Search

Abstract Aims Hospitalizations are common in patients with heart failure and are associated with high mortality, readmission and economic burden. Detecting early signs of worsening heart failure may enable earlier intervention and reduce hospitalizations. The HeartLogic algorithm is designed to predict worsening heart failure using diagnostic data from multiple device sensors. The main objective of this analysis was to evaluate the sensitivity of the HeartLogic alert calculation in predicting worsening heart failure events (HFEs). We also evaluated the false positive alert rate (FPR) and compared the incidence of HFEs occurring in a HeartLogic alert state to those occurring out of an alert state. Methods The HINODE study enrolled 144 patients (81 ICD and 63 CRT‐D) with device sensor data transmitted via a remote monitoring system. HeartLogic alerts were then retrospectively simulated using relevant sensor data. Clinicians and patients were blinded to calculated alerts. Reported adverse events with HF symptoms were adjudicated and classified by an independent HFE committee. Sensitivity was defined as the ratio of the number of detected usable HFEs (true positives) to the total number of usable HFEs. A false positive alert was defined as an alert with no usable HFE between the alert onset date and the alert recovery date plus 30 days. The patient follow‐up period was categorized as in alert state or out of alert state. The event rate ratio was the HFE rate calculated in alert to out of alert. Results The patient cohort was 79% male and had an average age of 68 ± 12 years. This analysis yielded 244 years of follow‐up data with 73 HFEs from 37 patients. A total of 311 HeartLogic alerts at the nominal threshold (16) occurred across 106 patients providing an alert rate of 1.27 alerts per patient‐year. The HFE rate was 8.4 times greater while in alert compared with out of alert (1.09 vs. 0.13 events per patient‐year; P

Abstract Aims Cardiac resynchronization therapy (CRT) is an established treatment for drug‐refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real‐world outcomes among CRT recipients with a history of hospitalization for acute HF. Methods and results This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120 ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II–IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline‐directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30 days of CRT implantation. The primary endpoint was all‐cause death or first hospitalization for HF; the secondary endpoint was all‐cause death. We enrolled 194 patients (75% male; mean age, 65 ± 13 years; 78% with non‐ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159 ± 26 vs. 171 ± 32 ms; P = 0.004), higher estimated glomerular filtration rate (55.2 ± 20.0 vs. 47.8 ± 24.7 mL/min/1.73 m2; P = 0.022), and more dilated cardiomyopathy. During a median follow‐up period of 29 months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6 months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6 months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27–0.97; P = 0.043). Conclusions Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS ≥ 120 ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

Abstract Background The relationships between frailty and clinical outcomes in elderly Japanese patients with non‐valvular atrial fibrillation (NVAF) after catheter ablation (CA) have not been established. We evaluated the frailty rate of patients undergoing CA for NVAF, examined whether CA for NVAF improves frailty, and analyzed the CA outcomes of patients with and without frailty. Methods Elderly Japanese patients (≥65 years; mean age: 72.8 years) who participated in the real‐world ablation therapy with anti‐coagulants in management of atrial fibrillation registry and who responded to the frailty screening index survey were included (n = 213). Frailty and AF recurrence were assessed preoperatively and at 3 and 6 months after CA. Results Twenty‐six patients (12.8%) were frail, 109 (53.7%) were pre‐frail, and 68 (33.5%) were robust. Cardiovascular (frailty: 0.5%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year) and cardiac (frailty: 0.5%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year) events, as well as major bleeding (frailty: 0.3%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year), were numerically more frequent in the frailty group. No deaths from cardiovascular or stroke/systemic thromboembolic events occurred. A large proportion of patients did not experience 3‐month (frailty: 96.2%; pre‐frailty: 96.3%; robust: 88.2%) or 6‐month (frailty: 88.5%; pre‐frailty: 91.7%; robust: 86.8%) AF recurrence after CA. Weight loss, walking speed, and fatigue improved in the frailty and pre‐frailty groups after CA. Conclusion Japanese patients aged ≥65 years with frailty or pre‐frailty had improved frailty screening index components, such as weight loss, walking speed and fatigue, after CA. Therefore, elderly patients with frailty or pre‐frailty may benefit from CA for NVAF.

Abstract Aims The aim of the Mid‐Q Response study is to test the hypothesis that adaptive preferential left ventricular‐only pacing with the AdaptivCRT algorithm has superior clinical outcomes compared to conventional cardiac resynchronization therapy (CRT) in heart failure (HF) patients with moderately wide QRS duration (≥120 ms and

Abstract Aims The HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients. Methods and results After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter‐defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT‐D), (iii) standard medical therapy (‘non‐device’: ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1–3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT‐D cohorts, considered as high‐voltage (HV) cohorts, were pooled for Kaplan–Meier analysis and propensity‐matched to Multicenter Automatic Defibrillator Implantation Trial‐Reduce Inappropriate Therapy (MADIT‐RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity‐matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT‐RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT‐D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT‐Pacing (8.4%, P = 0.05). Conclusions The mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline‐indicated CRT devices had poor outcomes.

Abstract Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very‐low‐density lipoprotein (VLDL) and low‐density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and DEA with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and DEA were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration‐to‐dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride (rs = 0.541, p

BackgroundAtrial fibrillation (AF) is the most common arrhythmia and often recurs despite catheter ablation. The recurrence of AF is often underdiagnosed by standard 24-hour electrocardiogram (ECG) because of its transient and silent nature. A garment-style ECG with a highly conductive textile electrode made of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate)(PEDOTPSS) and nanofiber (Garment ECG) has been developed that can provide longer-term continuous monitoring. This study investigated whether 2-week Garment ECG can reveal instances of AF recurrence in patients who are diagnosed as remaining in sinus rhythm by 24-hour Holter ECG.MethodsThe open-label randomized crossover study enrolled 67 patients (63.1±10.6 years old, 53 men) who had undergone initial AF ablation. Three months after ablation, patients were randomly assigned to group 1 (n = 35), 2-week Garment ECG followed by 24-hour Holter ECG, or group 2 (n = 32), 24-hour Holter ECG followed by 2-week Garment ECG. The detection of AF recurrence was compared between the two devices.ResultsThe Garment ECG showed AF recurrence in 12 patients (18%) compared to 4 patients for the Holter ECG (6%, p = 0.008). The ECG acquisition rate was higher for Holter ECG than for Garment ECG (100.0% [interquartile range 100.0-100.0%] versus 82.4% [71.1-91.0%], pConclusionsDespite the lower ECG acquisition rate, the 2-week Garment ECG revealed instances of AF recurrence after ablation in patients who were underdiagnosed by 24-hour Holter ECG.Trial registrationClinical Trial Registration: URL: https://jrct.niph.go.jp/en-latest-detail/jRCTs032180018 Unique Identifier: jRCTs032180018.

BackgroundThere is growing evidence indicating a close relationship between inflammation and atrial fibrillation (AF). Although underlying inflammatory atrial cardiomyopathy may contribute to the development of AF, the arrhythmogenic remodeling caused by atrial inflammation has not been elucidated in detail. Herein, we examined electrical, structural, and autonomic changes in the atria in a mouse model of autoimmune myocarditis.MethodsBALB/c mice were immunized with cardiac myosin peptide (MyHC-α614–629) conjugated with complete Freund’s adjuvant on days 0 and 7. Susceptibility to AF was assessed using right-atrial burst pacing.ResultsThe mice immunized with MyHC-α614–629 showed an inflammatory atrial cardiomyopathy phenotype, with enlarged atria; a high degree of inflammatory cell infiltration primarily consisting of CD4+ T cells, CD8+ T cells, Ly6GlowCD11b+ macrophages, and CD11c+ dendritic cells; and severe interstitial fibrosis with collagen deposition. These mice demonstrated significantly enhanced susceptibility to AF, as indicated by their increased AF induction rate and duration. In addition, the expression of potassium channels (Kcnh2, Kcnd3, and Kcnj2) and calcium handling-associated genes (Cacna1c, Camk2, Ryr2, and Atp2a2) was downregulated. Connexin 40 expression was significantly downregulated, leading to frequent lateralization to the inflamed atrium. Sympathetic and parasympathetic innervation and neurotrophin expression (nerve growth factor and brain-derived neurotrophic factor) were upregulated in the inflamed atria.ConclusionInflammatory atrial cardiomyopathy promotes susceptibility to AF via arrhythmogenic electrical, structural, and autonomic remodeling of the atria.

Abstract Background Randomized trials in Western countries have provided evidence that prophylactic implantable cardioverter‐defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life‐threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown. Methods The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2‐5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter‐defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT‐D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity‐matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life‐threatening VA symptoms for the ICD and CRT‐D cohorts. For nondevice and PA cohorts, the primary outcome is all‐cause mortality. Conclusions The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.

Background: Holter electrocardiogram (ECG) is the gold standard for ambulatory monitoring of atrial fibrillation (AF) but it is insufficient because of its limited recording time. Although several consumer ECG devices provide longer recording time, they generally do not undergo the regulatory process for medical use. Furthermore, current medical-grade devices for longer ECG monitoring are not continuous or too invasive for AF monitoring. A wearable ECG with a medical-grade dry textile electrode is a promising technology to remedy this limitation. This pilot study aimed to simultaneously compare the wearable and Holter ECGs for ambulatory monitoring in a clinical setting. Methods: This prospective observational study enrolled 18 patients who underwent AF ablation. One day after AF ablation, ambulatory ECG was obtained for three hours simultaneously using both the wearable and Holter ECG devices. Automatic ECG interpretations between devices were compared with correlation and agreement analyses. Results: Simultaneous ECG monitoring demonstrated a comparable analysis time and total heart beats between the two devices. Almost complete correlation and agreement were also demonstrated in all clinically relevant testing aspects except in R-wave amplitude (r = 0.743, p < .001). AF was detected in three patients. AF duration was the same in both ECG devices in two patients with continuous AF. In the remaining patient with intermittent AF, AF duration was shortened by 0.6% with the wearable ECG as compared to that with the Holter ECG. Conclusions: Simultaneous ECG comparison revealed a high consistency between the wearable and Holter ECG devices. The results of this study warrant further clinical studies for long-term monitoring of ambulatory ECG after AF ablation.

Abstract Background Brugada syndrome (BrS) is diagnosed in patients with ST‐segment elevation with spontaneous, drug‐induced, or fever‐induced type 1 morphology. Prognosis in type 2 or 3 Brugada electrocardiogram (Br‐ECG) patients remains unknown. The purpose of this study is to evaluate long‐term prognosis in non‐type 1 Br‐ECG patients in a large Japanese cohort of idiopathic ventricular fibrillation (The Japan Idiopathic Ventricular Fibrillation Study [J‐IVFS]). Methods From 567 patients with Br‐ECG in J‐IVFS, a total of 28 consecutive non‐type 1 patients who underwent programmed electrical stimulation (PES) (median age: 58 years, all male, previous sustained ventricular tachyarrhythmias [VTs] 1, syncope 11, asymptomatic 16) were enrolled. Cardiac events (CEs: sudden cardiac death or sustained VT/ventricular fibrillation) during the follow‐up period were examined. Results During a median follow‐up of 136 months, four patients (14%) had CEs. None of patients with PES‐ have experienced CEs. There was no statistically significant clinical risk factor for the development of CEs. Using the Kaplan–Meier method, the event‐free rate significantly decreased in a group with all 3 risk factors (symptom, wide QRS complex in lead V2, and positive PES) (p = .01). Conclusions Our study revealed long‐term prognosis in patients with non‐type 1 Br‐ECG. The combination analysis of these risk factors may be useful for the risk stratification of CEs in non‐type 1 Br‐ECG patients. The present study suggests that the patients with all these parameters showed high risk for CEs and need to be carefully followed.

Abstract Background Cardiac tamponade is a serious complication of catheter ablation for atrial fibrillation (AF). However, the outcomes of catheter ablation in patients of cardiac tamponade are unknown. Methods We performed catheter ablation in 2467 sessions of AF or a recurrence of AF between January 2007 and January 2016. Of these, 29 events in 27 patients (1.18%: 22 men; 64.5 ± 10.4 years; 17 with paroxysmal AF) of cardiac tamponade during or after the procedure were recorded. The clinical characteristics and outcomes of these 29 events were studied in detail. Results Of the 19 events where the ablation procedure was completed, seven events developed acute recurrence of AF (36.8%). Of the 10 events with an incomplete procedure, 10 exhibited AF recurrence (100.0%). Direct oral anticoagulants were used in seven events, and clinical outcomes were not significantly different compared to the remaining 21 events that were prescribed warfarin. Pericarditis occurred in 10 events (34.5%) after the procedure, and the incidence rate was lower in patients receiving prophylactic nonsteroidal anti‐inflammatory drugs or steroids (2/15, 13.3% vs 8/14, 57.1%; P = 0.013). Repeated sessions were performed in 12 events (two with a complete initial procedure, 10 with an incomplete initial procedure). Freedom from atrial arrhythmias was observed in 27 events (93.1%, 9 with antiarrhythmic drugs) over midterm follow‐up (3.1 ± 2.6 years). Conclusion Although cardiac tamponade caused by catheter ablation led to a high rate of acute AF recurrence and pericarditis, the midterm recurrence rates of AF are unaffected if the procedure can be completed.

Background. Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. Methods. We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. Results. In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. Conclusions. The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.

The purpose of this study was to examine, using a sequential model, factors associated with volunteer participation and sleep efficiency in Japanese older adults receiving treatment for hypertensive disease. A questionnaire survey was conducted to collect data on participant demographics, lifestyle, health status, and depression, and sleep activity monitors were used to objectively measure sleep status and sleep efficacy. Of the 167 respondents, the 59 being treated for hypertension were divided into two groups based on their participation in volunteering. Comparison between the groups showed significant differences in nocturnal awakening, sleep efficiency, and nap frequency. Volunteers had less nocturnal awakening, increased sleep efficiency, fewer naps, and decreased depression. Covariance structure analysis of the survey data and sleep measurements for hypertensive older adults in the volunteer group was performed by modeling the relationships between variables with a path diagram. Our model showed strong goodness of fit (χ2 test = 15.636, p = 0.111, GFI = 0.925, AGFI = 0.842, CFI = 0.925, RMSEA = 0.099). The findings of this study suggest that older adults with hypertension who participate in volunteer activities have less nocturnal awakening, improved sleep quality, and reduced risk of depression, and provides evidence to promote social participation in volunteering among older adults with hypertension.

Background: Several studies reported that cavotricuspid isthmus-dependent atrial flutter (typical AFL) frequently coexists with atrial fibrillation (AF); however, the underlying mechanisms have not been fully investigated. This study aimed to reveal the mechanisms of the initiation of typical AFL and the association between typical AFL and AF. Methods: Among 154 consecutive patients undergoing a first catheter ablation of AF, we investigated the appearance and mechanism of spontaneous initiation of typical AFL during catheter ablation. Then, we retrospectively investigated 67 consecutive patients without a previous AF episode who underwent typical AFL ablation. The occurrence and predictors of AF after catheter ablation were evaluated. Results: During AF ablation, spontaneous initiation of typical AFL occurred during sinus rhythm in eight (5.2%) patients. The initiations of typical AFL were pulmonary vein (PV) firings except in one patient, in whom paroxysmal AF following superior vena cava firing initiated reverse typical AFL after PV isolation. After typical AFL ablation, AF occurred in 23 (34.3%) patients (mean follow up, 28.2±20.3 months). Kaplan-Meier analysis showed the occurrence of AF after typical AFL ablation to be significantly higher in the patients with a larger left atrial diameter over 40 mm (log-rank test, P=0.046). Conclusions: PV firing through AF played an important role in initiating typical AFL. The occurrence of AF after typical AFL ablation was high, and a dilated left atrium was associated with increased occurrence of AF. These findings disclosed the close relationship between typical AFL and AF, especially PV firing.

Drug treatment and/or implantable cardioverter defibrillator (ICD) implantation are the most widely accepted first-line therapies for channelopathic patients who have recurrent syncope, sustained ventricular tachycardia (VT), or documented ventricular fibrillation (VF), or are survivors of cardiac arrest. In recent years, there have been significant advances in mapping techniques and ablation technology, coupled with better understanding of the mechanisms of ventricular tachyarrhythmia in channelopathies. Catheter ablation has provided important insights into the role of the Purkinje network and the right ventricular outflow tract in the initiation and perpetuation of VT/VF, and has evolved as a promising treatment modality for ventricular tachyarrhythmia even in channelopathies. When patients are exposed to a high risk of sudden cardiac death or deterioration of their quality of life due to episodes of tachycardia and frequent ICD discharges, catheter ablation may be an effective treatment option to reduce the risk of sudden cardiac death and decrease the frequency of cardiac events. In this review, we summarize the current understanding of catheter ablation for VT/VF in patients with channelopathies including Brugada syndrome, idiopathic VF, long QT syndrome, and catecholaminergic polymorphic VT.

The presented data were obtained from 982 consecutive patients receiving their first pacemaker implantation with right ventricular (RV) lead placement between January 2008 and December 2013 at two centers in Japan. Patients were divided into RV apical and septal pacing groups. Data of Kaplan–Meier survival analysis and Cox regression analysis are presented. Refer to the research article “Implications of right ventricular septal pacing for medium-term prognosis: propensity-matched analysis” (Mizukami et al., in press) [1] for further interpretation and discussion. Keywords: RV septal pacing, RV non-apical pacing, Prognosis, Heart failure, Mortality, Data

Percutaneous coronary intervention (PCI) may be complicated by periprocedural myocardial infarction (PMI) as manifested by elevated cardiac biomarkers such as creatine kinase (CK)-MB or troponin T. The occurrence of PMI has been shown to be associated with worse short- and long-term clinical outcome. However, recent studies suggest that PMI defined by biomarker levels alone is a marker of atherosclerosis burden and procedural complexity but in most cases does not have independent prognostic significance. Diagnostic multi-modality imaging such as intravascular ultrasound, optical coherence tomography, coronary angioscopy, near-infrared spectroscopy, multidetector computed tomography, and magnetic resonance imaging can be used to closely investigate the atherosclerotic lesion in order to detect morphological markers of unstable and vulnerable plaques in the patients undergoing PCI. With the improvement of technical aspects of multimodality coronary imaging, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology and patients outcomes. There were numerous published data regarding the relationship between pre-PCI lesion subsets on multi-modality imaging and post-PCI biomarker levels. In this review, we discuss the relationship between coronary plaque morphology estimated by invasive or noninvasive coronary imaging and the occurrence of PMI. Furthermore, this review underlies that the value of the multimodality coronary imaging approach will become the gold standard for invasive or noninvasive prediction of PMI in clinical practice.

Background: Even with the use of a reduced energy setting (20–25 W), excessive transmural injury (ETI) following catheter ablation of atrial fibrillation (AF) is reported to develop in 10% of patients. However, the incidence of ETI depends on the pulmonary vein isolation (PVI) method and its esophageal temperature monitor setting. Data comparing the incidence of ETI following AF ablation with and without esophageal temperature monitoring (ETM) are still lacking. Methods: This study was comprised of 160 patients with AF (54% paroxysmal, mean: 24.0±2.9 kg/m2). Eighty patients underwent ablation accompanied by ETM. The primary endpoint was defined as the occurrence of ETI assessed by endoscopy within 5 d after the AF ablation. The secondary endpoint was defined as AF recurrence after a single procedure. If the esophageal temperature probe registered >39 °C, the radiofrequency (RF) application was stopped immediately. RF applications could be performed in a point-by-point manner for a maximum of 20 s and 20 W. ETI was defined as any injury that resulted from AF ablation, including esophageal injury or periesophageal nerve injury (peri-ENI). Results: The incidence of esophageal injury was significantly lower in patients whose AF ablation included ETM compared with patients without ETM (0 [0%] vs. 6 [7.5%], p=0.028), but not the incidence of peri-ENI (2 [2.5%] vs. 3 [3.8%], p=1.0). AF recurrence 12 months after the procedure was similar between the groups (20 [25%] in the ETM group vs. 19 [24%] in the non-ETM group, p=1.00). Conclusions: Catheter ablation using ETM may reduce the incidence of esophageal injury without increasing the incidence of AF recurrence but not the incidence of peri-ENI.

Background Although an “obesity paradox” exists in patients after myocardial infarction, the association between obesity and the risk of sudden cardiac death (SCD) is limited. The aim of this study was to determine whether obesity is associated with an increased risk of SCD in Japanese survivors of acute myocardial infarction. Methods and Results Pooled data from 2 cohort studies in Japan, JCAD (Japanese Coronary Artery Disease) study and the Heart Institute of Japan Acute Myocardial Infarction‐II (HIJAMI‐II) registry, comprising of 6216 patients (mean age 65±11 years, 75.2% male) with acute myocardial infarction who were discharged alive, were studied. The patients were categorized into the following body mass index (BMI) groups at baseline according to the World Health Organization classification for Asian populations: BMI

Background: Lead V1 on electrocardiography (ECG) can detect the dominant frequency (DF) of atrial fibrillation (AF) in the right atrium (RA). Paroxysmal AF is characterized by a frequency gradient from the left atrium (LA) to the right atrium (RA). We examined the ability of magnetocardiography (MCG) to detect regional DFs in both the atria. Methods: Study subjects comprised 18 consecutive patients referred for catheter ablation of persistent AF. An MCG system with 64 magnetic sensors was used to perform MCG in the frontal, lateral, and back planes prior to the ablation procedure in each patient. DFMCG and organization index (OIMCG) were calculated using fast Fourier transformation. Intracardiac electrograms (ICEs) in both the atria and the coronary sinus (CS) were mapped at 17 sites. Regional DFsICE were also determined. Results: Mean LA DFICE was higher than mean RA DFICE (6.40±0.66 versus 6.16±0.80 Hz, P=0.03). DFMCG in the channel having the highest OIMCG was 6.61±0.88 Hz in the frontal plane, 6.52±0.64 Hz in the lateral plane, and 6.42±0.62 Hz in the back plane (P=0.3). In each plane, DFMCG correlated with DFICE at the RA appendage (R=0.95, P

Placement of an implantable cardioverter–defibrillator (ICD) is the only powerful treatment modality for Brugada syndrome in patients presenting with ventricular fibrillation (VF). For those whose first presentation is an electrical storm, pharmacologic therapy is typically used to control VF followed by ICD implantation. We report an alternative approach whereby, before ICD implantation, emergency catheter ablation of the VF-triggering premature ventricular contraction (PVC) resulted in long-term VF-free survival. The results suggest that, because VF triggers appear in a narrow time window, ablation of the culprit PVCs that initiate VF before the index PVCs subside is a reasonable alternative approach.

Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process.

Background: Cardiac resynchronization therapy (CRT) is known to be effective for patients with heart failure. However, despite data suggesting that routine atrioventricular (AV) and interventricular (VV) delay optimization may play significant roles in CRT, there is no standard on how and when the CRT device should be optimized. The aim of this study was to characterize the current practice of CRT optimization in Japan. Methods: A survey was conducted to collect information on the procedural aspects of AV and VV delay optimization. The key survey items concerned what method is used for optimization, when optimization is performed, and what factors limit repetitive optimization. Results: Fifty-two physicians participated in the survey. Echocardiography was the chosen method for assessing AV and VV delays by 79.6% and 65.3% of physicians, respectively, and routine optimization was performed by 28.3%. The majority optimized the settings only once at pre-hospital discharge or on an “as-needed” basis. The factors limiting repeated optimization were the lack of available time (71.2%), qualified staff (53.8%), and reliable methods (55.8%). Conclusions: Repetitive CRT optimization is infrequently performed in Japan. Lack of time, human resource, and reliable methods were the major factors affecting the number of routine CRT optimization.

BackgroundSpeckle tracking echocardiography (STE) is reported as a useful method to predict cardiac resynchronization therapy (CRT) responders. This study aimed to identify the incremental value of a STE parameter to predict CRT responders. Methods and ResultsWe enrolled 171 patients from the Speckle Tracking imaging for the Assessment of cardiac Resynchronization Therapy (START) study. CRT responders were defined as patients with ≥15% reduction of left ventricular (LV) end‐systolic volume at 6 months post‐CRT. Based on multivariable logistic regression analysis, incremental values of STE were assessed by c‐statistics, net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis. Six parameters (left bundle branch block or right ventricular pacing, use of beta‐blocker, blood urea nitrogen ≤3.0 mg/dL, LV end‐systolic diameter ≤50 mm, mitral regurgitation index ≤40%, and STE parameter standard deviation of time from QRS onset to first peak on the circumferential strain curves [TSD] ≥116 ms) were identified as the determinants. Compared to the multivariable logistic regression model without TSD (model 1), that with TSD (model 2) showed significant improvement to predict CRT responders: c‐statistic (0.86 vs 0.77; P

BackgroundBrugada syndrome is recognized as being associated with sudden cardiac death; however, the prevalence of non–type 1 Brugada‐type ECG (BrS) or atypical ST‐segment elevation in the right precordial leads (STERP) and the long‐term prognosis for those patients remain unknown. Methods and ResultsWe analyzed standard 12‐lead ECGs of 7178 apparently healthy participants (age range 40–64 years) who underwent health checkups from 1982 to 1986 in the Circulatory Risk in Communities Study, a prospective, large, community‐based cohort study in Japan. ECGs with J point amplitude ≥0.2 mV in the right precordial leads were divided into 3 groups: (1) type 1 BrS, (2) type 2 or 3 BrS (non‐type 1 BrS), and (3) STERP. The others served as the non–ST‐segment elevation group. We identified 8 participants (0.1%) with type1 BrS, 84 (1.2%) with non–type 1 BrS, and 228 (3.2%) with STERP. During a median follow‐up of 18.7 years (133 987.0 person‐years), sudden cardiac death was observed in no participants (0.0%) with type 1 BrS, in 1 (1.2%) with non–type 1 BrS, in 7 (3.1%) with STERP, and in 50 (0.7%) with non–ST‐segment elevation. Participants with STERP had a markedly elevated risk of sudden cardiac death (multivariable hazard ratio 3.9, 95% CI 1.7–9.0). ConclusionsSTERP was associated with an elevated risk of sudden cardiac death in a middle‐aged population.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. Because of inadequate efficacy of pharmacological therapy, catheter ablation of AF has evolved dramatically over the last decade. Although the success rate of ablation has improved, the ablation strategy is still extensive, and the ablation procedure is technically challenging. In the past decade, electrophysiologists were eager to obtain high success rates with extensive ablation. In the present decade, further clarification of the complex mechanism of AF is required to make ablation of AF safer and much more efficient. Because the mechanism of AF is very complex, and even somewhat mysterious, it may not be easy to attain a better understanding of the mechanism involved or to discover better guidance for catheter ablation. However, it is important to note that research into AF leads to better understanding of other cardiac and non-cardiac diseases because AF develops multifactorially in association with underlying systemic pathophysiologies.

Atrial fibrillation (AF) has been gaining much attention as one of the major causes of cerebral infarction. It is imperative to establish antithrombotic treatment for AF patients. Thus far, guidelines for antithrombotic treatment in the management of AF patients, including the verification of the efficacy of direct thrombin and factor Xa inhibitors, have been published from the United States, Europe, Canada, and Japan. When we look at the Asia-Pacific region, antithrombotic treatment has not yet been defined, and no such guidelines have been published in this regard. The Asia-Pacific Heart Rhythm Society (APHRS) conducted a Web-based survey between June and August 2011, to elucidate the current status of antithrombotic treatment in 9 countries. A total of 363 cardiologists in 9 countries examined 300 patients with cardiovascular disease per month on an average; of these patients, 37 (12%) had nonvalvular AF (NVAF; 6.5% in India to 16.9% in Australia). The survey revealed that NVAF patients were not always administered appropriate antithrombotic treatment. These data give us a foothold for the next step, i.e., the formulation, of the APHRS practice guidelines.

An implantation of a cardioverter-defibrillator was attempted in a 32-year-old man with atrial tachycardia, ventricular tachycardia and sinus node dysfunction. He had undergone a Senning operation and half closure of ventricular septal defect in order to correct a transposition of the great arteries. Cardiac catheterization revealed severe pulmonary hypertension and Eisenmenger syndrome. Prior knowledge of the complex cardiac anatomy obtained by magnetic resonance imaging helped in determining the suitable site for implanting the leads and planning the procedural strategy. With repletion of a large amount of saline and oral anticoagulation with warfarin, no complications related to thromboembolism occurred during a 10-month follow-up period.

We describe a patient with nonischemic cardiomyopathy who underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia (VT). RF ablation from a left ventricular (LV) endocardial site failed to eliminate the VT. Using a conventional ablation catheter with the temperature-controlled mode, RF ablation from the LV epicardium resulted in failed ablation because of low power due to a temperature limitation function. However, by using a pericardial pigtail catheter for manual infusion and removal of saline within the pericardial space, adequate energy could be delivered, and the ablation overlying the lowvoltage area successfully eliminated the VT.

Background: We investigated the efficacy and safety of strict voltage-based substrate mapping and radiofrequency catheter ablation (SV-substrate-map ablation) in patients with electrical storm. Methods and Results: SV-substrate-map ablation was performed in 15 patients suffering from multiple appropriate shocks (6.0 ± 3.8/day) from implantable cardioverter defibrillators (ICDs). Strict voltage criteria were defined as: non-arrhythmogenic areas, >0.6mV; low voltage areas, >0.1 to ≤0.6 mV; and scar, ≤0.1 mV. Using an electroanatomic mapping system, catheter ablation was performed at every possible arrhythmogenic region inside the low voltage areas. Further, we presented a review of the literature and investigated the published data on substrate-mapping guided ablation for electrical storm. After repeat endocardial ablation procedures in 4 patients and an epicardial approach in one, the targeted ventricular tachycardias (VTs) were successfully ablated, and the electrical storms were completely controlled in all. During a mean follow-up period of 801 ± 409 days, only one VT followed by an appropriate ICD shock was observed. No potential complications occurred during the procedure or follow-up. Our results were comparable or better than that of previous substrate-mapping guided ablation studies. Conclusion: SV-substrate-mapping ablation may be effective and safe for resolving serious clinical situations and prolonging the longevity of ICD devices in patients with electrical storms.

Electropharmacological effects of chronically administered amiodarone and candesartan on atria that had been remodeled against congestive heart failure were assessed using dogs (about 10 kg in weight) with chronic atrioventricular block. Amiodarone was administered orally in a dose of 200 mg/body per day for the initial 7 days followed by 100 mg for the following 21 days (n = 7). Candesartan was administered in a dose of 12 mg/body per day for 28 days (n = 7). All animals survived the 4-week experimental period, indicating the lack of risks for inducing cardiohemodynamic collapse or torsade de pointes by these drugs. The plasma amiodarone concentration was 353 ng/ml at 4 weeks of treatment. Before candesartan treatment (control), intravenous administration of 30 ng/kg of angiotensin II increased the mean blood pressure by 18 mmHg, which was significantly decreased to 1 mmHg by 4 weeks of treatment. Amiodarone prolonged the atrial effective refractory period without affecting inter-atrial conduction time and decreased the duration of the burst pacing-induced atrial fibrillation, whereas candesartan hardly affected these variables. These results indicate that amiodarone should become a pragmatic pharmacological strategy against atrial fibrillation in patients with chronically compensated heart failure and suggest that a much higher dose of candesartan may be needed to exert its efficacy in this model. Keywords:: amiodarone, candesartan, atrial fibrillation, atrioventricular block

Background: Holter electrocardiogram (ECG) is the gold standard for ambulatory monitoring of atrial fibrillation (AF) but it is insufficient because of its limited recording time. Although several consumer ECG devices provide longer recording time, they generally do not undergo the regulatory process for medical use. Furthermore, current medical-grade devices for longer ECG monitoring are not continuous or too invasive for AF monitoring. A wearable ECG with a medical-grade dry textile electrode is a promising technology to remedy this limitation. This pilot study aimed to simultaneously compare the wearable and Holter ECGs for ambulatory monitoring in a clinical setting. Methods: This prospective observational study enrolled 18 patients who underwent AF ablation. One day after AF ablation, ambulatory ECG was obtained for three hours simultaneously using both the wearable and Holter ECG devices. Automatic ECG interpretations between devices were compared with correlation and agreement analyses. Results: Simultaneous ECG monitoring demonstrated a comparable analysis time and total heart beats between the two devices. Almost complete correlation and agreement were also demonstrated in all clinically relevant testing aspects except in R-wave amplitude (r = 0.743, p < .001). AF was detected in three patients. AF duration was the same in both ECG devices in two patients with continuous AF. In the remaining patient with intermittent AF, AF duration was shortened by 0.6% with the wearable ECG as compared to that with the Holter ECG. Conclusions: Simultaneous ECG comparison revealed a high consistency between the wearable and Holter ECG devices. The results of this study warrant further clinical studies for long-term monitoring of ambulatory ECG after AF ablation.

Background: Holter electrocardiogram (ECG) is the gold standard for ambulatory monitoring of atrial fibrillation (AF) but it is insufficient because of its limited recording time. A wearable ECG with a medical-grade dry textile electrode is a promising technology to remedy this limitation. This pilot study aimed to simultaneously compare the wearable and Holter ECGs for ambulatory monitoring in a clinical setting. Methods: This prospective observational study enrolled 18 patients who underwent AF ablation. One day after AF ablation, ambulatory ECG was obtained for three hours simultaneously using both the wearable and Holter ECG devices. Automatic ECG interpretations between devices were compared with correlation and agreement analyses. Results: Simultaneous ECG monitoring demonstrated a comparable analysis time and total heart beats between the two devices. Almost complete correlation and agreement were also demonstrated in all clinically relevant testing aspects except in R-wave amplitude (r = 0.743, p < .001). AF was detected in three patients. AF duration was the same in both ECG devices in two patients with continuous AF. In the remaining patient with intermittent AF, AF duration was shortened by 0.6% with the wearable ECG as compared to that with the Holter ECG. Conclusions: Simultaneous ECG comparison revealed a high consistency between the wearable and Holter ECG devices. The results of this study warrant further clinical studies for long-term monitoring of ambulatory ECG after AF ablation.

Inherited arrhythmia syndromes (IASs) can cause life-threatening arrhythmias and are responsible for a significant proportion of sudden cardiac deaths (SCDs). Despite progress in the development of devices to prevent SCDs, the precise molecular mechanisms that induce detrimental arrhythmias remain to be fully investigated, and more effective therapies are desirable. In the present study, we screened a large-scale randomly mutagenized mouse library by electrocardiography to establish a disease model of IASs and consequently found one pedigree that exhibited spontaneous ventricular arrhythmias (VAs) followed by SCD within 1 y after birth. Genetic analysis successfully revealed a missense mutation (p.I4093V) of the ryanodine receptor 2 gene to be a cause of the arrhythmia. We found an age-related increase in arrhythmia frequency accompanied by cardiomegaly and decreased ventricular contractility in the Ryr2I4093V/+ mice. Ca2+ signaling analysis and a ryanodine binding assay indicated that the mutant ryanodine receptor 2 had a gain-of-function phenotype and enhanced Ca2+ sensitivity. Using this model, we detected the significant suppression of VA following flecainide or dantrolene treatment. Collectively, we established an inherited life-threatening arrhythmia mouse model from an electrocardiogram-based screen of randomly mutagenized mice. The present IAS model may prove feasible for use in investigating the mechanisms of SCD and assessing therapies. [ABSTRACT FROM AUTHOR]