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A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. LEARNING OBJECTIVE: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

Patients with dilated cardiomyopathy (DCM) sometimes show anti-mitochondrial M2 antibody (AMA-M2) positivity. We aimed to compare the characteristics of DCM cases with and without AMA-M2, and to describe cases of DCM with AMA-M2 positivity. A total of 84 patients with DCM were analyzed. Six patients (7.1 %) were positive for AMA-M2. Of these six patients, five (83.3 %) had primary biliary cirrhosis (PBC) and four (66.7 %) had myositis. Patients with AMA-M2 positivity had more atrial fibrillation and more premature ventricular contractions than those without. Left and right atrial longitudinal dimensions were larger in patients with AMA positivity (left atrium, 65.9 mm vs. 54.7 mm, p = 0.02; right atrium, 57.0 mm vs. 46.1 mm, p = 0.02). Of the six patients with AMA-M2 positivity, three underwent cardiac resynchronization therapy with defibrillator implantation and three required catheter ablation treatment. Steroids were used in three patients. One patient died of unresolved lethal arrhythmia and another required re-hospitalization for heart failure; the remaining four patients did not have adverse events. Patients with DCM with AMA-M2 positivity had a higher affinity for PBC and myositis than those without, and are characterized by atrial enlargement and arrhythmias. LEARNING OBJECTIVE: Patients with dilated cardiomyopathy sometimes exhibit anti-mitochondrial M2 antibody positivity. These patients are at higher risk for primary biliary cirrhosis and inflammatory myositis, and their cardiac disorders are characterized by atrial enlargement and various arrhythmias. The course of the disease up to the time of diagnosis and after steroid use varies, and the prognosis is poor in advanced cases.

Minerals are solid state nuclear track detectors - nuclear recoils in a mineral leave latent damage to the crystal structure. Depending on the mineral and its temperature, the damage features are retained in the material from minutes (in low-melting point materials such as salts at a few hundred degrees C) to timescales much larger than the 4.5 Gyr-age of the Solar System (in refractory materials at room temperature). The damage features from the $O(50)$ MeV fission fragments left by spontaneous fission of $^{238}$U and other heavy unstable isotopes have long been used for fission track dating of geological samples. Laboratory studies have demonstrated the readout of defects caused by nuclear recoils with energies as small as $O(1)$ keV. This whitepaper discusses a wide range of possible applications of minerals as detectors for $E_R \gtrsim O(1)$ keV nuclear recoils: Using natural minerals, one could use the damage features accumulated over $O(10)$ Myr$-O(1)$ Gyr to measure astrophysical neutrino fluxes (from the Sun, supernovae, or cosmic rays interacting with the atmosphere) as well as search for Dark Matter. Using signals accumulated over months to few-years timescales in laboratory-manufactured minerals, one could measure reactor neutrinos or use them as Dark Matter detectors, potentially with directional sensitivity. Research groups in Europe, Asia, and America have started developing microscopy techniques to read out the $O(1) - O(100)$ nm damage features in crystals left by $O(0.1) - O(100)$ keV nuclear recoils. We report on the status and plans of these programs. The research program towards the realization of such detectors is highly interdisciplinary, combining geoscience, material science, applied and fundamental physics with techniques from quantum information and Artificial Intelligence., Comment: 115 pages, many pictures of tracks. Please see the source file for higher resolution versions of some plots. v2: matches the published version

Aims Patients with acute heart failure (AHF) often present with an increased heart rate (HR), and the HR changes dramatically after initial treatment for AHF. However, the HR change after admission and the relationship between HR change in the early phase and prognosis have not been fully elucidated. Methods and results From a multicentre AHF registry, we retrospectively evaluated 1527 consecutive patients admitted with AHF. HR change (%) was calculated by [HR (at admission) − HR (24 h after admission)] × 100∕HR (at admission). The median HR change was 15.1% (range, 2.0–28.4%). The HR decreased most in the first 24 h and then gradually thereafter [admission: 98 (81–117) b.p.m., 24 h: 80 (70–92) b.p.m., 48 h: 78 (68–90) b.p.m., and 72 h: 77 (67–88) b.p.m.]. In Kaplan–Meier analysis, the cumulative event‐free rates in the composite endpoint of death and rehospitalization due to AHF showed better according to larger HR change (P = 0.012, log rank). Cox proportional hazards analysis showed that HR change was a prognostic factor for composite endpoint adjusted by age and sex [hazard ratio, 0.995; 95% confidence interval (CI), 0.991–0.998; P = 0.006]. HR change was associated with outcome adjusted by age and sex in patients with sinus rhythm (hazard ratio, 0.993; 95% CI, 0.988–0.999; P = 0.015), but not in patients with atrial fibrillation (hazard ratio, 0.996; 95% CI, 0.990–1.002; P = 0.15). Conclusions A decrease in HR in the first 24 h after admission indicates better prognosis in patients with AHF, although the prognostic influence may differ between patients with sinus rhythm and those with atrial fibrillation.

Aims In recent decades, haemodynamic parameters have been estimated for risk stratification and determining treatment strategies for patients with non‐ischaemic dilated cardiomyopathy (DCM). In various invasive procedures, the cardiac pumping capability is defined as cardiac power output (CPO), which is calculated by multiplying cardiac output by the mean arterial pressure. Lower CPO values in advanced heart failure predict adverse outcomes. However, few studies discuss the prognostic value of CPO in mild‐to‐moderate phase patients. This study aimed to determine the value of the cardiac power index (CPI) obtained from the resting CPO for predicting the prognosis of patients with New York Heart Association Functional Class II or III DCM. Methods and results From March 2000 to January 2020, a total of 623 cardiomyopathy patients were evaluated for haemodynamic parameters. Patients with secondary cardiomyopathy, ischaemic cardiomyopathy, valvular heart disease, and Class IV cardiomyopathy were excluded. A total of 176 DCM patients fulfilled the criteria for inclusion. Patients were 51.7 ± 12.5 years old (mean ± standard deviation) with a mean left ventricular ejection fraction of 32.1 ± 9.2%. The patients were divided into two groups by their median CPI (CPI

Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.

Aims Left ventricular reverse remodelling (LVRR) is a well‐established predictor of a good prognosis in patients with dilated cardiomyopathy (DCM). The prediction of LVRR is important when developing a long‐term treatment strategy. This study aimed to assess the clinical predictors of LVRR and establish a scoring system for predicting LVRR in patients with DCM that can be used at any institution. Methods and results We consecutively enrolled 131 patients with DCM and assessed the clinical predictors of LVRR. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, accompanied by a decrease in left ventricular end‐diastolic dimension (LVEDD) ≥ 10% on echocardiography at 1 ± 0.5 years after a diagnosis of DCM. The mean patient age was 50.1 ± 11.9 years. The mean LVEF was 32.2 ± 9.5%, and the mean LVEDD was 64.1 ± 12.5 mm at diagnosis. LVRR was observed in 45 patients (34%) at 1 ± 0.5 years. In a multivariate analysis, hypertension [odds ratio (OR): 6.86; P = 0.002], no family history of DCM (OR: 10.45; P = 0.037), symptom duration 5 in receiver‐operating characteristic curve analysis (area under the curve: 0.89; P 5 was an independent predictor compared with the presence of late gadolinium enhancement on cardiovascular magnetic resonance or the severity of fibrosis on endomyocardial biopsy (OR: 11.79; 95% confidence interval: 2.40–58.00; P = 0.002). Conclusions The LVRR predicting score using five predictors including hypertension, no family history of DCM, symptom duration

A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient’s condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE.

BACKGROUND Right ventricular dysfunction (RVD) in the setting of left ventricular (LV) myocardial damage is a major cause of morbidity and mortality, and the pulmonary artery pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure. However, it is unknown whether PAPi can predict the long-term prognosis of dilated cardiomyopathy (DCM) even in the mild to moderate phase. This study aimed to assess the ability of PAPi to stratify DCM patients without severe symptoms.Methods and Results:Between April 2000 and March 2018, a total of 162 DCM patients with stable symptoms were evaluated, including PAPi, and followed up for a median of 4.91 years. The mean age was 50.9±12.6 years and the mean LV ejection fraction (EF) was 30.5±8.3%. When divided into 2 groups based on median value of PAPi (low, L-PAPi [

Many patients with dilated cardiomyopathy (DCM) progress to heart failure (HF), although some demonstrate left ventricular (LV) reverse remodeling (LVRR), which is associated with better outcomes. The pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio has been used as a prognostic predictor in patients with HF, although this tool's usefulness in predicting LVRR remains unknown.Methods and Results: Data from a prospective observational study of 211 patients diagnosed in 2000-2020 with DCM were retrospectively analyzed. Sixty-nine patients with New York Heart Association class I or II HF were included. LVRR was observed in 23 patients (33.3%). The mean LV ejection fraction (29%) and LV end-diastolic dimension (64.5 mm) were similar in patients with and without LVRR. The PAD/AoD ratio was significantly lower in patients with LVRR than those without (81.4% vs. 92.4%, respectively; P=0.003). The optimal PAD/AoD cut-off value for detecting LVRR was 0.9 according to the receiver operating characteristic curve analysis. Multivariate analysis identified a PAD/AoD ratio ≥0.9 as an independent predictor of presence/absence of LVRR. Cardiac events were significantly more common in patients with a PAD/AoD ratio ≥0.9 than those with a ratio0.9, after a median follow up of 2.5 years (log-rank, P=0.007).The PAD/AoD ratio can predict LVRR in patients with DCM.

Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM.We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6-689.5) pg/mL vs. 96.5 (40.8-191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan-Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048).High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

Background The spleen is an important organ that stores blood, releases erythrocytes or monocytes, and destroys no-longer-needed platelets. It can reserve 20–30% of the total blood volume, and its size is reduced in hypovolemic shock. However, the clinical significance of the spleen size in patients with heart failure (HF) remains unclear. Purpose The purpose of this study was to investigate the relationship between spleen size, hemodynamic parameters, and prognosis in patients with HF. Methods A total of 219 patients with clinically stable HF were enrolled. All patients underwent right heart catheterisation and computed tomography. The spleen size was measured using computed tomography volumetry. In addition, spleen volume was assessed using the spleen volume index (SVI), corrected for body surface area. Cardiac events were composite endpoints of cardiac death, hospitalisation for worsening HF, fatal arrhythmias, implantation of cardiac devices, implantation of left ventricular assist devices, and unexpected percutaneous coronary intervention or cardiac surgery. Spearman's rank correlation coefficient was used to examine the relationship between spleen volume and hemodynamic parameters. Multivariate Cox hazard regression models were used to investigate whether SVI was an independent determinant of cardiac events. Results Of the 219 patients (median age, 54 [interquartile range] 46–64 years), 145 (66%) were males. The median (interquartile range) spleen volume and SVI was 118.0 (91.5–156.0) mL and 67.8 (54.9–87.2) mL/m2, respectively. SVI was positively correlated with cardiac output (r=0.269, P Conclusion The spleen size may affect the prognosis in patients with HF, reflecting haemodynamics, including systemic circulating blood volume status and sympathetic nerve activity. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background Left ventricular reverse remodeling (LVRR) is an important predictor for a good prognosis in patients with dilated cardiomyopathy (DCM). Previous reports indicated the pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio as a predictor of adverse outcomes in heart failure patients. However, the impact of the PAD/AoD ratio for predicting LVRR in patients with DCM is unknown. Aim The aim of this study is to investigate the association between PAD/AoD ratio and LVRR in patients with DCM. Methods From a prospective study, clinically stable DCM patients who were investigated the LVRR on echocardiography and underwent CT at baseline were enrolled. LVRR is defined as left ventricular (LV) ejection fraction increase of 10% and a decrease in indexed LV end-diastolic diameter of 10% compared to those at baseline. PAD and AoD data was collected with nonenhanced computed tomography images at baseline. Results In sixty-nine patients (mean age 50.0±13.3 years), the mean LV ejection fraction was 29.8%, and mean LV end-diastolic dimension was 64.5mm, and both of which data was no significant difference between patients with or without LVRR. LVRR was observed in 23 (33.3%) patients. The PAD/AoD ratio was significantly lower in patients with LVRR than without LVRR (81.4% vs. 92.4%, p=0.003). By ROC analysis, the best cut-off for the detection of LVRR was found for a PAD/AoD ratio of 0.9. From multivariate analyses, PAD/AoD ratio was identified as a significant predictor of LVRR. After a median follow-up duration of 2.5 years, the DCM patients with PAD/AoD≥0.9 revealed a significant higher cardiac event than those with PAD/AoD Conclusions The PAD/AoD ratio is useful for predicting LVRR in patients with DCM. The DCM patients with high PAD/AoD ratio had a poor long-term outcome. Funding Acknowledgement Type of funding sources: None. ROC curve for LVRR predictionKaplan-Meier survival curves

Background Autotaxin (ATX) has been reported to promote myocardial inflammation and subsequent cardiac remodeling through lysophosphatidic acid (LPA) production. However, the prognostic impact of ATX has not been clarified in dilated cardiomyopathy (DCM). Purpose We aimed to investigate the prognostic impact of ATX in patients with DCM. Methods We enrolled 104 DCM patients (49.8 years, 76 males). The subjects underwent blood sampling, echocardiography, cardiac catheterization, and endomyocardial biopsy. Gender differences in serum ATX levels have been reported, thus we divided the subjects into two groups using median serum ATX levels for men and women: High-ATX group and Low-ATX group. All patients were followed up by expert cardiologists. The cardiac event was defined as a composite of cardiac death and hospitalization for worsening heart failure. Results Eighty-nine percent of the subjects were classified as New York Heart Association functional class I or II. Female patients had higher serum ATX levels than male patients, with median values of 257.0 ng/mL and 203.5 ng/mL, respectively (Figure A). The average left ventricular ejection fraction and brain natriuretic peptide levels were 30.6% and 122.5 pg/mL. In survival analysis, cumulative event-free probability was significantly lower in High ATX group (p=0.007, Figure B). In Cox proportional hazards analysis, High-ATX was one of the independent predictors of composite cardiac events (Hazards Ratio, 2.575; p=0.043). On the other hand, high sensitive C-reactive protein and collagen volume fraction in myocardial samples were not significant predictors. Conclusion High serum ATX level was associated with poor prognosis in patients with DCM. Funding Acknowledgement Type of funding sources: None. Gender difference in autotaxin levelsSurvival analysis of cardiac events

Background Follistatin-like 1 (FSTL1) is a myocyte-secreted glycoprotein that could play a role in myocardial maintenance in response to harmful stimuli. We investigated the association between serum FSTL1 levels, especially focused on transcardiac gradient and the hemodynamics, to explore the prognostic impact of FSTL1 levels in patients with dilated cardiomyopathy (DCM). Methods Thirty-two ambulatory patients with DCM (23 men; mean age 59 years) were prospectively enrolled. Blood samples were simultaneously collected from the aortic root (Ao), coronary sinus (CS), as well as from the peripheral vein during cardiac catheterization in stable conditions. The transcardiac gradient of FSTL1 was calculated by the difference between serum FSTL1 levels of CS and Ao (FSTL1CS-Ao). Patients were divided into two groups based on the median of FSTL1CS-Ao: Low FSTL1CS-Ao group, Results Mean left ventricular ejection fraction and median plasma B-type natriuretic peptide levels were 30.9% and 92.3 pg/mL, respectively. FSTL1CS-Ao was negatively correlated with pulmonary capillary wedge pressure (r = -0.400, p = 0.023). Kaplan-Meier survival analysis showed that event-free survival rate was significantly lower in the Low FSTL1CS-Ao group than in the High FSTL1CS-Ao group (p = 0.013). Cox regression analyses revealed that the transcardiac gradient of FSTL1 was an independent predictor for cardiac events. Receiver operating characteristic curve analysis showed that the cut-off value of FSTL1CS-Ao for the prediction of cardiac events was -4.09 ng/mL with sensitivity of 82% and specificity of 86% (area under the curve, 0.87). Conclusions Fifty percent of patients had negative transcardiac gradient of FSTL1. Reduced transcardiac gradient of FSTL1 might be a novel prognostic predictor in DCM patients with impaired hemodynamics.

We report the results of a search for the inelastic scattering of weakly interacting massive particles (WIMPs) in the XENON1T dark matter experiment. Scattering off $^{129}$Xe is the most sensitive probe of inelastic WIMP interactions, with a signature of a 39.6 keV de-excitation photon detected simultaneously with the nuclear recoil. Using an exposure of 0.89 tonne-years, we find no evidence of inelastic WIMP scattering with a significance of more than 2$\sigma$. A profile-likelihood ratio analysis is used to set upper limits on the cross-section of WIMP-nucleus interactions. We exclude new parameter space for WIMPs heavier than 100 GeV/c${}^2$, with the strongest upper limit of $3.3 \times 10^{-39}$ cm${}^2$ for 130 GeV/c${}^2$ WIMPs at 90\% confidence level., Comment: 9 pages, 4 figures

We report on a search for nuclear recoil signals from solar $^8$B neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 keV to 1.6 keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant $^8$B neutrino-like excess is found in an exposure of 0.6 t $\times$ y. For the first time, we use the non-detection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as non-standard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 GeV/c$^2$ and 11 GeV/c$^2$ by as much as an order of magnitude.

The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the $^{222}$Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a $^{222}$Rn activity concentration of 10 $\mu$Bq/kg in 3.2 t of xenon. The knowledge of the distribution of the $^{222}$Rn sources allowed us to selectively eliminate critical components in the course of the experiment. The predictions from the emanation measurements were compared to data of the $^{222}$Rn activity concentration in XENON1T. The final $^{222}$Rn activity concentration of (4.5 $\pm$ 0.1) $\mu$Bq/kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment., Comment: 14 pages, 3 figures

The titration of cardioprotective agents is essential for successful treatment of heart failure (HF) patients with reduced left ventricular ejection fraction. However, hypotension is one of the limiting factors for titration. Ivabradine reduces heart rate without compromising systolic function by prolonging diastolic filling time. Herein two cases of dilated cardiomyopathy (DCM) are presented in which ivabradine improved blood pressure (BP)-limited tolerability and allowed for further titration of cardioprotective agents. In both cases, the introduction of ivabradine raised the BP, which permitted further increase of the dose of renin-angiotensin system inhibitors or beta-blockers. One major hypothesized mechanism of ivabradine-induced BP elevation has been postulated to be an increase in stroke volume due to prolonged ventricular diastolic filling time. However, ivabradine is not expected to increase BP for all HF patients. In those with small and poorly compliant ventricles with severe diastolic or restricted dysfunction, decreased heart rate and prolonged diastole may excessively suppress compensatory mechanisms, and thus may not lead to increased cardiac output and BP. In contrast, ivabradine potentially increases BP and improves BP-limited tolerability of cardioprotective agents in DCM patients with a large and compliant heart. In addition, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling. Learning objective: Ivabradine is usually used for heart failure patients with reduced ejection fraction when the tolerability of cardioprotective agents is maximized. This agent has no direct cardiac contractility-suppressing action. It potentially increases blood pressure and improves tolerability of cardioprotective agents in patients with a large and compliant heart such as dilated cardiomyopathy. Furthermore, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling.

Introduction: Follistatin-like 1 (FSTL1) is secreted from various tissues including myocardium and could play a cardioprotective role against harmful stimuli. It has been shown that the expression of FSTL1 protein in patients with heart failure is higher than that in healthy subjects. However, little is known about the association between serum FSTL1 levels and the cardiac prognosis. Hypothesis: We hypothesized that the transcardiac gradient of FSTL1 reflect myocardial FSTL1 and is useful for predicting prognosis in patients with non-ischemic dilated cardiomyopathy (NIDCM). Methods: Thirty-two NIDCM patients were enrolled. Blood samples were simultaneously collected from the aortic root (Ao), coronary sinus (CS) as well as peripheral vein during cardiac catheterization. The transcardiac gradient of FSTL1 was calculated by the difference between serum FSTL1 levels of CS and Ao (FSTL1 CS-Ao ). Patients were divided into two groups at the median of FSTL1 CS-Ao : Low FSTL1 CS-Ao group, CS-Ao group, > 0 ng/mL. The primary endpoint of this study was the occurrence of a cardiac event, which was defined as a composite of cardiac deaths and unexpected hospitalizations for worsening heart failure. Results: The median plasma B type natriuretic levels and mean left ventricular ejection fraction in the Low and High FSTL1 CS-Ao groups were 91.9 (21.7 - 277.5) vs. 94.1 (59.1 - 236.5) pg/mL (P = 1.000) and 31.4 ± 6.5 vs. 30.5 ± 7.3 % (P = 0.714), respectively. FSTL1 CS-Ao was negatively correlated with pulmonary capillary wedge pressure (R = -0.400, P = 0.023), mean pulmonary artery pressure (R = -0.40, P = 0.023) and right atrial pressure (R = -0.41, P = 0.019). Kaplan-Meier analysis showed that event-free survival rate was significantly lower in the Low FSTL1 CS-Ao group (p=0.0126). Conclusions: Transcardiac gradient of FSTL1 is associated with hemodynamics and low transcardiac gradient of FSTL1 might be associated with poor prognosis in NIDCM patients.

Introduction: Several studies have evaluated prognostic value of heart rate (HR) change during hospitalization in patients with acute heart failure (AHF). However, the relationship between HR change in early phase after admission and prognosis have not been fully elucidated. Hypothesis: The aim of this study was to evaluate the prognostic value of HR change in early phase in patients with AHF. Methods: We used a data of multicenter retrospective registry for the consecutive hospitalized patients due to AHF since January 2012 to March 2019. Patients were divided into three groups according to tertiles of HR at admission: lower tertile, HR 108 bpm. And, (HR [at admission] - HR [at 12 hour after admission]) * 100 / HR [at admission] was calculated as HR change (%). Results: Total of 1625 patients were analyzed. The median HR at admission was 96 bpm, and HR decreased to 81 bpm at 12 hours after admission (p < 0.001). Larger HR change was observed according to increase in HR at admission (HR change; lower tertile, 1.0%; middle tertile, 12.5%, higher tertile, 38.0%, p < 0.001). In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and re-hospitalization due to AHF showed better according to higher HR at admission (p < 0.001, log-rank) (Figure). After dividing the patient into two groups in each tertiles based on the median HR change, the cumulative event-free rates were comparable between higher HR change group and lower HR change group in all tertiles (Figure). Cox proportional hazards analysis showed that HR change was not the independent predictors of composite endpoint adjusted by covariates in each tertile (lower tertile, p = 0.81; middle tertile, p = 0.78; higher tertile, p = 0.90). Conclusions: HR decreased significantly until 12 hours after admission. However, HR change in early phase did not have prognostic value in patients with AHF.

Introduction: Interstitial fibrosis of myocardium is an important component of cardiac dysfunction. Myofibroblasts, which are activated fibroblasts, contribute to interstitial fibrosis in dilated cardiomyopathy (DCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts. Hypothesis: We hypothesized that the circulating serum HE4 levels were associated with future cardiac events in DCM. Methods: We enrolled 44 DCM patients with stable heart failure (HF) condition. Patients with cancer were excluded. We collected blood samples from peripheral vain (PV), ascending aorta (Ao), and coronary sinus (CS) during cardiac catheterization. They were divided into two groups at the median of PV HE4 levels: High PV group (>69 pmol/L); n=22, Low PV group (-0.15 pmol/L); n=22, Low CS-Ao group ( Results: The mean age, left ventricular ejection fraction (LVEF), and plasma BNP level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High PV group (p=0.025). Survival analysis revealed that the High PV group had a higher rate of cardiac events ( Figure ). However, there was no difference between two CS-Ao groups. As for the pathological analysis, not only the peripheral HE4 level but CS-Ao HE4 level did not significantly correlate with collagen volume fraction in biopsy samples. Conclusion: Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM. However, transcardiac gradient of plasma HE4 level might not be associated.

Background: In cardiogenic shock refractory to medical treatment, choosing and changing mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving the outcome. We aimed to clarify the differences in treatment course and outcome between Impella 5.0 and extracorporeal left ventricular assist device (eLVAD) in patients with cardiogenic shock refractory to medical therapy or other mechanical circulatory support. Methods: We performed a retrospective medical record review of consecutive patients who were treated with Impella 5.0 or eLVAD as a bridge to decision (BTD) at our medical center from December 2011 to January 2020. Results: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, one patients used Impella CP and four patients used peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) before Impella 5.0 implantation. On the other hand, of 19 patients managed with eLVAD, 11 patients used VA-ECMO before eLVAD implantation. In patients managed with Impella 5.0, Impella 5.0 was removed successfully in two patients (29%) and four patients (71%) underwent the operation for durable LVAD. In patients managed with eLVAD, eLVAD was successfully removed in three patients (16%), nine patients (47%) required durable LVAD, and seven patients (37%) died during eLVAD management. The period between implantation of Impella 5.0 or eLVAD to durable LVAD surgery was significantly shorter with Impella 5.0 (58 [38 - 95] vs. 235 [126 - 318] days, p=0.001). During durable LVAD implantation, cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cells transfusion was required with Impella 5.0 (149 [125 - 182] vs. 192 [170 - 250] minutes, p=0.042; 7.0 [5.0 - 9.5] vs. 15.0 [10.0- 2.0] units, p=0.019, respectively). There were 4 massive stroke events in eLVAD, but no massive stroke events in Impella 5.0. In Impella 5.0. Conclusions: Impella 5.0 facilitates smoother management as a BTD and reduces surgical invasiveness during durable LVAD implantation. Impella 5.0 would be a more effective option for success to cardiac recovery or next therapy than eLVAD.

Background: Fulminant myocarditis (FM) is a fatal disease that causes rapid-onset severe heart failure requiring inotropes or mechanical circulatory support (MCS). Because insufficient myocardial recovery requires durable left ventricular assist device or heart transplantation, the course of myocardial recovery should be predicted. Hypothesis: Cardiac troponins, which elevates due to myocardial damage, may associate with myocardial recovery in FM. Purpose: We aimed to investigate the relationship between cardiac troponin T (TnT) levels and myocardial recovery course in patients with FM. Method: We performed a retrospective medical record review of 19 patients with FM requiring MCS from May 2012 to January 2020. The serial changes of one-week left ventricular ejection fraction (LVEF) after MCS implantation according to TnT levels were evaluated. Results: Median age was 50 years and 10 patients were male. As for initial MCS, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pumping (IABP) were used in 13 patients, IABP in 4 patients, VA-ECMO in one patient, and impella 2.5 in one patient. Median peak TnT level within one week after MCS implantation were 4.43 (2.47 - 34.6) ng/mL. The patients were divided into High-TnT group and Low-TnT group according to median peak TnT level. All patients in both groups were alive until 7 days after MCS implantation, and LVEF on day 7 was significantly lower in the High-TnT group (Fig). TnT level was highest on day 1 and gradually decreased in the High-TnT group (Fig). Six patients died during hospitalization in the High-TnT group, in contrast, only one patient died in the Low-TnT group (p=0.020). Peak TnT level in patients with LVEF ≥30% (n=8) on day 7 was significantly lower than in patients with LVEF Conclusion: Higher TnT level showed impaired myocardial recovery in patients with FM.

The Migdal effect is attracting interest because of the potential to enhance the sensitivities of direct dark matter searches to the low-mass region. In spite of its great importance, the Migdal effect has not been experimentally observed yet. A realistic experimental approach towards the first observation of the Migdal effect in the neutron scattering was studied with Monte Carlo simulations. In this study, the potential background rate was studied together with the event rate of the Migdal effect by a neutron source. It was found that a table-top-sized $\sim (30~\mbox{cm})^3$ position-sensitive gaseous detector filled with argon or xenon target gas can detect characteristic signatures of the Migdal effect with sufficient rates (O($10^2\sim10^3$) events per day). A simulation result of a simple experimental set-up showed two significant background sources, namely the intrinsic neutrons and the neutron-induced gamma-rays. It is found that the intrinsic neutron background rate for the argon gas is at an acceptable level and some future study of the reduction of the gamma-rays from the laboratory would make the observation of the Migdal effect possible. The background for the xenon gas, on the other hand, is found to be much more serious than for the argon gas. Future works on the isotope separation as well as the reduction of the gamma-rays from the detector and laboratory will be needed before the Migdal effect can be observed for the xenon gas case.

Background and purpose Fluorine-18-flurodeoxyglucose positron emission tomography (18FDG-PET) is a useful examination assessing active inflammatory myocardium noninvasively in patients with cardiac sarcoidosis (CS). Though immunosuppression like prednisolone (PSL) and Methotrexate (MTX) as alternative therapy is used to suppress the inflammation, little is known about the rate of response and efficacy of MTX for intolerance to PSL therapy. Methods From Aug 2016, we prospectively enrolled CS with positively accumulated of FDG in the heart. The initial dose of PSL was 30mg/day, wherefrom the dose was tapered down 5mg/month until 6 months. After 6 months, follow-up 18FDG-PET was performed. Using 18FDG-PET images, we calculated total lesion glycolysis (TLG; SUVmeam x metabolic volume) and calculated the reduction rate of TLG. In order to estimate the response rate to PSL therapy, responder group (R-group) was defined as TLG reduction rate ≥70% and poor-responder group (PR-group) was defined as TLG reduction rate Results In 64 CS patients, 55 patients had serial 18FDG-PET before and 6 months after PSL therapy. 18FDG-PET images were acquired following 7 day's carbohydrate limitation and after at least 18-h fasting (mean free fatty acid level right before 18FDG-PET acquisition was 1.05 mEq/L). The mean age was 63.4 years old and 42 (76.4%) patients were female. Because of 6 months PSL therapy, even though there were no significant difference in BNP (from 59.9 (26.2–137.6) to 60.4 (18.5–122.0) (P=0.593), LV-Dd (from 50.9 (44.5–59.5) to 49.7 (45.5–61.3) (P=0.666) and LV-EF (from 49.5 (34.4–62.5) to 49.9 (38.0–62.0) (P=0.792) at pre and post therapy, respectively, TLG were detected significant reduction from 216.4 (74.2–411.6) to 0.8 (0.0–8.2), (p Conclusions 1) By immunosuppression therapy using PSL for CS, about 86% patients showed significant reduction of myocardial FDG accumulation. 2) When detected intolerance for PSL therapy, MTX might be effective for reduction of inflammation of sarcoidosis in the heart, which might be effective as an alternate therapy in CS. The TLG level after randomization Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Grant-in-aid for scientific research

XENONnT is a dark matter direct detection experiment, utilizing 5.9 t of instrumented liquid xenon, located at the INFN Laboratori Nazionali del Gran Sasso. In this work, we predict the experimental background and project the sensitivity of XENONnT to the detection of weakly interacting massive particles (WIMPs). The expected average differential background rate in the energy region of interest, corresponding to (1, 13) keV and (4, 50) keV for electronic and nuclear recoils, amounts to 12.3 ± 0.6 (keV t y)-1 and (2.2± 0.5)× 10−3 (keV t y)-1, respectively, in a 4 t fiducial mass. We compute unified confidence intervals using the profile construction method, in order to ensure proper coverage. With the exposure goal of 20 t y, the expected sensitivity to spin-independent WIMP-nucleon interactions reaches a cross-section of 1.4×10−48 cm2 for a 50 GeV/c2 mass WIMP at 90% confidence level, more than one order of magnitude beyond the current best limit, set by XENON1T . In addition, we show that for a 50 GeV/c2 WIMP with cross-sections above 2.6×10−48 cm2 (5.0×10−48 cm2) the median XENONnT discovery significance exceeds 3σ (5σ). The expected sensitivity to the spin-dependent WIMP coupling to neutrons (protons) reaches 2.2×10−43 cm2 (6.0×10−42 cm2).

Background The spleen has been recognized as an important organ with several functions such as a reservoir of blood volume, and an involvement in iron metabolism by processing of aged red blood cells and recycling iron. During exercise, spleen contracts, and red blood cells pooled in the spleen are recruited into the systemic circulation. So far, we reported that spleen size changed in advanced heart failure (HF) with left ventricular assist device (LVAD). In addition, spleen volume was related to pulmonary capillary wedge pressure (PCWP) or right atrial pressure (RAP) as parameters of cardiac preload. However, it remains unclear about the relationship between spleen volume and exercise capacity in advanced HF with LVAD. Purpose The purpose of this study was to investigate the associations between spleen volume and exercise capacity in advanced HF patients with LVAD. Methods We enrolled 27 HF patients (21 males, 45±12 years) with LVAD (HeartMate II™; Abbott, Chicago, IL, USA) for use as a bridge to heart transplantation. All patients underwent blood test, echocardiography, right heart catheterization, computed tomography (CT) and cardiopulmonary exercise testing (CPET). Spleen size was measured by CT volumetry. We excluded patients with splenic infarction or aortic valve closure surgery. Results At baseline, body mass index, blood brain natriuretic peptide levels, hemoglobin levels, left ventricular ejection fraction were 21.4±3.1 kg/m2, 73.8 (51.9–165.8) pg/mL, 12.1 (10.6–13.4) g/dL, 24.8±14.7%, respectively. Total cardiac output (CO), the sum of pump flow and CO of native heart was 4.6±0.9 L/min, and spleen volume was 184.9±48.8 mL. As for parameters of CPET, peak heart rate (HR), peak VO2, and peak O2 pulse were 128±25 beats/min, 14.2±3.3 mL/kg/min, and 6.6±1.9 mL/beat. At rest, there were significant correlations between spleen volume and PCWP (r=0.382, p=0.049), RAP (r=0.406, p=0.035) or pulsatility index (r=0.384, p=0.047), despite no correlations with total CO or pump flow. During exercise, there were significant interrelations of spleen volume with peak VO2 (r=0.451, p=0.018) and peak O2 pulse (r=0.427, p=0.026). Furthermore, peak VO2 was interrelated with peak HR (r=0.481, p=0.011) or hemoglobin levels (r=0.649, p Conclusion Spleen volume could be a useful predictor of exercise capacity in advanced HF patients with LVAD, reflecting splenic function to modulate cardiac preload and blood hemoglobin levels. Spleen volume and exercise parameters Funding Acknowledgement Type of funding source: None

Background Dilated cardiomyopathy (DCM) is characterized by a reduction in left and/or right ventricular myocardial contraction, dilatation of biventricular cavity and major cause of heart failure with high morbidity and mortality rates. Right ventricular dysfunction (RVD) recently have been received attention because of 34% of DCM had RVD and considered as a powerful predictor of impaired prognosis in DCM. Pulmonary Artery Pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure, however, it is unknown that even at early phase, PAPi can reflects latent right myocardial damage and predict long-term prognosis in stable DCM patients. Methods From April 2000 to March 2018, we enrolled 566 consecutive patients with cardiomyopathy. All patients underwent laboratory measurement, echocardiography, and cardiac catheterization to evaluate their general conditions. After excluded secondary cardiomyopathy, ischemic cardiomyopathy, and valvular heart disease, finally 162 DCM patients were enrolled. All enrolled patients had NYHA I/II/III and NYHA I/II were 150 patients (92.6%). PAPi was calculated as (systolic pulmonary artery pressure – diastolic pulmonary artery pressure (Pulmonary artery pulse pressure: PAPP)) / right atrial pressure. Median followed up for 4.85 years. In this study 149 patients were performed endomyocardial biopsy in order to exclude secondary cardiomyopathies and 95 patients were assessed using Sirius red staining. Myocardial fibrosis in biopsy specimen was assessed using Sirius red staining, and the positive region was quantified as the collagen volume fraction (CVF). Results The mean age and LV ejection fraction (EF) was 50.9±12.6 years and 30.5±8.3%, respectively. When divided into two groups by median PAPi value [PAPi Conclusion In the calculation of PAPi, PAPP reflects both RV contractility and left atrial filling pressure and this index considered as RV adaptive response to afterload. The denominator of the PAPP is defined by RA pressure, which serves as a marker of RV preload. Thus, PAPi reflect both preload and afterload of RV at the same time and even though estimated patients at early phase, RVD exists in DCM patients without severe myocardial fibrosis, and PAPi may help stratify DCM and predict cardiac events. Kaplan-Meier analysis Funding Acknowledgement Type of funding source: None

Background Sepsis is a systemic condition of profoundly impaired health in which an infection leads to a dysregulated host response, and consecutively causes organ dysfunction, shock, and even death. Septic cardiomyopathy (SCM) is one of the multiple organ dysfunctions. SCM is typically defined as left ventricular (LV) dysfunction, presented by decreased LV ejection fraction (LVEF). However, it remains unclear about the detailed mechanism of cardiac dysfunction. In addition, the prognostic impact of right heart dysfunction in SCM patients has not been fully investigated. Purpose The purpose of this study was to investigate the prognostic impact of right heart dysfunction in patients with SCM. Methods We used the MIMIC-III (Medical Information Mart for Intensive Care III) critical care database, which is a large, freely-available database comprising deidentified health-related data associated with over forty thousand patients who stayed in critical care units of the Beth Israel Deaconess Medical Center between 2001 and 2012. We retrospectively analyzed data of patients with septic shock on admission to intensive care unit (ICU). Septic shock was defined as the presence of any suspected infections, the need for vasopressors, and the lactate level exceeding 2 mmol/L, based on the Sepsis-3 criteria. Patients were performed portable transthoracic echocardiography (TTE) during hospitalization. LVEF and right ventricular (RV) function were determined predominately by visual estimation in the parasternal long-axis view. SCM was defined as having a minimum LVEF of 50% or less during hospitalization. Patients with hyperdynamic motion of LVEF >70% were excluded. Results In total, there were 2254 patients with septic shock. Of these, 604 patients who underwent TTE were enrolled, and 314 patients were diagnosed with SCM. At baseline, age, gender, Sequential Organ Failure Assessment (SOFA) score, maximum lactate levels, and maximum norepinephrine dosage were 70 [59–79] years, 194 males, 13 [11–15], 4.0 [2.7–6.2] mmol/L, and 0.20 [0.10–0.31] mcg/kg/min, respectively. All patients were treated with vasopressors. In Kaplan-Meier survival analysis, patients with SCM had increased 28-day mortality compared with those without SCM (log-rank, p=0.09). In addition, we divided SCM patients into two groups; SCM with and without RV dysfunction. SCM patients with RV dysfunction had significant increased 28-day mortality compared with those without RV dysfunction (log-rank, p=0.01) (Figure). In Cox proportional hazard regression analysis adjusted for age, male sex, SOFA score, and maximum lactate levels, RV dysfunction was an independent determinant of 28-day mortality (hazard ratio, 1.59; 95% confidence interval, 1.03–2.46; p=0.03). Conclusions The presence of RV dysfunction increased 28-day mortality in patients with SCM. It might be useful for predicting the prognosis of SCM to evaluate not only left heart function but also right heart function. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

The idea of a hermetic quartz chamber in a dual-phase xenon time projection chamber (TPC) has the potential to improve the detector sensitivity for direct dark matter searches in the future. A major challenge facing TPC detectors in future dark matter experiments will be the reduction of the internal background such as $^{222}$Rn and the deterioration of the ionization signal due to electronegative impurities. The hermetic quartz chamber can isolate the TPC’s sensitive volume from external interference and is thus expected to prevent contamination caused by radioactive and electronegative impurities, which originate from the outer detector materials. At the Kamioka Observatory in Japan, we have developed a TPC with a quartz chamber that contains a ⌀$ 48 \times 58$ mm volume of liquid xenon. At this development stage, we have not aimed for perfect hermeticity of the quartz chamber. Our aim here is twofold: first, to demonstrate via the use of a calibration source that the presence of quartz materials in the TPC does not impact its operation; and second, to perform quantitative measurements of the TPC’s characteristics. We successfully measured electron drift velocities of 1.2–1.7 mm/$\mu$s in liquid xenon under electric fields ranging from 75–384 V/cm, and also observed small S2 signals produced by a single ionized electron with a light yield of 16.5 $\pm$ 0.5 PE. These results were consistent with the expected values; therefore, our demonstrations provide a proof of principle for TPCs incorporating a quartz chamber.

We report results from searches for new physics with low-energy electronic recoil data recorded with the XENON1T detector. With an exposure of 0.65 t-y and an unprecedentedly low background rate of $76\pm2$ events/(t y keV) between 1 and 30 keV, the data enables sensitive searches for solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter. An excess over known backgrounds is observed at low energies and most prominent between 2 and 3 keV. The solar axion model has a 3.4$\sigma$ significance, and a 3D 90% confidence surface is reported for axion couplings to electrons, photons, and nucleons. This surface is inscribed in the cuboid defined by $g_{ae}, Comment: 26 pages, 15 figures. v2 added Ar37 background discussion and best-fit mass of bosonic dark matter, v3 updated Ar37 discussion, tritium estimation, and solar axion energy spectrum. Data in Fig. 2, 4, and 15, including unbinned energy points in Fig. 4, are available in 10.5281/zenodo.4088778

The metabolism of branched-chain amino acids (BCAAs) is reported to change in heart failure (HF) and correlate with cardiac function. However, the effect of BCAAs on HF remains controversial. We investigate the prognostic value of the plasma BCAA level in nonischemic dilated cardiomyopathy (NIDCM).This study enrolled 39 NIDCM patients, who underwent plasma amino acid (AA) analysis. The ratio of BCAAs to total AAs was calculated. All patients were divided into two groups at the median of BCAA/total AA ratio; high BCAA/total AA group (≥ 0.15, n = 20) and low BCAA/total AA group (< 0.15, n = 19). A cardiac event was defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia.The mean age was 51.1 ± 12.3 years and left ventricular ejection fraction (LVEF) was 32.7 ± 10.1%. In the low BCAA/total AA group, the body mass index and the total cholesterol level were lower than in the high BCAA/total AA group. The BCAA/total AA ratio was positively correlated with LVEF (r = 0.35, P = 0.031) and negatively correlated with brain natriuretic peptide (r = -0.37, P = 0.020). The low BCAA/total AA group had a lower cardiac event-free rate (5-year: 100% versus 73%; P = 0.019). In univariate analysis, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (hazard ratio: 0.045, P = 0.0014), hemoglobin (hazard ratio: 0.49 per 1 g/dL, P = 0.0022), and BCAA/total AA ratio < 0.15 (hazard ratio: not available, P = 0.0066) were major predictors for cardiac events.The BCAA/total AA ratio might be a useful predictor for future cardiac events in patients with NIDCM.

Heart failure (HF) is a hypercatabolic state that promotes branched-chain amino acid (BCAA) catabolic activity in the heart and skeletal muscle and reduces protein synthesis in the liver. Consequently, plasma free aromatic amino acids (AAAs) are increased. We investigated the prognostic value of the BCAA/AAA ratio (Fischer's ratio, FR) in patients with HF.We enrolled 157 consecutive patients hospitalized for worsening HF (81 men, 76 women; mean ± SD age 75 ± 14 years). Plasma BCAA levels (i.e. total leucine, isoleucine, valine) and AAA levels (i.e. total tyrosine, phenylalanine) were measured at a time when the patients were stabilized (at discharge). FR was calculated as the combined plasma BCAA levels divided by the AAA level. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF.The patients were divided into two groups based on the median FR (high-FR group: FR ≥ 3.1, n = 78; low-FR group: FR 3.1, n = 79). Compared with the high-FR group, low-FR patients were older, had more prior hospitalizations for HF, lower albumin and cholinesterase levels, and lower geriatric nutritional risk index (GNRI). Altogether, 46 cardiac events occurred during the follow-up period (221 ± 135 days), including 14 cardiac deaths and 32 hospitalizations for worsening HF. In a Kaplan-Meier survival analysis, the low-FR group had more cardiac events than the high-FR group (log-rank, p 0.001). The best cut-off value of FR was determined as 2.9 in the receiver operating characteristic curve for cardiac events. A multivariate Cox proportional hazards regression analysis showed that being in the low-FR group was an independent determinant of cardiac events from parameters of liver function tests and GNRI.FR might be useful for predicting future cardiac events in patients with HF, reflecting nutritional status which cannot be assessed by liver function tests and GNRI.

Direct dark matter detection experiments based on a liquid xenon target are leading the search for dark matter particles with masses above ∼5 GeV/c2, but have limited sensitivity to lighter masses because of the small momentum transfer in dark matter-nucleus elastic scattering. However, there is an irreducible contribution from inelastic processes accompanying the elastic scattering, which leads to the excitation and ionization of the recoiling atom (the Migdal effect) or the emission of a bremsstrahlung photon. In this Letter, we report on a probe of low-mass dark matter with masses down to about 85 MeV/c2 by looking for electronic recoils induced by the Migdal effect and bremsstrahlung using data from the XENON1T experiment. Besides the approach of detecting both scintillation and ionization signals, we exploit an approach that uses ionization signals only, which allows for a lower detection threshold. This analysis significantly enhances the sensitivity of XENON1T to light dark matter previously beyond its reach.

Aims In acute heart failure (AHF), immobilization is caused because of unstable haemodynamics and dyspnoea, leading to protein wasting. Neuromuscular electrical stimulation (NMES) has been reported to preserve muscle mass and improve functional outcomes in chronic disease. NMES may be effective against protein wasting frequently manifested in patients with AHF; however, whether NMES can be implemented safely without any adverse effect on haemodynamics has remained unknown. This study aimed to examine the feasibility of NMES in patients with AHF. Methods and results Patients with AHF were randomly assigned to the NMES or control group. The intensity of the NMES group was set at 10–20% maximal voluntary contraction level, whereas the control group was limited at a visible or palpable level of muscle contraction. The sessions were performed 5 days per week since the day after admission. Before the study implementation, we set the feasibility criteria with following items: (i) change in systolic blood pressure (BP) > ±20 mmHg during the first session; (ii) increase in heart rate (HR) > +20 b.p.m. during the first session; (iii) development of sustained ventricular arrhythmia, atrial fibrillation (AF), and paroxysmal supraventricular tachycardia during all sessions; (iv) incidence of new‐onset AF during the hospitalization period < 40%; and (v) completion of the planned sessions by >70% of patients. The criteria of feasibility were set as follows; the percentage to fill one of (i)–(iii) was ±20 mmHg or HR > +20 b.p.m. were observed in three cases in the NMES group (8.8%) and five in the control group (12.8%). New‐onset arrhythmia was not observed during all sessions in both groups. During hospitalization, one patient newly developed AF in the NMES group (2.9%), and one developed AF (2.6%) and two lethal ventricular arrhythmia in the control group. Thirty‐one patients in the NMES group (91%) and 33 patients in the control group (84%) completed the planned sessions during hospitalization. This study fulfilled the preset feasibility criteria. Conclusions NMES is feasible in patients with AHF from immediately after admission.

Silicon photomultipliers (SiPMs) have a low radioactivity, compact geometry, low operation voltage, and reasonable photo-detection efficiency for vacuum ultraviolet light (VUV). Therefore it has the potential to replace photomultiplier tubes (PMTs) for future dark matter experiments with liquid xenon (LXe). However, SiPMs have nearly two orders of magnitude higher dark count rate (DCR) compared to that of PMTs at the LXe temperature ($\sim$ 165 K). This type of high DCR mainly originates from the carriers that are generated by band-to-band tunneling effect. To suppress the tunneling effect, we have developed a new SiPM with lowered electric field strength in cooperation with Hamamatsu Photonics K. K. and characterized its performance in a temperature range of 153 K to 298 K. We demonstrated that the newly developed SiPMs had 6--54 times lower DCR at low temperatures compared to that of the conventional SiPMs., 9 pages,13 figures, 2 tables

In the last three decades, numerous terrestrial experiments were built to search for a faint interaction between Weakly Interacting Massive Particles (WIMP) and ordinary matter. Among them, experiments using dual-phase xenon time projection chambers (TPCs) are leading the search especially for high mass WIMPs. In these experiments, photomultipliers (PMTs) are used to detect the prompt primary scintillation and secondary electro-luminescence of ionized electrons generated following an interaction between WIMP and a Xe nucleus. However, PMTs have several important shortcomings: their residual radioactivity levels, cost, bulkiness, and stability at cryogenic temperatures. Therefore, several alternative technologies are under consideration toward future dark matter experiments using ~50 tons of liquid xenon (LXe). One such technology is silicon photomultipliers (SiPM). SiPM have very low radioactivity, compact geometry, low operation voltages and reasonable photo-detection efficiency for vacuum ultra violet (VUV) light. However, current SiPM still have ~two order of magnitude higher dark count rate compared to PMTs. In order to solve this problem, we are currently developing a new SiPM with the help of Hamamatsu. In this paper, we report the current status of the performance measurements of the new SiPM developed with Hamamatsu to improve the dark count rate (DCR).