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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.

The Impella 5.0 is an axial-flow percutaneous ventricular assist device used in patients with cardiogenic shock. Although the recommended period of use is 10 days or less, weaning can be delayed because of ongoing hemodynamic instability. In clinical practice, this device sometimes malfunctions during long-term management with heparin and must be replaced; however, the relationship between the duration of support with the initial and replacement Impella 5.0 and the changes in value of the purge system has not been fully elucidated. From July 2018 to May 2021, Impella 5.0 was implanted and used for more than 10 days in 11 patients at our institution. Four patients required Impella replacement because of device malfunction and the second Impella had purge system malfunction in all cases. The second Impella was used for a significantly shorter time than the first Impella (p = 0016). We calculated the ratio of purge pressure to purge flow rate and found that the ratio exceeded 50 mm Hg/mL/h in all cases with purge system malfunction. In conclusion, it is important to construct a treatment strategy considering the duration of use, because the risk of purge system malfunction is high after replaced Impella 5.0.

Two hydroxy-functionalized PAMAM Dendrimers (3OH-PAMAM and 4OH-PAMAM) were developed as immobilized liquid membranes (ILMs) to separate CO2 from a mixture of CO2 and N2. The hydroxy-functionalized PAMAM demonstrated excellent properties of CO2-selective separative material for CO2 membrane separation. The hydroxy-functionalized PAMAM dendrimers displayed greater water sorption and more CO2 separation properties than that of conventional PAMAM without hydroxy groups. The resulting ILMs of 4OH-PAMAM showed the highest CO2 over N2 selectivity of 7000 and above with CO2 permeance of 1.1×10−11 m3 (STP) m−2 s−1 Pa−1 (1.5 GPU, 1 GPU = 7.5 × 10−12 m3 (STP) m−2 s−1 Pa−1), with a membrane thickness of 100µm (CO2 permeability 147 Barrers), at 9.7 kPa CO2 partial under 130 kPa feed pressure with 80% RH at 40 °C. For the ILMs of dendrimers at over 60%RH, their PCO2 – α plots exceeded the upper bound line by Roberson in 2008 and that is a potential for CO2 separation from the gas mixture.

The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69-85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4-7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan-Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1-3], and the median age was 78 years (69-85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan-Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111-1.255; p 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065-1.249; p 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124-1.303; p 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF.

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.

Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P

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.

Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF).We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays.Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P0.001) were independently associated with the development of delirium.Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.

The spleen serves as a blood volume reservoir for systemic volume regulation in heart failure (HF) patients. Changes are seen in spleen size in advanced HF patients after left ventricular assist device (LVAD) implantation. The pulsatility index (PI) is an indicator of native heart contractility with hemodynamic changes in patients using LVAD. We hypothesized that the splenic volume was associated with the PI, reflecting the hemodynamics in advanced HF patients with LVADs. Herein, we investigated the relationship between splenic volume and PI in these patients. Forty-four patients with advanced HF underwent implantation of HeartMate II® (Abbott, Chicago, IL, USA) as a bridge to heart transplantation at the Nagoya University Hospital between October 2013 and June 2019. The data of 27 patients (21 men, median age 46 years) were analyzed retrospectively. All patients underwent blood tests, echocardiography, right heart catheterization, and computed tomography (CT). Spleen size was measured via CT volumetry; the splenic volume (median: 190 mL) correlated with right arterial pressure ( r = 0.431, p = 0.025) and pulmonary capillary wedge pressure ( r = 0.384, p = 0.048). On multivariate linear regression analysis, the heart rate (β = −0.452, p = 0.003), pump power (β = −0.325, p = 0.023), and splenic volume (β = 0.299, p = 0.038) were independent determinants of PI. The splenic volume was associated with PI, reflecting the cardiac preload in advanced HF patients with LVADs. Thus, spleen measurement using CT may help estimate the systemic volume status and understand the hemodynamic conditions in LVAD patients.

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 [

The Impella is an axial-flow percutaneous ventricular assist device for cardiogenic shock. In this report, we describe two patients who developed aortic insufficiency (AI) associated with Impella and required surgical intervention upon implantation of the durable left ventricular assist device (LVAD). Both patients presented with cardiogenic shock and underwent insertion of Impella 5.0 as a bridge to decision. The cardiac function in these patients did not improve and obtaining approval for heart transplantation required time. They were managed with Impella for 91 and 98 days, respectively. In both cases, moderate AI that was not present before Impella insertion was observed when the Impella was removed. Therefore, we performed aortic valve closure to control the AI during durable LVAD implantation. In patients with durable LVAD implantation, AI may occur and progress after the operation in several cases. Aortic valve surgery is often performed to prevent deterioration of AI, especially in patients with AI before the surgery. Hence, AI is an important complication following Impella device implantation as a bridge to decision. Careful observation of AI is essential when the Impella is removed as the evaluation of AI by echocardiogram during Impella management is cumbersome because of device-generated artifacts.

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.

Heart failure (HF) is a systemic inflammatory disease that causes hypotrophy and skeletal muscle loss. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been developed as a novel evaluation index for malnutrition, with reported usefulness in HF caused by ischemic heart disease. However, reports on the usefulness of malnutrition evaluated by the GLIM criteria in non-ischemic dilated cardiomyopathy (NIDCM) and its relationship with psoas muscle volume are lacking. We investigated the prognostic value of malnutrition evaluated using the GLIM criteria and its association with psoas muscle volume in patients with NIDCM. We enrolled 139 consecutive patients with NIDCM between December 2000 and June 2020. Malnutrition was evaluated using the GLIM criteria on admission. The median follow-up period was 4.7 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia. Furthermore, we measured the psoas muscle volume using computed tomography volumetry in 48 patients. At baseline, the median age was 50 years, and 132 patients (95.0%) had New York Heart Association functional class I or II HF. The median psoas muscle volume was 460.8 cm

The spleen is an important immune organ that releases erythrocytes and monocytes and destroys aged platelets. It also reserves 20-30% of the total blood volume, and its size decreases in hypovolemic shock. However, the clinical significance of splenic size in patients with heart failure (HF) remains unclear. We retrospectively analyzed the data of 206 patients with clinically stable HF gathered between January 2001 and August 2020 and recorded in a single-center registry. All patients underwent right heart catheterization and computed tomography (CT). Splenic size was measured using CT volumetry. The primary outcomes were composite cardiac events occurring for the first time during follow-up, namely, cardiac death and hospitalization for worsening HF. The median splenic volume and splenic volume index (SVI) were 118.0 mL and 68.9 mL/m

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

Introduction: Choice of mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving outcomes in patients with severe cardiogenic shock. We aimed to clarify the difference in treatment course and outcomes with the use of Impella 5.0 and an 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 implanted with Impella 5.0 or eLVAD as a bridge to decision at our medical center. Results: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, the Impella 5.0 was removed successfully in two patients and five patients underwent surgery for durable LVAD implantation. Of 19 patients managed with eLVAD, the eLVAD was successfully removed in 3 patients, 9 patients required durable LVAD, and 7 patients died during eLVAD management. The period between Impella 5.0 or eLVAD implantation to durable LVAD surgery was significantly shorter with Impella 5.0 (58 vs 235 days, p = 0.001). Cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cell transfusion was required with Impella 5.0 (149 vs 192 min, p = 0.042; 7.0 vs 15.0 units, p = 0.019). There were four massive stroke events with eLVAD, but no massive stroke event with Impella 5.0. Conclusion: Impella 5.0 facilitates smoother management as a bridge to decision and reduces surgical invasiveness during durable LVAD implantation.

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