhythmias. However, the relationship between PM hypertrophy and J-waves has not been investigated.To investigate the electrocardiographic characteristics, including the J-waves, in patients with solitary PM hypertrophy.We studied 101 patients with PM hypertrophy without LV hypertrophy (PMH group) and 159 age- and sex-matched control subjects (control group). The parameters of the 12-lead electrocardiogram and the echocardiogram were compared between the two groups.Compared with the control group, the PMH group had significantly higher incidence (15% vs. 33%, p=0.001) and amplitude (0.17±0.06mV vs. 0.28±0.17mV, p0.01) of J-waves; significantly longer QRS, QTc, and JTc intervals (p=0.0001, p0.0001, and p0.05, respectively); significantly greater Sokolow-Lyon index (p0.001); and significantly greater LV wall thickness and LV mass index (p0.0001 for each). Multivariate logistic regression analysis showed that only the PM hypertrophy was an independent predictor of the presence of J-waves.PM hypertrophy was related to the genesis of J-waves.

Cardiac resynchronization therapy (CRT) has been established as a treatment for patients with chronic heart failure (HF). We tested the hypothesis that assessment of coronary flow reserve (CFR) predicts the long-term outcome of CRT. The study consisted of 114 HF patients implanted with a CRT device for the treatment of advanced HF between April 2010 and April 2018. After excluding patients that withdrew from long-term follow-up and patients missing a baseline CFR measurement, we enrolled 53 eligible patients. CFR was determined non-invasively by transthoracic echocardiography. Based on the ROC curve for predicting the appearance of major adverse cerebral and cardiovascular events (MACCE), the level of preserved CFR was set at >1.35 in responders. Accurate follow-up information (mean 873 ± 498 days) was obtained in 23 patients with a preserved CFR (16 females; mean age 71 ± 7.9 years) and 11 patients with a depressed CFR (5 females; mean age, 73 ± 7.6 years) in responders. Kaplan–Meier survival analysis demonstrated that the depressed CFR group had a higher prevalence of MACCE than the preserved CFR group (log rank, 9.83; p = 0.0021). Multivariate analysis revealed that depressed CFR was associated with MACCE (hazard ratio 4.88, 95% confidence interval 1.13–26.5, p = 0.0329). Our results suggest that the assessment of CFR predicts the outcome in responders to CRT. Preservation of coronary circulation flow might underlie one of the mechanisms for a better response to CRT in responders.

Background Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), but the underlying mechanisms remain to be fully elucidated. Objective The purpose of this study was to examine, using human left atrial appendage (LAA) samples, the interactive relationship between the EAT profile and atrial myocardial fibrosis through histologic and biochemical analyses. Methods LAA samples were obtained from 59 consecutive AF patients during cardiovascular surgery. In histologic analysis, adipose tissue, atrial myocardial fibrosis, EAT fibrosis, macrophage infiltration, and matrix metalloproteinase-2 and hypoxia-inducible factor-1α (Hif-1α) expression were evaluated in LAA sections. In biochemical analysis, proinflammatory/fibrotic proteins in EAT, total collagen in left atrial (LA) myocardium, angiopoietin-like protein-2 (Angptl2)-related proteins in EAT, and proinflammatory/fibrotic proteins in serum were evaluated. Results Histology revealed that the severity of fibrotic remodeling of EAT was associated with LA myocardial fibrosis. Immunohistochemical and electron microscopic findings revealed that fibrotic remodeling of EAT was associated with infiltration of macrophages and myofibroblasts. Protein concentration analysis demonstrated that the total collagen in the LA myocardium was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor, and matrix metalloproteinase-2 and matrix metalloproteinase-9 in EAT. The proinflammatory and profibrotic cytokines/chemokines in EAT and the total collagen in the LA were also positively correlated with Angptl2 in EAT. Conclusion Our study demonstrated that fibrotic remodeling and cytokines/chemokines in peri-LA EAT were associated with atrial myocardial fibrosis as a substrate of AF. Our results also suggested that overexpression of Hif-1α and Angptl2 may be involved in these processes.