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Eosinophilic myocarditis (EM) is an under-diagnosed inflammatory heart disease that often leads to severe left ventricular (LV) dysfunction. Meanwhile, severe secondary mitral regurgitation (MR) with valve disruption, possibly requiring mitral valve repair, is rarely concomitant with EM. We present the case of a 64-year-old female diagnosed with heart failure with severe LV dysfunction and localized asynergy. Echocardiography revealed severe secondary MR with mitral valve disruption. Cardiac magnetic resonance imaging (CMR) showed transmural late-gadolinium enhancement localized in the anterior wall and diffuse high-signal areas on T2-weighted images, suggesting non-ischemic and inflammatory heart disease. Although the peripheral eosinophil count was not elevated on admission, it gradually increased during hospitalization. These findings encouraged us to perform endomyocardial biopsy, which confirmed myocardial eosinophilic infiltration with mild fibrosis and necrosis, leading to the diagnosis of EM. Immunosuppressive treatment with oral corticosteroids improved LV dysfunction and completely resolved severe secondary MR. The current case highlighted that comprehensive assessment of laboratory, imaging, and pathological examinations including CMR is crucial to develop the appropriate therapeutic strategy for refractory heart failure. Immunosuppressive treatment should be considered as the first therapeutic option even in EM cases with severe secondary MR, possibly requiring mitral valve repair. Learning objective The gradual increase in peripheral eosinophils during hospitalization, without significant peripheral eosinophilia on admission, is crucial for the diagnosis of eosinophilic myocarditis. Comprehensive assessment of laboratory, imaging, and pathological examinations including cardiac magnetic resonance imaging is mandatory when building an appropriate therapeutic strategy for refractory heart failure. Severe secondary mitral regurgitation with mitral valve disruption can be completely resolved via immunosuppressive treatment in cases of eosinophilic myocarditis.

Purposes The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified. Methods In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP). Results Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status. Conclusion In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure.

Background: Because the effectiveness of strengthening guideline-based therapy (GBT) to prevent heart failure (HF) rehospitalization of chronic HF patients remains unclear, this study investigated the characteristics of HF patients in the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) acute cohort. Methods and Results: We studied 254 rehospitalized HF patients from the KUNIUMI Registry. Optimized GBT was defined as a Class I or IIa recommendation for chronic HF based on the guidelines of the Japanese Circulation Society. The primary endpoint was all-cause death or first HF rehospitalization after discharge. Outcomes tended to be more favorable for patients who had rather than had not received optimized GBT (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.57-1.19; P=0.27). Similarly, among New York Heart Association (NYHA) Class IV patients, outcomes tended to be more favorable for those who had rather than had not undergone optimized GBT (HR 0.73; 95% CI 0.47-1.12; P=0.15). Importantly, outcomes were significantly more favorable among NYHA Class IV patients aged

The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients. Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 +/- 2 to 9 +/- 3, from 10 +/- 2 to 12 +/- 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 +/- 5 to 17 +/- 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 +/- 13 to 44 +/- 14 mL/m(2), P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Background High resting heart rate (HR) is a known marker of cardiovascular outcomes for heart failure (HF) patients. Ivabradine is a new class of HR lowering drug and a specific inhibitor of the If current in the sinoatrial node. Ivabradine substantially and significantly reduces major risks associated with HF when added to guideline-based treatment for left ventricular (LV) ejection fraction ≤35% and HR ≥70 bpm in sinus rhythm. On the other hand, HF with preserved ejection fraction (HFpEF) currently accounts for roughly half of all HF cases and usually presents as LV diastolic dysfunction. However, the association between HR reduction and LV diastolic function for HFpEF patients remains uncertain. Methods/design This investigation into the effect of IVAbradine on left ventricular diastolic function of patients with heart failure with Preserved Ejection Fraction (IVA-PEF) is a multicenter, prospective, uncontrolled, open-label, single assignment, and an interventional single-arm study to investigate the effect of ivabradine on LV diastolic function of HFpEF patients. The key inclusion criterion is HFpEF with resting HR ≥75bpm in sinus rhythm. After completed informed consent forms are obtained, patients will be given 5 mg/day of ivabradine during the study. LV diastolic function is assessed in terms of mitral inflow E and mitral e’ annular velocities (E/e’). The primary endpoint will be defined as a change in E/e′ between baseline and 3 months after the start of administration of ivabradine. Conclusion The findings of our trial may provide a new perspective on ivabradine for the treatment of HFpEF.

Left ventricular (LV) hypertrophy (LVH) is a frequent imaging finding in daily clinical practice, and its presence is associated with poor outcomes and ventricular arrhythmias. It is commonly detected in athletes, arterial hypertension, aortic stenosis, hypertrophic cardiomyopathy, cardiac amyloidosis, Fabry disease, or Friedreich’s ataxia. Echocardiography plays an important role in detecting LVH and underlying causes in current clinical practice. While echocardiography is essential for the quantification and early detection of LV structural findings for various cardiovascular diseases, it has been reported that speckle-tracking echocardiographic parameters are also useful for the detection of early LV structural abnormalities. In particular, global longitudinal strain (GLS) assessed by two-dimensional speckle-tracking echocardiography is reportedly a sensitive marker for early subtle abnormalities of LV myocardial performance, helpful for the prediction of outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS is determined as the averaged peak longitudinal strain of 18 LV segments from standard apical views and can be assessed as a polar plot. This polar plot longitudinal strain mapping offers an intuitive visual overview of the global and regional LV longitudinal myocardial function status of various cardiomyopathies with LVH. This mapping is clinically practicable and the plot patterns obtainable as the result of further development of this technique for clinical practice provide clues to the etiology of cardiomyopathies. This article reviews the efficacy of echocardiography for differential diagnosis of LVH, with a special focus on the utility of speckle-tracking longitudinal strain.

Indigo Naturalis, also known as Qing Dai (QD) is a compound obtained from Indigofera tinctoria, Isatis tinctoria, and Polygonum tinctoria and is known to ameliorate refractory ulcerative colitis (UC) by an unknown mechanism. QD maintains both homeostasis and the integrity of colon epithelia in mice that have experimentally induced colitis. The primary component of QD, indigo, comprises 42.4% of the compound. Indigo efficiently suppresses rectal bleeding and reduces the erosion of the colon epithelium, whereas it does not reduce weight loss or increase survival in a certain condition. Indigo is a ligand of the aryl hydrocarbon receptor (AhR), which is involved in the anti-colitis activity of QD. Here we investigate the effects of indigo on wound (erosion) closure in colon epithelial cells. Oral administration of indigo induced expression of Cytochrome P450 1A1 (Cyp1a1) in the colon but not in the liver, suggesting that indigo stimulates AhR from the luminal side of the colon. The erosion-closure activity tested in the scratch assays using Caco-2 cells was accelerated by addition of QD and indigo to the culture medium. QD and indigo also induced nuclear localization of AhR and expression of CYP1A1 in the Caco-2 cells. Acceleration of scratch wound closure was abolished by addition of the AhR-antagonist CH223191. Cell proliferation and actin polymerization were also shown to contribute to erosion closure. The results suggest that indigo exerts its erosion-healing effects by increasing proliferation and migration of colon epithelial cells via activation of AhR in intestinal epithelia.

We present an extremely rare case of mitral Ebstein's anomaly that resulted in severe mitral regurgitation (MR). A 41-year-old woman with a history of tuberous sclerosis underwent surgery. Preoperatively, it was assumed that MR had occurred due to leaflet tethering related to left ventricular posterior wall motion asynergy due to a scarred rhabdomyoma. However, surgical inspection revealed a dysplastic posterior leaflet adhering to the ventricular wall, which was completely covered by the endocardium. Both congenital mitral Ebstein's anomaly and acquired wall motion abnormality due to a scarred rhabdomyoma may have contributed to the development of severe MR in this case.

The aim of this study was to investigate the association of type 2 diabetes mellitus (T2DM) with the development of new-onset atrial fibrillation (AF) for non-ischemic dilated cardiomyopathy (DCM) patients. We also tested the hypothesis that sodium glucose cotransporter type 2 (SGLT2) inhibitors reduce the risk of development of new-onset AF for non-ischemic DCM patients. We retrospectively studied 210 patients with non-ischemic DCM and sinus rhythm, mean age of 59.0 ± 16.7 years and left ventricular ejection fraction of 31.0 ± 8.2% (all

PURPOSE Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis. MATERIALS AND METHODS Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4). RESULTS The mean ± standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54 ± 0.33 mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r = 0.87, P

BACKGROUND AND PURPOSE While the bladder vasculature is considered as a target of PDE5 inhibitors to improve bladder storage dysfunctions, its characteristics are largely unknown. Thus, the functional and morphological properties of arteries/arterioles of the bladder focusing on the NO-mediated signal transmission were explored. EXPERIMENTAL APPROACH Diameter changes in rat bladder arteries/arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in pericytes or smooth muscle cells (SMCs) of suburothelial arterioles were visualised using transgenic mice expressing GCaMP6 under control of the NG2- or parvalbumin-promoter. The perivascular innervation was investigated using fluorescence immunohistochemistry. KEY RESULTS In rat suburothelial arterioles and vesical arteries, tadalafil (100 nM) attenuated nerve-evoked sympathetic vasoconstrictions. In both vascular segments, tadalafil-induced inhibition of sympathetic vasoconstriction was prevented by N ω-propyl-l-arginine hydrochloride (l-NPA, 1 μM), an nNOS inhibitor or N ω-nitro-l-arginine (l-NA, 100 μM). Both vascular segments were densely innervated with nNOS-positive nitrergic nerves in close apposition to tyrosine hydroxylase-immunoreactive sympathetic nerves. In pericyte-covered pre-capillary arterioles of the mouse bladder where sympathetic nerves were absent, nerve stimulation evoked transient reductions in pericyte Ca2+ levels that were shortened by l-NPA and abolished by l-NA. In SMC-containing arterioles, tadalafil (10 nM) caused a l-NPA-sensitive suppression of sympathetic Ca2+ transients. In mice, nitrergic perivascular nerves were distributed in the arterioles and the pre-capillary arterioles. CONCLUSION AND IMPLICATIONS Both nitrergic nerve and nerve-evoked endothelial NO release appear to be involved in vasodilatory signal transmission in bladder vasculature. The NO-mediated signal transmission is a potential target for PDE5 inhibitor therapy in bladder dysfunctions.

A 53-year-old woman was admitted to another hospital because of a 2-month history of repeated chest pain and breathlessness. Laboratory examinations demonstrated the presence of hypereosinophilia (absolute count of 6,500/mu L). An endomyocardial biopsy confirmed eosinophilic infiltration with myocardial destruction. On cardiac magnetic resonance imaging, late gadolinium enhancement was clearly observed along the visceral pericardium as well as on the endocardial layer. Based on the multimodal imaging and histopathological fmdings, the final diagnosis of "Loffler pancarditis" was made. After the introduction of steroid therapy, the left ventricular contractile function significantly recovered. Furthermore, the late gadolinium enhancement of the visceral pericardium had attenuated.

We experienced a rare case of transdural herniation of cauda equina caused by increased pressure with spinal subdural extra-arachnoid hygroma (SSEH) following lumbar microsurgical decompression. A 68-year-old woman presented with complaints of right leg pain and intermittent claudication. By the diagnosis of L2/3 lumbar spinal stenosis, microsurgical decompression was performed. The surgery was successful with no issues arising such as damage to the dura mater. Lumbar magnetic resonance imaging (MRI) performed 8 days after the surgery confirmed asymptomatic SSEH on the ventral side of the cauda equina. However, posterior cervical pain and lower back pain developed 32 days after the surgery. Lumbar MRI demonstrated that SSEH had markedly increased and advanced from the lumbar spine to the cranium, compressing the spinal cord posteriorly. In addition, herniation of the cauda equina was confirmed in the dura. An emergency surgery was performed. The herniated cauda equina was fully positioned in the dural sac, and the arachnoid membrane with accumulation of spinal fluid on the ventral side was fenestrated. Immediately after the surgery, the patient’s symptoms disappeared. Sufficient caution is required regarding the possibility of SSEH associated with spinal failed back surgery syndrome as it can become excessively enlarged, leading to a poor prognosis.

Background Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear. Objective To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium. Methods and results The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels. Conclusion Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF.

Aims Guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) provided by the European Society of Cardiology state that echocardiography is recommended for the assessment of the myocardial structure and function of subjects with suspected HF including HF with reduced (HFrEF), mid‐range (HFmrEF), and preserved ejection fraction (HFpEF) as class I of recommendation and level C of evidence. However, the impact of timing of echocardiography on survival for hospitalized HF patients or the prevalence of echocardiography during their stay has not yet been fully investigated. Therefore, we designed and conducted a prospective multicentre study, Optimal Timing of Echocardiography for Heart Failure Inpatients in Japanese Institutions (OPTIMAL) study, to investigate and evaluate the prevalence of echocardiography during the in‐hospital stay of HF patients, and the impact of timing of echocardiography on their survival. Methods and results OPTIMAL was based on a nationwide, prospective, multicentre registry at 10 institutions in Japan endorsed by the Japanese Society of Echocardiography. A total of 601 patients hospitalized with HF were enrolled between August 2016 and July 2018 at the participating centres. Their mean age was 73.9 ± 13.0 years, left ventricular ejection fraction was 37.0% (26.0–50.0), and 256 patients (42.6%) were female. Admission echocardiography (admission echo) was categorized as either standard or point‐of‐care echocardiography performed within 3 days of admission, as was pre‐discharge echocardiography (pre‐discharge echo) within 3 days of discharge. The primary endpoint was defined as cardiovascular death over a median follow‐up period of 18.9 months (9.3–26.5 months). Admission echo was performed for 476 patients (79.2%) and pre‐discharge echo for 216 patients (35.9%). The primary endpoint of cardiovascular death occurred in 65 patients (10.8%). Kaplan–Meier curve findings indicated that survival of patients with pre‐discharge echo was significantly better than that of patients without it (log‐rank P

BACKGROUND AND AIMS Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P

We report a rare case of nonapoplectic pituitary adenoma that did not invade the cavernous sinus and was associated with isolated oculomotor nerve palsy. A 61-year-old male was admitted to our hospital due to diplopia that had gradually worsened from 6 months to presentation. He was diagnosed with right oculomotor nerve palsy, and brain magnetic resonance imaging (MRI) showed a mass lesion within the sella. The tumor was homogeneously enhanced on contrast-enhanced MRI. However, no findings suggestive of pituitary apoplexy were found. Brain computed tomography revealed the tumor to have eroded the right side of the posterior clinoid process by gradual expansion. Endoscopic transsphenoidal surgery was used for complete resection of the tumor. Intraoperative findings showed that the tumor did not invade the cavernous sinus. The histological diagnosis was pituitary adenoma, and symptom improvement was observed from the early postoperative stage onward. Surgical treatment is essential because oculomotor nerve palsy caused by the enlargement of pituitary adenoma is not expected to resolve if treated conservatively, unlike that caused by pituitary apoplexy.

Background Carotid free-floating thrombus (CFFT) is defined as a blood clot attached to the arterial wall with surrounding blood flow at its distal component. Although rare, it is a clinically significant cause of embolic stroke. CFFT within a stent has not been previously reported. Case Description We report a 64-year-old man who underwent carotid artery stenting for asymptomatic right carotid artery stenosis. Six months after carotid artery stenting, he was admitted to the emergency department 1 hour after onset of left hemiparesis and dysarthria. His National Institutes of Health Stroke Scale score was 10. His medical history was notable for hypertension, chronic renal insufficiency, and type 2 diabetes mellitus. Carotid ultrasonography showed a dumbbell-shaped CFFT attached to the carotid stent that was moving in synchrony with his heartbeat. CFFT removal was performed via an endovascular approach with manual suction using a Luer Lock syringe. The CFFT was completely removed without residual stenosis. Histologic examination suggested plaque rupture associated with a lipid-rich necrotic core. Conclusions Carotid plaque formation and plaque rupture can occur within a carotid stent and present as a CFFT.

Funding Acknowledgements Type of funding sources: None. Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity. Purpose Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of >10% to an absolute value of Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²). Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Abstract Figure.

PURPOSE This study aimed to develop a six degrees-of-freedom (6DoF) robotic moving phantom for evaluating the dosimetric impact of intrafraction rotation during respiratory-gated radiotherapy with real-time tumor monitoring in the lung. MATERIALS AND METHODS Fifteen patients who had undergone respiratory-gated stereotactic body radiotherapy (SBRT) with the SyncTraX system for lung tumors were enrolled in this study. A water-equivalent phantom (WEP) was set at the tip of the robotic arm. A log file that recorded the three-dimensional positions of three fiducial markers implanted near the lung tumor was used as the input to the 6DoF robotic moving phantom. Respiratory-gated radiotherapy was performed for the WEP, which was driven using translational and rotational motions of the lung tumor. The accuracy of the 6DoF robotic moving phantom was calculated as the difference between the actual and the measured positions. To evaluate the dosimetric impact of intrafraction rotation, the absolute dose distributions under conditions involving gating and movement were compared with those under static conditions. RESULTS For the sinusoidal patterns, the mean ± standard deviation (SD) of the root mean square errors (RMSEs) of the translation and rotation positional errors was

This study aimed to test the hypothesis that left ventricular dyssynchrony may negatively affect left atrial (LA) dyssynchrony and reservoir function, and cardiac resynchronization therapy (CRT) may improve LA function. It also assessed, whether residual LA dyssynchrony affects the prognosis in patients with heart failure with reduced ejection fraction (HFrEF). Ninety subjects were included: 40 HFrEF patients with a wide-QRS complex (≧130 ms), 28 HFrEF patients with a narrow-QRS, and 22 normal controls. LA global longitudinal strain (LA-GLS) and LA dyssynchrony were quantified by speckle-tracking strain analysis. LA dyssynchrony was defined as the maximal difference of time-to-peak strain (LA time-diff). All patients with a wide-QRS underwent CRT, and event-free survival was tracked for 24 months. At baseline, LA dyssynchrony was significantly more pronounced in patients with a wide-QRS HFrEF (342 ± 126 ms) than that in patients with a narrow-QRS (236 ± 127 ms, P < 0.001) and controls (186 ± 78 ms, P < 0.001). Six months after CRT, LA-GLS significantly improved from 11.9 ± 4.7 to 19.6 ± 10.1% (P < 0.05) and LA time-diff was reduced from 338 ± 123 to 245 ± 141 ms (P < 0.05) in responders only. Patients with an LA time-diff < 202 ms and those with an LA-GLS ≧14.6% six months after CRT showed significantly better outcomes than the others (P < 0.05, respectively). Among the responders, those with an LA time-diff < 202 ms after CRT showed a better prognosis than others (P < 0.05). CRT improved LA dyssynchrony and reservoir function through the improved left ventricular coordination. Reduced LA dyssynchrony and improved LA reservoir function after CRT lead to better outcomes.

Background: Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF. Methods: In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction. Results: LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048–19.90; P = .04). Conclusions: In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

Remodeling in the right-sided heart plays an important role in the management of pulmonary hypertension (PH) patients. However, the effect of balloon pulmonary angioplasty (BPA) on right ventricular (RV) and right atrial (RA) morphology of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. This study involved 45 CTEPH patients who underwent BPA with mean pulmonary artery pressure (mPAP) of 37.0 mmHg (all ≥ 25 mmHg). All patients underwent echocardiography and right-heart catheterization at baseline and 3 months after BPA. RV and RA remodeling was assessed as RV and the RA area, and RV systolic function was calculated by averaging peak speckle-tracking longitudinal strain of the RV free-wall (RV free-wall strain). Significant reverse remodeling in the right-sided heart was observed after BPA, resulting in improvement of mPAP and pulmonary vascular resistance (RV area: from 15.0 ± 5.3 to 9.6 ± 3.0 cm2, p

INTRODUCTION Two-dimensional measurements are self-evidently limited when seeking accurately to represent the three-dimensional complexity of the aortic root. Volumetric measurement, therefore, seems an ideal alternative for a more accurate assessment. MATERIALS AND METHODS We retrospectively analyzed 123 individuals undergoing cardiac computed tomography. We measured the dimensions of the sinuses of Valsalva using routine multiplanar short axis imaging. Three conventional two-dimensional methods were applied to measure the dimensions of the sinuses. These involved bisecting center of sinus-to-center of interleaflet triangle measures, along with center of sinus-to-center of sinus, and largest sinus-to-sinus measurements. We then quantified the volumes of the root using the volume-rendering method. RESULTS The mean dimensions of the sinuses were significantly greater when measured using the largest sinus-to-sinus method as opposed to center of sinus-to-center of interleaflet triangle and center of sinus-to-center of sinus methods (33.6 ± 3.6 mm vs. 31.1 ± 3.1 mm and 30.9 ± 3.3 mm, p

Early worsening heart failure (WHF), defined as worsening of symptoms and signs of heart failure requiring intensification of medical or mechanical therapy during an admission for acute decompensated heart failure (ADHF), has recently been recognized as a risk of morbidity or mortality after the discharge. Although echocardiographic parameters of left ventricular (LV) output has been shown to be associated with long-term outcome in heart failure patients, its predictive value for early WHF has not been elucidated. Prospect trial to Elucidate the utility of EchocarDiography-based Cardiac output in acute heart failure (PREDICT) is a multicenter, nonrandomized, prospective observational study to test the predictive value of echocardiographic LV output parameters for early WHF in ADHF patients. We will enroll patients admitted to 16 participating hospitals due to ADHF who did not receive positive inotropic agents as an initial therapy. Primary outcome will be set at early WHF defined as need for initiation of positive inotropic agents within 7 days after the admission. Predictive accuracy will be compared between Doppler echocardiographic LV output (stroke distance, stroke volume index, and cardiac index) and low perfusion findings assessed by physical examination. N/A. The PREDICT is expected to provide large data set to test the predictive value of echocardiographic LV output for early WHF in ADHF patients.

A 92-year-old man was referred to our hospital with decompensated heart failure. He was treated with diuretics and inotropic agents, but the clinical response was unsatisfactory. Echocardiography incidentally revealed an atrial septal defect (ASD) with a significant left-to-right shunt and pulmonary-to-systemic-blood-flow ratio of 2.36. Because the ASD was considered to be the primary cause of his treatment-resistant heart failure, the patient underwent transcatheter ASD closure. Shortly after shunt closure, his hemodynamics significantly improved, and he was discharged nine days later. This is an extremely rare case of a nonagenarian who showed an excellent clinical course after transcatheter ASD closure.

Bone-modifying agents (BMAs) are frequently used for the treatment of bone metastases. Both BMA and radiation therapy (RT) are effective; however, there are few studies that have evaluated the efficacy of the combination treatment. We evaluated the effectiveness of RT + BMA in breast cancer-induced osteolytic bone metastasis as compared to BMA alone. A total of 43 lesions in 25 patients were evaluated. The median follow-up period was 18 (range, 2–90) months. None of the lesions was treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating the local response. Patients with complete or partial response were considered as responders, while those with stable or progressive disease were considered as non-responders. The rate of response with RT + BMA was significantly higher than that with BMA alone (P = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMA alone group. The median time to response was 4 (range, 2–11) months in the RT + BMA group and 6 (range, 4–16) months in the BMA alone group. The overall survival rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year) (P = 0.029). In conclusion, RT combined with BMA was found to be more effective than BMA alone for the treatment of osteolytic bone metastasis, which thereby improves the prognosis.

Background The left ventricular apex commonly has a paper-thin structure. However, available data about its structure are limited to variable samples, methodologies, and results. Objective To investigate the structural anatomy of the left ventricular apex using living heart datasets with the latest computed tomography scanner. Methods One hundred thirty-one consecutive patients (median age, 73 years; 58% men) who underwent cardiac computed tomography were retrospectively analyzed. Patients with severe aortic stenosis were analyzed separately. Thickness and diameters of the thinnest part of the left ventricular apex during mid-diastole were measured using orthogonal multiplanar reconstruction images. The area of thinning was estimated using the formula for the ellipse. Results In 88 patients without severe aortic stenosis, the median thickness of the thinnest area of the left ventricular apex was only 0.9 mm. Among them, 74%, 99%, and 100% of cases displayed a left ventricular apex thinner than 1.0, 3.0, and 5.0 mm, respectively. The median area of the thinnest region was 5.6 mm2 . In 43 patients with severe aortic stenosis, the median thickness of the thinnest area of the left ventricular apex was 1.2 mm. Among them, 51%, 93%, and 100% of cases displayed a left ventricular apex thinner than 1.0, 3.0, and 5.0 mm, respectively. The median area of the thinnest region was 3.9 mm2 . Conclusions Localized thinning of the left ventricular apex is unexceptional, regardless of aortic stenosis with concentric left ventricular hypertrophy, thus highlighting the need for a reappreciation of this feature to avoid inadvertent catastrophic complications.

This case report concerns an 81-year-old woman with previously well-controlled hypertrophic obstructive cardiomyopathy (HOCM). She was referred to our hospital because of the acute onset of takotsubo syndrome. Echocardiography revealed basal hyperkinesis due to takotsubo syndrome superimposed on septal hypertrophy, which resulted in the reappearance of prominent left ventricular outflow tract obstruction (LVOTO). Although she developed cardiogenic shock triggered by atrial fibrillation, LVOTO was successfully mitigated by aggressive fluid resuscitation, rhythm control, and the administration of β-blocker. We herein report a rare case with catastrophic hemodynamics due to the incidental combination of HOCM and takotsubo syndrome.

Background Constrictive pericarditis (CP) is a pathological condition of the pericardium, resulting from fibrosis, scarring, and calcification of the pericardium. Other conditions have been reported to mimic ‘constrictive physiology’ despite the presence of an intact pericardium. However, there has been no report of pulmonary regurgitation (PR) mimicking the haemodynamic characteristics of CP. Case summary A 51-year-old woman was admitted to our institute because of severe right-sided heart failure. Transthoracic echocardiography revealed severe PR concomitant with significant dilatation of the right-sided heart. Septal bounce and the respiratory reciprocation of the transmitral and transtricuspid inflow velocities were also observed, indicating exacerbated ventricular interdependence. Cardiac catheter examination demonstrated elevated right atrial pressure with a prominent y descent, dip, and plateau waveform in the right ventricular pressure, and equalization of the diastolic pressure of all cardiac chambers, which are quite consistent with CP. On surgical inspection, however, there was no pericardial thickening or adhesion, indicating no obvious signs of CP. Discussion Pericardial constriction results from the relative relationship between intrapericardial volume and pericardial reserve. When the intrapericardial volume exceeds the physiological limit, the cardiac chambers compete with each other in a fixed pericardial space. In this case, prominent dilation of the right-sided chambers caused by severe PR resulted in overstretching of the pericardium above the pericardial reserve, which led to a characteristic haemodynamic picture that resembled CP. Thus, it is important to recognize the diagnostic pitfall in the preoperative evaluation of a ‘CP mimic physiology’.

Qing Dai/Indigo Naturalis (QD) has been shown to ameliorate ulcerative colitis (UC) in clinical trials; however, its mechanism remains elusive. This study investigates the effects of QD on murine dextran sulfate sodium salt-induced colitis. Oral administration of QD protected the animals from colitis as manifested by weight loss, diarrhea, and rectal bleeding. QD was distinguishingly more effective than 5-aminosalicylate. Focused microarray analysis of genes expressed in the distal colon suggested that QD influences the inflammatory pathway. Anti-inflammatory activity of QD was confirmed by the suppression of nitric oxide (NO) production in response to interleukin-1β in cultured hepatocytes. Some of the constituents in QD, such as tryptanthrin (TRYP) and indigo, suppressed NO production. TRYP maintained body weight but did not inhibit bleeding. Indigo, on the other hand, partially ameliorated bleeding, but did not maintain body weight. The combination of TRYP and indigo did not show additive ameliorating activity. The methanol extract of QD showed an anti-colitis activity like that of TRYP. In contrast, the methanol-insoluble QD fraction moderately ameliorated diarrhea and bleeding. Combining these two fractions resulted in full anti-colitis activity. Further clarification of the active constituents will help in the discovery of a safe and potent prescription for UC. Keywords: Ulcerative colitis, Dextran sulfate sodium salt, Qing Dai/Indigo Naturalis, Tryptanthrin, NO

A 72-year-old woman was referred to our institution with decompensated congestive heart failure owing to subacute severe aortic regurgitation and mitral regurgitation. Her blood sample tested positive for myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). Cardiac computed tomography revealed abnormal thickening and shortening of the aortic valvar leaflets as well as wall thickening of the sinuses of Valsalva. Based on the diagnosis of ANCA-associated vasculitis, predominantly involving the aortic root, prednisolone administration was initiated, which failed to improve the valvar dysfunction. The patient underwent aortic root replacement and mitral annuloplasty. Histopathology confirmed severe inflammation involving both the aortic valvar sinuses and leaflets.

BACKGROUND Configurational changes in the proximal aorta are relevant to the procedural difficulty of transcatheter aortic valve implantation (TAVI). Among several morphological changes involving the ascending aorta, elongation is characteristics of elderly patients with aortic stenosis and can compromise the success and safety of TAVI. However, the effect of ascending aortic elongation on the overall morphology of the proximal aorta has not been established. AIMS Our primary purpose was to investigate the effect of ascending aortic elongation on structural changes in the proximal aorta in TAVI candidates. MATERIALS & METHODS In total, 121 consecutive patients with severe aortic stenosis (mean age, 84.5 ± 5.3 years; 69% women) who had undergone preprocedural computed tomography before TAVI were enrolled. We examined the structural anatomy of the proximal aorta in detail, focusing on its elongation, dilatation, tilting, rotation, and wedging. RESULTS The mean length of the ascending aorta was 68.0 ± 9.2 mm, and the length was significantly correlated with dilatation (R = .278, p = .002), rightward tilting (R = .437, p

Background: Left ventricular (LV) longitudinal myocardial systolic dysfunction (LVSD) has been identified in type 2 diabetes mellitus (T2DM) patients, and it should be considered the first marker of a preclinical form of DM-related cardiac dysfunction. Overweight has been postulated to contribute to the development of LVSD in T2DM patients, but the impact of amount of body fat mass on LVSD in T2DM patients remains uncertain. Methods We studied 71 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) (all ≥55%) without coronary artery disease. LVSD for T2DM patients with preserved LVEF was identified as global longitudinal strain (GLS)

The purpose of this multi-institutional Phase II trial study was to prospectively investigate the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). TJ-14 was administered orally as a first-line treatment for ARE. The primary end point was efficacy at 1 week. The secondary end points were: (i) the efficacy of TJ-14 at 2 and 3 weeks after its administration, (ii) the quality of life score (FACT-G) at 1, 2 and 3 weeks after its administration, and (iii) adverse events. If the efficacy of TJ-14 was observed in eight patients or fewer, its efficacy was rejected. Results: Forty patients receiving pelvic radiotherapy were enrolled. Of these, 22 developed ARE and received TJ-14. Among these, 19 had cervical cancer and 9 received chemoradiotherapy. TJ-14 efficacy was shown in 19 out of the 22 patients (86%). Stool frequency per day at 1 week significantly decreased (mean ± SD: 4.9 ± 2.1 vs 3.7 ± 1.9, P = 0.02). This effect continued at 2 (2.2 ± 1.4, P = 0.004) and 3 weeks (2.1 ± 0.9, P = 0.05). Thirteen out of the 22 patients (59%) continued TJ-14 until the end of radiotherapy. FACT-G score deterioration was not observed after the administration of TJ-14. Grade 1 hypokalemia was observed in 4 patients, and Grade 1 constipation in 3. We concluded that TJ-14 is sufficiently promising to be examined in a Phase III trial. A randomized controlled trial is currently being planned.

An 80-year-old woman with rheumatoid arthritis presented with chest pain. Clinical examination revealed new-onset paroxysmal atrial fibrillation with symptomatic sinus pauses and worsening mitral regurgitation, which were both resistant to conventional therapies. Based on her skin lesions, an increase in pleural and pericardial effusion, possible myocardial involvement, and a positive finding for immune complex testing, rheumatoid vasculitis was diagnosed. Subsequent glucocorticoid therapy suppressed systemic inflammation, resulting in structural, functional, and electrical reverse remodeling of the left atrium with complete remission of atrial arrhythmias and also an improvement of mitral regurgitation. This case highlights the importance of evaluating the underlying disease activity in a case of de novo paroxysmal atrial fibrillation associated with systemic autoimmune disease.

BACKGROUND The underlying mechanism of mitral regurgitation (MR) in atrial fibrillation (AF) is an isolated annulus dilation caused by left atrial (LA) remodeling. However, the association of mitral valve (MV) geometry with MR in AF patients remains unclear.Methods and Results:We studied 96 AF patients with preserved left ventricular ejection fraction (LVEF). MV geometry was evaluated with 3-dimensional transesophageal echocardiography (3D-TEE). Mitral annulus area of the MR group (n=11, ≥ moderate) was significantly larger (10.6±1.8 vs. 8.2±1.5 cm2, P

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p

BACKGROUND Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Background: Pancreatic cancer (PC) exhibits extremely rapid growth, however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images. Methods: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis &gt, 1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion. Results: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively. Conclusions: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.