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Background: An abnormal Q wave is usually defined as an initial depression of the QRS complex having a duration of > or =40 ms and amplitude exceeding 25% of the following R wave in any contiguous leads on the 12-lead electrocardiogram (ECG). However, much smaller Q waves are sometimes recorded on the ECG. This study investigated the diagnostic value of the small Q wave recorded in precordial leads V(2) or V(3) on the ECG.Methods: We investigated 807 consecutive patients who underwent coronary angiography. A small Q wave was defined as any negative deflection preceding the R wave in V(2) or V(3) with <40-ms duration and <0.5-mV amplitude, with or without a small (<0.1-mV) slurred, spiky fragmented initial QRS deflection before the Q wave (early fragmentation). ECG and coronary angiographic findings were analyzed.Results: The small Q wave was present in 87 patients. Multiple logistic regression analysis revealed that presence of a small Q wave was a strong independent predictor of any coronary artery stenosis or left anterior descending artery (LAD) stenosis (odds ratio = 2.706, 2.902; P < 0.001, < 0.001, respectively).Conclusion: A small Q wave (<40-ms duration and <0.5-mV amplitude) in V(2) or V(3) with or without early fragmentation significantly predicted the presence of CAD and, especially, significant stenosis in the LAD. [ABSTRACT FROM AUTHOR]

This study investigated the types of gestures used, the frequency of the gestures, and the total time engaged in gestural communication by 11 visually impaired-sighted dydads; 12 sighted-sighted dyads; and 8 visually impaired-visually impaired dyads. Regardless of the type of dyad, the persons who were visually impaired used more adaptors and used gestures, emblems, and illustrators less often than did those who were sighted. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) following cardiovascular surgery is a common disease process and is associated with both morbidity and mortality. The aim of our study was to evaluate the cardiovascular and renal effects of an atrial natriuretic peptide (ANP, carperitide) and a B-type (or brain) natriuretic peptide (BNP, nesiritide) for preventing and treating AKI in cardiovascular surgery patients.Methods: Electronic databases, including PubMed, EMBASE and references from identified articles were used for a literature search.Results: Data on the infusion of ANP or BNP in cardiovascular surgery patients was collected from fifteen randomized controlled trials and combined. The infusion of ANP or BNP increased the urine output and creatinine clearance or glomerular filtration rate, and reduced the use of diuretics and the serum creatinine levels. A meta-analysis showed that ANP infusion significantly decreased peak serum creatinine levels, incidence of arrhythmia and renal replacement therapy. The meta-analysis also showed that ANP or BNP infusion significantly decreased the length of ICU stay and hospital stay compared with controls. However, the combined data were insufficient to determine how ANP or BNP infusion during the perioperative period influences long-term outcome in cardiovascular surgery patients.Conclusions: The infusion of ANP or BNP may preserve postoperative renal function in cardiovascular surgery patients. A large, multicenter, prospective, randomized controlled trial will have to be performed to assess the therapeutic potential of ANP or BNP in preventing and treating AKI in the cardiovascular surgical setting. [ABSTRACT FROM AUTHOR]

Background: The number of octo- and nonagenarians admitted to cardiac care units (CCUs) has been increasing in the context of an aging society; however, clinical details and outcomes for these patients are scarce. Methods and Results: Data from 2,242 consecutive patients admitted to the CCU between 2019 and 2021 (age <80 years, 1,390 [62%]; octogenarians, 655 [29%]; nonagenarians, 197 [8.7%]) were reviewed using the in-hospital database for the Tokyo CCU Network. The primary cause of admission was acute coronary syndrome in younger patients and octogenarians (58% and 49%, respectively) and acute heart failure (AHF) in nonagenarians (42%). The proportions of females, underweight, hypertension, atrial fibrillation, myocardial infarction, stroke, previous heart failure, anemia, and malnutrition were higher among octo- and nonagenarians than among younger patients. In-hospital and 1-year mortality rates were greater in octo- and nonagenarians (younger vs. octogenarian vs. nonagenarian, 2.0% vs. 3.8% vs. 5.6% and 4.1% vs. 11.9% vs. 19.0%, respectively). Multivariate analysis revealed that 1-year mortality was associated with octo-/nonagenarian status (odds ratio [OR] 2.24 and 2.64), AHF (OR 2.88), body mass index (OR per 1-kg/m 2 0.91), and albumin concentration (OR per 1-g/dL 0.27). Conclusions: Approximately 40% of patients admitted to the CCU were octo- or nonagenarians, and being an octo- or nonagenarian, having AHF, a lower body mass index, and lower albumin concentrations were associated with 1-year mortality after CCU admission., Competing Interests: The authors declare no potential conflicts of interest relevant to this article., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective α -2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions. We investigated the hypothesis that anti-inflammatory characteristics of DEX could lessen PAH that monocrotaline (MCT) causes in rats. In vivo, male Sprague-Dawley rats aged 6 weeks were subcutaneously injected with MCT at a dose of 60 mg/kg. Continuous infusions of DEX (2 µg/kg per hour) were started via osmotic pumps in one group (MCT plus DEX group) at day 14 following MCT injection but not in another group (MCT group). Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), and survival rate significantly improved in the MCT plus DEX group compared with the MCT group [RVSP, 34 mmHg ± 4 mmHg versus 70 mmHg ± 10 mmHg; RVEDP, 2.6 mmHg ± 0.1 mmHg versus 4.3 mmHg ± 0.6 mmHg; survival rate, 42% versus 0% at day 29 ( P < 0.01)]. In the histologic study, the MCT plus DEX group showed fewer phosphorylated p65-positive PASMCs and less medial hypertrophy of the pulmonary arterioles. In vitro, DEX dose-dependently inhibited human PASMC proliferation. Furthermore, DEX decreased the expression of interleukin-6 mRNA in human PASMCs treated with fibroblast growth factor 2 (FGF2). These consequences suggest that DEX improves PAH by inhibiting PASMC proliferation through its anti-inflammatory properties. Additionally, DEX may exert anti-inflammatory effects via blocking FGF2-induced nuclear factor κ B activation. SIGNIFICANCE STATEMENT: Dexmedetomidine, a selective α -2 adrenergic receptor agonist utilized as a sedative in the clinical setting, improves pulmonary arterial hypertension (PAH) by inhibiting pulmonary arterial smooth muscle cell proliferation through its anti-inflammatory effect. Dexmedetomidine may be a new PAH therapeutic agent with vascular reverse remodeling effect., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Takayasu arteritis can affect the coronary ostia, leading to myocardial ischemia. Coronary ostial angioplasty effectively treats coronary artery ostial lesions associated with Takayasu arteritis. We present a case of juvenile Takayasu arteritis with bilateral subclavian artery occlusions treated with a novel coronary artery ostial angioplasty using the external iliac artery., (© 2022. The Author(s).)

The in-hospital mortality rate among patients after surgery for acute type A aortic dissection (ATAAD) has improved chronologically. However, the relationship between the incidence of hospitalisation-associated disability (HAD) and acute cardiac rehabilitation in patients after surgery for ATAAD has not been reported. Therefore, this study evaluated factors related to HAD in patients after surgery for ATAAD. This single-centre retrospective observational study included 483 patients who required emergency surgery for ATAAD. HAD occurred in 104 (21.5%) patients following cardiovascular surgery. Factors associated with HAD were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.001), noninvasive positive pressure ventilation (NPPV; OR, 2.15; 95% CI, 1.10-4.19; p = 0.025), postoperative delirium (OR, 2.93; 95% CI, 1.60-5.37; p = 0.001), and timing of walking onset (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008). Furthermore, a late walking onset was associated with a higher risk of developing HAD and more severe functional decline. Early rehabilitation based on appropriate criteria has possibility of preventing HAD.

Background: Following cardiovascular surgery, patients are at high risk of requiring systemic management in the intensive care unit (ICU), resulting in hospitalization-associated disability (HAD). Predicting the risk of HAD during the postoperative course is important to prevent susceptibility to cardiovascular events. Assessment of physical function during the ICU stay may be useful as a prediction index but has not been established., Methods: This prospective observational study conducted at a high-volume cardiovascular center included 236 patients (34% female; median age, 73 years) who required an ICU stay of at least 72 hours after surgery and underwent postoperative rehabilitation. HAD was defined as a decrease in the discharge Barthel index (BI) score of at least 5 points relative to the preadmission BI score. Physical Function ICU Test-scored (PFIT-s), Functional Status Score for the ICU (FSS-ICU), and Medical Research Council (MRC)-sumscore were used to assess physical function at ICU discharge., Results: HAD occurred in 58 (24.6%) of the 236 patients following cardiovascular surgery. The cut-off points for HAD were 7.5 points for the PFIT-s (sensitivity 0.80, specificity 0.59), 24.5 points for the FSS-ICU (sensitivity 0.57, specificity 0.66), and 59.5 points for the MRC-sumscore (sensitivity 0.93, specificity 0.66). Multivariate logistic regression analysis revealed a PFIT-s of >7.5 points (odds ratio [OR], 4.84; 95% CI, 2.39-9.80; p < 0.001) and an MRC-sumscore of >59.5 points (OR, 2.43; 95% CI, 1.22-4.87; p = 0.012) as independent associated factors., Conclusions: We demonstrate that the PFIT-s and MRC-sumscore at ICU discharge may be helpful as a predictive indicator for HAD in patients having undergone major cardiovascular surgery., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Author(s). Published by IMR Press.)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines., Competing Interests: Financial and academic COIs as well as the role(s) of each committee member are disclosed in the additional file 1 (https://www.jsicm.org/pdf/guidelineEN/Additionalfile1.pdf). Financial COIs were disclosed in accordance with the standards used by the Japanese Association of Medical Sciences from 2017 through 2019., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Surgical repair of asymptomatic congenital left ventricular aneurysm is poorly reported. A 30-yearold man presented with an asymptomatic abnormal electrocardiogram. Computed tomography (CT) and angiography revealed a congenital left ventricular aneurysm, and surgical repair was conducted with endocardial linear infarct exclusion technique (ELIET). His postoperative course was uneventful. Postoperative CT showed an elliptical cardiac shape with no recurrence of aneurysm. ELIET would serve as a surgical procedure for congenital left ventricular aneurysm.

A 15-year-old boy with Noonan syndrome, who had been diagnosed with hypertrophic cardiomyopathy (HCM) at 4 and treated by drugs, was referred to our hospital because of progression of left ventricular outflow tract obstruction (LVOTO). Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy( LVH), LVOTO( systolic gradient:102 mmHg), and systolic anterior motion of the mitral valve( SAM) with mild mitral regurgitation(MR). We performed septal myectomy by transaortic and transapical approaches. Postoperative TTE revealed significant reduction in left ventricular outflow tract (LVOT) gradient (9 mmHg), resolution of SAM, and reduction in MR grade. The postoperative course was uneventful except for transient atrial tachyarrhythmia. Myectomy for HCM in a patient with Noonan syndrome is rare. This case suggests that myectomy is useful for the patients with Noonan syndrome.

Cryoballoon ablation is a well-established therapeutic tool for paroxysmal atrial fibrillation (PAF). We herein report a rare case of a 69-year-old man with PAF undergoing hemodialysis due to chronic kidney disease who developed hyperkalemia caused by possible cold agglutinin disease during cryoballoon ablation therapy. During the procedure, his electrocardiogram showed wide QRS when we finished cryoablation therapy. We detected hyperkalemia and performed urgent hemodialysis. We should bear in mind that cold agglutinin disease can occur during cryoballoon ablation.

Introduction: Pulmonary vein isolation (PVI) is widely performed for atrial fibrillation (AFib). However, it is insufficient to maintain sinus rhythm (SR) in persistent and long persistent atrial fibrillation (Per-AFib). Ablation of complex fractionated atrial electrograms (CFAEs) is currently classified as class IIb, However, the concept of length of potential was different between the current CFAE module of CARTO system and the definition of CFAE potential. The current CFAE module was configured in the shortest complex interval (SCI) mode, in which the meaning of length of potential was the interval of each component of fragmented potentials. That was a part of the potential. On the other hand, the meaning of the definition of CFAE potential was the length of fragmented potential itself. The purpose of this study was to essentially evaluate fragmented potentials by revisiting in interval confidence level (ICL) mode and express them on the map and prospectively investigate the efficacy and prognosis of a new tailored approach for defragmentation, which is called early area defragmentation (EADF)., Methods and Results: We acquired atrial potentials by modified CFAE module in ICL mode (K-CFAE potential) and visualized the distribution of K-CFAE potential (K-CFAE map). We performed PVI, and we ablated the fragmented areas based on the K-CFAE map. We enrolled 77 patients in this study (control group: 84 patients). After 24-month follow-up, 75.3% were able to maintain SR., Conclusions: K-CFAE mapping faithfully represented the distribution of fragmented areas. PVI, together with our new tailored approach, EADF, was successful in treating Per-AFib., (© 2019 Wiley Periodicals, Inc.)

Renin-angiotensin system (RAS) inhibitors may be useful in preventing the occurrence of paroxysmal atrial fibrillation (PAF). However, evaluation of such effect is difficult because many PAF episodes are asymptomatic and not all episodes are detected by intermittent electrocardiographic monitoring. A pacemaker has been developed with dedicated functions for AF detection and electrocardiogram storage. Accordingly, we examined the effect of losartan, an angiotensin receptor blocker on PAF occurrence using this new modality. We enrolled 70 consecutive patients who had undergone dual-chamber pacemaker implantation for sick sinus syndrome. Finally, 62 patients participated in the study. Thirty patients were randomized to the losartan group (mean 43 ± 12 mg/day) and 32 patients to the control group. They were followed up for 3 months. The frequency, the maximum duration and the total duration of PAF recorded by the stored electrocardiograms for the last 1 month during the observation period and study period were compared between the two groups. The change in the frequency of PAF from the observation period in the losartan and control groups was similar (-35 ± 25 vs. -67 ± 62 times; NS). However, the change in the maximum duration and the total duration of PAF was significantly shorter in the losartan group than in the control group (-493 ± 158 vs. -10 ± 69 min; p < 0.05, and -4007 ± 2334 vs. 1119 ± 714 min; p < 0.05, respectively). Losartan suppressed the maximum duration and the total duration of PAF in patients with sick sinus syndrome without hemodynamic changes. This is the first study to show the effect of a renin-angiotensin system inhibitor on the secondary prevention of PAF using the dedicated functions of a pacemaker for PAF detection and electrocardiogram storage.

Background: Polymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment., Methods: We retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group)., Results: The inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from 0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p < 0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p < 0.05)., Conclusions: The improvement group's inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.

Purpose: The purpose of this study was to evaluate the extent of endotoxin adsorption by polymyxin B-immobilized fiber column hemoperfusion (PMX) performed for a 24-hour treatment period in patients with septic shock., Materials and Methods: Nineteen patients with septic shock were retrospectively studied. The plasma endotoxin concentrations of blood drawn from the radial artery and from the outlet circuit of the PMX column were measured by kinetic turbidimetric limulus assay using an MT-358 Toxinometer (Wako Pure Chemical Industries, Ltd, Osaka, Japan) after 24 hours of PMX treatment. The endotoxin removal rate was defined by the following equation: ([radial artery endotoxin concentration - outlet circuit of PMX column endotoxin concentration]/radial artery endotoxin concentration) × 100%., Results: The patients had a median Acute Physiology and Chronic Health Evaluation II score of 29 at intensive care unit admission and a 28-day mortality of 47%. Before the start of the PMX treatment, the median radial arterial plasma endotoxin concentration was 16.48 pg/mL. After 24 hours of PMX treatment, the median radial plasma endotoxin concentration had decreased to 1.857 pg/mL, and the concentration at the outlet circuit of the PMX column was further decreased to 0.779 pg/mL. The median endotoxin removal rate was 74.4%., Conclusion: These findings suggest that 24-hour PMX treatment was effective in removing endotoxin continuously throughout the entire treatment period., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To assess the value of procalcitonin (PCT) for the differential diagnosis between infectious and non-infectious systemic inflammatory response syndrome (SIRS) after cardiac operation., Methods: Patients diagnosed with SIRS after cardiac surgery and admitted to Department of Cardiovascular Surgery of Tokyo Medical and Dental University Graduate School between April 1st, 2011 and March 31st, 2013 were retrospectively studied. A total of 142 patients with SIRS were included, and they were divided into infectious group (n =47) or non-infectious group ( n =95) according to the diagnostic criteria of the Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock: 2012 (SSCG2012). The patients with infectious SIRS were included, and there were 11 with sepsis, 12 with severe sepsis without shock, and 24 with septic shock respectively.The clinical data of patients were compared, and the receiver operating characteristic curve (ROC curve) was plotted to assess the diagnostic value of infection and non-infectious diseases for PCT, C-reactive protein ( CRP) and white blood cell count ( WBC ) , as well as the diagnosis of the severity of sepsis., Results: PCT, CRP, and WBC were significantly higher in the infectious SIRS group than those in the non-infectious SIRS group [ PCT ( J.Lg/L): 2.80 ( 1.24, 10.20) vs.0.10 (0.06, 0.21), Z=-9.020, P=O.OOl; CRP (mg/L): 158.0 (120.0, 199.0) vs. 58.0 (25.0, 89.0), Z=-7.264,P=O.OOl; WBC ( x 1Q9/L): 15.5 (11.0, 22.6) vs. 9.3 (7.2, 12.6), Z=-5.792, P=O.OOl ]. PCT had the highest sensitivity ( 91.5%) and specificity ( 93.7%) for differential diagnosis, with a cut-off value for infectious SIRS of0.4 7 fLg/L, and the cut-off value of CRP and WBC were 119.5 mg/L and l 0.85 X 1 09/L, respectively. There was no significant difference in WBC among sepsis group, severe sepsis group, and septic shock group (X 109/L: 12.40 (9.10, 24.20),13.30 ( 9.93, 16.93), 20.40 ( 13.45, 28.6), x2=5.638, P=0.060], while PCT, CRP had significant difference (PCT(fLg/L): 1.37 (0.72, 1.85), 3.16 (0.48, 13.24), 3.68 (1.67, 20.96), x2 =7.422, P=0.024; CRP (mg!L): 120.0(74.0, 180.0), 135.7 (81.7, 181.3), 171.1 (151.5, 306.0), x2 =9.524, P=0.009].PCT was more reliable than CRP in diagnosing severe sepsis without shock, but it was ineffective for diagnosing septic shock. The cut-off value of PCT for diagnosing severe sepsis without shock was 2.28 fLg/L, and the sensitivity was 66.7%, specificity was 90.9%.Cut-off value of CRP for the diagnosis of septic shock was 149.5 mg/L, with the sensitivity of 83.3%, and the specificity of 66.7%., Conclusions: PCT was a useful marker for the diagnosis of infectious SIRS after cardiac operation as compared with WBC and CRP. The optimal PCT cut-off value for diagnosing infectious SIRS was 0.47 fLg/L.

Background: This study was performed to assess the value of procalcitonin (PCT) for the differential diagnosis between infectious and non-infectious systemic inflammatory response syndrome (SIRS) after cardiac surgery., Methods: Patients diagnosed with SIRS after cardiac surgery between April 1, 2011 and March 31, 2013 were retrospectively studied. A total of 142 patients with SIRS, infectious (n = 47) or non-infectious (n = 95), were included. The patients with infectious SIRS included 11 with sepsis, 12 with severe sepsis without shock, and 24 with septic shock., Results: PCT, C-reactive protein (CRP), and the white blood cell (WBC) count were significantly higher in the infectious SIRS group than in the non-infectious SIRS group. PCT had the highest sensitivity and specificity for differential diagnosis, with a cut-off value for infectious SIRS of 0.47 ng/mL. PCT was more reliable than CRP in diagnosing severe sepsis without shock, but it was not useful for diagnosing septic shock. The PCT cut-off value for diagnosing severe sepsis without shock was 2.28 ng/mL., Conclusions: PCT was a useful marker for the diagnosis of infectious SIRS after cardiac surgery. The optimal PCT cut-off value for diagnosing infectious SIRS was 0.47 ng/mL.

Background: We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients., Methods and Results: We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0-1) (log-rank test χ(2)=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up., Conclusions: Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

Aims: Proliferation of pulmonary arterial smooth muscle cells (PASMCs) is one histological sign of pulmonary arterial hypertension (PAH). We hypothesized that a signalling cascade from fibroblast growth factor 2 (FGF₂) to plasminogen activator inhibitor 1 (PAI-1) and monocyte chemotactic protein-1 (MCP-1) via nuclear transcription factor nuclear factor kappaB (NF-kB) play a critical role in progression of PAH, and tested this hypothesis both in vivo and in vitro using a synthetic selective NF-kB inhibitor, N-(3,5-Bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide (IMD-0354)., Methods and Results: Monocrotaline (MCT) was injected into 75 Sprague-Dawley rats. Starting at day 14 after MCT injection, we administered IMD-0354 (MCT + IMD group) or vehicle (MCT group) daily. At day 32, 65% of the MCT + IMD group were alive compared with 0% of the MCT group. IMD-0354 prevented increase of right ventricular pressure, and suppressed proliferation and induced apoptosis of PASMCs. mRNA transcript levels of FGF₂, PAI-1, and tissue plasminogen activator (t-PA) were lower in MCT + IMD compared with MCT. In in vitro experiments, IMD-0354 inhibited p65 translocation to the nucleus promoted by FGF₂ in PASMCs. Furthermore, the time courses of extracellular signal-regulated kinase (Erk) 1/2, MCP-1, and PAI-1 stimulated with FGF₂ were each markedly shortened by IMD-0354., Conclusions: We speculate that the positive-feedback loop (Erk1/2-NF-kB-MCP-1-Erk1/2) is associated with progression of PAH by causing FGF₂-induced inflammation in MCT rats. IMD-0354 has potential as a new therapeutic tool for PAH.

Background: Patients with Takayasu arteritis (TA) often show recurrence under steroid treatment without an elevation of C-reactive protein (CRP). There is a report that matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and pentraxin3 (PTX3) could be sensitive biomarkers, but the characteristics of these biomarkers have not been established., Methods and Results: We enrolled 45 consecutive patients; 28 were grouped in an active phase as evidenced by clinical recurrence within 2 years of blood sampling. Circulating levels of high-sensitivity (hs)CRP, MMPs, and PTX3 were determined. Patients in an active phase showed higher levels of hsCRP, MMP-9, and PTX3. Area under the receiving operating characteristics curves of hsCRP and PTX3 were significantly higher than that of MMP-9. Among the 28 patients with active TA, 71% was positive for hsCRP and 82% for PTX3. Patients without recurrence showed significantly higher plasma levels of MMP-9. There was a positive correlation between the plasma MMP-3 level and the prednisolone dose. However, PTX3 and MMP-9 levels did not have such a correlation., Conclusions: PTX3 and MMP-9, which are not affected by prednisolone, could be sensitive biomarkers for assessing TA activity. Evaluation of MMP-9 may suggest prior existence of TA.

Myeloperoxidase secreted by macrophages and neutrophils in atherosclerotic lesions generates a tyrosyl radical in apolipoprotein (apo) AI, a major protein component of high-density lipoprotein (HDL), thus inducing the formation of apoAI-apoAII heterodimers. It can also cause nitration and chlorination of tyrosine residues. Determining the apoAI-apoAII heterodimer could provide useful information as to functional changes in HDL and/or the progression of atherosclerotic lesions. To this end, the apoAI-apoAII heterodimer was identified in normal human serum by immunoblotting; the band intensity was increased by treatment with myeloperoxidase. This apparent increase in heterodimer formation was quantitatively confirmed by ELISA. In normal human serum, a significant correlation between the concentrations of apoAI-apoAII heterodimer and free apoAII (r=0.763), but not free apoAI (r=0.093), was observed, indicating that heterodimer formation is likely induced on HDL particles carrying both apoAI and apoAII (Lp-AI/AII). In preliminary studies, the levels of apoAI-apoAII heterodimer were statistically higher in plasma from subjects with acute myocardial infarction (AMI) as compared to controls. These findings indicate the possibility that the apoAI-apoAII heterodimer, including nitration and chlorination modifications, may serve as an indicator of atherosclerotic lesions.

Background: Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) has been reported to correlate with poor prognosis, few studies have examined the effect of progression of hyponatremia on cardiac prognosis in ADHF patients who were normonatremic at admission., Methods and Results: Consecutive ADHF patients (n = 662) categorized as New York Heart Association Class III or IV were investigated retrospectively. Of these patients, 634 who survived to discharge were examined and 531 were normonatremic (serum sodium concentration [Na] ≥ 135 and ≤ 145 mmol/L) at admission. The 531 patients were divided into 2 groups: the non-developed group, who remained normonatremic at discharge (n = 455), and the developed group, who had progressed to hyponatremia (Na < 135 mmol/L) at discharge (n = 76). The cardiac event-free rate after 12 months was significantly lower in the developed group than in the non-developed group (22% vs. 71%; P < .0001). Although their baseline levels of brain natriuretic peptide and left ventricular ejection fraction were similar before discharge, the patients in the developed group exhibited higher fractional excretion of sodium and received higher doses of diuretics than did those in the non-developed group., Conclusion: Our data suggest that progression to hyponatremia during hospitalization is a robust predictor of poor cardiac prognosis in ADHF patients who were normonatremic at admission., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: With an aim to identify risk factors that can serve for prevention of atrioventricular (AV) block (AVB) during radiofrequency (RF) ablation, we conducted anatomical and electrophysiological investigations at the time of AV node ablation (AVNA)., Methods and Results: Ten patients who underwent AVNA were enrolled. RF energy was delivered from posterior region of septal annulus of the tricuspid valve to the His bundle potential (HBP) recording site using a stepwise approach. In each delivery, atrial/ventricle potential amplitude ratio (A/V ratio), HBP, and juctional ectopy (JE) that appeared during RF delivery were evaluated. Furthermore, fluoroscopic distance between ablation site and HBP recording site (anatomical H-ABL distance) and electrophysiological H-ABL interval were measured. HBP was recorded in 25 of total 70 RF deliveries. When HBP was recorded, the A/V ratio was significantly greater in the group with AVB than without AVB (1.6 ± 2.3 mV vs 0.1 ± 0.2 mV, P = 0.02). The minimum cycle length (CL) of JE was significantly shorter in the group with AVB than without AVB (438 ± 112 ms vs 557 ± 178, ms, P = 0.04). AVB developed frequently when H-ABL distance was less than 15 mm from right anterior oblique view 30° and 12 mm from left anterior oblique view 45° and when H-ABL interval was less than 10 ms. AVB did not develop over the above values., Conclusions: HBP with high A/V ratio, JE with short CL, short H-ABL distance, and short H-ABL interval of less than 10 ms should be avoided to prevent AVB during RF ablation at the near site of AV node., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Objectives: The aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases., Background: The clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment., Methods: Thirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects., Results: The max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p < 0.001 each). Given a max SUV cutoff of 2.1, sensitivity for active-phase TA was 92.6%, specificity 91.7%, positive predictive value 96.2%, and negative predictive value 84.6%. In receiver-operating characteristic curves comparison, max SUV was superior to C-reactive protein (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). Max SUV was significantly higher in relapsing on treatment cases (n = 17) than in stable on treatment cases (n = 12) (median value, 2.6 vs. 1.9; p < 0.001)., Conclusions: FDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The 'evidence' in evidence-based medicine (EBM) is often limited to knowledge obtained from randomized controlled clinical trials (RCT). Most RCTs, however, have strict enrollment criteria which make patient background characteristics and clinical histories significantly different from those encountered in actual practice. Thus it is important to accumulate and analyze data obtained in daily practice to gain insight into a larger clinical picture. Recent developments in information technology and its lowered cost have enabled us to record clinical activity in much greater detail at a lower cost. These factors prompted us to design and develop a coronary angiography and intervention reporting system (CAIRS) to collect data and analyze outcomes of coronary intervention. The resulting advanced CAIRS can record detailed data on coronary angiographic and interventional procedures.To date, data on 10,025 cases of coronary angiography, of which 3,574 were interventional, have been collected over a 5.5 year period. There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall mean age was 67.0 ± 11.5. The mean age of males was 66.3 ± 11.4 and that of females was 69.0 ± 11.4. About one-third of the patients never underwent a PCI procedure at our institution. For patients that underwent at least one PCI procedure at our institution, the prescription rate of statin increased from 50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have also implemented the same system at another institution and compared the data on stent usage between the two institutions, which revealed vastly different stent usage profiles.In conclusion, we have successfully developed and implemented an advanced coronary angiography and intervention reporting system which we call CAIRS. Implementing the same system at multiple institutions and analyzing data collected from several institutions will provide detailed and timely insight into the 'real world' of coronary angiography and interventional procedures and their outcome.

Background: We aimed to describe the recent clinical characteristics of Takayasu arteritis (TA)., Methods and Results: We enrolled 106 consecutive TA patients and compared the clinical characteristics of patients with TA onset before 1999 and after 2000, patients with onset at age less than 39 years and more than 40 years, patients with monophasic and relapsing-remitting clinical course, and patients with and without human lymphocyte antigen (HLA)-B52 allele. Among the patients with TA onset after 2000, the time from onset to diagnosis had decreased; the frequency of occlusion in aortic arch branches and the complication of moderate or severe aortic regurgitation (AR) had decreased, and the maximum dose of prednisolone and the use of immunosuppressive agents had increased. In patients with onset at age more than 40 years, the complications of coronary artery lesions and hypertension had increased, and the incidence of moderate or severe AR had decreased. In the relapsing-remitting group, the maximum dose of prednisolone and the use of immunosuppressive agents had increased, and the mean dose reduction rate of prednisolone was significantly high. There was no significant difference between patients with and without HLA-B52 allele., Conclusions: The prognosis of TA patients has improved over the past decade, which may be related to early diagnosis because of the development of noninvasive diagnostic imaging tools and improved medical treatments.

Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) leads to cardiac dysfunction. We examined whether Telmisartan, an angiotensin (Ang) II type I receptor blocker (ARB), could improve the recovery of LV function in a rat model of MI. The effect of Telmisartan as a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was also investigated. After 28 days of MI, a significant improvement of survival was observed in the Telmisartan-treated rat group compared with the vehicle control rat group, non-PPAR-γ agonistic ARB (Losartan)-treated rat group, and Telmisartan plus specific PPAR-γ antagonist (GW9662)-treated rat group. Although no significant differences of blood pressure or infarct size were observed among these four groups, the Telmisartan group had better systolic and diastolic LV function. There was a significant reduction of the plasma brain natriuretic peptide level, cardiac fibrosis area, infiltration of macrophages, size of cardiomyocytes, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive myocytes, activation of matrix metalloproteinases-2 and -9 (MMPs-2/9), and expression of transforming growth factor β-1 (TGF-β1), connective tissue growth factor (CTGF), and osteopontin (OPN), while expression of PPAR-γ and activation of tissue inhibitor of metalloproteinase-1 (TIMP-1) was enhanced, in the noninfarcted myocardium of rats from the Telmisartan group compared with the other three groups. To mimic ischemic conditions in vitro, neonatal rat cardiomyocytes and cardiac fibroblasts were incubated in hypoxic condition for 24 h. Increased transcriptional activation of PPAR-γ and TIMP-1, and inhibition of TGF-β1 expression were observed in cardiomyocytes, while decreased activation of MMPs-2/9 and decrease in CTGF and OPN expression was seen in cardiac fibroblasts cultured with Telmisartan. In conclusion, Telmisartan prevented unfavorable cardiac remodeling through a reduction of cardiac hypertrophy and fibrosis. An anti-inflammatory effect and PPAR-γ activation were suggested to be important in addition to suppression of Ang II activity.

Aims: Adiponectin (APN) has been reported to protect against ischaemia-reperfusion injury and hypertrophy. However, few reports have investigated the cardioprotective effects of APN in doxorubicin (DOX)-induced cardiomyopathy; therefore, we studied the cardioprotective mechanisms of APN in this model., Methods and Results: In an in vivo study, we quantified the cardiac pathohistology of C57BL/6 mice [wild-type (WT) mice], APN transgenic mice with high APN concentrations [APN transgenic sense (SE) mice], and those with reduced APN concentrations [APN transgenic antisense (AS) mice] after intraperitoneal injections of DOX (4 mg/kg) weekly for 6 weeks. The survival rate after 14 days was significantly increased in APN-SE mice (WT vs. APN-AS vs. APN-SE: 40 vs. 17 vs. 73%, P < 0.05). We assessed myocardial pathohistological changes and observed that fibrosis and apoptosis were significantly decreased in APN-SE mice compared with those of the other groups. We also assessed DOX-induced apoptotic mechanisms in vitro using cultured cardiomyocytes isolated from neonatal WT mice. The expression of adenosine monophosphate-activated protein kinase (AMPK) and anti-apoptotic factor Bcl-2 increased, but that of pro-apoptotic factor Bax decreased in cardiomyocytes treated with highly concentrated APN. The protective effects of APN were reversed by the addition of an AMPK inhibitor (dorsomorphin) to the culture medium., Conclusion: These data suggest that APN improved cardiac function through anti-apoptotic effects by up-regulation of AMPK in DOX-induced cardiomyopathy in mice.

Background: Although some β-blockers are effective for patients after acute myocardial infarction (AMI), few studies have compared their additive effects on renin-angiotensin system inhibitors (RAS-Is)., Methods and Results: The 251 consecutive AMI patients administered angiotensin-converting-enzyme inhibitors (ACE-Is) or angiotensin-II receptor blockers (ARBs) were retrospectively investigated and divided into 2 groups: treated without β-blockers (no-β-blocker group, n=80) or treated with β-blockers before discharge (β-blocker group, n=171; carvedilol [n=91] or bisoprolol [n=80]). The doses of RAS-Is used for patients in the no-β-blocker group were at least double those used in the β-blocker group. No significant differences between the 2 groups were observed with regard to baseline characteristics. After a 12-month follow-up, the survival and cardiac event-free rates in the β-blocker group were significantly higher than those in the no-β-blocker group. The percent change in blood pressure did not significantly differ between the 2 groups, but the levels of brain natriuretic peptide, metalloproteinase-2, and metalloproteinase-9 and the left ventricular ejection fraction improved significantly in the β-blocker group compared with the no-β-blocker group. Regarding the 2 β-blockers, carvedilol treatment produced more favorable outcomes than bisoprolol., Conclusions: The data suggest that treatment with RAS-I in combination with β-blocker is more effective for patients after AMI than treatment with RAS-I alone.

Background: The role of adiponectin (APN), an adipose tissue-specific secretory protein, on chronic rejection after cardiac transplantation in APN-sense transgenic mice (APN-SE) was evaluated., Methods and Results: Heterotopic cardiac transplantation in major histocompatibility complex class II-mismatched mice was performed. B6.C-H-2(bm12)KhEg (Bm12) hearts were transplanted into APN-SE, and allografts were harvested at 8 weeks after transplantation. Quantitative polymerase chain reaction (PCR) and immunohistochemical staining showed that the expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients. Neointimal hyperplasia was significantly decreased in allografts transplanted into APN-SE (luminal occlusion, 8.9 ± 2.2%) compared to those transplanted into controls (49.4 ± 10.5%; P=0.011). APN-SE showed significantly reduced mRNA levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-γ and MCP-1 were reduced in APN-SE recipients. Proliferation of smooth muscle cells stimulated with activated T cells was suppressed by APN addition, and this effect was canceled by treatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor., Conclusions: APN plays a critical role in the attenuation of chronic rejection by suppressing inflammatory cytokine and chemokine expression and enhancing APN receptor expression. APN plays a beneficial role in reducing the progression of cardiac allograft vasculopathy through the AMPK pathway.

Background: Although carvedilol and bisoprolol are effective medicines for the treatment of patients with heart failure (HF), only a few reports have compared their effects. This study was designed to compare the effects of them in patients with severe HF., Methods and Results: A total of 655 consecutive patients with HF, categorized as New York Heart Association Class 3 or 4, were retrospectively investigated. Of these patients, 217 were administered beta-blockers after admission and were divided into 2 groups (carvedilol, n=110; bisoprolol, n=107). No significant differences were observed in their characteristics between the 2 groups prior to the introduction of the beta-blockers. After 18 months of follow-up, there were no significant differences in the survival and cardiac event-free rates between the 2 groups. In contrast, there were several significant differences in patients with atrial fibrillation (AF) (carvedilol, n=40; bisoprolol, n=43). The percent changes in heart rate and brain natriuretic peptide level improved significantly in the bisoprolol group than in the carvedilol group. Furthermore, more patients in the bisoprolol group were defibrillated from AF to sinus rhythm than those in the carvedilol group (48% vs 16%; P=0.03)., Conclusions: Our data suggest that the 2 beta-blockers are equally effective in the improvement of severe HF, but bisoprolol shows favorable effects in patients with AF.

Background: Chronic rejection remains the most prominent cause of graft failure after transplantation. Recently, it was reported that telmisartan can function as a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) in addition to a blocker of angiotensin II receptor. We investigated the effect of telmisartan on chronic rejection., Methods: Hearts from Bm12 mice were transplanted into C57BL/6 mice (Class II mismatch), and allografts were harvested at 8 weeks after transplantation. Recipient mice were fed either control chow or chow containing telmisartan (10 mg/kg/day) from 1 day before transplantation. Proliferation assays of smooth muscle cells (SMCs), which were isolated from the aorta of B/6 mice, was performed., Results: Although severe neo-intimal hyperplasia developed in allografts from control mice fed chow (luminal occlusion 70.9 +/- 6.1%), neo-intimal hyperplasia was significantly attenuated in allografts from mice fed chow containing telmisartan (30.0 +/- 10%, p < 0.001). Expression of interferon (IFN)-gamma and interleukin (IL)-15 mRNAs and matrix metalloproteinase (MMP)-2 in allografts was significantly lower in telmisartan-treated mice than in control mice. Proliferation of smooth muscle cells (SMCs) in response to fetal bovine serum was suppressed significantly by telmisartan (10 micromol/liter). The PPARgamma antagonist blocked telmisartan-induced suppression of SMC proliferation., Conclusions: Telmisartan attenuates SMC proliferation via PPARgamma activity and suppresses neo-intimal hyperplasia after transplantation. Telmisartan may be useful for suppressing chronic allograft rejection., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Biomarkers are needed for early risk stratification and improved inpatient management to obtain better outcomes in acute pulmonary embolism (PE) patients. The aim of the present study was to evaluate biomarkers of right ventricular dysfunction (RVD) in order to predict a complicated clinical course and long-term respiratory complications in acute PE.We retrospectively enrolled 50 consecutive patients hospitalized for acute PE. Plasma brain natriuretic peptide (BNP), troponin-I, fibrin degradation products, D-dimer, C-reactive protein, and arterial pH were measured to assess their prognostic significance. RVD was evaluated by echocardiography at admission, the clinical course during hospitalization was monitored for the development of complications (death, cardiopulmonary resuscitation, mechanical ventilation or circulatory shock), and the need for home oxygen therapy (HOT) was assessed at/after discharge.Thirty-two patients (64%) had RVD at admission, 6 (12%) developed a complicated clinical course, and 7 (14%) required HOT. Plasma BNP was significantly higher in patients with RVD (median value, 319.3 versus 50.5 pg/mL, P = 0.001). Plasma BNP was also significantly higher (median value, 1307.9 versus 102.6 pg/mL, P = 0.02) and arterial pH significantly lower (acidic) (median value, 7.371 versus 7.438, P = 0.008) in patients who developed a complicated clinical course. In addition, plasma BNP was also significantly higher in patients who required HOT (median value, 505.1 versus 91.1 pg/mL, P = 0.02). Plasma BNP at admission is not only a reliable marker of RVD and predictor of short-term prognosis, but also a predictor of long-term respiratory prognosis in acute PE patients.

4-1BB, a member of the tumor necrosis factor receptor (TNFR) family, binds the 4-1BB ligand (4-1BBL), works as a costimulatory molecule, and regulates T cell-mediated immune responses. Although inflammation is an essential pathological feature of myocarditis, the role of 4-1BB in experimental autoimmune myocarditis (EAM) remains unclear. Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish EAM. 4-1BB-immunoglobulin (4-1BBIg) was administered intraperitoneally (n=6) a total of 9 times (3 times per week). Rats were killed on day 21 to study effects of 4-1BB/4-1BBL pathway blockade. For controls, isotype-matched human IgG was administered in other EAM rats (n=6). Histologic and echocardiographic examination showed development of EAM attenuated by 4-1BBIg. Suppression of mRNA expression for IL-1alpha, IL-1beta, IL-4, IL-6, and TNF-alpha was noted in the heart tissue treated with 4-1BBIg. Treatment with 4-1BBIg reduced production of Th1-type cytokines, and inhibited T cell proliferation in vitro. In the 4-1BB signaling pathway in splenocytes, 4-1BBIg suppressed JNK, p38, and IkappaB activity but not that of ERK1/2. Blockade of T cell activation through the 4-1BB/4-1BBL pathway regulates development of EAM; therefore, 4-1BB may be an effective target for treating myocarditis.

Background: Few reports regarding the definition, epidemiology, and pathophysiology of acute decompensated heart failure (ADHF) are available. The clinical characteristics of 194 consecutive ADHF patients with abrupt onset of symptoms were investigated., Methods and Results: Patients with acute coronary syndromes including acute myocardial infarction, acute pneumonia, severe valvular disease, and end-stage renal disease that required dialysis therapy were excluded. Patients were divided into 2 groups: rapid-progression group, onset within 24 hours before admission (n = 78); and gradual-progression group, onset more than 24 hours before admission (n = 52). No significant differences were observed in the age, gender, prescriptions, and hematological data between the 2 groups. The proportion of patients who drank excessive water was higher in the rapid-progression group. Systolic blood pressure, diastolic blood pressure, heart rate, left ventricular ejection fraction, and left ventricular wall thickness were greater in patients in the rapid-progression group. Indexes indicating left ventricular diastolic function were significantly deteriorated in the rapid-progression group., Conclusion: Excessive water intake, acute hypertension, and diastolic dysfunction are associated with the pathophysiology of abrupt-onset ADHF. Hypertensive patients with diastolic dysfunction should be treated cautiously to prevent the occurrence of ADHF.