Efficacy of Computed Tomography-Based Evaluation of Myocardial Extracellular Volume Combined With Red Flags for Early Screening of Concealed Cardiac Amyloidosis in Patients With Atrial Fibrillation.

BACKGROUND: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.Methods and Results: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate (99 mTc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 mTc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 mTc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing. CONCLUSIONS: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

Risk stratification of ventricular fibrillation in patients with symptomatic Brugada syndrome using pharmacological tests.

BACKGROUND: 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. OBJECTIVE: The aim of this study was to identify a risk predictor of VF in patients with BrS using pharmacological tests. METHODS: 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. RESULTS: 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 amplitude >0.1 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). CONCLUSION: 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.

Usefulness of Prehospital 12-Lead Electrocardiography System in ST-Segment Elevation Myocardial Infarction Patients in Oita　- Comparison Between Urban and Rural Areas, Weekday Daytime and Weekday Nighttime/Holidays.

BACKGROUND: We have reported that a prehospital 12-lead electrocardiography system (P-ECG) contributed to transport of suspected acute coronary syndrome (ACS) patients to appropriate institutes and in this study, we compared its usefulness between urban and rural areas, and between weekday daytime and weekday nighttime/holiday.Methods and Results: Consecutive STEMI patients who underwent successful primary percutaneous coronary intervention after using P-ECG were assigned to the P-ECG group (n=123; 29 female, 70±13 years), and comparable STEMI patients without using P-ECG were assigned to the conventional group (n=117; 33 females, mean age 70±13 years). There was no significant difference in door-to-reperfusion times between the rural and urban cases (70±32 vs. 69±29 min, P=0.73). Door-to-reperfusion times in the urban P-ECG group were shorter than those in the urban conventional group for weekday nighttime/holiday (65±21 vs. 83±32 min, P=0.0005). However, there was no significance different between groups for weekday daytime. First medical contact to reperfusion time (90±22 vs. 105±37 min, P=0.0091) in the urban P-ECG group were significantly shorter than in the urban conventional groups for weekday nighttime/holiday, but were not significantly different between the groups for weekday daytime. CONCLUSIONS: P-ECG is useful even in urban areas, especially for patients who develop STEMI during weekday nighttime or while on a holiday.

Predictors of outcome after catheter ablation for atrial fibrillation: Group analysis categorized by age and type of atrial fibrillation.

BACKGROUND: 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. METHODS AND RESULTS: 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 aged >75 years (N = 53, 14.4%), diabetes was significantly associated with AF recurrence (p = .021). No significant parameters were found in the patients with PeAF aged >75 years (N = 15, 4.1%). CONCLUSIONS: Our findings indicate that the risk factors for AF recurrence after catheter ablation differed by age and AF type.

Innovations in online classes introduced during the COVID-19 pandemic and their educational outcomes in Japan.

BACKGROUND: The novel coronavirus disease (COVID-19) pandemic emerged in Japan in February 2020, forcing the adoption of online education by university medical schools across Japan. The advantages and disadvantages of online education have been studied in Japan; however, the educational outcome of online classes conducted during the COVID-19 pandemic has not been completely evaluated. In this study, we examined the relationship between lecture format (e.g., face-to-face or online) and performance of third-year university students in their organ-specific cardiovascular course examination. METHODS: This retrospective, nonclinical, and noninterventional comparative educational study included 550 third-year medical students who took a cardiovascular course between April 2018 and May 2022. Cardiovascular coursework was conducted in-person in 2018 and 2019, online in 2020 and 2021, and again in-person in 2022. The course comprised 62 lecture and 2 problem-based learning (PBL) sessions. A quiz was set up in advance on Moodle based on all lectures conducted in 2021 and 2022. A written examination was administered at the end of the course to evaluate the knowledge of students. The student online course evaluation questionnaires were administered in 2020 and 2021. Examination scores and proportion of failures in each year were compared. RESULTS: The mean examination scores were significantly higher in 2021 and 2022 than in 2018, 2019, and 2020 (p < 0.05). Univariate and multivariate analyses adjusted for the class type, online quiz, and PBL revealed that only online quiz was significantly associated with better examination results (p < 0.05). A student course evaluation survey indicated that the online format did not interfere with the students' learning and was beneficial. CONCLUSIONS: The introduction of online classes into medical education due to the COVID-19 pandemic was as effective as face-to-face classes owing to learning management system and other innovations, such as online quizzes. Online education may confer more benefits when provided in a combination with face-to-face learning after COVID-19 pandemic.

Prehospital 12-Lead Electrocardiography System in Oita Assisted Transport of "True" Acute Coronary Syndrome Patients to Optimal Institutes.

BACKGROUND: 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 (P<0.01). 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). CONCLUSIONS: Prehospital 12-lead ECG can assist in transporting ACS-suspect patients to the optimal treatment facility.

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

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.

Reduction of bleeding complications on puncture site after percutaneous coronary intervention using a 6.5-French sheathless guiding catheter.

BACKGROUND: 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. METHODS AND RESULTS: 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/m2 vs. 23.6 ± 3.7 kg/m2, p = 0.02). In males, there was no significant difference in the complication rate at the puncture site between the sheathless GC and sheathed GC groups (19.3% vs. 18.6%, p = 0.88). However, the complication rate at the puncture site in females was higher in the sheathed GC group than in the sheathless GC group (36% vs. 15.5%, p = 0.02). A multiple logistic regression analysis revealed that the use of a 6.5-Fr sheathless GC independently reduced the complications in female patients (p = 0.006). CONCLUSION: The 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.

Fragmented QRS as a risk marker for the occurrence of ventricular fibrillation in patients with variant angina.

BACKGROUND: Variant angina (VA) is caused by reversible coronary artery spasm, which is characterized by chest pain with ST-segment elevations on standard 12-lead electrocardiogram (ECG) at rest. Ventricular fibrillation (VF) is often caused by VA attack, but the risk stratification is not well understood. The purpose of this study was to evaluate the impact of fragmented QRS (fQRS) on VF occurrence in VA patients. METHODS: Ninety-four patients who showed ST elevation on 12-lead ECGs with total or nearly total occlusion in response to coronary spasm provocation test were enrolled. Among them, 16 patients had documented VF before hospital admission (n = 12) or experienced VF during provocation test (n = 4) (VF occurrence group). The fQRS was defined as the presence of spikes within the QRS complex of two or more consecutive leads. RESULTS: The prevalence of fQRS was more often observed in the VF occurrence group than in the non-VF occurrence group (63% [10/16] vs. 27% [21/78], p = 0.009). Univariate analyses revealed that age, history of syncope, QTc, and the presence of fQRS were associated with VF occurrence (p = 0.004, 0.005, 0.029, and 0.008, respectively). Furthermore, upon multivariate analyses using those risk factors, age, QTc, and fQRS predicted VF occurrence independently (p = 0.007, 0.041, and 0.014, respectively). CONCLUSIONS: The present study demonstrated that fQRS in VA patients is a risk factor for VF. The fQRS may be a useful factor for the risk stratification of VF occurrence in VA patients.

Effects of canagliflozin on human myocardial redox signalling: clinical implications.

AIMS: Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans. METHODS AND RESULTS: Study 1 included 364 patients undergoing cardiac surgery. Right atrial appendage biopsies were harvested to quantify superoxide (O2.-) sources and the expression of inflammation, fibrosis, and myocardial stretch genes. In Study 2, atrial tissue from 51 patients was used ex vivo to study the direct effects of canagliflozin on NADPH oxidase activity and nitric oxide synthase (NOS) uncoupling. Differentiated H9C2 and primary human cardiomyocytes (hCM) were used to further characterize the underlying mechanisms (Study 3). SGLT1 was abundantly expressed in human atrial tissue and hCM, contrary to SGLT2. Myocardial SGLT1 expression was positively associated with O2.- production and pro-fibrotic, pro-inflammatory, and wall stretch gene expression. Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1signalling and improved NOS coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro. These were attenuated by knocking down SGLT1 in hCM. Canagliflozin had striking ex vivo transcriptomic effects on myocardial redox signalling, suppressing apoptotic and inflammatory pathways in hCM. CONCLUSIONS: We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings reveal a novel mechanism contributing to the beneficial cardiac effects of canagliflozin.

Usefulness of subcutaneous implantable cardioverter-defibrillator therapy in patients with Brugada syndrome.

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.

Role of fragmented QRS and Shanghai score system in recurrence of ventricular fibrillation in patients with early repolarization syndrome.

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.

Potential Risk of Hypoglycemia in Patients with Heart Failure.

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.

Seasonal variations of weather conditions on acute myocardial infarction onset: Oita AMI Registry.

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.

Assessment of coronary flow reserve predicts long-term outcome of responders to cardiac resynchronization therapy.

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.

Early repolarization is involved in ventricular fibrillation in patients with variant angina.

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.

A case of Wolff-Parkinson-White syndrome presenting spontaneous mutual frequent transition between atrioventricular reciprocating tachycardia and atrioventricular nodal re-entrant tachycardia.

Atrioventricular reciprocating tachycardia (AVRT) and atrioventricular nodal re-entrant tachycardia (AVNRT) can coexist and present unidirectional transition (from AVRT to AVNRT, or from AVNRT to AVRT) in a single patient. Actually, such cases have already been reported previously. However, a case with spontaneous bidirectional transition of both tachycardias during supraventricular tachycardia has never been reported. This article describes a case with spontaneous, mutual, and frequent transition between AVRT and AVNRT.

Exaggerated Reactivity of Parasympathetic Nerves Is Involved in Ventricular Fibrillation in J-Wave Syndrome.

INTRODUCTION: Brugada syndrome (BrS) and early repolarization syndrome (ERS) are termed the J-wave syndrome. In most cases of J-wave syndrome, ventricular fibrillation (VF) often occurs around midnight or in the early morning when parasympathetic tone is augmented. OBJECTIVE: The purpose of this study was to clarify the relationship between VF and autonomic nervous activity in patients with J-wave syndrome. METHODS AND RESULTS: We enrolled 28 consecutive patients with J-wave syndrome (20 BrS and 8 ERS) in whom implantable cardioverter defibrillators (ICDs) were implanted between January 2002 and December 2014. Eleven patients (39%) experienced ICD shock delivery due to VF recurrence after ICD implantation (recurrent-VF group). We investigated baroreflex sensitivity (BRS) using the phenylephrine method, heart rate variability (HRV) with Holter electrocardiography, plasma levels of norepinephrine, and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy to estimate autonomic nervous function. Upon measurement of HRV, plasma levels of norepinephrine, and 123 I-MIBG testing, there was no significant difference between recurrent-VF and nonrecurrent-VF groups. However, BRS was significantly higher in the recurrent-VF group than in the nonrecurrent-VF group (P = 0.03). Kaplan-Meier curves suggested that high-BRS patients had higher VF recurrence than those with nonhigh-BRS (P = 0.04). Cox proportional hazards regression analyses showed that high BRS was associated independently with VF recurrence (P = 0.002). CONCLUSIONS: Our results suggest that exaggerated reactivity of parasympathetic nerves, as represented by increased BRS, may underlie VF in patients with J-wave syndrome.

Hyperleptinemia Exacerbates High-Fat Diet-Mediated Atrial Fibrosis and Fibrillation.

BACKGROUND: 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.