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Abstract Malnutrition is classified into marasmus and kwashiorkor in children. However, the clinical significance of these aspects is unclear in adult patients with heart failure (HF). We divided 2308 adult patients with HF into four groups according to marasmus type (body mass index

Abstract Background The relationship between liver fibrosis and left atrial (LA) remodeling in atrial fibrillation (AF) remains uncertain. We examined the associations between the fibrosis‐4 (FIB4) index, an indicator of liver fibrosis, and both LA low‐voltage areas (LVAs) on electroanatomic mapping and AF recurrence postablation. Methods We recruited 343 patients who underwent radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CBA) for AF. First, the association between the FIB4 index and LA LVAs (5 cm2) compared to those without. Additionally, the quantitative size of LVAs showed a positive correlation with the FIB4 index (R = .642, p

Abstract Aims We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure. Methods and results We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter‐quartile range) age 69.0 (59.0–78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut‐off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI

Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01–0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B‐type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow‐up period, cardiac events occurred in 87 patients. In the Kaplan–Meier analysis, cardiac event rate increased across increasing HVSI (log‐rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right‐sided HF and is associated with adverse prognosis in patients with HF.

Idiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I2) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I2 analogs can cause thyroid gland swelling and abnormal thyroid function. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she began complaining of neck swelling and was diagnosed with Graves’ disease. The patient’s thyroid function was controlled by thiamazole and levothyroxine; nevertheless, her thyroid gland enlargement worsened as the epoprostenol dose was titrated. After 20 years, she developed respiratory failure with a giant goiter leading to airway stenosis, and she passed away. The pathological autopsy confirmed a massive goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Abstract Although the prevalence of cognitive impairment and depression is higher in patients with atrial fibrillation (AF) than in the general population, the mechanism has not been fully examined and impact of catheter ablation (CA) of AF also remains unclear. Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex. We assessed brain activities by NIRS, depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D) and cognitive function by Mini-Mental State Examination (MMSE). We then compared the results between AF patients (paroxysmal AF n = 18 and persistent AF n = 14) and control subjects (n = 29). Next, we also followed up persistent AF patients who kept sinus rhythm at 3 months after CA (n = 8) and measured their brain activities using NIRS, CES-D and MMSE after CA to investigate the associations of changes in brain activities with changes in both CES-D and MMSE. Our results showed that (1) frontal and temporal brain activities were lower in patients with persistent AF than both in control subjects and paroxysmal AF patients (P

Background: Tartrate-resistant acid phosphatase type 5b (TRACP5b) is derived from osteoclasts, and has been used as a marker of osteoporosis (bone resorption). Although heart failure (HF) is associated with catabolic bone remodelling, serum TRACP5b levels have not been rigourously examined in patients with HF. Methods: We conducted a prospective observational study of 688 decompensated HF patients who had been discharged and whose TRACP5b had been measured. These patients were divided into tertiles on the basis of serum TRACP5b levels: first (TRACP5b < 316 mU/dL, n = 229), second (TRACP5b 316-489 mU/dL, n = 229), and third (TRACP5b ≥ 490 mU/dL, n = 230). We compared the patient baseline characteristics, exercise capacity, and their postdischarge prognosis, including cardiac mortality and cardiac events such as cardiac death and worsening HF. Results: Age was significantly higher, and prevalence of female sex and anemia was significantly higher in the third tertile than in the first and second tertiles (P < 0.05, respectively). Circulating TRACP5b levels were correlated with peak breath-by-breath oxygen consumption, but not with left ventricular ejection fraction. In the Kaplan-Meier analysis (mean follow-up, 426 days), cardiac mortality and cardiac event rates progressively increased from the first to the third tertiles (P < 0.05, respectively). In the multivariable Cox proportional hazard analysis, the third tertile was an independent predictor of cardiac mortality and cardiac events (cardiac mortality hazard ratio, 2.493; P = 0.040; cardiac events hazard ratio, 1.687; P = 0.030). Conclusions: High serum levels of TRACP5b, a marker of bone resorption, are associated with high cardiac mortality and cardiac events, accompanied by impaired exercise capacity. Résumé: Introduction: La TRACP5b (de l’anglais, tartrate-resistant acid phosphatase type 5b, soit l’isoforme 5 b de la phosphatase acide résistante au tartrate) qui est dérivée des ostéoclastes a été utilisée comme marqueur de l’ostéoporose (la résorption de l’os). Bien que l’insuffisance cardiaque (IC) soit associée au remodelage osseux catabolique, les concentrations sériques de TRACP5b n’ont pas été rigoureusement examinées chez les patients atteints d’IC. Méthodes: Nous avons mené une étude prospective observationnelle auprès de 688 patients atteints d’IC décompensée qui avaient obtenu leur sortie de l’hôpital et pour lesquels nous avions les mesures de TRACP5b. Nous avons réparti ces patients en tertiles en fonction des concentrations sériques de TRACP5b : le premier (TRACP5b < 316 mU/dL, n = 229), le deuxième (TRACP5b 316-489 mU/dL, n = 229) et le troisième (TRACP5b ≥ 490 mU/dL, n = 230). Nous avons comparé les caractéristiques initiales des patients, leur capacité à l’effort et leur pronostic après la sortie de l’hôpital, à savoir la mortalité d’origine cardiaque et les événements cardiaques tels que la mort cardiaque et l’aggravation de l’IC. Résultats: L’âge était significativement plus élevé, et la prévalence du sexe féminin et de l’anémie était significativement plus élevée dans le troisième tertile que dans les premier et deuxième tertiles (P < 0,05, respectivement). Les concentrations circulantes de TRACP5b corrélaient avec la consommation d’oxygène maximale « respiration par respiration », mais non avec la fraction d’éjection ventriculaire gauche. Dans l’analyse de Kaplan-Meier (durée moyenne de suivi, 426 jours), les taux de mortalité d’origine cardiaque et d’ événements cardiaques augmentaient progressivement du 1er tertile au 3e tertile (P < 0,05, respectivement). Dans l’analyse multivariable selon le modèle des risques proportionnels de Cox, le 3e tertile était un prédicteur indépendant de la mortalité d’origine cardiaque et des événements cardiaques (rapport de risque de mortalité d’origine cardiaque, 2,493; P = 0,040; rapport de risque d’événements cardiaques, 1,687; P = 0,030). Conclusions: Les concentrations sériques élevées de TRACP5b, un marqueur de la résorption de l’os, sont associées à la hausse des taux de mortalité d’origine cardiaque et d’ événements cardiaques, accompagnés de la diminution de la capacité à l’effort.

Background Although multiorgan networks are involved in the pathophysiology of heart failure (HF), interactions of the heart and the liver have not been fully understood. Hepatokines, which are synthesized and secreted from the liver, have regulatory functions in peripheral tissues. Here, we aimed to clarify the clinical impact of the hepatokine selenoprotein P in patients with HF. Methods and Results This is a prospective observational study that enrolled 296 participants consisting of 253 hospitalized patients with HF and 43 control subjects. First, we investigated selenoprotein P levels and found that its levels were significantly higher in patients with HF than in the controls. Next, patients with HF were categorized into 4 groups according to the presence of liver congestion using shear wave elastography and liver hypoperfusion by peak systolic velocity of the celiac artery, which were both assessed by abdominal ultrasonography. Selenoprotein P levels were significantly elevated in patients with HF with liver hypoperfusion compared with those without but were not different between the patients with and without liver congestion. Selenoprotein P levels were negatively correlated with peak systolic velocity of the celiac artery, whereas no correlations were observed between selenoprotein P levels and shear wave elastography of the liver. Kaplan‐Meier analysis demonstrated that patients with HF with higher selenoprotein P levels were significantly associated with increased adverse cardiac outcomes including cardiac deaths and worsening HF. Conclusions Liver‐derived selenoprotein P correlates with hepatic hypoperfusion and may be a novel target involved in cardiohepatic interactions as well as a useful biomarker for predicting prognosis in patients with HF.

Background: Hypochloremia reflects neuro-hormonal activation in patients with heart failure (HF). However, the prognostic impact of persistent hypochloremia in those patients remains unclear. Methods: We collected the data of patients who were hospitalized for HF at least twice between 2010 and 2021 (n = 348). Dialysis patients (n = 26) were excluded. The patients were divided into four groups based on the absence/presence of hypochloremia (p < 0.001) and cardiac death (hazard ratio 3.919, p < 0.001). Conclusions: In patients with HF, prolonged hypochloremia over two hospitalizations is associated with an adverse prognosis.

Abstract Background Both increases in red cell distribution width (RDW) levels and autonomic dysfunction are considered to be correlated with worsening heart failure. However, the relation of RDW levels to autonomic function remains uncertain. We aimed to investigate the association of RDW levels in heart failure with autonomic function, evaluated by heart rate variability (HRV) and heart rate turbulence (HRT), and prognosis. Methods We studied 222 hospitalized patients with stable heart failure before discharge, and Holter recordings (HRV and HRT) were performed. Additionally, RDW levels were measured, and high RDW was defined as over 14.5%. We then divided the patients into two groups based on RDW levels: high RDW group (>14.5%, n = 92) and low RDW group (≤14.5%, n = 130). The relation of RDW to autonomic function and prognosis was assessed. Results In the high RDW group, severely impaired HRV and HRT were found compared to the low RDW group. In the linear regression analysis after the adjustment of multiple confounders, RDW levels were correlated with a low‐frequency (LF) to high‐frequency (HF) ratio and very low‐frequency (VLF) power (LF to HF ratio, β = −0.146, P = .027, and VLF power, β = −0.137, P = .041, respectively). During the observation period (median 1400 days), cardiac events (re‐hospitalization of heart failure, cardiac death or sudden death) were found in 73 (32.8%) patients. The Kaplan‐Meier analysis demonstrated that the high RDW group had a higher rate of cardiac events compared to the low RDW group (45.6% vs 23.8%, log‐rank P

Abstract We aimed to clarify clinical implications of intrarenal hemodynamics assessed by intrarenal Doppler ultrasonography (IRD) and their prognostic impacts in heart failure (HF). We performed a prospective observational study, and examined IRD and measured interlobar renal artery velocity time integral (VTI) and intrarenal venous flow (IRVF) patterns (monophasic or non-monophasic pattern) to assess intrarenal hypoperfusion and congestion in HF patients (n = 341). Seven patients were excluded in VTI analysis due to unclear imaging. The patients were divided into groups based on (A) VTI: high VTI (VTI ≥ 14.0 cm, n = 231) or low VTI (VTI

Abstract Aims Recently, B‐type natriuretic peptide (BNP) has been attracting attention as a predictor of stroke in patients with atrial fibrillation or those with prior stroke experience. However, the association between BNP and stroke has not been examined in patients with chronic heart failure (CHF). In the current study, we assessed whether BNP is associated with future occurrence of stroke in patients with CHF. Methods and results We prospectively studied 1803 consecutive patients who were admitted for decompensated HF and assessed the predictive value of circulating BNP levels for occurrence of post‐discharge stroke. A total of 69 (3.8%) patients experienced a stroke (the stroke group) during the post‐discharge follow‐up period of a median of 1150 days. The stroke group showed a higher CHADS2 score. With respect to past medical history, the stroke group had a higher prevalence of arterial hypertension, atrial fibrillation, prior stroke, and chronic kidney disease. Echocardiographic parameters showed no significant differences between the two groups. In contrast, BNP levels were significantly higher in the stroke group than in the non‐stroke group (452.1 vs. 222.7 pg/mL, P

BackgroundIt has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension that can lead to right-sided heart failure (HF). However, the clinical significance of RVSI in HF patients has not been sufficiently examined. We aimed to examine the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF.MethodsWe performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). RVSI was calculated as follows: RVSI = (cardiac cycle time-venous flow time)/cardiac cycle time. The patients were classified to three groups based on RVSI: control group (RVSI = 0, n = 260, 67%), low RVSI group (0 < RVSI ≤ 0.21, n = 63, 16%) and high RVSI group (RVSI > 0.21, n = 65, 17%). We examined associations of RVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF.ResultsThere were significant correlations of RVSI with mean right atrial pressure (mRAP; R = 0.253, P < 0.001), right atrial area (R = 0.327, P < 0.001) and inferior vena cava diameter (R = 0.327, P < 0.001), but not with cardiac index (R = −0.019, P = 0.769). During the follow-up period (median 412 days), cardiac events occurred in 60 patients. In the Kaplan–Meier analysis, the cumulative cardiac event rate increased with increasing RVSI (log-rank, P = 0.001). In the multivariate Cox proportional hazard analysis, the cardiac event rate was independently associated with RVSI (high RVSI group vs. control group: hazard ratio, 1.908; 95% confidence interval, 1.046–3.479, P = 0.035).ConclusionRVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.

BackgroundD-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsConsecutive 169 patients planned for cardiotoxic chemotherapy were enrolled and followed up for 12 months. All patients underwent echocardiography and blood test at baseline and at 3-, 6-, and 12 months.ResultsThe patients were divided into two groups based on the level of D-dimer (>1.65 μg/ml or ≦ 1.65 μg/ml) at baseline before chemotherapy: high D-dimer group (n = 37) and low D-dimer group (n = 132). Left ventricular ejection fraction (LVEF) decreased at 3- and 6 months after chemotherapy in high D-dimer group [baseline, 65.2% (62.8–71.4%); 3 months, 62.9% (59.0–67.7%); 6 months, 63.1% (60.0–67.1%); 12 months, 63.3% (58.8–66.0%), p = 0.03], but no change was observed in low D-dimer group. The occurrence of CTRCD within the 12-month follow-up period was higher in the high D-dimer group than in the low D-dimer group (16.2 vs. 4.5%, p = 0.0146). Multivariable logistic regression analysis revealed that high D-dimer level at baseline was an independent predictor of the development of CTRCD [odds ratio 3.93, 95% CI (1.00–15.82), p = 0.047].ConclusionWe should pay more attention to elevated D-dimer levels not only as a sign of cancer-associated thrombosis but also the future occurrence of CTRCD.

Abstract Background The clinical significance of premature ventricular complexes (PVCs) in heart failure (HF) remains unclear. We aimed to clarify the associations of PVC burden with re‐hospitalization and cardiac death in HF patients. Methods We studied 435 HF patients (271 men, mean age 65 years). All patients were hospitalized for worsening HF. After optimal medications, echocardiography, 24 hours Holter monitoring and cardiopulmonary exercise testing were performed before discharge. The clinical characteristics and outcomes of the HF patients were investigated. Results During a median follow‐up period of 2.3 years, there were 125 (28.7%) cardiac events (re‐hospitalization due to worsening HF, fatal arrhythmias, or cardiac death). The patients with cardiac events had higher PVC burden compared to those without (median 0.374%/d [interquartile range 0.013‐1.510] vs median 0.026%/d [interquartile range 0.000‐0.534], P 0.145%/d) to be a predictive factor of cardiac events (area under the curve: 0.64). Kaplan‐Meier analysis demonstrated that cardiac events were more frequent in patients with high‐PVC burden (>0.145%/d, n = 194) compared to those with low‐PVC burden (≤0.145%/d, n = 241). Furthermore, the high‐PVC burden patients had left ventricular (LV) and atrial dilatation, reduced LV ejection fraction, and impaired exercise capacity, compared to the low‐PVC burden patients. In Cox proportional hazards analysis, high‐PVC burden was significantly associated with cardiac events with a hazard ratio of 2.028 (95% confidence interval: 1.418‐2.901, P

Background Blood‐based DNA methylation patterns are linked to types of diseases. FKBP prolyl isomerase 5 (FKBP5), a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte FKBP5 DNA methylation in patients with dilated cardiomyopathy (DCM) remain unclear. Methods and Results The present study enrolled patients with DCM (n=31) and age‐matched and sex‐matched control participants (n=43). We assessed FKBP5 CpG (cytosine‐phosphate‐guanine) methylation of CpG islands at the 5′ side as well as putative promoter regions by methylation‐specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood. FKBP5 CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in patients with DCM. Leukocyte FKBP5 and IL‐1β (interleukin 1β) mRNA expression levels were significantly higher in patients with DCM than in controls. The protein expressions of DNMT1 (DNA methyltransferase 1) and DNMT3A (DNA methyltransferase 3A) in leukocytes were significantly reduced in patients with DCM. In vitro methylation assay revealed that FKBP5 promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting that the decreased FKBP5 CpG methylation was functionally associated with elevation of FKBP5 mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5‐expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling. Conclusions Our findings demonstrate a link between specific CpG hypomethylation of leukocyte FKBP5 and DCM. Blood‐based epigenetic modification in FKBP5 may be a novel molecular mechanism that contributes to the pathogenesis of DCM.

Aims: We aimed to assess the associations of CAVI with exercise capacity in heart failure (HF) patients. In addition, we further examined their prognosis.Methods: We collected the clinical data of 223 patients who had been hospitalized for decompensated HF and had undergone both CAVI and cardiopulmonary exercise testing.Results: For the prediction of an impaired peak oxygen uptake (VO2) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. In the multivariate logistic regression analysis for predicting impaired peak VO2, high CAVI was found to be an independent factor (odds ratio 2.343, P = 0.045). We divided these patients based on CAVI: the low-CAVI group (CAVI < 8.9, n = 145) and the high-CAVI group (CAVI ≥ 8.9, n = 78). Patient characteristics and post-discharge cardiac events were compared between the two groups. The high-CAVI group was older (69.0 vs. 58.0 years old, P < 0.001) and had lower body mass index (23.0 vs. 24.1 kg/m2, P = 0.013). During the post-discharge follow-up period of median 1,623 days, 58 cardiac events occurred. The Kaplan–Meier analysis demonstrated that the cardiac event rate was higher in the high-CAVI group than in the low-CAVI group (log–rank P = 0.004). The multivariate Cox proportional hazard analysis revealed that high CAVI was an independent predictor of cardiac events (hazard ratio 1.845, P = 0.035).Conclusion: High CAVI is independently associated with impaired exercise capacity and a high cardiac event rate in HF patients.

Background: A biomarker of fibrin formation, the soluble fibrin monomer complex (SFMC), is abnormally elevated in a variety of clinical situations of hypercoagulability. The aim of the present study was to examine the prognostic impact of SFMC, with regard to increased risk of major cardio- and cerebrovascular events (MACCE) and all-cause mortality, on patients with heart failure (HF). Methods and Results: We conducted a prospective observational study where we analyzed data of 723 hospitalized patients with decompensated HF who were discharged alive and whose SFMC had been measured in a stable condition prior to discharge. The patients were divided into tertiles based on SFMC levels: the first (SFMC

Background: Red blood cell distribution width (RDW) is associated with prognosis in widespread cardiovascular fields, but little is known about relationship with the onset of cancer therapeutics-related cardiac dysfunction (CTRCD).Objectives: The purpose of this study was to assess whether RDW could predict the onset of CTRCD by anthracycline.Methods: Consequential 202 cancer patients planed for anthracycline treatment were enrolled and followed up for 12 months. The patients were divided into 2 groups based on the median value of baseline RDW before chemotherapy [low RDW group, n = 98, 13.0 [12.6–13.2]; high RDW group, n = 104, 14.9 [13.9–17.0]]. Cardiac function was assessed serially by echocardiography at baseline (before chemotherapy), as well as at 3, 6, and 12 months after chemotherapy with anthracycline.Results: Baseline left ventricular end systolic volume index and ejection fraction (EF) were similar between two groups. After chemotherapy, EF decreased at 3- and 6-month in the high RDW group [baseline, 64.5% [61.9–68.9%]; 3-month, 62.6% [60.4–66.9%]; 6-month, 63.9% [60.0–67.9%]; 12-month, 64.7% [60.8–67.0%], P = 0.04], but no change was observed in low RDW group. The occurrence of CTRCD was higher in high RDW group than in low RDW group (11.5 vs. 2.0%, P = 0.008). When we set the cut-off value of RDW at 13.8, sensitivity and specificity to predict CTRCD were 84.6 and 62.0%, respectively. Multivariable logistic regression analysis revealed that baseline RDW value was an independent predictor of the development of CTRCD [odds ratio 1.390, 95% CI [1.09–1.78], P = 0.008]. The value of net reclassification index (NRI) and integrated discrimination improvement (IDI) for detecting CTRCD reached statistical significance when baseline RDW value was added to the regression model including known risk factors such as cumulative anthracycline dose, EF, albumin, and the presence of hypertension; 0.9252 (95%CI 0.4103–1.4402, P < 0.001) for NRI and 0.1125 (95%CI 0.0078–0.2171, P = 0.035) for IDI.Conclusions: Baseline RDW is a novel parameter to predict anthracycline-induced CTRCD.

Background It has been reported that liver stiffness assessed by transient elastography are correlated with right atrial pressure, which is associated with worse outcome in patients with heart failure (HF). We aimed to clarify clinical implications of hepatic hemodynamic evaluation (liver congestion and hypoperfusion) by abdominal ultrasonography in patients with HF. Methods and Results We performed abdominal ultrasonography, right‐heart catheterization, and echocardiography, then followed up for cardiac events such as cardiac death or worsening HF in patients with HF. Regarding liver congestion, liver stiffness assessed by shear wave elastography (SWE) of the liver was significantly correlated with right atrial pressure determined by right‐heart catheterization (R=0.343; P

BackgroundIt has been reported that recovery of left ventricular ejection fraction (LVEF) is associated with better prognosis in heart failure (HF) patients with reduced EF (rEF). However, change of LVEF has not yet been investigated in cases of HF with preserved EF (HFpEF).Methods and resultsConsecutive 1082 HFpEF patients, who had been admitted to hospital due to decompensated HF (EF >50% at the first LVEF assessment at discharge), were enrolled, and LVEF was reassessed within 6 months in the outpatient setting (second LVEF assessment). Among the HFpEF patients, LVEF of 758 patients remained above 50% (pEF group), 138 patients had LVEF of 40%–49% (midrange EF, mrEF group) and 186 patients had LVEF of less than 40% (rEF group). In the multivariable logistic regression analysis, younger age and presence of higher levels of troponin I were predictors of rEF (worsened HFpEF). In the Kaplan-Meier analysis, the cardiac event rate of the groups progressively increased from pEF, mrEF to rEF (log-rank, p

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z‐drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P=0.010), had a higher prevalence of depression (17.4% versus 8.9%; P

Background The prevalence of depression and/or anxiety disorders is reported to be higher in patients with heart failure (HF) than in the general population, and patients with HF also have coexisting cognitive problems. Recently, the development of near‐infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex, with a high time resolution. The aim of the current study was to determine the associations between frontal brain activity and depressive symptoms, anxiety status, and cognitive function in patients with HF. Methods and Results We measured and compared frontal brain activity determined by NIRS during a verbal fluency task in patients with HF (n=35) and control subjects (n=28). The Center for Epidemiologic Studies Depression Scale for assessment of depressive symptoms, State‐Trait Anxiety Inventory for assessment of anxiety status, Mini‐Mental State Examination for assessment of cognitive function, and NIRS were simultaneously conducted. NIRS showed that frontal brain activity was significantly lower in the HF group than in the control subjects (28.5 versus 88.0 mM·mm; P

BackgroundThe prognostic impact of platelet distribution width (PDW), which is a specific marker of platelet activation, has been unclear in patients with heart failure (HF).Methods and resultsWe conducted a prospective observational study enrolling 1,746 hospitalized patients with HF. Patients were divided into tertiles based on levels of PDW: 1st (PDW < 15.9 fL, n = 586), 2nd (PDW 15.9-16.8 fL, n = 617), and 3rd (PDW ≥ 16.9, n = 543) tertiles. We compared baseline patients' characteristics and post-discharge prognosis: all-cause death; cardiac death; and cardiac events. The 3rd tertile showed the highest age and levels of B-type natriuretic peptide compared to other tertiles (1st, 2nd, and 3rd tertiles; age, 69.0, 68.0, and 70.0 years old, P = 0.038; B-type natriuretic peptide, 235.2, 171.9, and 241.0 pg/mL, P < 0.001). Left ventricular ejection fraction was equivalent among the tertiles. In the Kaplan-Meier analysis, rates of all endpoints were the highest in the 3rd tertile (log-rank P < 0.001, respectively). The Cox proportional hazard analysis revealed that the 3rd tertile was associated with adverse prognosis (all-cause death, hazard ratio [HR] 1.716, P < 0.001; cardiac death, HR 1.919, P < 0.001; cardiac event, HR 1.401, P = 0.002).ConclusionsHigh PDW is a novel predictor of adverse prognosis in patients with HF.

Background: Acetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. Methods: This study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. Results: We divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate

Abstract Background Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients. Methods Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality. Results In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P

Abstract Background Breath acetone is a noninvasive biomarker of heart failure; however, its significance in heart failure patients with diabetes mellitus has yet to be clarified. The objective of this study is to investigate whether exhaled acetone concentration is a noninvasive biomarker in heart failure patients with diabetes mellitus. Methods This study prospectively included 35 diabetic patients with stage C heart failure and 20 diabetic patients with or at risk of heart failure (stage A or B). Exhaled breath was collected after an overnight fast. Results The stage C group had significantly higher brain natriuretic peptide levels, larger left ventricular diameter, lower left ventricular ejection fraction, and more frequent use of β-blocker, compared with the stage A or B group. The stage C group had higher exhaled acetone concentrations than the stage A or B group (p = 0.013). Exhaled acetone concentration was correlated with total ketone bodies (r = 0.588, p

Abstract Background Effective treatments in heart failure (HF) patients with ischemic etiology have not been fully established. Nicorandil, combination of nitrate component and sarcolemmal adenosine triphosphate-sensitive potassium channel opener, is a potent vasodilator of coronary and peripheral vessels and has been used as an antianginal agent. Therefore, we examined impacts of nicorandil on cardiac mortality in ischemic HF patients. Methods Consecutive 334 HF patients with ischemic etiology were retrospectively registered and divided into 2 groups based on oral administration of nicorandil: nicorandil group (n = 116) and non-nicorandil group (n = 218). We retrospectively examined cardiac mortality. Results In the Kaplan-Meier analysis (mean follow-up period 963 days), cardiac mortality was significantly lower in the nicorandil group than in the non-nicorandil group (11.2% vs. 19.7%, P = 0.032). In the Cox proportional hazard analysis, usage of nicorandil was a suppressor of cardiac mortality (hazard ratio 0.512, 95% confidence interval 0.275–0.953, P = 0.035), and this result was consistent in several subgroup analyses, such as left ventricular ejection fraction, percutaneous coronary intervention, coronary artery bypass graft, diabetes, β-blockers, and statins. Conclusion Nicorandil is potentially effective for reducing mortality in patients with ischemic heart failure. Trial registration This was a retrospective study.

Background: It has been recently reported that liver stiffness assessed by transient elastography reflects right atrial pressure (RAP) and is associated with worse outcomes in patients with heart failure (HF). However, the relationship between shear wave dispersion (SWD, a novel indicator of liver viscosity) determined by abdominal ultrasonography and RAP, and the prognostic impact of SWD on HF patients have not been fully examined. We aimed to clarify the associations of SWD with parameters of liver function test (LFT) and right heart catheterization (RHC), as well as with cardiac events such as cardiac death and worsening HF, in patients with HF. Methods: We performed abdominal ultrasonography, LFT and RHC in HF patients (n = 195), and followed up for cardiac events. We examined associations between SWD and parameters of LFT and RHC. Results: There were significant correlations between SWD and circulating levels of direct bilirubin (R = 0.222, p = 0.002), alkaline phosphatase (R = 0.219, p = 0.002), cholinesterase (R = −0.184, p = 0.011), and 7S domain of collagen type IV (R = 0.177, p = 0.014), but not with RAP (R = 0.054, p = 0.567) or cardiac index (R = −0.015, p = 0.872). In the Kaplan–Meier analysis, cardiac event rate was significantly higher in the high SWD group (SWD ≥ 10.0 (m/s)/kHz, n = 103) than in the low SWD group (SWD < 10.0 (m/s)/kHz, n = 92; log-rank, p = 0.010). In the Cox proportional hazard analysis, high SWD was associated with high cardiac event rates (hazard ratio, 2.841; 95% confidence interval, 1.234–6.541, p = 0.014). In addition, there were no interactions between SWD and all subgroups, according to the subgroup analysis. Conclusions: SWD assessed by abdominal ultrasonography reflects liver fibrosis rather than liver congestion, and is associated with adverse prognosis in HF patients.

Background: The Glasgow-Blatchford Score (GBS) is one of the most widely used scoring systems for predicting clinical outcomes for gastrointestinal bleeding (GIB). However, the clinical significance of the GBS in predicting GIB in patients with heart failure (HF) remains unclear. Methods and Results: We conducted a prospective observational study in which we collected the clinical data of a total of 2236 patients (1130 men, median 70 years old) who were admitted to Fukushima Medical University Hospital for acute decompensated HF. During the post-discharge follow-up period of a median of 1235 days, seventy-eight (3.5%) patients experienced GIB. The GBS was calculated based on blood urea nitrogen, hemoglobin, systolic blood pressure, heart rate, and history of hepatic disease. The survival classification and regression tree analysis revealed that the accurate cut-off point of the GBS in predicting post-discharge GIB was six points. The patients were divided into two groups: the high GBS group (GBS > 6, n = 702, 31.4%) and the low GBS group (GBS ≤ 6, n = 1534, 68.6%). The Kaplan–Meier analysis showed that GIB rates were higher in the high GBS group than in the low GBS group. Multivariate Cox proportional hazards analysis adjusted for age, malignant tumor, and albumin indicated that a high GBS was an independent predictor of GIB (hazards ratio 2.258, 95% confidence interval 1.326–3.845, p = 0.003). Conclusions: A high GBS is an independent predictor and useful risk stratification score of post-discharge GIB in patients with HF.

Background The Get With the Guidelines–Heart Failure (GWTG‐HF) risk score was developed using American Heart Association GWTG‐HF program data and predicts in‐hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG‐HF risk score in patients with HF after discharge. Methods and Results We examined the GWTG‐HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG‐HF risk score (low, moderate, and high score groups). The plasma B‐type natriuretic peptide level significantly increased with increasing GWTG‐HF risk score severity (median values of B‐type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all‐cause deaths and 407 (28.0%) cardiac events in follow‐up periods. A Kaplan‐Meier survival curve demonstrated that event rates of all‐cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG‐HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction

BACKGROUND:Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease. METHODS:We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH. RESULTS:Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients. CONCLUSION:DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.

BackgroundIt has been recently reported that histamine H2 receptor antagonists (H2RAs) are associated with impairment of ventricular remodeling and incident heart failure. In addition, favorable pleiotropic effects and adverse effects of proton pump inhibitors (PPIs) on cardiovascular disease have also been reported. We examined the associations of acid suppressive therapy using H2RAs or PPIs with cardiac mortality in patients with heart failure. Methods and ResultsIn total, 1191 consecutive heart failure patients were divided into 3 groups: a non–acid suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group (n=664). In the follow‐up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan–Meier analysis, cardiac mortality was significantly lower in the PPI group than in the H2RA and non–acid suppressive therapy groups (11.0% versus 21.3% and 16.8%, respectively; log‐rank P=0.004). In the multivariable Cox proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P=0.002; H2RAs: hazard ratio 0.855, P=0.579). The propensity‐matched 1:1 cohort was assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality was significantly lower in the PPI group than in the H2RA group in the postmatched cohort (log‐rank P=0.025). In the Cox proportional hazards analysis, the use of PPIs was a predictor of cardiac mortality in the postmatched cohort (hazard ratio 0.528, P=0.028). ConclusionsPPIs may be associated with better outcome in patients with heart failure.

AIMS: Liver dysfunction due to heart failure (HF) is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. METHODS AND RESULTS: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is designated as an intractable disease by the Ministry of Health, Labour and Welfare of Japan, and has an extremely poor prognosis if untreated. Surgical pulmonary endarterectomy is the curative treatment for cases in which the organized thrombi are located in the central part of the pulmonary artery, but there had been no effective treatment for cases in which the thrombi are located in the peripheral part of the pulmonary artery. Recently, balloon pulmonary angioplasty (BPA), a transcatheter procedure to dilate stenotic or occluded lesions in the peripheral pulmonary artery, has been rapidly developed. Although BPA was once a globally abandoned procedure due to hemorrhagic complications, Japanese experts have improved the technique, and its safety and efficacy have been enhanced. As a result, BPA is now being reevaluated worldwide. This review describes the history and development of BPA in the treatment of CTEPH, as well as the status of this treatment in Fukushima Prefecture. [ABSTRACT FROM AUTHOR]