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Objectives The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. Background The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. Methods The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. Results NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of −2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Conclusions Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227)

Objectives The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. Background The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. Methods In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. Results Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p Conclusions No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291)

Background Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications. Objectives The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF. Methods A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period. Results A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p 70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133). Conclusions This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.

Aims A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. Methods and results We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (≥50 cases/year, N = 3) or low-volume operator (

Background In myocardial ischemia–reperfusion injuries, the involvement of the Na + /H + exchanger (NHE) is considered to be one of the pathogenic mechanisms following reperfusion. TY-51924 is a novel hydrophilic NHE inhibitor with a lower risk of central neurotoxicity than previous NHE inhibitors. This open-label, dose-escalating study was undertaken to investigate the safety, efficacy, and pharmacokinetics of TY-51924 in patients with ST-elevation myocardial infarction (STEMI). Methods Consent was obtained from a total of 30 patients with first anterior STEMI. After 12 patients were determined to be ineligible, the remaining 18 patients, each of whom was undergoing primary percutaneous coronary intervention (pPCI), received TY-51924 intravenously up to 10, 20, or 30 mg/kg as the low-, medium-, or high-dose groups, respectively ( n = 6 in each group). The primary endpoints were safety (up to 7 days) and plasma drug concentration. The myocardial salvage index (MSI) was measured by 201 Tl/ 123 I-beta-methyl- p -iodophenyl pentadecanoic acid single photon emission computed tomography (SPECT) 3–5 days after pPCI. Results No side effects were observed. Plasma drug concentrations increased dose-dependently, and were subsequently eliminated rapidly. MSIs were 0.118, 0.335, and 0.192 in the low-, medium-, and high-dose groups, respectively. In additional analysis, the combined MSIs in the medium- and high-dose groups were significantly higher than those in the low-dose group, in patients with a longer time from symptom onset to reperfusion ( p = 0.0247). Conclusions No side effects were observed even at the highest dose with this novel hydrophilic NHE inhibitor. Therefore, TY-51924 is thought to be safe in patients with STEMI, even at the highest dose. Potential cardioprotective effects of intravenous TY-51924 might be expected based on the results obtained for the MSIs using SPECT at 20–30 mg/kg. However, further large-scale, double-blind, placebo-controlled clinical studies are required to confirm the efficacy and safety implied in the current study.

Some patients with persistent atrial fibrillation (AF) acquire long-term freedom from AF by pulmonary vein (PV) isolation alone. The aim of the present study was to evaluate the characteristics of their atrial substrate.We studied 20 patients with persistent AF to examine the distribution of fractionated atrial potentials (FAP) and that of the anatomic sites of ganglionated plexi (GPs) with vagal reflexes elicited by high frequency stimulation (HFS) with the use of the CARTO system before and after the PV isolation.Both the %FAP area defined as a proportion of the FAP area to the total left atrial area (34.3 ± 10.3 to 21.5 ± 10.2%; P0.0001) and number of GP sites with vagal reflexes (4.0 [3.0, 5.0] to 2.0 [1.0, 2.8]; P0.0001) were markedly decreased after the PV isolation. Seven (35%) patients had AF recurrences, and they had a greater %FAP area after the PV isolation than those without (32.8 [22.1, 37.3] versus 13.8 [10.9, 19.9]%; P = 0.0049). A %FAP area after the PV isolation of20% was significantly associated with an AF recurrence (odds ratio 20.0, 95% confidence interval 2.26470.34; P = 0.018). No significant difference was found between the patients with and without AF recurrence in the reduction rate of anatomic sites of GPs with a vagal reflex induced by the HFS.A more marked reduction in the FAP area by the PV isolation was significantly associated with a better outcome in patients with persistent AF.

Aims Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics has the potential risk of fatal respiratory depression. Dexmedetomidine works its sedative action via α2-adrenergic receptors, and is less associated with respiratory depression. We tested the usability of dexmedetomidine as a procedural sedative during ablation of atrial fibrillation (AF). Methods and results Consecutive patients were randomized to be treated with dexmedetomidine ( n = 43) or thiamylal ( n = 44) as sedatives during AF ablation. Apnoeic and body movement events were monitored using a novel portable respiratory monitor, the SD-101, during the procedure. Although the majority of the patients receiving dexmedetomidine required rescue sedations with thiamylal, the respiratory disturbance index (RDI) defined as the total number of sleep-disordered breathing events divided by the recording time (10.4 ± 5.1 vs. 18.2 ± 8.1 events/h; P < 0.0001) and movement index defined as the number of body movement events per hour (7.6 ± 6.1 vs. 11.0 ± 5.5 events/h; P = 0.0098) were both significantly lower in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear regression analysis including potential factors revealed that dexmedetomidine vs. thiamylal was solely and independently associated with the RDI ( β = −0.62; P = 0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with dexmedetomidine and thiamylal. Conclusion Procedural sedation with dexmedetomidine may assure safety and patient immobility during AF ablation, and therefore may be a potential alternative for that with GABAergic anaesthetics.

Background— Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. Methods and Results— We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene ( ALMS1 ) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. Conclusions— The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

Although several predictors of an electrical storm (ES) are indicated in patients with idiopathic dilated cardiomyopathy (IDCM), whether the severity of the myocardial tissue damage (SMTD) evaluated by myocardial perfusion SPECT (MPS) has an association with an ES remains unclear. The purpose of this study was to elucidate the clinical significance of SMTD for the prediction of ES in IDCM patients with an ICD. Thirty-seven (27 men, mean age 58 ± 15 years) IDCM patients receiving ICD implantations for secondary prevention with preoperative MPS were enrolled in this study. The medical history, physical and laboratory findings, electrocardiograms, echocardiograms and MPS findings were evaluated. The SMTD was assessed by the summed scores of 17 segments using a 4-point system (0, normal ~3, severe defect). During a mean follow-up of 43.9 ± 30.7 months, an ES developed in 12/37 (32.4 %) patients. The SMTD score predicted an ES with a 92 % sensitivity and 56 % specificity, at a cut-off score of 10. In addition, a multivariate analysis showed that the SMTD score remained an independent predictor of an ES (HR 1.09/score 1 increase, 95 % CI 1.01–1.19, p = 0.02). The SMTD score was significantly associated with three indices of late potentials on the signal-averaged electrocardiograms, and was significantly higher in patients with positive late potentials (p = 0.0006). SMTD score assessed by MPS has a strong correlation to the late potentials and higher SMTD score may increase the risk of ES among patients with IDCM and an ICD.

Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications.The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF.A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period.A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133).This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.

Aims Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. Methods and results We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Conclusions Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias.

Introduction: The purpose of this study was to investigate whether the effects of renin–angiotensin system inhibitors (RASIs) after encircling ipsilateral pulmonary veins isolation (EIPVsI) for atrial fibrillation (AF) differed between patients with non-dilated and dilated left atria. Materials and methods: We retrospectively studied 292 consecutive patients (mean age=61±11 years, 75% males) who underwent successful EIPVsI for paroxysmal or persistent AF. RASIs’ effects were compared between the patients with a non-dilated left atrium of

Background: The TAXUS Japan Postmarket Surveillance Study (TAXUS-PMS) enrolled patients receiving percutaneous coronary intervention in real-world clinical practice. This analysis focuses on outcomes in the overall patient population and in a subgroup of diabetic patients. Methods and Results: Between July 2007 and December 2008, 2,132 patients (with 2,504 lesions) were consecutively enrolled at 56 sites in Japan. One-year outcomes were analyzed. The prevalence of patients with diabetes was 44% (21% of diabetics were insulin-treated) and 5.5% of patients were receiving ongoing hemodialysis. The majority of patients received paclitaxel-eluting stents (PES) for `off-label' indications (68.2%). The rate of major adverse cardiovascular events (cardiac death, myocardial infarction, and target vessel revascularization (TVR)) at 1 year was 8.2%, driven mainly by TVR (6.9%). No differences in TVR, late loss or restenosis rates were found between diabetic and non-diabetic patients; outcomes in insulin- compared with oral hypoglycemic-treated diabetic patients, were similar. Multiple stent implantation and ostial lesion location were independent predictors for both major adverse cardiac events (MACE) and target lesion revascularization (TLR). Hemodialysis was an independent predictor for MACE but not TLR whereas in-stent restenosis was an independent predictor for TLR. Conclusions: TAXUS-PMS demonstrated a consistent, positive effect of PES in complex clinical cases. PES diminished the increased risk of clinical restenosis in diabetic patients, leading to a similar low risk of cardiac events in diabetic and non-diabetic patients. (Circ J 2011; 75: 2573-2580)

Background Cardiac resynchronization therapy (CRT) has been reported to improve cardiac performance. However, CRT in patients with advanced heart failure is not always accompanied by an improvement in survival rates. We investigated the association between hemodynamic studies and long-term prognosis after CRT. Methods A total of 68 consecutive patients receiving CRT devices due to advanced heart failure were assessed by hemodynamic study and long-term outcome after implantation of the device. Hemodynamic parameters were measured both with the CRT on and off. Results Patients demonstrated significant improvement in the maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) and QRS duration after periods with the CRT on. During the follow-up period of 34.9 ± 17.6 months, basal LV dP/dtmax and isovolemic LV pressure half-time (T1/2), but not percent change in LV dP/dtmax, were independent predictors of cardiac mortality or hospitalization due to heart failure after multivariate Cox regression analysis. The Kaplan-Meier survival analysis revealed that patients in the lowest basal LV dP/dtmax tertile or the longest basal T1/2 tertile exhibited a significantly higher cardiac-caused mortality or heart failure hospitalization. Conclusions Lower LV dP/dtmax or longer T1/2 independently predicts cardiac mortality or heart failure hospitalization in patients receiving CRT. The assessment of the basal LV dP/dtmax and T1/2 could provide useful information in long-term prognosis after CRT. Copyright © 2010 Wiley Periodicals, Inc. This work was supported by grant from the Grant-in-Aid for Young Scientists, the Nakashima Foundation, and the Kowa Life Science Foundation to RS. Hirohiko Suzuki, MD and Masayuki Shimano, MD equally contributed to the work.

A 62 year-old female hemodialysis patient underwent parathyroidectomy to treat secondary hyperparathyroidism. On the preoperative assessment, the plasma levels of parathyroid hormone (PTH) and B-type natriuretic peptide (BNP) were elevated. Echocardiography showed reduced left ventricular (LV) contraction. Myocardial iodine-123-15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (123I-BMIPP) scintigraphy showed moderately reduced tracer uptake in the postero-inferior area on single-photon emission computed tomography and decreased washout on the planar images. After parathyroidectomy, the plasma levels of PTH and BNP decreased, followed by improvement in LV contraction. Myocardial 123I-BMIPP scintigraphy revealed that the washout on planar images had increased, which suggests that myocardial 123I-BMIPP scintigraphy is useful for estimating the effect of parathyroidectomy on cardiac function. (Circ J 2009; 73: 1956-1960)

Objective: Little is known about the clinical features in patients with cardiac sarcoidosis who receive cardiac resynchronization therapy (CRT). We aimed to clarify the clinical response to CRT in patients with cardiac sarcoidosis. Methods: We compared the clinical data on CRT between heart failure patients with cardiac sarcoidosis and those with other etiologies at 3 cardiovascular centers. The primary endpoint was composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Results: The patients with cardiac sarcoidosis (N=18) were more likely than those without cardiac sarcoidosis (N=141) to be female (83.3% vs. 22.7%; P Conclusions: Outcomes after the CRT may be acceptable in patients with cardiac sarcoidosis. A poor left ventricular reverse remodeling and higher occurrence of ventricular arrhythmias may characterize them.

Background In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the Na+/H+ exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI. Methods In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3–5 days after pPCI and safety up to 7 days. Results Baseline characteristics were similar in the two groups. MSI 3–5 days after pPCI (0.200 vs. 0.290, p = 0.56), 3 months after pPCI (0.470 vs. 0.500, p = 0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (≥38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p = 0.03). TY-51924 did not adversely influence hemodynamics. Conclusions TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow.

The pathogenesis of unstable angina pectoris (UAP) following percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA) has not been adequately investigated, so the present study aimed to determine whether thrombi are present in restenotic lesions. The study group comprised 14 patients (16 arterial branches) with angina pectoris in whom either PTCA or DCA was performed and who had developed UAP associated with restenosis, and who then underwent DCA of the restenosed lesion (R-UAP group). The control groups comprised individuals with UAP undergoing DCA with no prior history of PTCA or DCA (P-UAP group; n=29, 29 branches), patients with acute myocardial infarction (AMI group; n=34, 34 branches), and patients with stable angina pectoris (SAP group; n=31, 33 branches). The presence of thrombi was determined by light microscopy of histologic specimens. Thrombus was present in only 1 of the 16 (6.3%) branches in the R-UAP group, 21 of the 29 (72.4%) branches in the P-UAP group, and in 25 of the 34 (73.5%) in the AMI group. In the SAP group, it was detected in only 2 of the 33 (7.1%) branches. The incidence of thrombus was significantly lower in the R-UAP group than in the P-UAP group. In conclusion, the role of thrombus is limited in causing post-interventional UAP at restenosed sites. (Jpn Circ J 2001; 65: 505 - 508)

OBJECTIVESWe examined whether preinterventional arterial remodeling influenced the interventional results after stenting.BACKGROUNDArterial remodeling is seen in atherosclerotic lesions, and it may play an important role in the early stage of atherosclerosis.METHODSWe examined 113 lesions that underwent elective stenting using tubular slotted stents under intravascular ultrasound guidance. The lesions were divided into three groups—adequate, intermediate and inadequate remodeling group—according to preinterventional arterial remodeling. The patients were subjected to coronary angiography and intravascular ultrasound evaluation on average 6.4 months after stenting.RESULTSAt baseline and immediately after stenting, there were no differences in quantitative angiographic analysis among remodeling groups. However, the plaque cross-sectional area (CSA) in the minimal lumen CSA at preintervention and intimal hyperplasia CSA at follow-up were significantly larger in the adequate remodeling group than in the inadequate remodeling group. The restenosis rate of stenting for the lesions with inadequate arterial remodeling was very low (9.4%). A significant positive correlation was found between preinterventional plaque CSA and intimal hyperplasia CSA at follow-up (r = 0.47, p < 0.0001). Moreover, remodeling index significantly correlated with relative intimal hyperplasia CSA (r = 0.28, p < 0.01).CONCLUSIONSPreinterventional arterial remodeling influenced the development of intimal hyperplasia after stenting.

BACKGROUND The relationship between pulmonary vein (PV) potential (PVP) disappearance patterns during encircling ipsilateral pulmonary vein isolation (EIPVI) of atrial fibrillation (AF), and outcome was examined. METHODS AND RESULTS A total of 352 consecutive AF patients (age, 61±12 years; 269 men, 76.4%; paroxysmal AF, n=239; persistent AF, n=73; and long-standing persistent AF, n=40) who underwent initial AF ablation were studied. After EIPVI with a double Lasso technique, pacing was performed from the PV carina to confirm isolation of the carina. PVP disappearance patterns were classified into 3 types: A, both superior and inferior PVP disappeared simultaneously; B, superior and inferior PVP disappeared separately; and C, additional RF applications were required inside the encircling lesions to eliminate the PVP after creating anatomical encircling lesions. The relationship between these patterns and outcome was examined. Six groups were defined according to the combination of right and left ipsilateral PVP disappearance patterns. The incidence of A-A, A-B, B-B, A-C, B-C, and C-C was 7.1%, 14.2%, 16.2%, 15.3%, 27.3%, and 19.9%, respectively. AF recurrence-free rate at 2 years for these 6 groups was 96%, 81%, 78%, 64%, 64%, and 59%, respectively (P

The association of an insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene or the serum activity of ACE with coronary artery disease (CAD) was investigated in Japanese men and women. The ACE genotype of 947 CAD subjects who underwent coronary angiography and of 893 control subjects was determined by polymerase chain reaction analysis. No association of the DD genotype or the D allele with CAD was observed in men or women. In a low risk group (defined by a body mass index below the median value and the absence of a history of hypertension, diabetes mellitus, and hypercholesterolemia), there was also no association between the ACE gene polymorphism and CAD. No significant difference in serum ACE activity was detected between CAD subjects and controls of all genotypes or of the same genotype, whereas a significant association was apparent between serum ACE activity and ACE genotype for both CAD subjects and controls among both men and women. These results indicate that the ACE I/D polymorphism and genotype associated variation in serum ACE activity are not risk factors for CAD in Japanese men or women.

To address safety concerns with first-generation drug-eluting stents (DESs), the everolimus-eluting stent (EES) has been developed as a second-generation DES. The study aim was to: (1) demonstrate that use of the EES in Japanese patients is non-inferior to use of the paclitaxel-eluting stent (PES) in US patients; and (2) compare vessel response to the EES in Japanese vs US patients.The SPIRIT III Japan Registry, a prospective single-arm multicenter study was a part of the SPIRIT III global clinical program using harmonization by doing. The primary endpoint was in-segment late loss at 8 months, compared to US PES.A total of 88 subjects were enrolled in the Japan EES group. Angiographic in-segment late loss was significantly less in Japan EES vs US PES (0.15 ± 0.34 mm vs 0.28 ± 0.48 mm, respectively; P=.0185; Pnon-inferio r.0001), while target vessel failure (TVF; 8.0% vs 9.9%) and major adverse cardiac events (MACE) at 9 months (5.7% vs 8.8%) were not significantly different between the 2 groups. No differences were observed between Japan and US EES populations in terms of late loss, TVF, or MACE. Neointimal volume and postprocedural incomplete stent apposition rate were lower in Japan EES vs US EES/PES.The SPIRIT III Japan Registry met the primary endpoint of lower late loss in the Japan EES group vs the US PES group, with comparable results for EES between the Japanese and US patients.

Aims Encircling ipsilateral pulmonary veins (PVs) isolation (EIPVsI) with the double-Lasso technique has proven to be effective to cure atrial fibrillation (AF). However, in this technique, PV mapping with circular catheters may miss a non-isolation of the PV carina. The purpose of this study was to reveal the incidence and clinical significance of a non-isolation of the PV carina after EIPVsI. Methods and results We studied 81 consecutive paroxysmal AF patients (age 61 ± 12 years, 56 men), in whom EIPVsI was successfully performed in one encircling line with the endpoint of the demonstration of bidirectional conduction block between the PVs and left atrium (LA) with the double-Lasso technique. After a successful EIPVsI, pacing from the PV carina was performed and it captured the LA in 17 (21.0%) patients. During a mean follow-up period of 19 ± 13 months, AF recurred in 13 (16.0%) patients. A multivariate Cox proportional analysis revealed that a non-isolation of the PV carina after the EIPVsI was a significant predictor (hazard ratio = 3.91, 95% confidence interval = 1.13–14.16, P = 0.03) of AF recurrence. Conclusions Pulmonary vein mapping with the double-Lasso technique did miss the non-isolation of the PV carina after a successful EIPVsI, which was an independent predictor of AF recurrence after the EIPVsI. Pacing from the PV carina may be required to confirm the electrical isolation of the PV carina after EIPVsI with the double-Lasso technique.

In-stent restenosis has been a longstanding problem after percutaneous coronary intervention. The introduction of the drug-eluting stent (DES) successfully reduced the rate of restenosis; however, it is not completely diminished. Although restenosis occurs less frequently compared to the bare-metal stent (BMS), DES restenosis remains a familiar problem due to the increasing total number of implanted DESs as well as the targeting of more complex lesions. In addition, worse outcomes after repeat revascularization compared to BMS restenosis are reported in DES restenosis. Management of DES restenosis is an emerging issue, which requires careful evaluation of the restenosed lesion, together with cautious determination of therapeutic strategy. In this review, available repeat revascularization procedures for DES restenosis as well as possible impacting factors on the outcomes are discussed.

We conducted a retrospective study (1981-1990) to determine whether the efficacy of intracoronary thrombolysis (ICT) could be evaluated from data obtained solely after recanalization. We investigated 55 successful ICT patients (38 with anterior and 17 with inferior myocardial infarction (MI)), and 31 control infarct patients without recanalization. The total serum creatine phosphokinase release (sigma CPK), the extent of infarction measured by T1-201 single photon emission computed tomography (total DS) and the disturbance of regional wall motion (asyn.%) were investigated as parameters for distinguishing the successful ICT and control groups. Discriminatory ability for the two groups was highest with the total DS in all patients. Only the total DS differed significantly between the two groups in patients with inferior infarction. Misidentification of control patients as successful patients was least frequent (25.5%) when using the total DS. These findings suggest that the effectiveness of ICT for acute MI may be assessed on the basis of data obtained solely after recanalization, with the total DS being particularly useful.

A 56-year-old man with atrial fibrillation and complete left bundle branch block (CLBBB) developed heart failure refractory to the initial medical treatment. Both the CLBBB and cardiac dysfunction completely recovered only with an advanced medical regimen for rate control and heart failure. This report describes a case with reversible CLBBB following tachycardia-induced cardiomyopathy, who was not a candidate for cardiac resynchronization therapy.

The TAXUS Japan Postmarket Surveillance Study (TAXUS-PMS) enrolled patients receiving percutaneous coronary intervention in real-world clinical practice. This analysis focuses on outcomes in the overall patient population and in a subgroup of diabetic patients.Between July 2007 and December 2008, 2,132 patients (with 2,504 lesions) were consecutively enrolled at 56 sites in Japan. One-year outcomes were analyzed. The prevalence of patients with diabetes was 44% (21% of diabetics were insulin-treated) and 5.5% of patients were receiving ongoing hemodialysis. The majority of patients received paclitaxel-eluting stents (PES) for `off-label' indications (68.2%). The rate of major adverse cardiovascular events (cardiac death, myocardial infarction, and target vessel revascularization (TVR)) at 1 year was 8.2%, driven mainly by TVR (6.9%). No differences in TVR, late loss or restenosis rates were found between diabetic and non-diabetic patients; outcomes in insulin- compared with oral hypoglycemic-treated diabetic patients, were similar. Multiple stent implantation and ostial lesion location were independent predictors for both major adverse cardiac events (MACE) and target lesion revascularization (TLR). Hemodialysis was an independent predictor for MACE but not TLR whereas in-stent restenosis was an independent predictor for TLR.TAXUS-PMS demonstrated a consistent, positive effect of PES in complex clinical cases. PES diminished the increased risk of clinical restenosis in diabetic patients, leading to a similar low risk of cardiac events in diabetic and non-diabetic patients.

BACKGROUND Whether the Wolff-Parkinson-White syndrome (WPW) is associated with repolarization abnormalities is controversial. The QRST isointegral map (I-map) is theoretically independent of the activation sequence and dependent on repolarization properties. There have been no reports concerning the effects of radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization properties analyzed by I-mapping. METHODS AND RESULTS I-maps were constructed from data recorded in 38 patients with WPW to investigate repolarization properties and their body surface distribution in a physiological state, without pharmacological influences, and in 13 ablated patients to elucidate the effects of RF ablation on repolarization properties. Patients were divided into three groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10 patients with type B (right-sided AP); and group C, 13 patients who were successfully ablated. Group C consisted of three subgroups: subgroup CA, 7 patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I-maps of WPW were highly (r = .87) correlated with the mean normal I-map, the location of the minimum in groups A and B differed significantly from that in normals. The minimum was located over the upper right anterior chest in normal subjects, over the back in 82% of 22 patients with type A WPW including ablated patients (groups A+CA), and over the mid to lower right anterior chest in 62% of 13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA and B+CB had an abnormally low QRST area ("-2SD area") over the back and right anterior chest, respectively. The abnormally located minimum and the "-2SD area" were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After RF ablation, the distribution of the minimum, initially abnormal, became normal over a period of days or weeks, and the "-2SD area" disappeared over 1 week in all 7 patients. Correlation coefficients between I-maps and the mean normal I-map increased after RF ablation. CONCLUSIONS (1) WPW is often associated with abnormalities in repolarization properties. (2) Repolarization abnormalities were located over the back in type A WPW and over the right mid to lower chest in type B WPW: (3) The abnormalities remain immediately after RF ablation and gradually normalize. These findings support the concept that ST-T abnormalities in 12-lead ECGs following RF ablation are attributable to "cardiac memory."

BACKGROUND: Cardiac resynchronization therapy (CRT) has been reported to improve cardiac performance. However, CRT in patients with advanced heart failure is not always accompanied by an improvement in survival rates. We investigated the association between hemodynamic studies and long‐term prognosis after CRT. METHODS: A total of 68 consecutive patients receiving CRT devices due to advanced heart failure were assessed by hemodynamic study and long‐term outcome after implantation of the device. Hemodynamic parameters were measured both with the CRT on and off. RESULTS: Patients demonstrated significant improvement in the maximum first derivative of left ventricular (LV) pressure (LV dP/dt(max)) and QRS duration after periods with the CRT on. During the follow‐up period of 34.9 ± 17.6 months, basal LV dP/dt(max) and isovolemic LV pressure half‐time (T(1/2)), but not percent change in LV dP/dt(max), were independent predictors of cardiac mortality or hospitalization due to heart failure after multivariate Cox regression analysis. The Kaplan‐Meier survival analysis revealed that patients in the lowest basal LV dP/dt(max) tertile or the longest basal T(1/2) tertile exhibited a significantly higher cardiac‐caused mortality or heart failure hospitalization. CONCLUSIONS: Lower LV dP/dt(max) or longer T(1/2) independently predicts cardiac mortality or heart failure hospitalization in patients receiving CRT. The assessment of the basal LV dP/dt(max) and T(1/2) could provide useful information in long‐term prognosis after CRT. Copyright © 2010 Wiley Periodicals, Inc. This work was supported by grant from the Grant‐in‐Aid for Young Scientists, the Nakashima Foundation, and the Kowa Life Science Foundation to RS. Hirohiko Suzuki, MD and Masayuki Shimano, MD equally contributed to the work.

Congenital diseases causing an obstruction of the right ventricular outflow are difficult to precisely diagnose, especially in elderly patients. Here, we describe a 76-year-old woman who presented to our hospital with shortness of breath on exertion and was finally diagnosed as infundibular pulmonary stenosis by multiple modalities. Surgery was successfully performed and the symptom was relieved. This case underscored the usefulness of multiple modalities for the precise assessment of the right ventricular outflow obstruction and the effectiveness of surgery even in elderly patients with infundibular pulmonary stenosis.

Understanding the clinical characteristics of transthyretin familial amyloid polyneuropathy (TTR-FAP) is critical for early diagnosis and timely referral for liver transplantation. Here, we describe a 52-year-old man who had slight paresthesia for four years and whose final diagnosis of TTR-cardiac amyloidosis caused by sporadic FAP was delayed despite annual electrocardiography. Curative liver transplantation was postponed because of progressive cardiac involvement. This experience highlights the difficulties associated with diagnosing TTR-FAP, especially when it is sporadic, and underscores the importance of slight changes in ECG that could indicate FAP.

Coronary artery spasm has an important function in the etiology of variant angina and other acute coronary syndromes. Abnormal activation of Rho-family GTPases has been observed in cardiovascular disorders, but the function of genetic variability in Rho-family GTPases remains to be evaluated in cardiovascular disorders. We examined the genetic variability of Rho-family GTPases and their regulators in coronary artery spasm. We performed a comprehensive candidate gene analysis of 67 single nucleotide polymorphisms with amino-acid substitution in Rho-family GTPases and their regulators in 103 unrelated Japanese patients with acetylcholine-induced coronary artery spasm and 102 control Japanese subjects without acetylcholine-induced coronary artery spasm. We noted an association of the single nucleotide polymorphism of ARHGAP9 (rs11544238, Ala370Ser) with coronary artery spasm (odds ratio =2.67). We found that ARHGAP9 inactivated Rac as RacGAP and that the mRNA level of ARHGAP9 was strongly detected in hematopoietic cells. ARHGAP9 negatively regulated cell migration. The Ala370Ser polymorphism counteracted ARHGAP9-reduced cell migration, spreading and adhesion. The Ala370Ser polymorphism in the ARHGAP9 gene is associated with coronary artery spasm. These data suggest that the polymorphism of ARHGAP9 has a critical function in the infiltration of hematopoietic cells into the endothelium and inflammation leading to endothelial dysfunction.

Background: Left atrium (LA) dilation plays an important role in development and persistence of atrial fibrillation (AF). Some cases show structural reverse remodeling of LA after catheter ablation of AF. The aim of this study was to assess the clinical significance of LA reverse remodeling. Method and Results: Echocardiographic data before and after ablation was obtained in 173 cases who underwent pulmonary vein isolation from January 2006 to April 2008 (74.0% men, 61.0±11 years old; paroxysmal AF 114, persistent AF 34, permanent AF 25). Mean atrial diameter before ablation was 39.0±6.1mm (paroxysmal 37.7±5.6mm, persistent 40.7±5.3mm, and permanent 43.0±6.8mm) and LA reverse remodeling was defined as 10% decrement of LA transverse diameter. Half of the cases were taking anti-arrhythmic drugs after ablation, and AF recurrence occurred in 16.8% (29/173) during mean follow up period of 8.5±6.3 months. Reverse remodeling of LA was seen in 34.1% (59/173) and AF recurrence rate in this group was 11.9% (7/59), whereas 19.3% (22/114) without reverse remodeling (P=0.29). However, limited in patients with LA diameter over 40mm (44.5%; 77/173), 3.2% (1/31) of AF recurrence was seen in those with reverse remodeling, while 21.7% (10/46) without reverse remodeling (P=0.04). LA reverse remodeling was observed significantly frequent in patients without history of hypertension(41.5% without hypertension vs 25.6% with hypertension, P=0.036). Conclusion: LA reverse remodeling after catheter ablation of AF in dilated LA patient is a simple and useful predictor for non-recurrence of AF. Hypertension could be a disturbance for LA reverse remodeling.

Aims We assessed the effects of cardiac re-synchronization therapy (CRT) in patients who developed otherwise unexplained heart failure (HF) during right ventricular apical (RVA)-pacing for acquired complete atrioventricular block (CAVB). Methods and results Eighteen consecutive CAVB patients with HF during RVA-pacing were assessed with haemodynamic studies immediately and 12 months after CRT-upgrade. Ten patients had idiopathic CAVB and 13 showed normal left ventricular (LV) function at RVA-pacemaker implantation. HF developed after 81+ 10 months. RVA-pacing duration correlated (r ¼ 0.49, P , 0.05) with LV ejection fraction (LVEF) deterioration. Biventricular- (BiV) and LV-pacing acutely improved the systolic function comparably, but only BiV improved diastolic function. One-year post-CRT-initiation, New York Heart Association classification improved 35+ 3% (P , 0.05) and the number of hospitalizations decreased 85 + 3% (P , 0.0001). CRT decreased LV end-diastolic diameter (LVEDd) 7+ 2% (P , 0.01) and increased LVEF by 23+ 7% (P , 0.01). The CRT-induced reduction in LVEDd tended to be greater in patients with RVApacing for ,5 years vs. .5 years (7.7+ 2.5 vs. 3.6+ 1.0 mm, P ¼ 0.08). Conclusion CRT-upgrade improves the cardiac function and symptoms in CAVB patients with HF progression related to RVA-pacing. Because adverse LV-remodelling may be partly irreversible, consideration should be given to BiV- and LV-pacing upgrade as soon as possible after the indications appear, and prospective studies of the optimal timing of CRT-upgrade may be useful.

Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. Large-scale association studies that examine many gene polymorphisms simultaneously are required to predict genetic risk for hypertension. The population of the present study comprised 1940 unrelated Japanese individuals, including 1067 subjects with hypertension (574 men, 493 women) and 873 controls (533 men, 340 women). The genotypes for 33 single nucleotide polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that 2 polymorphisms (825C→T in the G protein β3 subunit gene and 190G→A in the CC chemokine receptor 2 gene) were significantly associated with hypertension in men and that one polymorphism (−238G→A in the tumor necrosis factor α gene) was significantly associated with hypertension in women. These results suggest that 2 and 1 genes may be susceptibility loci for hypertension in Japanese men and women, respectively, and that genotyping of these polymorphisms may prove informative for prediction of the genetic risk for hypertension.

Background —Intracellular calcium overload is believed to play an important role in development of reperfusion arrhythmias. Dipyridamole, an inhibitor of cellular uptake of adenosine, may prevent or terminate reperfusion arrhythmias by reducing intracellular calcium overload. Methods and Results —First, we tested for a preventive effect of dipyridamole. Sixty-one patients who underwent primary PTCA for treatment of acute anterior wall myocardial infarction were enrolled in this prospective study. Patients were divided into dipyridamole (DP) and nondipyridamole (non-DP) groups. The 2 groups had similar baseline characteristics. In the DP group, dipyridamole 0.5 mg/kg was infused intravenously for 3 minutes immediately before reperfusion during primary PTCA. Arrhythmias after reperfusion were analyzed from continuous ECG recordings. None of the patients in the DP group (n=23) had accelerated idioventricular rhythms (AIVR) or ventricular tachycardia (VT). In contrast, 7 (18.4%) had AIVR and 3 (7.9%) had VT in the non-DP group (n=38; P Conclusions —These results indicate that administration of dipyridamole can prevent and terminate reperfusion arrhythmias such as AIVR and VT. cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion-induced AIVR and VT.

Background T-wave abnormalities after catheter ablation in patients with manifest Wolff-Parkinson-White (WPW) syndrome have been attributed to a continuation of repolarization abnormalities induced by preexcitation (cardiac memory). Methods and Results To clarify changes in repolarization properties, we analyzed the activation-recovery interval (ARI) obtained from body-surface maps and the relationship between the activation time (AT) and ARI in 30 patients with WPW syndrome (group A, 18 patients with manifest left-sided accessory pathway; group B, 7 patients with manifest right-sided accessory pathway; and group C, 5 patients with concealed left-sided accessory pathway) before, 1 day after, and 1 week after ablation. The ARI significantly decreased 1 week after ablation compared with before and 1 day after ablation over the preexcited area in groups A and B. Correlation coefficients between the AT and ARI showed a significantly ( P r =−.58) and 1 week after ( r =−.64) ablation than 1 day after ablation ( r =−.46) in groups A and B. In group C, the ARI and correlation coefficients between the AT and ARI showed no significant changes. Conclusions These findings suggest a prolongation of the action-potential duration over the preexcited area before and just after ablation as ventricular “electrical remodeling,” a decrease in the inverse relationship between the AT and action-potential duration 1 day after ablation, and a gradual recovery of the action-potential duration over the preexcited area and inverse relationship 1 week after ablation.

Nobori stent (Terumo Co., Tokyo Japan), is the new concept Drug Eluting Stent which has unique bioabsorbable polymer (Poly-Lactic Acid) and the anti-proliferative agent Biolimus A9. We investigated the safety and the efficacy of Nobori stent comparing to Cypher stent in Japanese population by a

Background: An ablation targeting ganglionated plexi (GP) with pulmonary vein isolation (PVI) and/or left atrium (LA) modification has been reported to have the potential to improve an outcome after ablation of atrial fibrillation (AF). However, it is not clear whether PVI per se affects the GP. Methods and Results: We identified the sites of LA showing a high grade atrioventricular (AV) block by an application of high frequency stimuli (HFS) as the location of GPs (superior left GP [SLGP], anterior right GP [ARGP], Marshall tract GP [MTGP], inferior right GP, inferior left GP) in a 75 year-old-woman presenting with drug refractory persistent AF. After successful PVI using a generally accepted approach with CARTO system, the high grade AV block induced by the HFS that had been observed before the PVI was in turn not identified at the location of SLGP, ARGP and MTGP. Conclusions: PVI possibly provides GP modification as one of the therapeutic effects for AF.

Background: Although many experimental data support the suppressive effect of RASIs on the occurrence of AF, recent clinical trials revealed no benefit of RASIs to prevent AF. However, if appropriate patients were selected, RASIs could work more effectively. In this study, we hypothesized that RASIs was effective in patients with normal LA. Methods: We retrospectively studied 178 consecutive patients (mean age=60±12 yrs, 76% males) with normal LA (LA