Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. CONCLUSIONS: Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Risk stratification of invasive cervical cancer diagnosed after cervical conization.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) diagnosis is based on colposcopy-aided histological examination. However, its accuracy in CIN diagnosis is limited. Some invasive cervical cancers (ICCs) are diagnosed after cervical conization. Therefore, risk stratification of undetected ICC is particularly important for the management of patients with CIN. This study aimed to identify the risk factors for undetected ICC. We especially focused on the association of human papillomavirus (HPV) genotypes. METHODS: We retrospectively reviewed the clinicopathological characteristics (including age, parity, and preoperative diagnosis) and HPV genotypes of 348 patients diagnosed with CIN or adenocarcinoma in situ (AIS) who underwent cervical conization at our hospital between 2008 and 2016. The relationship between preoperative factors, including HPV genotypes and post-conization ICC, was evaluated. RESULTS: Among the 348 patients, 322, 7, and 19 had preoperative CIN3, CIN2, and AIS, respectively; 181 were nulliparous. The median patient age was 41 (23-83) years. HPV genotyping was performed on 237 patients. Overall, post-conization ICC was detected in 16 patients (4.6%). Multivariate analysis showed that nulliparity and HPV16 positivity were the independent risk factors for post-conization ICC (OR: 6.01, P = 0.0302; OR: 5.26, P = 0.0347, respectively). The combination of HPV16 status and parity improved diagnostic accuracy. Seven of 53 HPV16-positive cases (13%) without childbirth history were diagnosed with post-conization ICC. In contrast, none of the HPV16-negative cases with childbirth history was diagnosed with post-conization ICC. CONCLUSION: HPV16 positivity and nulliparity were identified as risk factors for undetected ICC. Careful treatment selection and preoperative scrupulous examination are especially important in these cases.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

Efficacy of Pulmonary Artery Pulsatility Index as a Measure of Right Ventricular Dysfunction in Stable Phase of Dilated Cardiomyopathy.

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 [<3.06] and high, H-PAPi [≥3.06]), even though there were no differences in B-type natriuretic peptide or pulmonary vascular resistance, the probability of cardiac event survival was significantly higher in the L-PAP than in the H-PAP group by Kaplan-Meier analysis (P=0.018). Furthermore, Cox's proportional hazard regression analysis revealed that PAPi was an independent predictor of cardiac events (hazard ratio: 0.782, P=0.010). CONCLUSIONS: Even in patients identified with DCM in the mild to moderate phase, PAPi may help stratify DCM and predict cardiac events.

Spleen size improvement in advanced heart failure patients using a left ventricular assist device.

The spleen has been recognized as an important organ that holds a reserve of 20% to 30% of the total blood volume. Spleen contraction and splenic volume reduction occur in patients with hypovolemic shock. However, the change in the spleen volume and the association between spleen size and hemodynamic parameters remain unclear in patients with advanced heart failure (HF) who need left ventricular assist device (LVAD) support. This study was performed to investigate the change in spleen size and the relationship between spleen size and hemodynamic parameters before and after LVAD implantation in patients with advanced HF. We enrolled 20 patients with advanced HF on LVAD support. All patients underwent right heart catheterization and computed tomography before and after LVAD implantation. The spleen size was measured by computed tomography volumetry. We excluded patients with a mean right atrial pressure (RAP) of <5 mm Hg because of the possibility of hypovolemia and those with a cardiac index of >2.2 L/min/m2 before LVAD implantation. The splenic volume significantly increased from 160.6 ± 46.9 mL before LVAD implantation to 224.6 ± 73.5 mL after LVAD implantation (P < .001). Before LVAD implantation, there was a significant negative correlation between spleen volume and systemic vascular resistance (SVR). After LVAD implantation, however, there were significant correlations between spleen volume and the cardiac index, RAP, and pulmonary capillary wedge pressure despite the absence of a significant correlation between spleen volume and SVR. Furthermore, one patient developed reworsening HF because of LVAD failure due to pump thrombosis. In this case, the splenic volume was 212 mL before LVAD implantation and increased to 418 mL after LVAD implantation, although it decreased to 227 mL after LVAD failure. The spleen size may change depending on hemodynamics in patients with advanced HF with LVAD support, reflecting sympathetic nerve activity and the systemic volume status.

Aortic insufficiency associated with Impella that required surgical intervention upon implantation of the durable left ventricular assist device.

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.

Usefulness of Plasma Branched-Chain Amino Acid Analysis in Predicting Outcomes of Patients with Nonischemic Dilated Cardiomyopathy.

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.

Mesoscopic Architectures Made of Electrically Charged Binary Colloidal Nanosheets in Aqueous System.

Inorganic layered materials can be converted to colloidal liquid crystals through exfoliation into inorganic nanosheets, and binary nanosheet colloids exhibit rich phase behavior characterized by multiphase coexistence. In particular, niobate-clay binary nanosheet colloids are characterized by phase separation at a mesoscopic (∼several tens of micrometers) scale whereas they are apparently homogeneous at a macroscopic scale. Although the mesoscopic structure of the niobate-clay binary colloid is advantageous to realize unusual photochemical functions, the structure itself has not been clearly demonstrated in real space. The present study investigated the structure of niobate-clay binary nanosheet colloids in detail. Four clay nanosheets (hectorite, saponite, fluorohectorite, and tetrasilisic mica) with different lateral sizes were compared. Small-angle X-ray scattering (SAXS) indicated lamellar ordering of niobate nanosheets in the binary colloid. The basal spacing of the lamellar phase was reduced by increasing the concentration of clay nanosheets, indicating the compression of the liquid crystalline niobate phase by the isotropic clay phase. Scattering and fluorescence microscope observations using confocal laser scanning microscopy (CLSM) demonstrated the phase separation of niobate and clay nanosheets in real space. Niobate nanosheets assembled into domains of several tens of micrometers whereas clay nanosheets were located in voids between the niobate domains. The results clearly confirmed the spatial separation of two nanosheets and the phase separation at a mesoscopic scale. Distribution of clay nanosheets is dependent on the employed clay nanosheets; the nanosheets with large lateral length are more localized or assembled. This is in harmony with larger basal spacings of niobate lamellar phase for large clay particles. Although three-dimensional compression of the niobate phase by the coexisting clay phase was observed at low clay concentrations, the basal spacing of niobate phase was almost constant irrespective of niobate concentrations at high clay concentrations, which was ascribed to competition of compression by clay phase and restoring of the niobate phase.

Early Blood Pressure Reduction by Intravenous Vasodilators Is Associated With Acute Kidney Injury in Patients With Hypertensive Acute Decompensated Heart.

BACKGROUND: Intravenous vasodilators are commonly used in patients with hypertensive acute decompensated heart failure (ADHF), but little is known about their optimal use in blood pressure (BP) management to avoid acute kidney injury (AKI). The purpose of this study was to investigate the association between systolic BP (SBP) changes and the incidence of AKI in patients with hypertensive ADHF.Methods and Results:Post-hoc analysis was performed on a prospectively enrolled cohort. We investigated 245 patients with ADHF and SBP >140 mmHg on arrival (mean age, 76 years; 40% female). We defined "SBP-fall" as the maximum percent reduction in SBP 6 h after intravenous treatment. AKI was defined as serum creatinine (SCr) ≥0.3 mg/dL, or urine output <0.5 mL/kg/h (n=66) at 48 h. Mean SBP and SCr levels on arrival were 180 mmHg and 1.21 mg/dL, respectively. Patients with AKI had significantly larger SBP-fall than the others (36.7±15.3% vs. 27.2±15.3%, P<0.0001). Logistic regression analysis showed an odds ratio per 10% SBP-fall for AKI of 1.49 (95% confidence interval 1.29-1.90, P=0.001). SBP-fall was significantly associated with the number of concomitant used intravenous vasodilators (P=0.001). The administration of carperitide was also independently associated with increased incidence of AKI. CONCLUSIONS: Larger SBP-fall from excessive vasodilator use is associated with increased incidence of AKI in patients with hypertensive ADHF.

Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1 years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (-) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9-7.5) years], patients experienced 7 cardiac events. Kaplan-Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (-) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

TFE3 is a bHLH-ZIP-type transcription factor that regulates the mammalian Golgi stress response.

The Golgi stress response is a mechanism by which, under conditions of insufficient Golgi function (Golgi stress), the transcription of Golgi-related genes is upregulated through an enhancer, the Golgi apparatus stress response element (GASE), in order to maintain homeostasis in the Golgi. The molecular mechanisms associated with GASE remain to be clarified. Here, we identified TFE3 as a GASE-binding transcription factor. TFE3 was phosphorylated and retained in the cytoplasm in normal growth conditions, whereas it was dephosphorylated, translocated to the nucleus and activated Golgi-related genes through GASE under conditions of Golgi stress, e.g. in response to inhibition of oligosaccharide processing in the Golgi apparatus. From these observations, we concluded that the TFE3-GASE pathway is one of the regulatory pathways of the mammalian Golgi stress response, which regulates the expression of glycosylation-related proteins in response to insufficiency of glycosylation in the Golgi apparatus.

Changes in fetal presentation in the preterm period and the prediction of non-cephalic delivery.

OBJECTIVE: Since fetal presentation is an essential factor for planning mode of delivery, the estimation of fetal presentation at delivery is important in prenatal management. This study aimed to clarify the transition of fetal presentation during pregnancy and to propose practical strategy to predict final fetal presentation. METHODS: During the period of 2 years, fetal presentations were analyzed using ultrasonography during the prenatal visits at and after 22 weeks of gestation in a single facility. The relationship between the transition of fetal presentation and final presentation at delivery was analyzed. Further, a prediction model was developed to predict the final fetal presentation at birth. RESULTS: Among 1737 singleton pregnancies with full-term delivery, non-cephalic delivery occurred in 76 pregnancies (4.4%). Non-cephalic presentation in later half of the gestational period was associated with low incidence of spontaneous cephalic version. Furthermore, we found that in 46% of women with a final non-cephalic delivery, the non-cephalic presentation continued during whole of the observational period without spontaneous cephalic version. Based on the analyzed data of this cohort, we show that in a group of women with non-cephalic presentation at 35/36 weeks, the best predictability for spontaneous cephalic version depended on whether the cephalic presentation was observed at least once at and after 30 weeks of gestation. CONCLUSION: Our findings suggest that information on the changes in fetal presentation during gestation contributes to the prediction of the fetal presentation at delivery and planning mode of delivery.

Inhibition of FGFR Reactivates IFNγ Signaling in Tumor Cells to Enhance the Combined Antitumor Activity of Lenvatinib with Anti-PD-1 Antibodies.

Combination therapies consisting of immune checkpoint inhibitors plus anti-VEGF therapy show enhanced antitumor activity and are approved treatments for patients with renal cell carcinoma (RCC). The immunosuppressive roles of VEGF in the tumor microenvironment are well studied, but those of FGF/FGFR signaling remain largely unknown. Lenvatinib is a receptor tyrosine kinase inhibitor that targets both VEGFR and FGFR. Here, we examine the antitumor activity of anti-PD-1 mAb combined with either lenvatinib or axitinib, a VEGFR-selective inhibitor, in RCC. Both combination treatments showed greater antitumor activity and longer survival in mouse models versus either single agent treatment, whereas anti-PD-1 mAb plus lenvatinib had enhanced antitumor activity compared with anti-PD-1 mAb plus axitinib. Flow cytometry analysis showed that lenvatinib decreased the population of tumor-associated macrophages and increased that of IFNγ-positive CD8+ T cells. Activation of FGFR signaling inhibited the IFNγ-stimulated JAK/STAT signaling pathway and decreased expression of its target genes, including B2M, CXCL10, and PD-L1. Furthermore, inhibition of FGFR signaling by lenvatinib restored the tumor response to IFNγ stimulation in mouse and human RCC cell lines. These preclinical results reveal novel roles of tumor FGFR signaling in the regulation of cancer immunity through inhibition of the IFNγ pathway, and the inhibitory activity of lenvatinib against FGFRs likely contributes to the enhanced antitumor activity of combination treatment comprising lenvatinib plus anti-PD-1 mAb. SIGNIFICANCE: FGFR pathway activation inhibits IFNγ signaling in tumor cells, and FGFR inhibition with lenvatinib enhances antitumor immunity and the activity of anti-PD-1 antibodies.

Recurrent fulminant non-rheumatic streptococcal myocarditis proven by endomyocardial biopsy and autopsy.

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.

Associations between hemodynamic parameters at rest and exercise capacity in patients with implantable left ventricular assist devices.

BACKGROUND: Hemodynamic parameters at rest are known to correlate poorly with peak oxygen uptake (VO2) in heart failure. However, we hypothesized that hemodynamic parameters at rest could predict exercise capacity in patients with left ventricular assist device (LVAD), because LVAD pump rotational speed does not respond during exercise. Therefore, we investigated the relationships between hemodynamic parameters at rest (measured with right heart catheterization) and exercise capacity (measured with cardiopulmonary exercise testing) in patients with implantable LVAD. METHODS: We performed a retrospective medical record review of patients who received implantable LVAD at our institution from November 2013 to December 2017. RESULTS: A total of 20 patients were enrolled in this study (15 males; mean age, 45.8 years; median duration of LVAD support, 356 days). The mean peak VO2 and cardiac index (CI) were 13.5 mL/kg/min and 2.6 L/min/m2, respectively. CI and hemoglobin level were significantly associated with peak VO2 (CI: r = 0.632, p = 0.003; hemoglobin: r = 0.520, p = 0.019). In addition, pulmonary capillary wedge pressure, right atrial pressure, and right ventricular stroke work index were also significantly associated with peak VO2. In multiple linear regression analysis, CI and hemoglobin level remained independent predictors of peak VO2 (CI: ß = 0.559, p = 0.006; hemoglobin: ß = 0.414, p = 0.049). CONCLUSIONS: CI at rest and hemoglobin level are associated with poor exercise capacity in patients with LVAD.

Prognostic impact of transcardiac gradient of follistatin-like 1 reflecting hemodynamics in patients with dilated cardiomyopathy.

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, <0 ng/mL; High FSTL1CS-Ao group, ≥0 ng/mL. Cardiac events were defined as a composite of cardiac deaths and hospitalizations for worsening heart failure. 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.

Impact of predictive value of Fibrosis-4 index in patients hospitalized for acute heart failure.

BACKGROUND: Abnormalities in liver function tests commonly occur in patients with acute heart failure (AHF). The Fibrosis-4 (FIB4) index, a non-invasive and easily calculated marker, has been used for hepatic diseases and reflects adverse prognosis. It is not clearly established whether the FIB4 index at admission can predict adverse outcomes in patients with AHF. METHODS AND RESULTS: From a multicenter AHF registry, we retrospectively evaluated 1162 consecutive patients admitted due to AHF (median age 78 [69-85] years and 702 patients [60.4%] were male). The FIB4 index at admission was calculated as: age (yrs) × aspartate aminotransferase [U/L]/(platelets count [103/µL] × âˆšalanine aminotransferase [U/L]. The median value of the FIB4 index at admission was 2.79. All-cause mortality and rehospitalization due to HF at 12 months were investigated as a composite endpoint and occurred in 142 (12.2%) patients and 232 (20%) patients, respectively. Kaplan-Meyer analysis shows a significant increase in the composite endpoint from the first to fourth quartile group of the FIB4 index values (log-rank, p < 0.001). Multivariate Cox regression model revealed the FIB4 index was an independent risk predictor for composite endpoint in patients with AHF (3 months: HR ratio 1.013 [95% Confidence interval (CI):1.001-1.025]; p = 0.03, 12 months: HR 1.015 [95% CI:1.005-1.025]; p = 0.003, respectively). However, neither aspartate aminotransferase, alanine aminotransferase, nor platelet count was found to be a significant predictor. CONCLUSIONS: Hepatic dysfunction evaluated with the FIB4 index at admission is a predictor of the composite endpoint of all-cause mortality and rehospitalization in AHF patients.

Predictors of residual mitral regurgitation after left ventricular assist device implantation.

Patients with advanced heart failure often have functional mitral regurgitation. Left ventricular assist device implantation improves functional mitral regurgitation through left ventricular unloading. However, residual mitral regurgitation after left ventricular assist device implantation leads to adverse outcomes, and whether patients need concomitant mitral valve surgery is not fully elucidated. Therefore, this study aimed to elucidate the predictors of residual mitral regurgitation and to describe the temporal changes in residual mitral regurgitation. We retrospectively enrolled 15 patients with implantable continuous-flow left ventricular assist device, who had significant mitral regurgitation on echocardiography before left ventricular assist device implantation. Three patients had residual mitral regurgitation (mitral regurgitation color jet area/left atrial area >0.2) 1 month after left ventricular assist device implantation. We investigated factors associated with residual mitral regurgitation and compared patients with or without residual mitral regurgitation. On univariate analysis, mitral valve tethering area and mitral regurgitation vena contracta before left ventricular assist device implantation were significantly associated with residual mitral regurgitation (odds ratio, 1.03; p = 0.036 and odds ratio, 10.45; p = 0.0087). One month after left ventricular assist device implantation, the mean pulmonary capillary wedge pressure and pulmonary artery pressure were higher in patients with residual mitral regurgitation (pulmonary capillary wedge pressure: 11.3 ± 3.5 vs 6.4 ± 3.4 mmHg, p = 0.029 and pulmonary artery pressure: 21.3 ± 4.0 vs 15.9 ± 3.3 mmHg, p = 0.023). However, the mitral regurgitation grading and hemodynamics were not significantly different 6 months after left ventricular assist device implantation. The hospitalization-free survival was not significantly different between the two groups. Mitral valve tethering area and mitral regurgitation vena contracta were predictors of residual mitral regurgitation. Residual mitral regurgitation improved until 6 months after left ventricular assist device implantation and might not affect the prognosis.

Association between splenic volume and pulsatility index in patients with left ventricular assist devices.

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 (ß = -0.452, p = 0.003), pump power (ß = -0.325, p = 0.023), and splenic volume (ß = 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.

A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation.

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. .