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BACKGROUND Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction pattern on magnetocardiography (MCG) can predict CRT responders.Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean [±SD] LV ejection fraction [LVEF] 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or

Background The new guideline (NG) published by the Japanese Circulation Society (JCS) places emphasis on previous arrhythmic syncope and inducibility of ventricular fibrillation (VF) by ≤2 extrastimuli during programmed electrical stimulation (PES) for deciding the indication of an implantable cardioverter-defibrillator in patients with Brugada syndrome (BrS). This study evaluated the usefulness of the NG and compared it with the former guideline (FG) for risk stratification of patients with BrS.Methods and Results:This was a multicenter (7 Japanese hospitals) retrospective study involving 234 patients with BrS who underwent PES at baseline (226 males; mean age at diagnosis: 44.9±13.4 years). At diagnosis, 46 patients (20%) had previous VF, 100 patients (43%) had previous syncope, and 88 patients (37%) were asymptomatic. We evaluated the difference in the incidence of VF in each indication according to the new and FGs. During the follow-up period (mean: 6.9±5.2 years), the incidence of VF was higher in patients with Class IIa indication according to the NG (NG: 16/45 patients [35.6%] vs. FG: 16/104 patients [15.4%]), while the incidence of VF in patients with other than class I or IIa indication was similarly low in both guidelines (NG: 2/143 patients [1.4%] vs. FG: 2/84 patients [2.4%]). Conclusions This study validated the usefulness of the NG for risk stratification of BrS patients.

BACKGROUND The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P

Background The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear. Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model. Conclusions The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

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

Background Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. Conclusions MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.

Background A global study designed to demonstrate the safety and efficacy of a transcatheter pacing system included 38 Japanese patients enrolled at 4 sites. Subgroup analysis to evaluate the performance of the leadless intracardiac transcatheter pacing system in Japanese patients was performed.Methods and Results:Safety and efficacy outcomes, patient and implant procedure characteristics, and patient and physician acceptability from the Japanese population were compared with those from outside Japan. Differences in patient characteristics, implant procedure characteristics and patient acceptability were observed. There were no major complications in Japanese patients and pacing thresholds remained low and stable throughout follow-up. There were no observable differences between Japanese patients and patients from outside Japan in the freedom from major complication rate at 12-months post-implant (100.0% vs. 95.7%, P=0.211) or physician acceptability. Conclusions Although some differences in specific baseline characteristics, such as body size and pacing indication, and in implant procedure characteristics, including anticoagulation strategy and hospitalization period, were observed in the Japanese patients, transcatheter pacemaker performance was similar to that in the global trial. (Clinical Trial Registration: ClinicalTrials.gov ID NCT02004873.).

BACKGROUND A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients. METHODS AND RESULTS Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P

Background:The relationship between outcome of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) and the severity of left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM) remains unknown.Methods and Results:Twenty-two HCM patients (12 female, aged 65±11 years) with paroxysmal (n=5; 23%) or persistent (n=17; 77%) AF were enrolled. LV diastolic function was evaluated according to the ratio of the mitral inflow early filling velocity to the velocity of the early medial mitral annular ascent (E/e’) measured on pulsed wave and tissue Doppler assessments in all patients. Pulmonary vein isolation was performed in all patients. A second procedure was performed in 3 patients. During a follow-up of 21±12 months, sinus rhythm was maintained in 13 of 22 patients (59%). E/e’ was significantly higher in the patients with AF recurrence than in those without (18±7 vs. 11±3; P

BACKGROUND Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known. METHODS AND RESULTS We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. "BrS masked by CRBBB" was defined on ECG as

Acute kidney injury (AKI) and acute hyperglycemia are associated with unfavorable outcomes. The impact of acute hyperglycemia on the development of AKI after acute myocardial infarction (AMI), however, remains unclear. This study was undertaken to assess the relationship between admission glucose and incidence of AKI after AMI.This study consisted of 760 patients with AMI admitted to the National Cerebral and Cardiovascular Center within 48h after symptom onset. Blood sample was obtained on admission and repeated sampling was done at least every 1 or 2 days during the first week. AKI was diagnosed as increase in serum creatinine ≥0.3mg/dl or ≥50% within any 48h. Ninety-six patients (13%) had AKI during hospitalization for AMI, and these patients had higher in-hospital mortality than those without AKI (25% vs. 3%, P0.001). Patients with AKI had higher plasma glucose (PG) on admission than those without (222±105mg/dl vs. 166±69mg/dl, P0.001). The incidence of AKI increased as admission PG rose: 7% with PG120mg/dl; 9% with PG 120-160mg/dl; 11% with PG 160-200mg/dl; and 28% with PG200mg/dl (P0.01). On multivariate analysis admission PG was an independent predictor of AKI (odds ratio, 1.10; 95% confidence interval: 1.03-1.18, P=0.02).Admission hyperglycemia might have contributed to the development of AKI in patients with AMI.

Background: We evaluated the safety and efficacy of a bolus injection of landiolol hydrochloride, an ultrashort-acting β1-selective antagonist, as an additional treatment after premedication with an oral β-blocker to reduce heart rate prior to multidetector-row computed tomography (MDCT) coronary angiography (CAG). Methods and Results: A total of 458 patients who underwent MDCT CAG were retrospectively enrolled. Image quality and hemodynamic parameters were compared in patients before and after approval of landiolol hydrochloride. If heart rate reduction was insufficient after premedication with an oral β-blocker, a bolus injection of landiolol hydrochloride (n=66) or other drugs (n=30) was used. The percentage of evaluable images per segment in patients after approval of landiolol (99.3%) was greater than that in patients before approval of landiolol (97.4%, P

Background: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no proven medical therapy to treat these diseases, and lung transplantation is thought to be the only cure. Administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and could be fatal in these patients. Methods and Results: Eight patients were treated with epoprostenol for 387.3±116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD or PCH by pathological examination. The maximum dose of epoprostenol given was 55.3±10.7ng·kg-1·min-1 (range, 21.0-110.5ng·kg-1·min-1). With careful management, epoprostenol therapy significantly improved the 6-min walk distance (97.5±39.2 to 329.4±34.6m, P

Background Pacing at the right atrial septum (RAS) appears to be superior to that performed at the right atrial appendage for preventing paroxysmal atrial fibrillation and for reducing complications. However, atrial lead insertion at the RAS is difficult and time-consuming. Although a few useful devices have been reported, handling of the atrial lead around the RAS is sometimes difficult even with those devices. Therefore, in the present study a long-straight sheath (LSS) was used in an attempt to secure sufficient space for handling the atrial lead around the RAS. Methods and Results Seventy-six consecutive patients who underwent insertion of an atrial lead at the RAS from a left-sided approach were examined. The non-LSS group comprised 24 patients and the LSS group had 52. The success rate of atrial lead insertion was significantly higher in the LSS group than in the non-LSS group [50/52 (96.1%) vs 13/24 (54.2%); p

Background Most of the patients with pulmonary arterial hypertension (PAH) receiving intravenous epoprostenol have experienced catheter-related infections during long-term treatment. Catheter hub was reported to be the most important source of catheter-related infections. To prevent the catheter-related infections, we have introduced a closed hub system and compared the incidence of catheter-related infections with that in patients using a non-closed hub system. Methods and Results We evaluated the results obtained on 24 occasions in 20 patients with PAH between June 1999 and December 2005. On 11 occasions, a non-closed hub system was used and on 13 cases a closed hub system. We classified the catheter-related infection into a catheter-related bloodstream infection (CRBSI) group or a tunnel infection group based on the pathway of bacteria. The CRBSI rate was 0.89 per 1,000 catheter days in the non-closed hub system group vs 0.10 per 1,000 catheter days in the closed hub system group. Kaplan - Meier analysis showed that the risk of CRBSI significantly decreased in the closed hub system group. None of the patients died as a direct consequence of catheter-related infection during the study period. Conclusions We successfully prevented CRBSI by using a closed hub system. (Circ J 2007; 71: 559 - 564)

Background Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), and furthermore whether carvedilol, a vasodilating β-blocker with antioxidant activity, could reduce the levels. Methods and Results Serum levels of 8-OHdG were measured by enzyme immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients significantly decreased by 19%, together with amelioration of heart failure. Conclusions Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage. (Circ J 2006; 70: 1001 - 1005)

Background It has been reported that recording electrocardiograms (ECGs) in the 3rd intercostal space (ICS) is one method that can be used for detecting Brugada syndrome; however, the prevalence of Brugada-type ECGs recorded in the 3rd ICS and the usefulness of recording the ECG in the 3rd ICS in accordance with recently established electrocardiographic criteria is unknown. Methods and Results ECGs were recorded in both the 4th and 3rd ICS in 17 Brugada-type ECG patients (group A) and in 206 consecutive male subjects (group B). Brugada-type ECGs were divided into 3 types. In group A, the prevalence of type 1 ECG, which is a coved-type ECG with ST-segment elevation of ≥2 mm, increased from 23.5% to 64.7% when ECG was recorded in the 3rd ICS. The conversion to type 1 ECG was found to be related to induction of ventricular arrhythmia. In group B, the prevalence of Brugada-type ECG increased from 1.5% to 5.8% when the ECG was recorded in the 3rd ICS. Conclusions Recording the ECG in the 3rd ICS is useful for identifying high-risk patients with Brugada-type ECG and for detecting concealed Brugada-type ECG. (Circ J 2004; 68: 135 - 138)

Background Primary pulmonary hypertension (PPH) is a rare disease characterized by progressively increased resistance of the pulmonary arteries associated with vascular remodeling. Infiltration of inflammatory cells in affected vessels is a common pathological finding. Monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic and activating factor for monocytes and leukocytes, but its significance in PPH is unclear. Methods and Results Serum MCP-1 concentrations were measured in 16 PPH patients and the results were compared with those in 16 normal controls. MCP-1 concentrations in PPH patients (265.6±29.5 pg/ml) were significantly elevated compared with those in normal controls (119.6±6.9 pg/ml, p

Background Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, plays an important role in the earliest events of atherogenesis. However, direct evidence of the effects of MCP-1 on atherosclerosis in chronic hemodialysis (HD) patients has not been reported. Methods and Results The serum MCP-1 concentrations and the intimal - medial thickness (IMT) in the carotid arteries were measured in 42 non-diabetic chronic HD patients and 20 age-matched controls. The expression of MCP-1 was examined immunohistochemically in radial arterial tissues obtained from the HD patients. IMT and the serum concentration of MCP-1 in the HD patients were both significantly greater than in controls. Multiple regression analysis revealed that the serum concentration of MCP-1 was an independent factor influencing IMT. Tissue immunostaining showed that MCP-1 is expressed in both endothelial and smooth muscle cells and that its level of expression correlates with the serum concentration of MCP-1. Conclusions An increase in MCP-1 may be an important factor in the progression of atherosclerosis in non-diabetic HD patients. (Circ J 2004; 68: 671 - 676)