Simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) Definition Predicts Bleeding Events in Patients With Heart Failure.

BACKGROUND: It has recently been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition, which excludes 6 rare criteria, is comparable to the original ARC-HBR definition in predicting major bleeding in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention. In this study, we investigated whether the simplified ARC-HBR definition could be applied to patients with heart failure (HF) to identify those at high bleeding risk (HBR).Methods and Results:In all, 2,437 patients hospitalized for HF were enrolled in this study. Patients were divided into 2 groups based on the simplified ARC-HBR definition: those at HBR (n=2,026; 83.1%) and those not (non-HBR group; n=411; 16.9%). The HBR group was older (72.0 vs. 61.0 years; P<0.001) and had a lower prevalence of CAD (31.1% vs. 36.5%; P=0.034) than the non-HBR group. Kaplan-Meier analysis showed that post-discharge bleeding events defined as hemorrhagic stroke or gastrointestinal bleeding were more frequent in the HBR than non-HBR group (log-rank P<0.001). The simplified ARC-HBR definition accurately predicted bleeding events (Fine-Gray model; hazard ratio 2.777, 95% confidence interval 1.464-5.270, P=0.001). CONCLUSIONS: The simplified ARC-HBR definition predicts a high risk of bleeding events in patients with HF.

Recovered Left Ventricular Ejection Fraction and Its Prognostic Impacts in Hospitalized Heart Failure Patients with Reduced Ejection Fraction.

It has been recently recognized that recovery of left ventricular ejection fraction (EF), termed "recovered EF", occurs in a proportion of heart failure patients with reduced EF (HFrEF), and is associated with better prognosis. However, the clinical characteristics of "recovered EF" have not been fully examined.Consecutive 567 patients hospitalized due to HFrEF (EF < 40% at 1st assessment at hospital discharge) were enrolled, and EF was re-assessed within half a year in an outpatient setting (2nd assessment). Among these HFrEF patients, 235 remained EF < 40% (reduced, rEF group), 82 changed to EF 40-49% (midrange, mrEF group), and 250 recovered to EF > 50% (preserved, pEF group "recovered EF" ) at the 2nd examination. Age was lower and body mass index and systolic blood pressure were higher in pEF than in rEF. The prevalence of atrial fibrillation (AF) and usage of an implantable cardiac defibrillator and cardiac resynchronization therapy were highest in pEF. Left ventricular end diastolic dimension (LVDd) was the smallest in the pEF group. Multivariable logistic regression analysis revealed that younger age, presence of AF, and lower levels of LVDd were predictors of "recovered EF". Kaplan-Meier analysis found that pEF presented the lowest cardiac event rate (P = 0.003) and all-cause mortality (P = 0.001). In multivariable Cox proportional hazard analyses, pEF (versus rEF) was an independent predictor of both cardiac event rate (HR = 0.668, 95%CI 0.450-0.994, P = 0.046) and all-cause mortality (HR = 0.655, 95%CI 0.459-0.934, P = 0.019).Hospitalized HFrEF patients with recovered EF are associated with younger age, higher presence of AF, and better prognosis.

Prior History and Incidence of Cancer Impacts on Cardiac Prognosis in Hospitalized Patients With Heart Failure.

BACKGROUND: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF.Methods and Results:Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030). CONCLUSIONS: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

Change of Exhaled Acetone Concentration in a Diabetic Patient with Acute Decompensated Heart Failure.

In heart failure patients, exhaled acetone concentration, a noninvasive biomarker, is increased according to heart failure severity. Moreover, exhaled acetone concentration is also known to be affected by diabetes mellitus. However, there have been no reports on exhaled acetone concentration in heart failure patients with diabetes mellitus. A 77-year old man was admitted to our hospital with acute decompensated heart failure and atrioventricular block. He had controlled diabetes mellitus under insulin treatment with hemoglobin A1c of 6.5%. He underwent treatment of diuretics and permanent pacemaker implantation. His condition improved and he was discharged at Day 12. Due to the heart failure improvement, his levels of exhaled acetone concentration decreased from 1.623 ppm at admission to 0.664 ppm at discharge. This is the first report to reveal a change of exhaled acetone concentration in a diabetic patient with acute decompensated heart failure.

Prognostic significance of spleen shear wave elastography and dispersion in patients with heart failure: the crucial role of cardio-splenic axis.

INTRODUCTION: The interaction between the heart and spleen plays a crucial role among cardiac and multiple organ networks, particularly in heart failure (HF). Ultrasound shear wave imaging is a non-invasive technology capable of quantifying tissue quality, but its significance in the spleen in patients with HF is poorly understood. METHODS AND RESULTS: This prospective observational study enrolled hospitalized 232 patients with HF undergoing abdominal ultrasonography. We used shear wave elastography (SWE) to assess spleen tissue elasticity and shear wave dispersion (SWD) to assess spleen tissue viscosity. Clinical, echocardiography, right heart catheterization, and outcome data were collected. Spleen SWE was negatively correlated with right ventricular fractional area change (R = - 0.180, P = 0.039), but not with right-sided pressure or congestion indices. When patients were divided into three groups based on tertile values of splenic parameters, Kaplan-Meier analysis demonstrated that patients with the highest spleen SWE and SWD had lower event-free survival rates from cardiac deaths and decompensated HF over a median 494-days follow-up period (P < 0.0001 and P < 0.0001, respectively). In a multivariable Cox proportional hazard model, both spleen SWE and SWD were independently associated with increased risks of adverse cardiac events (hazard ratio, 4.974 and 1.384; P = 0.003 and P < 0.0001). Mechanistically, we evaluated mRNA expressions of CD36, a monocyte/macrophage-associated molecule, in peripheral leukocytes, and found that enhanced spleen stiffness was associated with the upregulation of CD36 expressions. CONCLUSION: Share wave imaging of the spleen is useful for stratifying the prognosis of HF patients and may suggest a role of the cardio-splenic axis in HF pathogenies.

Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

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.

Impaired brain activity in patients with persistent atrial fibrillation assessed by near-infrared spectroscopy and its changes after catheter ablation.

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 < 0.01), (2) frontal and temporal brain activities were improved in more than half of the persistent AF patients who kept sinus rhythm at 3 months after CA, especially in those who presented impaired brain activity before CA, and (3) improvement of frontal brain activity was associated with improvement of CES-D (R = - 0.793, P = 0.019), whereas improvement of temporal brain activity was associated with improvement of MMSE (R = 0.749, P = 0.033). NIRS measurement showed reduced frontal and temporal brain activities in the persistent AF patients, CA improved frontal and temporal brain activities in some of these patients, and associated with improvement of depressive state and/or improvement of cognitive function.

Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure.

BACKGROUND: Interactions of the heart and the liver remain to be fully understood in the pathophysiology of heart failure (HF). Hepatokines are proteins synthesized and secreted from the liver and regulate systemic metabolisms of peripheral tissues. This study sought to clarify the clinical relevance of hepatokine Fetuin-A in patients with HF. METHODS AND RESULTS: We enrolled 217 participants including 187 hospitalized patients with HF and 30 control subjects who were sought with a comparable age- and sex profile and who had never had HF or structural cardiac abnormalities. First, we examined the levels of Fetuin-A and found that its levels were significantly lower in patients with HF than in the controls. Next, HF patients were categorized into four groups based on hepatic hemodynamics assessed by abdominal ultrasonography which determines liver hypoperfusion by peak systolic velocity (PSV) of the celiac artery and liver stiffness by shear wave elastography (SWE). Fetuin-A levels were significantly decreased in HF patients with liver hypoperfusion compared to those without, but were not different between HF patients with and without elevated liver stiffness. Correlation analysis revealed that circulating Fetuin-A was positively correlated with PSV of the celiac artery but not with SWE of the liver. Kaplan-Meier analysis demonstrated that HF patients with lower Fetuin-A levels were significantly associated with increased adverse outcomes including cardiac deaths and decompensated HF. CONCLUSIONS: Liver-derived hepatokine Fetuin-A may be a novel target involved in the cardio-hepatic interactions, as well as a useful biomarker for predicting the prognosis in patients with HF.

B-type natriuretic peptide is associated with the occurrence of bleeding events in heart failure patients with a history of coronary artery disease.

BACKGROUND: Bleeding risk in heart failure (HF) patients with coronary artery disease (CAD) has not yet been fully investigated. METHODS: We analyzed the data of 677 patients with a previous history of CAD who were hospitalized for HF. The patients were divided into three groups based on the tertiles of B-type natriuretic peptide (BNP) levels: Low, Middle, and High BNP groups (n = 225, 226, and 226, respectively). The primary endpoint was post-discharge bleeding events, which was defined as hemorrhagic stroke and gastrointestinal bleeding. RESULTS: The High BNP group was the oldest (Low, Middle, High, 67.0, 74.0, and 75.0 years, respectively; p < 0.001), showed the lowest left ventricular ejection fraction (56.0%, 50.7%, and 40.3%, respectively; p < 0.001), and contained more patients at high bleeding risk (HBR) defined by the simplified version of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition (65.3%, 85.4%, and 93.8%, respectively, p < 0.001). Kaplan-Meier analysis demonstrated that post-discharge bleeding events occurred most frequently in the High BNP group (log-rank p = 0.008). In the Cox proportional hazard analysis, compared to the Low BNP group as a reference, the High BNP group was independently associated with bleeding events after adjustment for age, sex, simplified ARC-HBR definition, and left ventricular ejection fraction (hazard ratio 3.208, 95% confidence interval 1.078-9.544, p = 0.036). CONCLUSIONS: High BNP is associated with bleeding events in HF patients with a history of CAD.

Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background: It 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. Methods: We 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. Results: There 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). Conclusion: RVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.

Increases in Hepatokine Selenoprotein P Levels Are Associated With Hepatic Hypoperfusion and Predict Adverse Prognosis in Patients With Heart Failure.

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.

Soluble fibrin monomer complex is associated with cardio- and cerebrovascular events in patients with heart failure.

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 < 1.7 µg/ml, n = 250), second (≤1.8 SFMC < 2.9 µg/ml, n = 233), and third (3.0 µg/ml ≤ SFMC, n = 240) tertiles. The prevalence of chronic kidney disease and anemia was significantly higher in the third tertile than in the first and second tertiles. In contrast, age, sex, CHADS2-Vasc score, left ventricular ejection fraction, and prevalence of hypertension, diabetes and atrial fibrillation did not differ among the tertiles. In the Kaplan-Meier analysis, accumulated event rates of both MACCE and all-cause mortality progressively increased from the first to third tertiles (log-rank P < 0.05, respectively). In the multivariate Cox proportional hazard analysis, the third tertile was found to be an independent predictor of MACCE (HR 2.014, P = 0.046) and all-cause mortality (HR 1.792, P = 0.036). CONCLUSION: SFMC is an independent predictor of adverse prognosis in patients with HF.

Cardio-Ankle Vascular Index Reflects Impaired Exercise Capacity and Predicts Adverse Prognosis in Patients With Heart Failure.

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.

Serum TRACP5b, a Marker of Bone Resorption, Is Associated With Adverse Cardiac Prognosis in Hospitalized Patients With Heart Failure.

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.

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 ¼, 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.

Cardio-Ankle Vascular Index Predicts Post-Discharge Stroke in Patients with Heart Failure.

AIM: We aimed to evaluate the significance of the cardio-ankle vascular index (CAVI) to predict stroke in patients with heart failure (HF). METHODS: This was a prospective observational study, which recruited clinical data from a total of 557 patients who had been hospitalized for HF and undergone CAVI. According to the receiver operating characteristic curve analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.64. We divided the patients into two groups: the high-CAVI group (HF patients with CAVI ≥ 9.64, n=111, 19.9%) and the low-CAVI group (HF patients with CAVI ＜9.64, n=446, 80.1%). We compared the patients' characteristics and post-discharge prognosis. The primary endpoint was stroke. RESULTS: The high-CAVI group was older (73.0 vs. 65.5 years old, P＜0.001). Male sex (73.9% vs. 61.4%, P=0.015), coronary artery disease (47.7% vs. 36.1%, P=0.024), and diabetes mellitus (54.1% vs. 37.4%, P=0.001) were more prevalent in the high-CAVI group. In contrast, there was no difference in left ventricular ejection fraction, and prevalence of hypertension and dyslipidemia. The Kaplan-Meier analysis demonstrated that post-discharge stroke rate was higher in the high-CAVI group than in the low-CAVI group (log-rank P=0.005). In multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of stroke, with an adjusted hazard ratio of 3.599, compared to low CAVI. CONCLUSION: CAVI independently predicts stroke in patients with HF.

Liver Congestion Assessed by Hepatic Vein Waveforms in Patients With Heart Failure.

BACKGROUND: It has been reported that the pattern of hepatic vein (HV) waveforms determined by abdominal ultrasonography is useful for the diagnosis of hepatic fibrosis in patients with chronic liver disease. We aim to clarify the clinical implications of HV waveform patterns in patients with heart failure (HF). METHODS: We measured HV waveforms in 350 HF patients, who were then classified into 3 categories based on their waveforms: those with a continuous pattern (C group); those whose V wave ran under the baseline (U group), and those with a reversed V wave (R group). We performed right-heart catheterization, and examined the rate of postdischarge cardiac events, such as cardiac death and rehospitalization due to worsening HF. RESULTS: The number of patients in each of the 3 HV waveform groups was as follows: C group, n = 158; U group, n = 152, and R group, n = 40. The levels of B-type natriuretic peptide (R vs C and U; 245.8 vs 111.7 and 216.6 pg/mL; P < 0.01) and mean right atrial pressure (10.5 vs 6.7 and 7.2 mm Hg; P < 0.01) were highest in the R group compared with the other groups. The Kaplan-Meier analysis found that cardiac event-free rates were lowest in the R group among all groups (log-rank P < 0.001). In the multivariable Cox proportional hazard analysis, the R group was found to be an independent predictor of cardiac events (hazard ratio, 4.90; 95% confidence interval, 2.23-10.74; P < 0.01). CONCLUSION: Among HF patients, those with reversed V waves had higher right atrial pressure and were at higher risk of adverse prognosis.

INTRODUCTION: Nous avons appris que le tracé ondulatoire de la veine hépatique (VH) à l'échographie abdominale est utile au diagnostic de la fibrose hépatique chez les patients atteints d'une maladie chronique du foie. Nous avons pour objectif de clarifier les implications cliniques des tracés ondulatoires de la VH chez les patients atteints d'insuffisance cardiaque (IC). MÉTHODES: Nous avons mesuré les ondulations de la VH de 350 patients atteints d'IC et les avons ensuite classifiés en trois catégories selon leurs ondulations : ceux qui avaient un tracé continu (groupe C); ceux dont l'onde V se présentait selon les valeurs de référence (groupe U); ceux qui avaient une onde V inversée (groupe R). Nous avons réalisé un cathétérisme cardiaque droit et examiné le taux d'événements cardiaques après la sortie de l'hôpital tels que la mort d'origine cardiaque et la réhospitalisation en raison de l'aggravation de l'IC. RÉSULTATS: Le nombre de patients dans chacun des trois groupes d'ondulations de la VH était réparti comme suit : groupe C, n = 158; groupe U, n = 152 et groupe R, n = 40. Les concentrations en peptides natriurétiques de type B (R vs C et U; 245,8 vs 111,7 et 216,6 pg/ml; P < 0,01) et la pression moyenne de l'oreillette droite (10,5 vs 6,7 et 7,2 mmHg; P < 0.01) étaient plus élevées dans le groupe R que dans les autres groupes. La méthode de Kaplan-Meier a montré que les taux sans événement cardiaque étaient plus faibles dans le groupe R que dans les autres groupes (P du test logarithmique par rangs < 0,001). À l'analyse multivariée selon le modèle à risques proportionnels de Cox, nous avons observé que le groupe R était un prédicteur indépendant des événements cardiaques (rapport de risque, 4,90; intervalle de confiance à 95 %, 2,23-10,74; P < 0,01). CONCLUSION: Chez les patients atteints d'IC, ceux qui avaient des ondes V inversées avaient une pression plus élevée de l'oreillette droite et étaient exposés à un risque plus élevé de pronostic défavorable.

Impaired Frontal Brain Activity in Patients With Heart Failure Assessed by Near-Infrared Spectroscopy.

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<0.001). Next, we examined the associations between frontal brain activity and the findings of Center for Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory, Mini-Mental State Examination, and verbal fluency task. There were significant correlations between frontal brain activity and State-Trait Anxiety Inventory (R=-0.228, P=0.046), Mini-Mental State Examination (R=0.414, P=0.017), and verbal fluency task (R=0.338, P=0.007), but not with Center for Epidemiologic Studies Depression Scale (R=-0.160, P=0.233). Conclusions Frontal brain activity assessed by NIRS is reduced and is associated with high anxiety status and low cognitive function in patients with HF.

Clinical Implications of Hepatic Hemodynamic Evaluation by Abdominal Ultrasonographic Imaging in Patients With Heart Failure.

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<0.01), right atrial end-systolic area, and inferior vena cava diameter determined by echocardiography. Regarding liver hypoperfusion, peak systolic velocity (PSV) of the celiac artery was correlated with cardiac index determined by right-heart catheterization (R=0.291; P<0.001) and tricuspid annular plane systolic excursion determined by echocardiography. According to the Kaplan-Meier analysis, HF patients with high SWE and low PSV had the highest cardiac event rate (log-rank P=0.033). In the Cox proportional hazard analysis, high SWE and low PSV were associated with high cardiac event rate (high SWE: hazard ratio [HR], 2.039; 95% CI, 1.131-4.290; low PSV: HR, 2.211; 95% CI, 1.199-4.449), and the combination of high SWE and low PSV was a predictor of cardiac events (HR, 4.811; 95% CI, 1.562-14.818). Conclusions Intrahepatic congestion and hypoperfusion determined by abdominal ultrasonography (liver SWE and celiac PSV) are associated with adverse prognosis in patients with HF.

Intrarenal Doppler ultrasonography reflects hemodynamics and predicts prognosis in patients with heart failure.

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 < 14.0 cm, n = 103); and (B) IRVF patterns: monophasic (n = 36) or non-monophasic (n = 305). We compared post-discharge cardiac event rate between the groups, and right-heart catheterization was performed in 166 patients. Cardiac index was lower in low VTI than in high VTI (P = 0.04), and right atrial pressure was higher in monophasic than in non-monophasic (P = 0.03). In the Kaplan-Meier analysis, cardiac event rate was higher in low VTI and monophasic groups (P < 0.01, respectively). In the Cox proportional hazard analysis, the combination of low VTI and a monophasic IRVF pattern was a predictor of cardiac events (P < 0.01). IRD imaging might be associated with cardiac output and right atrial pressure, and prognosis.

Shear Wave Dispersion Predicts Liver Fibrosis and Adverse Outcomes in Patients with Heart Failure.

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.