Esophageal thermal lesions in radiofrequency ablation for atrial fibrillation: A prospective comparative study of thermal sensors.

BACKGROUND: Esophageal thermal lesion (ETL) is a complication of radiofrequency ablation for atrial fibrillation (RFAF). To prospectively compare the incidence of ETL, we used two linear, five- and three-sensor esophageal thermal monitoring catheters (ETMC5 and ETMC3). We also evaluated the predictors of ETL. METHODS: Patients receiving their first RFAF (n = 106) were randomized into two groups, ETMC5 (n = 52) and ETMC3 (n = 54). Ablation was followed by esophagogastroduodenoscopy within 3 days. RESULTS: Esophageal thermal lesion was detected in 7/106 (6.6%) patients (ETMC5: 3/52 [5.8%] vs. ETMC3: 4/54 [7.4%]; p = 1.0). The maximum temperature and number of measurements > 39.0°C did not differ between the groups (ETMC5: 40.5°C and 5.4 vs. ETMC3: 40.6°C and 4.9; p = .83 and p = .58, respectively). In ETMC5 group, the catheter had to be moved significantly less often (0.12 vs. 0.42; p = .0014) and fluoroscopy time was significantly shorter (79.2 min vs. 101.7 min; p = .0038) compared with ECMC3 group. The total number of ablations in ETMC5 group was significantly greater (50.2 vs. 37.7; p = .030) and ablation time was significantly longer (52.1 min vs. 40.1 min; p = .0039). Only body mass index (BMI) was significantly different between patients with and without ETL (21.4 ± 2.5 vs. 24.3 ± 3.4; p = .022). CONCLUSIONS: The incidence of ETL was comparable between ETMC5 and ETMC3 groups; however, fluoroscopy time, total ablation time, and total number of ablations differed significantly. Lower BMI may increase the risk of developing ETL.

Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial.

AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study.

BACKGROUND: The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined. METHODS: This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured. RESULTS: The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000-1.036, p = 0.034). CONCLUSIONS: These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.

Clinical predictors for bradycardia and supraventricular tachycardia necessitating therapy in patients with unexplained syncope monitored by insertable cardiac monitor.

BACKGROUND: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known. HYPOTHESIS: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs. METHODS: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT. RESULTS: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT. CONCLUSION: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope.

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients　- A Randomized Controlled Trial.

BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. CONCLUSIONS: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Caesarean Section of Multifetal Pregnancy.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 0/7 and 38 6/7 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long U -shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.

J-Wave Elevation in the Inferior Leads Predicts Lethal Ventricular Arrhythmia Initiated by Premature Ventricular Contractions With Right Bundle Branch Block and Superior Axis.

BACKGROUND: Lethal ventricular arrhythmia (VA) can be initiated by idiopathic premature ventricular contractions (PVCs) originating from the left ventricular (LV) inferior wall. Furthermore, J-wave elevation in the inferior leads on ECG is sometimes associated with lethal VA. However, the relationship between these PVCs and J-wave elevation in patients with lethal VA is unclear, so we investigated it in the present study.Methods and Results:We studied 32 consecutive patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with right bundle branch block (RBBB) and superior axis. Thee PVCs were originating from the inferior wall of the LV. Lethal VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal VA. The ratio of J-wave elevation in lethal VA was significantly higher as compared with non-lethal VA (100% vs. 11.1%, P<0.0001). Furthermore, no patients with J-wave elevation in the inferior leads had recurrence of lethal VA after RF ablation of the PVCs. CONCLUSIONS: We speculate that J-wave elevation in the inferior leads might be a predictor of lethal VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs was a useful method of treating lethal VA.

Idiopathic basal crux ventricular arrhythmias with left bundle branch block and superior axis: A comparison with inferior-septal valvular arrhythmias.

INTRODUCTION: Left bundle branch block (LBBB) with superior axis is common in patients with idiopathic-ventricular arrhythmia (VA) originating from the tricuspid annulus (TA) and rarely from the cardiac basal crux and mitral annulus (MA). We described the electrocardiography and electrophysiological findings of idiopathic-VA presenting with LBBB and superior axis. METHODS AND RESULTS: We described 42 idiopathic-VA patients who had an LBBB and superior axis; 15 basal crux-VA, 17 TA-VA, and 10 MA-VA. No patient had a structural heart disease. Among patients with idiopathic-VA referred for ablation, we investigated the electrocardiogram and clinical characteristics of basal crux-VA as compared with other LBBB and superior axis-VA. The left ventricular ejection fraction with MA-VA was significantly lower in comparison with basal crux-VA (P = .01). All patients had a positive R wave in lead I and aVL. The maximum deflection index with basal crux-VA was significantly higher in comparison with TA-VA or MA-VA (P = .01). Patients with basal crux-VA presented with QS wave in lead II more frequently as compared with TA-VA or MA-VA (P = .001). All MA-VA patients had Rs wave in V6, and basal crux-VA, and TA-VA patients had a monophasic R wave or Rs wave in V6. Basal crux-VA patients underwent ablation in the middle cardiac vein (MCV) or coronary sinus (success rate: 94%, recurrence rate: 6%). CONCLUSIONS: We could distinguish basal crux-VA, TA-VA, and MA-VA, using a combination of clinical and electrocardiographic findings. These findings might be useful for counseling patients about an ablation strategy. Ablation via the MCV is effective for eliminating basal crux-VA.

Association left ventricular lead and ventricular arrhythmias after upgrade to cardiac resynchronization therapy in patients with implantable cardioverter defibrillators.

BACKGROUND: There are some controversial reports related to the pro-arrhythmic or anti-arrhythmic potential of cardiac resynchronization therapy (CRT) and little is known about the relationship between ventricular arrhythmia (VA) and left ventricular (LV)-lead threshold. HYPOTHESIS: Upgrade CRT is anti-arrhythmic effect of VA with implantable cardioverter-defibrillator (ICD) patients and has a relationship with the incident of VA and LV-lead threshold. METHODS: Among 384 patients with the implantation of CRT-defibrillator (CRT-D), 102 patients underwent an upgrade from ICD to CRT-D. We divided patients into three groups; anti-arrhythmic effect after upgrade (n = 22), pro-arrhythmic effect (n = 14), and unchanging-VA events (n = 66). The VA event was determined by device reports. We described the electrocardiography parameters, LV-lead characteristics, and clinical outcomes. RESULTS: Before upgrade, the numbers of VA were 305 episodes and the numbers of ICD therapy were 157 episodes. While after upgrade, the numbers of VA were 193 episodes and the number of ICD therapy were 74 episodes. Ventricular tachycardia cycle length (VT-CL) after upgrade was significantly slower as compared to those with before upgrade. Pro-arrhythmic group was significantly higher with delta LV-lead threshold (after 1 month-baseline) as compared to those with anti-arrhythmic group (0.74 vs -0.21 V). Furthermore, pro-arrhythmic group was significantly bigger with delta VT-CL (after 3 months-before 3 months) as compared to those with anti-arrhythmic group (P = .03). CONCLUSIONS: We described upgrade-CRT was associated with reduction of VA, ICD therapies and VT-CL. While 14 patients had a pro-arrhythmic effect and LV lead threshold might be associated with VA-incidents.

Thrombomodulin can predict the incidence of second events in patients with acute coronary syndrome: Single-center, retrospective cohort study.

BACKGROUND: Plasma levels of atherothrombosis-related markers such as endothelial biomarkers have been reported to predict the risk of first acute coronary syndrome (ACS) events. Percutaneous coronary intervention (PCI) by balloon angioplasty and stenting established as a treatment for ACS enabled early discharge and early clinic care. The procedure of PCI, however, may itself be associated with arterial injury with endothelial dysfunction. The clinical significance of those biomarkers for second events in patients after PCI has not yet been completely understood to identify patients who need strict follow-up. METHODS: After the exclusion of 100 patients (60 deaths during hospitalization, 40 severe renal failure), 400 ACS patients (291 males, 71.1±13.0 years) who had undergone successful PCI followed by biomarker assessment within the first postoperative hour were enrolled. We evaluated atherothrombosis-related biomarkers: thrombomodulin (TM), C-reactive protein (CRP), and D-dimer, prothrombin fragment F1+2, and plasminogen activator inhibitor-1, other than those assessed by routine biochemical tests. The outcome after PCI in ACS patients was assessed by the incidence of major adverse cardiovascular events (MACEs). RESULTS: MACEs occurred in 112 patients during the follow-up period (813.9±474.8 days). As in previous reports, patients with MACEs showed decreased left ventricular ejection fraction (LVEF) by echocardiography, elevated brain natriuretic peptide and HbA1c than patients without MACEs. Not only these markers but also TM were significantly associated with MACEs in multivariate analysis. There were no significant correlations between MACEs and CRP. The association between TM and MACEs was especially high (odds ratio 2.73) and unaffected by the stage of cardiac (≤40, 40

Modulation of sympathetic preganglionic neuron activity via adrenergic receptors.

The sympathetic preganglionic neurons (SPNs) play a key role in the sympathetic nervous system. Previous reports have suggested that norepinephrine (NE) directly affects SPNs via both inhibitory hyperpolarization interactions mediated by α2 receptors and excitatory depolarization interactions mediated by α1 receptors. It remains poorly understood, however, whether the excitability of SPNs can be inhibited indirectly (presynaptically) as well as directly (postsynaptically). We intracellularly recorded 41 SPNs using the whole-cell patch-clamp technique in spinal cord slice preparations of neonatal rats. We examined the effects of NE or dexmedetomidine hydrochloride (Dxm) (α2-adrenergic receptor agonist) on SPNs by analyzing the excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). EPSPs were dominant in 15 SPNs (EPSP-SPNs) and IPSPs were dominant in 7 SPNs (IPSP-SPNs) at baseline. We were unable to analyze the postsynaptic potentials in the other 19 SPNs, due to high frequency of action potential firings (firing-SPNs). At baseline, the membrane potentials and resistances of each type of SPN were similar. NE (1 µM) gradually depolarized the EPSP-SPNs and IPSP-SPNs (P < 0.001) and NE significantly increased the EPSP frequency of the EPSP-SPNs (P < 0.05). Dxm (10 nM) after application of NE decreased the EPSP frequency of the EPSP-SPNs (P < 0.001) and the EPSP voltage and IPSP voltage of the IPSP-SPNs (P < 0.05). In 5 of the 19 firing-SPNs, NE induced membrane hyperpolarization (P < 0.05) and completely inhibited firings. Dxm had no effect in these neurons. The SPNs received inhibitory modulation through α2-adrenergic receptors. Some SPNs can be directly inhibited via effects independent of the α2 receptors.

Small dense low-density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease.

AIM: The study objective was to investigate whether small dense low-density lipoprotein cholesterol (sdLDL-C) is superior to low-density lipoprotein cholesterol (LDL-C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention. METHODS: sdLDL-C measured by a homogeneous assay, remnant lipoprotein cholesterol, LDL particle diameter and other biomarkers were compared in 345 men aged ≥65 years with stable coronary artery disease. Baseline LDL-C was 100.5 ± 30.1 mg/dL. CE including cardiovascular death, onset of acute coronary syndrome, need for arterial revascularization, hospitalization for heart failure, surgery procedure for cardiovascular disease and hospitalization for stroke were monitored for 5 years. RESULTS: CE occurred in 96 patients during the study period. LDL-C, sdLDL-C non-high-density lipoprotein cholesterol, apolipoprotein B, remnant lipoprotein cholesterol, glucose, glycated hemoglobin and brain natriuretic peptide were significantly higher; LDL particle diameter and apolipoprotein A-1 were significantly lower in patients with than in those without CE. Age-adjusted Cox regression analysis showed that sdLDL-C per 10 mg/dL, but not LDL-C, was significantly associated with CE (HR 1.206, 95% CI 1.006-1.446). A significant association of sdLDL-C and incident CE was observed in statin users (HR 1.252, 95% CI 1.017-1.540), diabetes patients (HR 1.219, 95% CI 1.018-1.460), patients without diabetes (HR 1.257, 95% CI 1.019-1.551) and patients with hypertriglyceridemia (HR 1. 376, 95% CI 1.070-1.770). CONCLUSIONS: sdLDL-C was the most effective predictor of residual risk of future CE in stable coronary artery disease patients using statins and in high-risk coronary artery disease patients with diabetes or hypertriglyceridemia. Geriatr Gerontol Int 2018; 18: 965-972.

Neopterin Counters Vascular Inflammation and Atherosclerosis.

BACKGROUND: Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed. METHODS AND RESULTS: We investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte-derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E-deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF-α (tumor necrosis factor α)-induced upregulation of MCP-1 (monocyte chemotactic protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF-α-induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF-κB (nuclear factor-κB) downregulation. Neopterin suppressed oxidized low-density lipoprotein-induced foam cell formation associated with CD36 downregulation and upregulation of ATP-binding cassette transporters A1 and G1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II-induced migration and proliferation via c-Src/Raf-1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E-deficient mice. CONCLUSIONS: Our results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.

Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia.

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E-deficient (ApoE-/-) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE-/- mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury-induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.

Effects of Cardiac Rehabilitation on High-Density Lipoprotein-mediated Cholesterol Efflux Capacity and Paraoxonase-1 Activity in Patients with Acute Coronary Syndrome.

AIMS: We evaluated whether exercised-based cardiac rehabilitation (CR) can ameliorate the HDL function, i.e., cholesterol efflux capacity (CEC) and paraoxonase-1 activity in patients with acute coronary syndrome (ACS). METHODS: This study is a retrospective analysis of stored serum from patients with ACS following successful percutaneous coronary intervention. The CEC, measured by a cell-based ex vivo assay using apolipoprotein B-depleted serum and 3H-cholesterol labeled macrophages and arylesterase activity (AREA) at the onset or early phase of ACS, and the follow-up periods were compared between 69 patients who completed the five-month outpatient CR program (CR group) and 15 patients who did not participate and/or dropped out from CR program (non-CR group). RESULTS: Apolipoprotein A-I (apoA-I) and CEC significantly increased by 4.0% and 9.4%, respectively, in the CR group, whereas HDL-cholesterol and AREA were not changed during the follow-up periods in both groups. Among CR patients, the CEC significantly increased, irrespective of the different statin treatment, while HDL-cholesterol and apoA-I significantly increased in patients treated with rosuvastatin or pitavastatin. Although CEC and AREA were significantly correlated each other, there is a discordance between CEC and AREA for their correlations with other biomarkers. Both CEC and AREA were significantly correlated with apoA-I rather than HDL-cholesterol. Changes in CEC and those in AREA were significantly correlated with those in apoA-I (rho=0.328, p=0.002, and rho=0.428, p＜0.0001, respectively) greater than those in HDL-cholesterol (rho=0.312, p= 0.0042,and rho=0.343, p=0.003, respectively). CONCLUSIONS: CR can improve HDL function, and it is beneficial for secondary prevention.

Performance of Leadless Pacemaker in Japanese Patients vs. Rest of the World　- Results From a Global Clinical Trial.

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.).

Predictors of Mortality, Rehospitalization for Syncope and Cardiovascular Events in Patients With Cardiovascular Syncope.

BACKGROUND: Predictors of poor outcomes remain unknown for cardiovascular syncope patients after discharge.Methods and Results:We reviewed the medical records of consecutive patients admitted to hospital with cardiovascular syncope. We then performed Cox stepwise logistic regression analysis to identify significant independent factors for death, rehospitalization for syncope, and cardiovascular events. The study group was 206 patients with cardiovascular syncope. Of them, bradycardia was diagnosed in 50%, tachycardia in 27%, and structural disease in 23%. During a 1-year follow-up period, 18 (8%) and 45 (23%) patients, respectively, were rehospitalized for syncope or a cardiovascular event, and 10 (4%) died. Independent predictors of cardiovascular events were systolic blood pressure <100 mmHg (odds ratio [OR] 3.25; 95%confidence interval [CI] 1.41-7.51, P=0.006) and implantation of a pacemaker (OR 0.19; 95% CI 0.05-0.51, P=0.0005) (inverse association). Drug-induced syncope (OR 4.57; 95% CI 1.54-12.8, P=0.007) was an independent risk factor for rehospitalization. Finally, a history of congestive heart failure (OR 11.0; 95% CI 2.78-54.7, P=0.0006) and systolic blood pressure <100 mmHg (OR 5.40; 95% CI 1.30-22.7, P=0.02) were identified as significant independent prognostic factors for death. CONCLUSIONS: Drug-induced syncope, hypotension, no indication for a pacemaker, and a history of congestive heart failure are risk factors post-discharge for patients with cardiovascular syncope and careful follow-up of these patients for at least 1 year is recommended.

Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist.

BACKGROUND: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis. METHODS AND RESULTS: We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice in vivo. KP-10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10 stimulated mRNA expression of tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with upregulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and 2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10 into ApoE-/- mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were completely canceled by P234 infusion in ApoE-/- mice. CONCLUSIONS: Our results suggest that KP-10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the KP-10/GPR54 system may serve as a novel therapeutic target for atherosclerotic diseases.

Immediate discontinuation of ablation during pulmonary vein isolation remarkably decreases the incidence of esophageal thermal lesions even when using steerable sheaths.

BACKGROUND: Left atrial-esophageal fistulas (LAEFs) are serious complications with high mortality after atrial fibrillation radiofrequency ablation (AFRA). Decreasing the incidence of esophageal thermal lesions (EsoTLs) that may lead to LAEFs is important. The aim of this study was to suppress EsoTL development and determine the appropriate alarm setting for a temperature-monitoring probe by using steerable sheath (STS) methods. METHODS: We enrolled 82 consecutive patients (mean, 61.9±11.7 years; 75.6% men) who underwent AFRA, including pulmonary vein isolation for symptomatic, drug-refractory atrial fibrillation with esophageal temperature monitoring by using STS between January 2011 and April 2014. All patients underwent upper gastrointestinal endoscopy (UGE) 1-3 days after AFRA. The timing of ablation discontinuation in the first 17 patients was determined by each physician during AFRA (only monitoring group, OM). In the next 65 patients, physicians were to immediately discontinue ablation when an alarm set at 39 °C went off (instruction group, INS). We compared two groups with respect to the incidence of EsoTLs. RESULTS: Among the 82 patients, 5 (6.1%) had EsoTLs after AFRA. EsoTLs occurred in 3 of 17 patients (17.6%) and 2 of 65 patients (3.1%) in the OM and INS groups, respectively. The incidence of EsoTLs in the INS group was significantly lower than that in the OM group (p=0.0254). EsoTL did not occur at maximal temperature less than 39 °C, measured by using esophageal temperature-monitoring probe. CONCLUSIONS: Immediate discontinuation of ablation during pulmonary vein isolation remarkably decreased the incidence of EsoTLs, even when using STS.