Prognostic impact and predictors of persistent renal dysfunction in acute kidney injury after percutaneous coronary intervention for acute myocardial infarction.

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75 years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.

Evaluation of the A2B Score for Prediction of Survival in Patients With Heart Failure in a Nationwide Cohort in Japan.

BACKGROUND: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A2B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort. METHODS AND RESULTS: We examined the 2-year mortality in relation to the A2B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A2B score was determined by assigning points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10-11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A2B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A2B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively). CONCLUSIONS: The A2B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

Derivation and validation of a clinical predictive model of NT-proBNP ≥125 pg/mL to detect pre-heart failure.

BACKGROUND: Several guidelines recommend the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to diagnose heart failure (HF); however, no screening criteria for measuring NT-proBNP in asymptomatic patients exist. We develop/validate a clinical prediction model for elevated NT-proBNP to support clinical outpatient decision-making. METHODS: In this multicenter cohort study, we used a derivation cohort (24 facilities) from 2017 to 2021 and a validation cohort at one facility from 2020 to 2021. Patients were aged ≥65 years with at least one risk factor of HF. The primary endpoint was NT-proBNP ≥125 pg/mL. The final model was selected using backward stepwise logistic regression analysis. Diagnostic performance was evaluated for sensitivity and specificity, the area under the curve (AUC), and calibration. In total, 1645 patients (derivation cohort, n = 837; validation cohort, n = 808) were included, of whom 378 (23.0 %) had NT-proBNP ≥125 pg/mL. Body mass index, age, systolic blood pressure, estimated glomerular filtration rate, cardiothoracic ratio, and heart disease were used as predictors and aggregated into a BASE-CH score of 0-11 points. RESULTS: Internal validation resulted in an AUC of 0.74 and an external validation AUC of 0.70. CONCLUSIONS: Based on available clinical and laboratory variables, we developed and validated a new risk score to predict NT-proBNP ≥125 pg/mL in patients at risk for HF or with pre-HF.

Overexpression of GRK2 in vascular smooth muscle leads to inappropriate hypertension and acute heart failure as in clinical scenario 1.

Clinical scenario 1 (CS1) is acute heart failure (HF) characterized by transient systolic blood pressure (SBP) elevation and pulmonary congestion. Although it is managed by vasodilators, the molecular mechanism remains unclear. The sympathetic nervous system plays a key role in HF, and desensitization of cardiac ß-adrenergic receptor (AR) signaling due to G protein-coupled receptor kinase 2 (GRK2) upregulation is known. However, vascular ß-AR signaling that regulates cardiac afterload remains unelucidated in HF. We hypothesized that upregulation of vascular GRK2 leads to pathological conditions similar to CS1. GRK2 was overexpressed in vascular smooth muscle (VSM) of normal adult male mice by peritoneally injected adeno-associated viral vectors driven by the myosin heavy chain 11 promoter. Upregulation of GRK2 in VSM of GRK2 overexpressing mice augmented the absolute increase in SBP (+ 22.5 ± 4.3 mmHg vs. + 36.0 ± 4.0 mmHg, P < 0.01) and lung wet weight (4.28 ± 0.05 mg/g vs. 4.76 ± 0.15 mg/g, P < 0.01) by epinephrine as compared to those in control mice. Additionally, the expression of brain natriuretic peptide mRNA was doubled in GRK2 overexpressing mice as compared to that in control mice (P < 0.05). These findings were similar to CS1. GRK2 overexpression in VSM may cause inappropriate hypertension and HF, as in CS1.

Heart failure with preserved ejection fraction phenogroup classification using machine learning.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. METHODS AND RESULTS: We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. CONCLUSIONS: ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).

Derivation and validation of a machine learning-based risk prediction model in patients with acute heart failure.

BACKGROUND: Risk stratification is important in patients with acute heart failure (AHF), and a simple risk score that accurately predicts mortality is needed. The aim of this study is to develop a user-friendly risk-prediction model using a machine-learning method. METHODS: A machine-learning-based risk model using least absolute shrinkage and selection operator (LASSO) regression was developed by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF), and its performance was externally validated in the validation cohort (NARA-HF) and compared with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry risk (ADHERE). RESULTS: In-hospital deaths in the derivation and validation cohorts were 76 (5.1 %) and 61 (4.9 %), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4 V-RS). Even though 4 V-RS comprised fewer variables, in the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; p = 0.059) and a significant improvement in net reclassification (0.359; 95 % CI, 0.10-0.67; p = 0.006). 4 V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p = 0.426) and net reclassification (0.176; 95 % CI, -0.08-0.43; p = 0.178). CONCLUSIONS: The 4 V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF.

New Classification for the Combined Assessment of the Fractional Excretion of Urea Nitrogen and Estimated Plasma Volume Status in Acute Heart Failure.

Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, P<0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; P<0.001]). Conclusions The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.

Trajectory of serum chloride levels during decongestive therapy in acute heart failure.

BACKGROUND: Hypochloremia is a risk factor for poor outcomes in patients with acute heart failure (AHF). However, the changes in serum chloride levels during decongestion therapy and their impact on prognosis remain unknown. METHODS: In total, 2798 patients with AHF were retrospectively studied and divided into four groups according to their admission and discharge serum chloride levels: (1) normochloremia (n=2,192, 78%); (2) treatment-associated hypochloremia, defined as admission normochloremia with a subsequent decrease (<98 mEq/L) during hospitalization (n=335, 12%); (3) resolved hypochloremia, defined as admission hypochloremia that disappeared at discharge (n=128, 5%); (4) persistent hypochloremia, defined as chloride <98 mEq/L at admission and discharge (n = 143, 5%). The primary outcome was all-cause death, and the secondary outcomes were cardiovascular death and a composite of cardiovascular death and rehospitalization for heart failure after discharge. RESULTS: The mean age was 76 ± 12 years and 1584 (57%) patients were men. The mean left ventricular ejection fraction was 46 ± 16%. During a median follow-up period of 365 days, persistent hypochloremia was associated with an increased risk of all-cause death (adjusted hazard ratio [95% confidence interval]: 2.27 [1.53-3.37], p < 0.001), cardiovascular death (2.38 [1.46-3.87], p < 0.001), and a composite of cardiovascular death and heart failure rehospitalization (1.47 [1.06-2.06], p = 0.022). However, the outcomes were comparable between patients with resolved hypochloremia and normochloremia. CONCLUSIONS: Persistent hypochloremia was associated with worse clinical outcomes, while resolved hypochloremia and normochloremia showed a comparable prognosis. Changes in serum chloride levels can help identify patients with poor prognoses and can be used to determine subsequent treatment strategies.

Prediction of optical coherence tomography-detected calcified nodules using coronary computed tomography angiography.

Diagnosis of calcified nodules (CNs) is critical in the proper management of coronary artery disease, but CNs can be detected only using intracoronary imaging modalities. This study aimed to investigate the ability of coronary computed tomography angiography (CCTA) in predicting CNs detected using optical coherence tomography (OCT). From 138 patients who underwent OCT-guided percutaneous coronary intervention (PCI) after CCTA evaluation, 141 PCI target vessels were retrospectively enrolled and classified into CN (12 vessels/11 patients; CNs in the PCI culprit lesion) and non-CN (129 vessels/127 patients; without CNs) groups based on the OCT analysis. Retrospective CCTA analysis revealed significantly higher coronary artery calcification score (CACS), calcified plaque volume (CPV), and maximum calcified plaque area (MCPA) of the target vessel in the CN group than in the non-CN group. Receiver operating characteristic curve indicated that CACS ≥ 162 (area under the ROC curve (AUC 0.76, sensitivity 83.3%, specificity 54.2%), CPV ≥ 20.1 mm3 (AUC 0.83, sensitivity 100%, specificity 57.3%), and MCPA ≥ 4.51 mm2 (AUC 0.87, sensitivity 91.7%, specificity 78.3%) were the best cutoff values for predicting CNs. MCPA showed the highest AUC among all the CCTA parameters. In conclusion, CCTA is useful for predicting OCT-detected CNs in PCI target vessels.

Association between class of foundational medication for heart failure and prognosis in heart failure with reduced/mildly reduced ejection fraction.

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45-0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF.

Transthyretin Amyloid Cardiomyopathy: Impact of Transthyretin Amyloid Deposition in Myocardium on Cardiac Morphology and Function.

BACKGROUND: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is increasingly being recognized as a cause of left ventricular (LV) hypertrophy (LVH) and progressive heart failure in elderly patients. However, little is known about the cardiac morphology of ATTR-CM and the association between the degree of TTR amyloid deposition and cardiac dysfunction in these patients. METHODS: We studied 28 consecutive patients with ATTR-CM and analyzed the relationship between echocardiographic parameters and pathological features using endomyocardial biopsy samples. RESULTS: The cardiac geometries of patients with ATTR-CM were mainly classified as concentric LVH (96.4%). The relative wall thickness, a marker of LVH, tended to be positively correlated with the degree of non-cardiomyocyte area. The extent of TTR deposition was positively correlated with enlargement of the non-cardiomyocyte area, and these were positively correlated with LV diastolic dysfunction. Additionally, the extent of the area containing TTR was positively correlated with the percentage of cardiomyocyte nuclei stained for 8-hydroxy-2'deoxyguanosine, a marker of reactive oxygen species (ROS). ROS accumulation in cardiomyocytes was positively correlated with LV systolic dysfunction. CONCLUSION: Patients with ATTR-CM mainly displayed concentric LVH geometry. TTR amyloid deposition was associated with cardiac dysfunction via increased non-cardiomyocyte area and ROS accumulation in cardiomyocytes.

New Conversion Formula Between B-Type Natriuretic Peptide and N-Terminal-Pro-B-Type Natriuretic Peptide　- Analysis From a Multicenter Study.

BACKGROUND: Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.Methods and Results: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (r2=0.900, P<0.0001). The correlation coefficients between the actual and converted values of log NT-proBNP in the internal and external validation sets were 0.942 (P<0.0001) and 0.891 (P<0.0001), respectively. We applied this formula to samples obtained from patients administered with sacubitril/valsartan. After treatment initiation, NT-proBNP levels decreased and actual BNP levels increased. However, the calculated BNP levels decreased roughly parallel to the NT-proBNP levels. CONCLUSIONS: This new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.

Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure.

AIMS: Acute heart failure (AHF) is a clinical syndrome with a poor prognosis and a major public health concern worldwide. The aim of this study was to investigate whether carperitide administration improves the 1 year prognosis of patients with AHF and to check whether there is an optimal dose of the drug. METHODS AND RESULTS: We analysed the data of COOPERATE-HF-J (the Consortium for Pooled Data Analysis regarding Hospitalized Patients with Heart Failure in Japan), combining two cohorts (NARA-HF and REALITY-AHF), which included 2435 patients with acute decompensated heart failure. The patients were divided into no carperitide (NO-ANP, n = 1098); very low-dose carperitide (VLD-ANP, <0.02 µg/kg/min, n = 593); and low-dose carperitide groups (LD-ANP, ≥0.02 µg/kg/min, n = 744). The primary endpoint was cardiovascular mortality within 1 year after admission. The secondary endpoints were all-cause mortality and rehospitalization due to worsening heart failure within 1 year after admission. The median carperitide doses in the VLD-ANP and LD-ANP groups were 0.013 and 0.025 µg/kg/min, respectively. Kaplan-Meier analysis showed that cardiovascular mortality and all-cause mortality were significantly lower in the LD-ANP group than in the NO-ANP and VLD-ANP groups (P < 0.001 and P = 0.002, respectively). Multivariable Cox regression analysis for cardiovascular and all-cause mortality revealed that LD-ANP was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission, even after adjusting other covariates (hazard ratio: 0.696 and 0.791, 95% confidence interval: 0.513-0.944 and 0.628-0.997, P = 0.020 and 0.047, respectively). CONCLUSIONS: Low-dose carperitide was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission. Our results suggest the necessity for well-designed randomized controlled trials to determine the doses of carperitide that could improve clinical outcomes in patients with AHF.

Usefulness of Incorporating Hypochloremia into the Get With The Guidelines-Heart Failure Risk Model in Patients With Acute Heart Failure.

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as <98 mmol/L. The external validation and comparison of model performance were performed in an independent group of 1,256 patients with AHF (validation cohort). All models were tested for in-hospital mortality. Hypochloremia was observed in 9.4% and 12.2% of the derivation and validation cohorts, respectively. Hypochloremia was an independent predictor of in-hospital mortality in the derivation cohort (odds ratio 2.02; p = 0.028). In the validation cohort, the GWTG-HF, GWTG-BNP, and GWTG-BNP-Cl risk scores demonstrated good discrimination (area under the curve: 0.742, 0.749, and 0.763, respectively). However, the GWTG-BNP-Cl risk score was more reliable than the GWTG-HF and GWTG-BNP risk scores in risk reclassification (net reclassification improvement: 0.491 and 0.408, respectively; p <0.01 for both). Moreover, this score demonstrated a good calibration of the GWTG-BNP-Cl model (Hosmer-Lemeshow test: p = 0.479). In conclusion, incorporating hypochloremia into the preexisting risk model improves the model performance.

Prevalence of mitral annular calcification and its association with mitral valvular disease.

BACKGROUND: Mitral annular calcification (MAC) is increasingly observed in elderly population. The purpose of this study was to investigate incidence of MAC and its association with mitral valvular disease (MVD). METHODS: A total of 13,483 consecutive patients who underwent echocardiography were enrolled. MAC was defined as an echo-dense, shelf-like structure with an irregular, lumpy appearance involving the mitral valve annulus, with acoustic shadowing. Prevalence of MAC and its association with significant mitral stenosis (MS) or mitral regurgitation (MR) were studied. Significant (≥moderate) MS was defined as mean transmitral valvular pressure gradient > 5 mm Hg and significant MR was defined as ≥moderate MR based on quantitative or semi-quantitative Doppler methods. RESULTS: MAC was present in 1881 of 13,483 patients (14%). Patients with MAC (MAC group) was older and more female gender than those without MAC (non-MAC group). Significant MS was present in 2.2% of MAC and in .6% of the non-MAC group (p < 0.0001). Significant MR was present in 11.9% of MAC and in 5.0% of the non-MAC group (p < 0.0001). Co-existence of MAC and aortic valve replacement (AVR) was associated with increased prevalence of MVD (MS:11.4%, MR:17.2%, respectively). CONCLUSION: MAC was present in 14% of the patients and was associated with significant MVD. Co-existence of MAC and AVR may increase the risk of MVD.

Prognostic Value of Fractional Excretion of Urea Nitrogen at Discharge in Acute Decompensated Heart Failure.

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.

Impact of Atrial Fibrillation on the Prognosis of Acute Decompensated Heart Failure With and Without Mitral Regurgitation.

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.

Involvement of chronic inflammation via monocyte chemoattractant protein-1 in uraemic cardiomyopathy: a human biopsy study.

AIMS: Patients undergoing dialysis, even those without coronary artery disease or valvular abnormalities, sometimes present with reduced heart function, which resembles dilated cardiomyopathy (DCM). This condition is known as uraemic cardiomyopathy (UCM). The mechanisms of UCM development are not fully understood. Previous studies demonstrated that the balance between placental growth factor (PlGF) and fms-like tyrosine kinase-1 (Flt-1) is correlated with renal function, and PlGF/Flt-1 signalling is involved in the development of cardiovascular diseases in patients with chronic kidney disease. This study was conducted to evaluate the pathogenesis of UCM and clarify the differences in the mechanisms of UCM and DCM by using human endomyocardial biopsy and blood samples. METHODS AND RESULTS: The clinical and pathological features of 30 patients on dialysis with reduced cardiac function [left ventricular ejection fraction (LVEF) ≤50%] (UCM group; mean age: 58.5 ± 9.4 years and LVEF: 39.1 ± 7.2%), 196 DCM patients (DCM group; mean age: 62.7 ± 14.0 years and LVEF: 33.5 ± 8.8%) as controls with reduced cardiac function (LVEF ≤ 45%), and 21 patients as controls with normal cardiac function (control group; mean age: 56.2 ± 19.3 years and LVEF: 67.5 ± 6.7%) were analysed. The percentage of the interstitial fibrosis area in the UCM group was greater than that in the DCM group (P = 0.045). In UCM patients, the percentage of the interstitial fibrosis area was positively correlated with the duration of renal replacement therapy (P < 0.001). The number of infiltrated CD68-positive macrophages in the myocardium and expression of monocyte chemoattractant protein-1 (MCP-1) in cardiomyocytes were significantly greater in the UCM group than in the other groups (P < 0.001, respectively). Furthermore, while the serum level of soluble form of Flt-1, an endogenous inhibitor of PlGF, in the UCM group was lower compared with that in the DCM group (P < 0.001), the serum levels of PlGF and PlGF/soluble form of Flt-1 ratio and plasma level of MCP-1 in the UCM group were higher than those in the DCM group (P < 0.001, respectively). CONCLUSIONS: These results suggest that activated PlGF/Flt-1 signalling and subsequent macrophage-mediated chronic non-infectious inflammation via MCP-1 in the myocardium are involved in the pathogenesis of UCM.