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Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.

Background Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. Conclusions The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.

A 42-year-old woman visited our hospital due to syncope. Contrast-enhanced CT revealed portosystemic shunt, portal vein hypoplasia, and multiple liver nodules. The histological examination of a liver biopsy specimen exhibited portal vein hypoplasia and revealed that the liver tumor was positive for glutamine synthetase. The patient was therefore diagnosed with congenital extrahepatic portosystemic shunt type II, and with focal nodular hyperplasia (FNH)-like nodules. She had the complication of severe portopulmonary hypertension and underwent complete shunt closure by balloon-occluded retrograde transvenous obliteration (B-RTO). The intrahepatic portal vein was well developed at 1 year after B-RTO, and multiple liver nodules completely regressed. Her pulmonary hypertension also improved.

Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice. Methods: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed. Results: Pemafibrate reduced both triglyceride and non-high-density lipoprotein-cholesterol levels ( P ＜0.01), without affecting body weight. It also decreased circulating levels of AA ( P ＜0.001), thromboxane B 2 ( P ＜0.001), prostaglandin E 2 , leukotriene B 4 ( P ＜0.05), and 5-hydroxyeicosatetraenoic acid ( P ＜0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ 12,14 -prostaglandin J 2 , which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations ( P ＜0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it ( P ＜0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function. Conclusion: Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.

The survival outcomes of pT1N0–3 or pT2–3N0 gastric cancer after curative resection are favorable without adjuvant chemotherapy. However, some patients develop recurrence and details of these recurrences remain unclear. This study aimed to evaluate the prognostic factors in patients with pT1N0–3 or pT2–3N0 gastric cancer. We retrospectively reviewed the medical records of 1219 patients with pT1N0–3 or pT2–3N0 gastric cancer who underwent curative gastrectomy without neoadjuvant or adjuvant chemotherapy between April 2007 and March 2012 at Cancer Institute Hospital. This cohort included 895 pT1N0, 73 pT1N1, 23 pT1N2, 6 pT1N3, 130 pT2N0, and 92 pT3N0 patients. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) for pT1N0–3 and pT2–3N0 gastric cancer were 98.9% (95% CI 98.1–99.4) and 97.7% (95% CI 96.7–98.4), respectively. Age (HR 3.56, 95% CI 2.10–6.03) and lymphovascular involvement (hazard ratio (HR) 2.98, 95% CI 1.76–5.04) were independent prognostic factors in a multivariate analysis for RFS. The 5-year RFS for patients aged ≥75 years or with lymphovascular involvement were 94.4% (95% CI 89.8–97.0) and 95.1% (95% CI 92.5–96.8), respectively. The survival outcomes of pT1N0-3 and pT2-3N0 were excellent, even in patients with aged >75 years or lymphovascular involvement which were risk factors. However, the sample size of T1N3 gastric cancer is small, so larger sample size and risk factor analysis are required.

Background Radiofrequency (RF) ablation of typical atrioventricular nodal reentrant tachycardia (tAVNRT) is performed without revealing out the location of antegrade slow pathway (ASp). In this study, we studied a new electrophysiological method of identifying the site of ASp. Methods This study included 19 patients. Repeated series of very high‐output single extrastimulations (VhoSESts) were delivered at the anatomical slow pathway region during tAVNRT. Tachycardia cycle length (TCL), coupling interval (CI), and return cycle (RC) were measured and the prematurity of VhoSESts [ΔPM (= TCL – CI)] and the prolongation of RCs [ΔPL (= RC – TCL)] were calculated. Pacing sites were classified into two categories: (i) ASp capture sites [DSPC(+) sites], where two different RCs were shown, and ASp non‐capture sites [DSPC(‐) sites], where only one RC was shown. RF ablation was performed at DSPC(+) sites and/or sites with catheter‐induced mechanical trauma (CIMT) to ASp. Results DSPC(+) sites were shown in 13 patients (68%). RF ablation was successful in all patients without any degree of atrioventricular block nor recurrence. Total number of RF applications was 1.8 ± 1.1. Minimal distance between successful ablation sites and DSPC(+)/CIMT sites and His bundle (HB) electrogram recording sites was 1.9 ± 0.8 mm and 19.8 ± 6.1 mm, respectively. ΔPL of more than 92.5 ms, ΔPL/TCL of more than 0.286, and ΔPL/ΔPM of more than 1.565 could identify ASp with sensitivity of 100%, 91.1%, and 88.9% and specificity of 92.9%, 97.0%, and 97.6%, respectively. Conclusions Sites with ASp capture and CIMT were close to successful ablation sites and could be useful indicators of tAVNRT ablation., A case of Direct Slow Pathway Capture (DSPC) during typical atrioventricular nodal reentrant tachycardia.

Aim: Recent studies have demonstrated that selective sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. Method: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE−/−) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. Result: Canagliflozin decreased blood glucose (P < 0.001) and total cholesterol (P < 0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P < 0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P < 0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P < 0.05, both). Methylglyoxal also decreased the phosphorylation of eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs. Conclusion: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE−/− mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.

Aim: The bioactive lipid, sphingosine-1-phosphate (S1P), has various roles in the physiology and pathophysiology of many diseases. There are five S1P receptors; however, the role of each S1P receptor in atherogenesis is still obscure. Here we investigated the contribution of S1P receptor 2 (S1P2) to atherogenesis by using a specific S1P2 antagonist, ONO-5430514, in apolipoprotein E-deficient ( Apoe −/− ) mice. Methods: Apoe −/− mice fed with a western-type diet (WTD) received ONO-5430514 (30 mg/kg/day) or vehicle. To examine the effect on atherogenesis, Sudan IV staining, histological analysis, qPCR, and vascular reactivity assay was performed. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments. Results: WTD-fed Apoe −/− mice had significantly higher S1P2 expression in the aorta compared with wild-type mice. S1P2 antagonist treatment for 20 weeks reduced atherosclerotic lesion development ( p ＜0.05). S1P2 antagonist treatment for 8 weeks ameliorated endothelial dysfunction ( p ＜0.05) accompanied with significant reduction of lipid deposition, macrophage accumulation, and inflammatory molecule expression in the aorta compared with vehicle. S1P2 antagonist attenuated the phosphorylation of JNK in the abdominal aorta compared with vehicle ( p ＜0.05). In HUVEC, S1P promoted inflammatory molecule expression such as MCP-1 and VCAM-1 ( p ＜0.001), which was attenuated by S1P2 antagonist or a JNK inhibitor ( p ＜0.01). S1P2 antagonist also inhibited S1P-induced JNK phosphorylation in HUVEC ( p ＜0.05). Conclusions: Our results suggested that an S1P2 antagonist attenuates endothelial dysfunction and prevents atherogenesis. S1P2, which promotes inflammatory activation of endothelial cells, might be a therapeutic target for atherosclerosis.

Background Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. Methods and Results We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). Conclusions Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.

Hepatectomy for gastric cancer liver metastases (GCLM) has a 5-year survival rate of 9-42%; however, indications for hepatectomy remain unclear. Many researchers have reported prognostic factors for GCLM after hepatectomy, but surgical indications vary according to the literature. Furthermore, the indication for optimal candidates for neoadjuvant chemotherapy and intensive chemotherapy is also unclear. To understand the indications for surgery and chemotherapy intended for hepatectomy for GCLM, a new treatment algorithm was created based on previously reported evidence from the viewpoint of hepatic surgeons.

BackgroundCardiovascular diseases are the second most common cause of mortality among cancer survivors, after death from cancer. We sought to assess the impact of cancer on the short-term outcomes of acute myocardial infarction (AMI), by analysing data obtained from a large-scale database.MethodsThis study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. We identified patients who were hospitalised for primary AMI between April 2012 and March 2017. Propensity Score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 21 clinically relevant covariates. The main outcome was in-hospital mortality.ResultsWe split 1 52 208 patients into two groups with or without cancer. Patients with cancer tended to be older (cancer group 73±11 years vs non-cancer group 68±13 years) and had smaller body mass index (cancer group 22.8±3.6 vs non-cancer 23.9±4.3). More patients in the non-cancer group had hypertension or dyslipidaemia than their cancer group counterparts. The non-cancer group also had a higher rate of percutaneous coronary intervention (cancer 92.6% vs non-cancer 95.2%). Patients with cancer had a higher 30-day mortality (cancer 6.0% vs non-cancer 5.3%) and total mortality (cancer 8.1% vs non-cancer 6.1%) rate, but this was statistically insignificant after PS matching.ConclusionCancer did not significantly impact short-term in-hospital mortality rates after hospitalisation for primary AMI.

Chylothorax is a relatively rare complication of esophagectomy but can lead to fatal conditions. The aim of this report was to present a case of lymphangiography from the para-aortic lymph node (PALN) under computed tomography (CT) guidance, which could be an alternative modality to ultrasound sonography from the groin. A 58-year-old man was diagnosed as having postoperative chylothorax after esophagectomy following neoadjuvant chemotherapy. As the pleural effusion did not improve, intranodal lipiodol lymphangiography from the inguinal lymph node was performed but was unsuccessful. Therefore, CT-guided lymphangiography from the left PALN was performed, and the pleural effusion drainage significantly disappeared. CT-guided lipiodol lymphangiography from the PALN for chylothorax after esophagectomy was safe and thus can be considered an alternative treatment option to ultrasonography-guided intranodal lymphangiography. The flexible use of CT and ultrasonography for lymphangiography may improve the treatment outcomes of chylothorax after esophagectomy.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE-/-) mice. Eight-week-old nondiabetic ApoE-/- mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE-/- mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE-/- mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.

Background: Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery. Methods and Results: We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. Conclusions: The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.

Abnormal pulmonary vascular response to exercise can be a marker of early pulmonary arterial hypertension (PAH). We have previously demonstrated that the pressure-flow relationship of mean pulmonary artery pressure (mPAP) to cardiac output (CO) measurement could be applied to predict future

Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.

Background The prognosis of patients with cancer‐venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer‐associated VTE, compared with a matched cohort without cancer using real‐world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD‐DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score‐matched analysis with 25 148 patients with VTE, patients with cancer had higher total in‐hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31–2.11; P P P Conclusions Patients with cancer had a higher in‐hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.

Purpose Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA. Methods Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared. Results AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites. Conclusions Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site.

Background The overlap time of transmitral flow can be a novel marker of subclinical left ventricular dysfunction for predicting adverse events in heart failure (HF). We aimed to (1) investigate the role of overlap time of the E-A wave in association with clinical parameters and (2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF. Methods We prospectively evaluated 153 patients hospitalized with HF (mean age 68 ± 15 years; 63% male). The primary endpoint was readmission following HF or cardiac death. Results During a median period of 25 months, 43 patients were readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission scores and ratios of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event-free survival, independent of elevated left atrial pressure based on guidelines. When overlap time was added to the model based on clinical variables and elevated left atrial pressure, the C-statistic significantly improved from 0.70 (95% CI: 0.63–0.77) to 0.77 (95% CI: 0.69–0.83, compared) (P = 0.035). Conclusion This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in patients with HF.

Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission.One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up.Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02).LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.

Introduction: We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with the matched cohort without cancer using real-world big data of VTE. Background: Cancer is associated with a high incidence of Venous Thromboembolism (VTE) and there are many guidelines/recommendations about VTE. However, the prognosis of cancer-VTE patients is not well known because of a lack of big data. Moreover, there is also no knowledge on how cancer type is related to prognosis. Methods: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We identified 28,247 patients who were first hospitalized with VTE from April 2012 to March 2017. 26.0% were cancer patients. Compared with national statistics of cancer incidence in 2015 from National Cancer Center of Japan, the proportion of gynecological cancer patients was higher, but other cancer types had similar prevalence rates. Propensity score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. Results: We included 24,576 patients after exclusion. The median age was 71years (range: 59-80 years), and 42.0% were male. On PS-matched analysis with 12,418 patients, patients with cancer had higher total in-hospital mortality (9.5% vs. 3.8%, P Conclusions: Patients with cancer had a higher in-hospital mortality for VTE than those without cancer, especially in pancreatic, biliary tract and liver cancers.

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function.Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%.Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116–117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects.Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.

Recent studies reported cardioprotective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors; however, the underlying mechanisms are still obscure. Here, we investigated whether empagliflozin attenuates atherogenesis and endothelial dysfunction in diabetic apolipoprotein E-deficient (ApoE-/-) mice. Male streptozotocin (STZ) - induced diabetic ApoE-/- mice were treated with empagliflozin for 12 or 8 weeks. Empagliflozin lowered blood glucose (P

We recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens.Eighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated.Thirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8 months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29-0.77, p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0.20-0.61, p 0.001). ORR was 68.6% in this cohort. Higher response rate (85.2% vs 58.1%, p = 0.020) and deeper response (- 49.0% vs - 40.0%, p = 0.018) were also found in the homo-HER2 group.Similar to surgical specimens, we verified clinical significance of HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens.

Background It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography. Methods We prospectively enrolled 58 chronic heart failure patients with reduced left ventricular ejection fraction (aged 62 ± 11 years; 69% male; left ventricular ejection fraction 43% ± 7%) who had received optimized medical treatment in a CR program for 5 months. We performed preload echocardiographic studies using leg positive pressure (LPP) to assess the echocardiographic parameters during preload augmentation. We defined 41 patients as a development cohort to assess the predictive value of echocardiographic variables. Next, we validated results in the remaining 17 patients as a validation cohort. Results In the development cohort, significant improvement in peak oxygen uptake (VO2) (>10%) after CR was observed in 58% patients. In a multivariable logistic regression model, the significant predictor of improvement in exercise capacity was right ventricular (RV) strain during LPP (odds ratio: 3.96 per 1 standard deviation; P = 0.01). An RV strain value of −16% during LPP had a good sensitivity of 0.79 and a specificity of 0.71 to identify patients with improvement in peak VO2. In the validation cohort, an optimal cutoff value of RV strain value was the same (area under the curve: 0.77, sensitivity: 0.78, specificity: 0.65). Conclusions RV strain during LPP may be an echocardiographic parameter for assessing beneficial effects of CR.

Background and aims: Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/-) mice. Methods: Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0.1% ticagrelor (approximately 120 mg/kg/day). Non-treated animals on WTD served as control. Atherosclerotic lesions were examined by en-face Sudan IV staining, histological analyses, quantitative RT-PCR analysis, and western blotting. Endothelial function was analyzed by acetylcholine-dependent vasodilation using aortic rings. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments. Results: Ticagrelor treatment for 20 weeks attenuated atherosclerotic lesion progression in the aortic arch compared with control (p < 0.05). Ticagrelor administration for 8 weeks attenuated endothelial dysfunction (p < 0.01). Ticagrelor reduced the expression of inflammatory molecules such as vascular cell adhesion molecule-1, macrophage accumulation, and lipid deposition. Ticagrelor decreased the phosphorylation of JNK in the aorta compared with control (p < 0.05). Ticagrelor and a JNK inhibitor ameliorated impairment of endothelium-dependent vasodilation by adenosine diphosphate (ADP) in wild-type mouse aortic segments. Furthermore, ticagrelor inhibited the expression of inflammatory molecules which were promoted by ADP in HUVEC (p < 0.001). Ticagrelor also inhibited ADP-induced JNK activation in HUVEC (p < 0.05). Conclusions: Ticagrelor attenuated vascular dysfunction and atherogenesis through the inhibition of inflammatory activation of endothelial cells. These effects might be a potential mechanism by which ticagrelor decreases cardiovascular events in patients with ACS.

Aim: To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. Methods: We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg positive pressure (LPP), and changes of TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. Results: The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39 - 0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA ≤ -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). Conclusions: Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure.

Aim: Statins have a protective impact against cardiovascular diseases through not only lipid-lowering effects but also pleiotropic effects, including activation of the endothelial nitric oxide synthase (eNOS) system. We aimed to clarify the protective effects of a statin against atherogenesis and ischemia in eNOS－/－ mice. Methods: Study 1. eNOS－/－ Apolipoprotein E (ApoE)－/－ mice were treated with a vehicle or pitavastatin (0.3 mg/kg/day) for 4 weeks. Study 2. eNOS－/－ mice were also treated with a vehicle or the same dose of pitavastatin for 2 weeks prior to hind-limb ischemia. Results: In Study 1, pitavastatin attenuated plaque formation and medial fibrosis of the aortic root with decreased macrophage infiltration in eNOS－/－ ApoE－/－ mice. PCR array analysis showed reductions in aortic gene expression of proatherogenic factors, including Ccl2 and Ccr2 in pitavastatin-treated double mutant mice. In addition, pitavastatin activated not only atherogenic p38MAPK and JNK but also anti-atherogenic ERK1/2 and ERK5 in the aorta of the double mutant mice. In Study 2, pitavastatin prolonged hind-limb survival after the surgery with increased BCL2-to-BAX protein ratio and inactivated JNK. Enhanced expression of anti-apoptotic genes, including Vegf, Api5, Atf5, Prdx2, and Dad1, was observed in the ischemic limb of pitavastatin-treated eNOS－/－ mice. Furthermore, pitavastatin activated both aortic and skeletal muscle AMPK in the eNOS-deficient vascular injury models. Conclusion: Pitavastatin exerts eNOS-independent protective effects against atherogenesis and hind-limb ischemia in mice, which may occur via modifications on key molecules such as AMPK and diverse molecules.

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, primarily occurs during childhood between the ages of 3 and 15 years and is the most common form of systemic vasculitis in children ; its occurrence in adults has been rarely reported. Such low incidence could be attributable to either under-diagnosis or misdiagnosis. Thus, not only pediatricians but also physicians should be able to diagnose IgAV accurately to manage the patients appropriately and avoid its associated complications. In addition, treatment of adult onset IgAV with renal involvement has not been fully established yet. We describe here a case of adult onset IgAV complicated by proteinuria and pharyngitis, which was cured by no specific treatment. J. Med. Invest. 66 : 344-346, August, 2019.

Protein S (PS) deficiency is an inherited thrombophilia associated with an increased risk of venous thromboembolism (VTE). In Japan, unfractionated heparin followed by warfarin has been historically applied for the treatment of VTE. Recent evidence showed that direct oral anticoagulants (DOACs) were non-inferior to standard therapy with warfarin, with significantly less bleeding in patients with VTE. However, it is unknown whether DOACs are effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report a case of recurrent venous thrombosis during edoxaban therapy in a patient with protein S deficiency, which was successfully treated using high-dose apixaban therapy. J.Med. Invest. 66 : 182-184, February, 2019.

Background: Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world registry database of heart failure (HF) hospitalizations. Methods: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). A first analysis was performed to assess the trend of echocardiographic examinations between 2012 and 2016. A secondary analysis was performed to assess whether echocardiographic use was associated with in-hospital mortality in 2015. Results: During this period, the use of echocardiography grew at an average annual rate of 6%. Patients with echocardiography had declining rates of hospital mortality, and these trends were associated with high hospitalization costs. In the 2015 sample, a total of 52,832 echocardiograms were examined, corresponding to 65.6% of all HF hospital admissions for that year. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted odds ratio (OR): 0.48 for use of echocardiography and 0.78 for the third tertile; both p < 0.001). Conclusions: The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality.

Background It is unknown whether canagliflozin, a selective sodium glucose co-transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which is associated with insulin resistance and is a risk factor for coronary artery disease. Methods and results We administered 100 mg of canagliflozin for 6 months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, and skeletal muscle mass by using impedance methods, and EAT thickness by using echocardiography. Canagliflozin treatment for 6 months decreased hemoglobin A1c level from 7.1 ± 0.5% to 6.7 ± 0.6% (P

Change in 6-minute walk distance (6MWD) has been used as a clinical marker in pulmonary hypertension. Determinants and worsening of 6MWD remain a matter of debate because nonpulmonary factors have an impact on the 6MWD. We hypothesized that future reduction of 6MWD in patients with systemic sclerosis (SSc) was more closely associated with cardiac dysfunction. We prospectively performed standard clinical and echocardiographic evaluations in SSc patients with the 6-minute walk test at enrollment. Features associated with the 6MWD were sought in a multiple linear regression analysis and compared using standardized β. Worsening of the 6MWD was defined as a 15% reduction and served as the primary outcome. Eighty-one patients were included. In the multivariate analysis, baseline 6MWD was related to SSc severity score (β = -0.250, p = 0.024), left atrial volume index (β = -0.222, p = 0.046), right ventricular fractional area change (β = 0.252, p = 0.025), and the ratio of mean pulmonary artery pressure and cardiac output (β = -0.31, p = 0.002). During follow-up, 20 patients reached the primary outcome. In sequential Cox models, a model based on right ventricular fractional area change at baseline (chi-square 4.8) was improved by left atrial volume index (chi-square 10.3, p = 0.007). In conclusion, determinants and worsening of 6MWD are explained by cardiac factors. When using the 6MWD as a clinical marker in pulmonary hypertension patients, their left ventricular diastolic function and right ventricular systolic function should be taken into consideration.

This study sought to assess the time course of presumptive tachycardia-induced cardiomyopathy and the predictors of left ventricular (LV) functional recovery in such patients.Tachycardia-induced cardiomyopathy is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of LV systolic function were found occasionally. The diagnosis of tachycardia-induced cardiomyopathy can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited.LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65 ± 16 years; 61% men) with tachyarrhythmia and reduced left ventricular ejection fraction (LVEF) without any other known cardiovascular disease, and 30 age and sex-matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution.Compared with control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: 0.59 per 1 SD; p = 0.04) and higher RALSR (hazard ratio: 11.2 per 1 SD; p 0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (hazard ratio: 22.9 per 1 SD; p = 0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88).The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF.

The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.

Primary non-Hodgkin bone lymphoma (PBL) can involve solitary or multiple destructive bone lesions such as those of the femur or pelvis humerus, and some cases have osteolytic lesions. PBL is a rare disease in adults. Thus, PBL is rarely considered a differential diagnosis of the osteolytic tumor. In addition, PBL can be underdiagnosed because patients do not experience symptoms or show objective abnormalities in the early stage. Here, we reported an elderly patient with PBL in multiple bones, including the cranial and femoral bones that were fractured due to falling. J. Med. Invest. 66 : 347-350, August, 2019.

An arteriovenous fistula of the superficial temporal artery (STA) is a direct and abnormal communication between the STA, feeding artery, and superficial temporal vein, draining veins that bypass the capillary network. Several cases of trauma-induced or iatrogenic-induced arteriovenous fistula (AVF) of the STA have been reported ; however, spontaneous AVF of the STA not associated with trauma or medical treatment are extremely rare. Herein, we present a case of spontaneous AVF of the STA diagnosed in old age. J. Med. Invest. 66 : 209-210, February, 2019.

Pes anserinus pain syndrome is a common, clinically defined condition that is characterized by pain around the medial knee and tenderness over the upper medial tibia. The anserine bursa could be the site of proliferative and inflammatory conditions due to knee osteoarthritis, leading to pain and fluid retention. However, rupture of the pes anserinus is rare. Herein, we present a case of rupture of the pes anserine bursa in a patient with pes anserine pain syndrome and osteoarthritis. Physicians should consider rupture of the pes anserine bursa as a differential diagnosis of acute unilateral lower leg swelling. J. Med. Invest. 66 : 211-212, February, 2019.

The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019.

Aims Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. Methods and results LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: −18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). Conclusion Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.

Background Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. Results Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. Conclusions The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy.

Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P P Ser1177 phosphorylation in the aorta (P −/−) mice did not affect endothelial function and eNOSSer1177 phosphorylation in the aorta compared with non-diabetic PAR2−/− mice. FXa or a PAR2 agonist significantly impaired endothelial function in aortic rings obtained from WT mice, but not in those from PAR2−/− mice. FXa promoted JNK phosphorylation (P Ser1177 phosphorylation (P P Ser1177 phosphorylation (P

Diabetic patients have coagulation abnormalities, in which thrombin plays a key role. Whereas accumulating evidence suggests that it also contributes to the development of vascular dysfunction through the activation of protease-activated receptors (PARs). Here we investigated whether the blockade of thrombin attenuates endothelial dysfunction in diabetic mice. Induction of diabetes by streptozotocin (STZ) increased the expression of PAR1, PAR3, and PAR4 in the aorta. STZ-induced diabetic mice showed impairment of endothelial function, while the administration of dabigatran etexilate, a direct thrombin inhibitor, significantly attenuated endothelial dysfunction in diabetic mice with no alteration of metabolic parameters including blood glucose level. Dabigatran did not affect endothelium-independent vasodilation. Dabigatran decreased the expression of inflammatory molecules (e.g., MCP-1 and ICAM-1) in the aorta of diabetic mice. Thrombin increased the expression of these inflammatory molecules and the phosphorylation of IκBα, and decreased the phosphorylation of eNOSSer1177 in human umbilical endothelial cells (HUVEC). Thrombin significantly impaired the endothelium-dependent vascular response of aortic rings obtained from wild-type mice. Inhibition of NF-κB attenuated thrombin-induced inflammatory molecule expression in HUVEC and ameliorated thrombin-induced endothelial dysfunction in aortic rings. Dabigatran attenuated the development of diabetes-induced endothelial dysfunction. Thrombin signaling may serve as a potential therapeutic target in diabetic condition.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thromboembolic events including venous thromboembolism (VTE) in association with the presence of antiphospholipid antibodies. The standard treatment of VTE historically consists of anticoagulation therapy with warfarin, a vitamin K antagonist. Recently, direct oral anticoagulants, including rivaroxaban have become available for the treatment of VTE. However, the choice of anticoagulant, and the duration of anticoagulation in patients with APS has not been determined yet due to lack of evidence. Here, we report a case of recurrent venous thrombosis after discontinuation of rivaroxaban therapy and avoiding sedentary lifestyle in a patient with APS. We suggest that indefinite anticoagulation therapy might be needed even in low-risk APS cases.

ObjectivesThere is a high prevalence of left ventricular diastolic dysfunction (LVDD) in systemic sclerosis (SSc) which is associated with high mortality. Thus, early detection of LVDD could be important in management of SSc. We hypothesised that exercise echocardiography in SSc patients with normal resting haemodynamics may expose early phase LVDD, which could affect its prognosis, defined as cardiovascular death and unplanned hospitalisation for heart failure.MethodsBetween January 2014 and December 2018, we prospectively enrolled 140 patients with SSc who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (ResultsDuring a median period of 3.6 years (IQR 2.0–5.1 years), 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly greater than in those without events (8.9±3.8 mm Hg/L/min vs 3.0±1.7 mm Hg/L/min; p=0.002, and 2.2±0.9 mm Hg/L/min vs 0.9±0.5 mm Hg/L/min; p1.4 mm Hg/L/min) and impaired pulmonary vascular reserve (ΔmPAP/ΔCO>3.0 mm Hg/L/min) had worse outcomes compared with those without these abnormalities (pConclusionThe 6MW stress echocardiography revealed impaired LV cardiac reserve in SSc patients with normal resting haemodynamics. Furthermore, LV cardiac reserve independently associates with clinical worsening in SSc, providing incremental prognostic utility, in addition to pulmonary vascular parameters.

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 &plusmn, 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p &lt, 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p &lt, 0.001). In the sub-group analysis, mortalities in patients with age &lt, 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and &beta, blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.

Middle-aged marathon runners have an increased risk of developing atrial fibrillation (AF). A previous study described that repetitive marathon running was associated with left atrial (LA) dysfunction. However, whether this change is common in marathon runners and which runners are at risk of LA dysfunction remain unknown. The purpose of this study was to determine which factors could predict LA dysfunction. We prospectively examined 12 healthy amateur volunteers (9 males, 31 ± 8 years old) who participated in a full marathon. All echocardiographic measurements and speckle-tracking echocardiography were performed before and after the marathon. The endpoint was defined as reduced LA reservoir strain 1 day after the marathon (non-responder group). Seven participants were in the non-responder group. Age (35 ± 9 vs. 26 ± 2 years, p = 0.020), augmentation index (76 ± 12 vs. 55 ± 8, p = 0.002), and diastolic blood pressures (83 ± 11 vs. 70 ± 7 mmHg, p = 0.021) in the non-responder group were significantly higher compared with the responder group. In multivariate linear regression analysis, only the augmentation index was an independent predictor of reduced LA reservoir function after the marathon (β = − 0.646, p = 0.023). The augmentation index was a predictive marker for reduction in LA reservoir function after a marathon in healthy amateur volunteers.

Background: The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters. Methods and Results: We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9–93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ≥58 years, PAC count ≥80 beats/day, maximum RR interval ≥1.64 s, and LAD ≥4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. Conclusions: A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.