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Objectives The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-ph...

Patient reported outcomes (PROs) are gradually being incorporated into daily practice to assess individual health-related quality of life (QOL). However, despite accumulating evidence of the prognostic utility of heart failure (HF)-specific QOL indices, evidence on the generic QOL score is scarce, especially in patients with HF with preserved ejection fraction (HFpEF).Patient data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5-level (EQ-5D-5L) data were obtained at discharge to evaluate patients' health-related QOL. The study population (n = 864) was divided into tertiles based on their EQ-5D-5L index as follows: low EQ-5D-5L 0.038-0.664 (n = 287), middle EQ-5D-5L 0.665-0.867 (n = 293), and high EQ-5D-5L 0.871-1.000 (n = 284). A total of 206 patients died over a mean follow-up period of 2.0 ± 1.2 years. Kaplan-Meier analysis revealed that the risk of mortality increased with the tertile of the EQ-5D-5L index (34% vs. 23% vs. 14%, P 0.001). Cox multivariable analysis revealed that patients with EQ-5D-5L index in the low and middle tertiles had a significantly greater risk of mortality than those with EQ-5D-5L index in the high tertile [low EQ-5D-5L: adjusted hazard ratio (HR): 1.81 (1.12-2.92), P = 0.002, middle EQ-5D-5L: adjusted HR 1.91 (1.21-3.03), P = 0.006]. Among the dimensions of EQ-5D-5L, mobility (P = 0.014), self-care (P = 0.023) and usual activities (P = 0.008) were significant factors associated with all-cause mortality after multivariable adjustment.EQ-5D-5L is useful tool for risk stratification in patients with HFpEF.

Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.

Objective: We aim to clarify the differences in the association between re-admission for heart failure (HF) and left atrial (LA) overload indices by sex in heart failure and a preserved ejection fraction (HFpEF). Methods: We analyzed 898 HFpEF patients hospitalized for acute decompensated HF. Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re-admission for HF during the first year. Results: The ratio of diastolic elastance to arterial elastance (p = 0.014), a relative index of LA pressure overload, in men and LA volume index (LAVI, p = 0.020) in women were significant for re-admission for HF during the first year in the multivariable Fine–Gray analysis. Stroke volume (SV)/LA volume (LAV), another index for LAV overload, was not a significant prognostic factor of re-admission for HF during this time. Conclusion: LA overload was an important prognostic factor for HF re-readmission during the first year after enrolment in patients with HFpEF, but the indices relating to LA overload differed by sex.

We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown.From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization.Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P 0.001) and HF rehospitalization (P 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD.More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression.UMIN000021831.

Aims Cardiohepatic interactions have been a focus of attention in heart failure (HF). The model for end‐stage liver disease excluding international normalized ratio (MELD‐XI) score has been shown to be useful for predicting poor outcomes in patients with acute decompensated HF (ADHF). Furthermore, the fibrosis‐4 (FIB‐4) index, a simple marker to assess liver fibrosis, predicts adverse prognoses in patients with HF as well. However, there is little information available on the prognostic significance of the combination of the MELD‐XI score and FIB‐4 index in patients with ADHF and its association with left ventricular ejection fraction (LVEF) subgroup. Methods and results We prospectively studied 466 consecutive patients who were admitted for ADHF [HF with reduced LVEF (LVEF

Aims Co‐morbidities are associated with poor clinical outcomes in patients with chronic heart failure, while cardiac iodine‐123 (I‐123) metaiodobenzylguanidine (MIBG) imaging provides prognostic information in such patients. We sought to prospectively investigate the incremental prognostic value of cardiac MIBG imaging over the co‐morbid burden, in patients admitted for acute decompensated heart failure (ADHF). Methods and results In 433 consecutive ADHF patients with survival to discharge, we measured the co‐morbidity using age‐adjusted Charlson co‐morbidity index (ACCI), commonly employed to evaluate a weighted and scored co‐morbid condition, adding additional points for age. In cardiac MIBG imaging, the cardiac MIBG heart‐to‐mediastinum ratio (late HMR) was measured on the delayed image. Over a follow‐up period of 2.9 ± 1.5 years, 160 patients had a cardiac event (a composite of cardiac death and unplanned hospitalization for worsening heart failure). Patients with high ACCI (≥6: median value) had a significantly greater risk of a cardiac event. In multivariate Cox analysis, the ACCI and late HMR were significantly and independently associated with a cardiac event. In both high and low ACCI subgroups (ACCI ≥ 6 and

The stress variations during polarization of iron thin film electrode in pH 8.4 borate buffer solution have been measured by a cantilever bending method to investigate the correlation between stress evolution and electrochemical reaction of the iron electrode. The stress variations toward compressive direction during active dissolution of iron result from the relaxation of the residual tensile stress due to the decrease in thickness of the iron electrode. The stress variations toward tensile direction in the pre-passive region are brought by the anodic deposition of ferrous ions once dissolved into solution. The successive potential steps for each interval of 1 h in the passive region between 0.20 and 0.90 V induce the stress variations toward compressive direction at potentials more positive than 0.30 V in connection with the growth of the inner (barrier) layer in the passive film. The electrostriction stress in the inner layer of the passive film formed on iron at 0.90 V has been estimated from the stress relaxation in the cathodic potential sweep after 1-h passivation at 0.90 V. In addition, the stress variations toward compressive direction during cathodic reduction of the passive film are attributed to the volume expansion due to the formation of iron (II) hydroxide at the intermediate step of the cathodic reduction at pH 8.4. Furthermore, the rapid stress variations toward compressive direction during hydrogen evolution at potentials more negative than 0.52 V are caused by the volume expansion in near the surface region of the iron thin film electrode due to hydrogen adsorption or absorption.

Aims Cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging provides prognostic information in patients with chronic heart failure (HF). However, there is little information available on the prognostic role of cardiac 123I-MIBG imaging in patients admitted for acute decompensated heart failure (ADHF), especially relating to reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) < 40%], mid-range ejection fraction (HFmrEF; 40% ≤ LVEF < 50%) and preserved ejection fraction (HFpEF; LVEF ≥ 50%). Methods and results We studied 349 patients admitted for ADHF and discharged with survival. Cardiac 123I-MIBG imaging, echocardiography, and venous blood sampling were performed just before discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (late H/M) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The endpoint was cardiac events defined as unplanned HF hospitalization and cardiac death. During a follow-up period of 2.1 ± 1.4 years, 128 patients had cardiac events (45/127 in HFrEF, 28/78 in HFmrEF, and 55/144 in HFpEF). On multivariable Cox analysis, late H/M was significantly associated with cardiac events in overall cohort (P = 0.0038), and in subgroup analysis of each LVEF subgroup (P = 0.0235 in HFrEF, P = 0.0119 in HFmEF and P = 0.0311 in HFpEF). Kaplan–Meier analysis showed that patients with low late H/M (defined by median) had significantly greater risk of cardiac events in overall cohort (49% vs. 25% P < 0.0001) and in each LVEF subgroup (HFrEF: 48% vs. 23% P = 0.0061, HFmrEF: 51% vs. 21% P = 0.0068 and HFpEF: 50% vs. 26% P = 0.0026). Conclusion Cardiac sympathetic nerve dysfunction was associated with poor outcome in ADHF patients irrespective of HFrEF, HFmrEF, or HFpEF.

Background: The novel nutrition index; triglyceride (TG) х total cholesterol (TC) х body weight (BW) index (TCBI) has been reported to be an easy and useful predictor for patients with coronary artery disease. However, there is no information available on the prognostic role of TCBI in the patients admitted for acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods and Results: We studied 605 patients admitted for ADHF in our prospective cohort study (HFrEF[LVEF Conclusion: TCBI at the discharge, a simple and novel nutrition index, provides a prognostic value for the prediction of total mortality in ADHF patients with HFrEF and HFpEF, although the prognostic significance of TCBI in patients with HFpEF was weakened by adjustment for relevant covariates.

Backgrounds: It is widely recognized that thyroid dysfunction is a potential cause of heart failure (HF). In HF, one of the alterations of thyroid functions is referred to as low T 3 syndrome marked by a reduction in serum free triiodothyronine (T 3 ) with normal levels of thyroid-stimulating hormone (TSH). However, there is little information available about the association between low T 3 syndrome and future cardiac events in patients with acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods and Results: We studied 565 patients admitted for ADHF with survival discharge in our prospective cohort study. Laboratory data including free T 3 , thyroxine and TSH were obtained at discharge. Among the patients with euthyroid (0.35 μU/mL 3 syndrome (free T 3 ≦1.68 pg/mL). The primary end point of this study was all-cause death (ACD). During a mean follow up period of 2.9±1.4 years, 121 patients died. Study subjects were stratified into two LVEF subgroup as follows; 239 patients had LVEF3 group had the greater risk of ACD than those with the normal free T 3 group in both LVEF subgroup (log-rank p=0.0233 in HFrEF and p=0.0265 in HFpEF). Multivariate Cox analysis showed that free T 3 was significantly associated with ACD after multivariable adjustment for major confounders, such as age, sex, systolic blood pressure and plasma brain natriuretic peptide level in both LVEF subgroup (p=0.0039 in HFrEF, p=0.0487 in HFpEF). Conclusion: Low T 3 syndrome was significantly associated with poor outcome in ADHF patients with both HFrEF and HFpEF.

Backgrounds: Aortic pulsatility index (API), calculated as (systolic - diastolic blood pressure)/pulmonary capillary wedge pressure, is a novel hemodynamic measurement representing cardiac filling pressures, and contractility and has been shown to be associated with adverse clinical outcome in patients with advanced heart failure (HF). On the other hand, cardiohepatic interactions have been a focus of attention in HF, and liver dysfunction in HF patients is caused by liver congestion, which is related to liver stiffness. It has been recently reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4(FIB4) index predicts the poor outcome in HF patients. However, there is no information available on the prognostic value of the combination of API and FIB4 index in patients with acute decompensated heart failure (ADHF). Methods and Results: We studied 238 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. API was obtained at the admission. FIB4 index was calculated by the formula: age(yrs) х AST[U/L]/(platelets [10 9 /L] х (ALT[U/L]) 1/2 ). FIB4 index >2.67 was defined as abnormal, as previously reported. During a follow up period of 5.2±4.4 yrs, 58 patients had cardiovascular death (CVD). At multivariate Cox analysis, API and FIB4 index were significantly associated with CVD, independently of serum creatinine level and prior heart failure hospitalization, after the adjustment with hemoglobin and serum albumin levels. The patients with both lower API ≤1.905 (AUC 0.665[0.584-0.546]) and abnormal FIB4 index had a significantly increased risk of CVD than those with either lower API or abnormal FIB4 index and none of them (50% vs 23% vs 16%, p=0.0003, respectively). Conclusion: The combination of API and FIB4 index might be useful for stratifying ADHF patients at higher risk for CVD.

Backgrounds: Comorbidities are strongly associated with poor clinical outcome in heart failure patients (pts). AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes in acute decompensated heart failure (ADHF) pts. On the other hand, systemic inflammation plays a critical role in the outcomes of heart failure and malnutrition is also associated with poor outcome in heart failure pts. It has been recently reported that advanced lung cancer inflammation index (ALI), which is calculated as body mass index х serum albumin / neutrophil to lymphocyte ratio (NLR), is an independent prognostic marker in several types of cancer. We sought to investigate the prognostic value of the combination of AHEAD score and ALI in pts admitted for ADHF. Methods and Results: We studied 260 pts admitted for ADHF and discharged with survival. At the discharge, we evaluated AHEAD score (range 0-5, atrial fibrillation, hemoglobin 70 years, creatinine >130 μmol/L, and diabetes mellitus) and measured ALI. The study endpoint was cardiovascular-renal poor outcome (CVR), defined as cardiovascular death and the development of end-stage renal disease requiring renal replacement therapy. During a follow-up period of 5.1±4.2 years, 77 pts had CVR. At multivariate Cox analysis, AHEAD score and ALI were significantly associated with CVR, independently of prior heart failure hospitalization, systolic blood pressure and serum sodium level. Pts with both high AHEAD score (≥3 determined by ROC analysis: AUC 0.651[0.582-0.719]) and low ALI ( Conclusion: The combination of AHEAD score and ALI would be useful for stratifying patients at risk for cardiovascular-renal poor outcome in ADHF pts.

A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores.We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- ( 4%), intermediate- (4-12%), and high-risk ( 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated.There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores.The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF.UMIN000015246, 25 September 2014.

ObjectiveThe pathophysiological heterogeneity of heart failure with preserved ejection fraction (HFpEF) makes the conventional ‘one-size-fits-all’ treatment approach difficult. We aimed to develop a stratification methodology to identify distinct subphenotypes of acute HFpEF using the latent class analysis.MethodsWe established a prospective, multicentre registry of acute decompensated HFpEF. Primary candidates for latent class analysis were patient data on hospital admission (160 features). The patient subset was categorised based on enrolment period into a derivation cohort (2016–2018; n=623) and a validation cohort (2019–2020; n=472). After excluding features with significant missingness and high degree of correlation, 83 features were finally included in the analysis.ResultsThe analysis subclassified patients (derivation cohort) into 4 groups: group 1 (n=215, 34.5%), characterised by arrythmia triggering (especially atrial fibrillation) and a lower comorbidity burden; group 2 (n=77, 12.4%), with substantially elevated blood pressure and worse classical HFpEF echocardiographic features; group 3 (n=149, 23.9%), with the highest level of GGT and total bilirubin and frequent previous hospitalisation for HF and group 4 (n=182, 29.2%), with infection-triggered HF hospitalisation, high C reactive protein and worse nutritional status. The primary end point—a composite of all-cause death and HF readmission—significantly differed between the groups (log-rank pConclusionsThis study indicated the feasibility of clinical application of the latent class analysis in a highly heterogeneous cohort of patients with acute HFpEF. Patients can be divided into 4 phenotypes with distinct patient characteristics and clinical outcomes.Trial registration numberUMIN000021831.

Background: Congestion is one of the main predictors of poor outcome in patients with heart failure (HF); thus, a simple tool to evaluate plasma volume (PV), which can be used for risk stratification of HF patients, is necessary. We sought to compare the prognostic values of commonly used formulas for the estimation of PV and relative PV status (PVS) in patients admitted with acute decompensated HF (ADHF). Methods and Results: We analyzed 384 consecutive ADHF patients who survived to discharge. The PV was calculated by 3 commonly used formulas (Strauss, Kaplan, and Hakim), and the relative PVS was calculated using the Hakim formula at both admission and discharge. The primary endpoint was a composite of all-cause mortality and hospitalization for worsening HF. The secondary endpoints were pump failure death (PFD) and sudden cardiac death (SCD). During a median follow-up of 743 days, 175 patients reached the primary endpoint, 28 patients had PFD, and 20 patients had SCD. Multivariate Cox analysis revealed that among the PV indices, only the PVS values at admission and discharge were independent predictors of the primary endpoint. In addition, the PVS values at admission and discharge were independent predictors of PFD and SCD in the multivariate analysis. Conclusions: Among the indices of PV, the calculated PVS may be the most useful for predicting prognosis in ADHF patients.

BACKGROUND Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices. OBJECTIVE The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF). METHODS We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality. RESULTS During a mean ± SD follow-up period of 2.5 ± 1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P

In situ X-ray absorption spectroscopy (XAS) was applied to investigate the Sn adlayer on platinized (pl-) Pt electrode in deaerated 0.2 M HClO4 solution containing 10−3 M Sn2+ in relation to the effect of Sn addition on electrocatalysis of Pt. A periodical emersion method under potentiostatic polarization, using pl-Pt plate (roughness factor Sr = 770) as a working electrode was employed to detect sensitively the sub-monolayer coverage of Sn on Pt. The Sn K-edge absorption spectra in a scanning XAS mode were measured by monitoring the Sn Kα1 fluorescence line. The Sn K-edge absorption near-edge structure (XANES) has indicated that the Sn species adsorbed on the pl-Pt electrode is partly oxygenated in the Sn-underpotential (UPD) region between − 0.05 and 0.25 V (RHE) which is overlapped with the UPD region of hydrogen. The extended X-ray absorption fine structure (EXAFS) analysis has supported a Sn overlayer model in which Sn atom occupies the hollow site of the nearest neighbor Pt atoms and is further bound with oxygen atoms in the Sn-UPD region. The coordination number of the Sn–Pt bond or Sn–Sn bond decreases with increasing potential, while the coordination number of the Sn–O bond increases reversely. In the potential region between 0.45 and 0.85 V (RHE), the EXAFS analysis has suggested that two-dimensional surface Sn oxide forms on the pl-Pt electrode, which is supported from the potential-pH equilibrium diagram of the Sn/H2O system.

Background: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. Methods: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. Results: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group ( P =0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group ( P =0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization ( P =0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. Conclusions: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm ; Unique identifier: UMIN000026315.

Background: Diuretic resistance is associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). However, little information is available on the prognostic significance of diuretic resistance in ADHF patients, relating to reduced, mid-range, or preserved left ventricular ejection fraction (LVEF). Methods: We studied 400 consecutive patients who were admitted for ADHF and survived to discharge. Diuretic resistance (DR) was defined by furosemide dose per body weight (BW) at discharge. Patients were classified by DR, and high dose group (higher DR) was defined by furosemide dose of > median value of DR (0.580). The endpoint was a composite of all-cause mortality and unplanned hospitalization for worsening heart failure. Results: There were 139 patients with heart failure with reduced LVEF (HFrEF, LVEF Conclusions: In this study, higher DR was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF.

Introduction: Previous studies suggest that conventional right ventricular (RV) pacing may have a deleterious effect on left ventricular (LV) function. However, there are no reports examining the effects of permanent pacemakers (PM) in patients with heart failure with preserved ejection fraction (HFpEF) admitted with acute decompensated heart failure (ADHF). Methods and Results: Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka. Echocardiographic measurements were performed just before and 1 year after discharge. We analyzed 623 patients (median age: 81[30-101] years) after exclusion of patients on dialysis. At the admission, 55 of 623 patients had a previously implanted pacemaker (PM(+)). There were no significant differences in baseline clinical characteristics before discharge such as age, gender, renal function, echocardiographic parameters between PM(+) and PM(-) groups. One year after discharge, left ventricular ejection fraction (LVEF) in PM(+) group was significantly lower (58.3±8.6 vs 62.3±8.4%, p=0.005) than those in PM(-) group. During a mean follow-up period of 1.25±0.84years, 171patients had heart failure hospitalization (HFH). At the multivariate Cox analysis, pacemaker was significantly associated with HFH, independently of age, serum NT-proBNP level, and LVEF after the adjustment with NYHA functional class, sex, and hemoglobin. Kaplan-Meier curve analysis revealed that patients in PM(+) group had a significantly higher risk of HFH than those in PM(-) group. Conclusion: The development of cardiac systolic and diastolic dysfunction occurred in patients with HFpEF with a RV pacemaker implantation, which would be associated with poor outcome.

Backgrounds: Controlled heart rate (HR) and increased pulse pressure (PP) are related to better outcomes in stable heart failure. Hemodynamic response to stress evaluated by an acute hemodynamics index (AHI), the product of HR and PP, has been reported to be associated with poor outcomes in patients admitted for acute decompensated heart failure (ADHF). However, there is no information available on the long-term prognostic value of the serial change of AHI during hospitalization in patients admitted for ADHF. Methods and Results: We studied 259 patients admitted for ADHF and discharged with survival. We measured AHI (HR x PP/1000) at admission and discharge. AHI significantly decreased from admission to discharge (6.98±3.04 to 3.81±1.21 bpm·mmHg, p Conclusions: Cardiac death was frequently observed in ADHF patients who had less degree of the decrease in AHI during hospitalization. The change of AHI during hospitalization would be a simple and useful marker for risk stratification in patients admitted for ADHF.