Elevated blood bicarbonate levels and long-term adverse outcomes in patients with chronic heart failure.

AIMS: The bicarbonate (HCO3 -) buffer system is crucial for maintaining acid-base homeostasis and blood pH. Recent studies showed that elevated serum HCO3 - levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3 - in chronic heart failure (CHF). METHODS: This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6 ± 14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3 - levels and followed them to register cardiac events. RESULTS: Among the patients, 17.3% (120 patients) had HCO3 - levels exceeding 26 mmol/L. Patients presenting HCO3 - > 26 mmol/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3 - between 22 and 26 (379 patients) or those with HCO3 - < 22 mmol/L (195 patients). During a median follow-up period of 1950 days, Kaplan-Meier analysis revealed that patients with HCO3 - > 26 mmol/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P < 0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3 - > 26 mmol/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P < 0.01 and 0.02, respectively), while HCO3 - < 22 mmol/L was not associated with these events (hazard ratios, 0.99 and 1.19; P = 0.98 and 0.43, respectively). CONCLUSIONS: Elevated blood HCO3 - levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

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.

Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and 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.

Acute myocardial infarction caused by Kawasaki disease requires more intensive therapy: Insights from the Japanese registry of All Cardiac and Vascular Diseases-Diagnosis Procedure combination.

BACKGROUND: Kawasaki disease (KD) induces coronary arteritis, which causes subsequent coronary aneurysms, and contributes to acute myocardial infarction (AMI). However, the differences regarding real-world treatment selection and mortality between AMI-complicated KD and AMI due to typical atherosclerosis (AMI-non KD) are unknown. AIM: The aim of the present study was to examine the current treatment strategy and prognosis of AMI-complicated KD compared with AMI due to typical atherosclerosis. METHOD: We used data from 2012 to 2019 from a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination. RESULTS: Compared to the AMI-non KD patients (n = 70,227), the AMI-complicated KD patients (n = 73): (1) underwent percutaneous coronary intervention (PCI) less often and more coronary artery bypass grafting, intracoronary thrombolysis or intravenous coronary thrombolysis more often; (2) underwent stentless PCI using old balloon angioplasty or rotablator, when they underwent PCI; and (3) needed in-hospital cardiopulmonary resuscitation and intensive mechanical therapy such as intra-aortic balloon pump, percutaneous cardiopulmonary support or a respirator. Both the AMI-non KD and AMI-complicated KD patients had similar in-hospital mortality rates. CONCLUSIONS: Compared with AMI-non KD patients, AMI-complicated KD patients underwent non-PCI strategies such as bypass surgery or thrombolysis, and required intensive therapy with mechanical supports more often, but presented similar in-hospital mortality. When the AMI-complicated KD patients underwent PCI, stentless PCI using balloon angioplasty or rotablator was performed more often compared with the AMI-non KD patients.

Clinical usefulness of the pattern of non-adherence to anti-platelet regimen in stented patients (PARIS) thrombotic risk score to predict long-term all-cause mortality and heart failure hospitalization after percutaneous coronary intervention.

BACKGROUND: The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) thrombotic risk score has been proposed to estimate the risk of stent thrombotic events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS thrombotic risk score for long term all-cause and cardiac mortalities, as well as hospitalization due to heart failure, has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS thrombotic risk score for all-cause and cardiac mortalities and hospitalization due to heart failure following PCI. METHODS AND RESULTS: Consecutive 1,061 patients who underwent PCI were divided into three groups based on PARIS thrombotic risk score; low- (n = 320), intermediate- (n = 469) and high-risk (n = 272) groups. We followed up on all three groups for all-cause mortality, cardiac mortality and hospitalization due to heart failure. Kaplan-Meier analysis showed that all outcomes were highest in the high-risk group (P < 0.001, P = 0.022 and P < 0.001, respectively). Multivariate Cox proportional hazard analysis, adjusted for confounding factors, showed that the risk of all-cause mortality and hospitalization due to heart failure of the high-risk group were higher than those of the low-risk group (hazard ratios 1.76 and 2.14, P = 0.005 and P = 0.017, respectively). CONCLUSION: The PARIS thrombotic risk score is a significant prognostic indicator for all-cause mortality and hospitalization due to heart failure in patients after PCI.

Prognostic Effects of Changes in Right Ventricular Fractional Area Change in Patients With Heart Failure.

BACKGROUND: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC).Methods and Results: This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25-35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality. CONCLUSIONS: Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure 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.

Temporal Trends in the Practice Pattern for Sleep-Disordered Breathing in Patients With Cardiovascular Diseases in Japan　- Insights From the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination.

BACKGROUND: After the publication of the Japanese Circulation Society guideline of sleep-disordered breathing (SDB) in 2010, with new evidence and changes to the health insurance system, trends in the practice pattern for SDB in patients with cardiovascular disease (CVD) might have changed.Methods and Results: This study evaluated the temporal changes in the practice pattern for SDB by using a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination (JROAD-DPC), from 2012 to 2019. The main findings were: (1) the number of CVD patients diagnosed with SDB increased (especially those with atrial fibrillation [AF] and heart failure [HF]); (2) the number of diagnostic tests for SDB performed during hospitalization increased for AF patients (from 1.3% in 2012 to 1.8% in 2019), whereas it decreased for other CVD patients; (3) the number of patients diagnosed with SDB increased in each type of CVD, except for patients with acute myocardial infarction (AMI); (4) continuous positive airway pressure (CPAP) treatment increased for AF patients (from 15.2% to 17.5%); (5) CPAP treatment decreased for patients with angina pectoris (AP) and AMI, and any treatment decreased for HF patients (from 46.1% to 39.7%); and (6) SDB was treated more often in HF patients than in AF, AP, and AMI patients (41.7% vs. 17.2%, 19.1% and 20.4%, respectively). CONCLUSIONS: The practice pattern for SDB in CVD patients has changed from 2012 to 2019.

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.

Prognostic Value of the Pattern of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) Bleeding Risk Score for Long-Term Mortality After Percutaneous Coronary Intervention.

The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score has been proposed to predict the risk of bleeding events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS bleeding risk score for long term all-cause mortality, cardiac mortality and hospitalization due to heart failure has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS bleeding risk score for all-cause and cardiac mortalities and hospitalization due to heart failure after PCI. Consecutive 1061 patients who had undergone PCI were divided into 3 groups based on the PARIS bleeding risk score; low (n = 112), intermediate (n = 419) and high-risk groups (n = 530). We prospectively followed up the 3 groups for all-cause and cardiac mortalities and hospitalization due to heart failure. Kaplan-Meier analysis revealed that all of the outcomes were highest in the high-risk group among the 3 groups (P < 0.001, P < 0.001 and P < 0.001 respectively). Multivariable Cox proportional hazard analysis, adjusted for confounding factors, revealed that all-cause mortality of the intermediate or high-risk groups was higher than those of the low-risk group (adjusted hazard ratio 6.06 and 12.50, P = 0.013 and P < 0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.

Calciprotein Particles Induce IL-1ß/α-Mediated Inflammation through NLRP3 Inflammasome-Dependent and -Independent Mechanisms.

Calciprotein particles (CPPs) are nanoparticles composed of calcium phosphate crystals and fetuin-A and have been implicated in diseases associated with inflammation. In the current study, we investigated the molecular mechanisms underlying CPP-induced inflammation in mice. CPPs predominantly upregulated IL-1ß and IL-1α and provided priming and activation signals for the NLRP3 inflammasome in murine macrophages. Pharmacological and genetic inhibition of the NLRP3 inflammasome revealed that CPPs induced the release of IL-1ß and IL-1α via NLRP3 inflammasome-dependent and -independent mechanisms, respectively. CPPs also induced necrotic cell death, but gasdermin D was dispensable for CPP-induced IL-1ß release and necrotic cell death. Although phagocytosis of CPPs was required for CPP-induced IL-1ß/α release and necrotic cell death, lysosomal dysfunction and K+ efflux were mainly involved in CPP-induced NLRP3 inflammasome activation and subsequent IL-1ß release but not in CPP-induced IL-1α release and necrotic cell death. In vivo experiments showed that CPP administration evoked acute inflammatory responses characterized by neutrophil accumulation via both IL-1ß and IL-1α. In particular, CPP-induced neutrophil inflammation was mediated predominantly through an IL-1α-induced CXCL1/CXCR2 signaling pathway. These results provide new insights into the mechanism underlying CPP-induced inflammation and suggest that targeting both IL-1ß and IL-1α is necessary to regulate the CPP-induced inflammatory response and to treat CPP-associated inflammatory disorders.

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.

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.

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.

Crucial role of NLRP3 inflammasome in a murine model of Kawasaki disease.

Kawasaki disease (KD) is a systemic febrile syndrome during childhood that is characterized by coronary arteritis. The etiopathogenesis of KD remains to be elucidated. NLRP3 inflammasome is a large multiprotein complex that plays a key role in IL-1ß-driven sterile inflammatory diseases. In the present study, we investigated the role of NLRP3 inflammasome in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS) and found that NLRP3 inflammasome is required for the development of CAWS-induced vasculitis. CAWS administration induced IL-1ß production, caspase-1 activation, leukocyte infiltration, and fibrotic changes in the aortic root and coronary arteries, which were significantly inhibited by a deficiency of IL-1ß, NLRP3, and ASC. In vitro experiments showed that among cardiac resident cells, macrophages, but not endothelial cells or fibroblasts, expressed Dectin-2, but did not produce IL-1ß in response to CAWS. In contrast, CAWS induced caspase-1 activation and IL-1ß production in bone marrow-derived dendritic cells (BMDCs), which were inhibited by a specific caspase-1 inhibitor and a deficiency of NLRP3, ASC, and caspase-1. CAWS induced NLRP3 and pro-IL-1ß expression through a Dectin-2/Syk/JNK/NF-κB pathway, and caspase-1 activation and cleavage of pro-IL-1ß through Dectin-2/Syk/JNK-mediated mitochondrial ROS generation, indicating that CAWS induces the priming and activation of NLRP3 inflammasome in BMDCs. These findings provide new insights into the pathogenesis of KD vasculitis, and suggest that NLRP3 inflammasome may be a potential therapeutic target for KD.

Short-term outcome of percutaneous coronary intervention with directional coronary atherectomy followed by drug-coated balloon: a preliminary report.

Directional coronary atherectomy (DCA) is a unique technique used in percutaneous coronary intervention (PCI) which involves the removal of plaque from the coronary artery. Treatment with a drug-coated balloon (DCB) appears to be effective, especially when a predilatation of the lesion is performed appropriately. We hypothesize that the combination therapy of DCA with DCB is an effective strategy in PCI. PCI with DCA followed by DCB was performed for 23 patients from December 2014 to April 2017. All DCA procedures were performed under the guidance of intravascular ultrasound (IVUS) findings and all procedures were successfully performed without incurring major complications such as a coronary perforation. Plaque area (PA) was reduced from 77.3 ± 10.4% at baseline to 50.9 ± 9.2% after DCA and luminal cross-sectional area (CSA) after PCI was enlarged from 3.6 ± 1.8 to 9.3 ± 3.3 mm2. Follow-up coronary angiography (CAG) performed at 6-10 months showed no cases having incurred restenosis. Plaque area at follow-up CAG was 52.0 ± 8.5% and luminal CSA was 9.5 ± 2.1 mm2. There were no cases undergoing target vessel revascularization (TVR) and target lesion revascularization (TLR) during the follow-up periods. PCI with DCA followed by DCB might be an effective strategy for de novo lesions.

Quadricuspid pulmonary valve stenosis treated by transcatheter pulmonary valvuloplasty with inoue balloon catheter.

The quadricuspid pulmonary valve is a relatively common congenital anomaly which is rarely complicated clinically and also tends to be under-diagnosed. The following case report shows a 62-year-old man with exertional dyspnea due to quadricuspid pulmonary valve stenosis that was diagnosed by using electrocardiography-gated multiple detector computed tomography. He was then treated effectively by transcatheter balloon pulmonary valvuloplasty using an Inoue balloon catheter. .

Successful revascularization of advanced coronary artery disease associated with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is caused by loss-of-function mutations of the ATP-binding cassette subfamily C member 6 gene. A 58-year-old man was diagnosed as having PXE based on typical findings in orbital and skin biopsies. Coronary computed tomography (CT) showed severe coronary stenosis in the proximal right coronary artery (RCA), and chronic total occlusion (CTO) of the mid left anterior descending coronary artery (LAD) with bridging collaterals. Coronary angiography revealed 99% stenosis in the RCA (#1) and CTO in the mid LAD (#7) with well-developed collaterals from the LAD to the RCA. We performed percutaneous coronary intervention (PCI) and achieved complete revascularization. Intravascular ultrasound (IVUS) showed a superficial high echoic component around the vessels throughout the length of coronary arteries including non-stenotic regions. In the IVUS findings, the main cause of stenosis of the RCA lesion was large amounts of plaque, and the cause of the CTO in the LAD was coronary negative remodeling. In this case, coronary CT was clinically useful in the identification of ischemic heart disease. Since IVUS demonstrates variable findings in each coronary artery lesion and the morphologic characteristics might alter the strategy of PCI, IVUS should be performed at the time of PCI in PXE patients. .