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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.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.We used data from 2012 to 2019 from a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination.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.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.

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).The practice pattern for SDB in CVD patients has changed from 2012 to 2019.

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.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.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.

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 (P0.001, P0.001 and P0.001 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 P0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.

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-1β 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-1β 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-1β release and necrotic cell death. Although phagocytosis of CPPs was required for CPP-induced IL-1β/α release and necrotic cell death, lysosomal dysfunction and K+ efflux were mainly involved in CPP-induced NLRP3 inflammasome activation and subsequent IL-1β 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-1β 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-1β and IL-1α is necessary to regulate the CPP-induced inflammatory response and to treat CPP-associated inflammatory disorders.

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).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.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;Among HF patients, those with reversed V waves had higher right atrial pressure and were at higher risk of adverse prognosis.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).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.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 (RChez 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.

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, and25% 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.Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.

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 = &minus, 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 = &minus, 0.015, p = 0.872). In the Kaplan&ndash, Meier analysis, cardiac event rate was significantly higher in the high SWD group (SWD &ge, 10.0 (m/s)/kHz, n = 103) than in the low SWD group (SWD &lt, 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&ndash, 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.

Introduction: Kawasaki disease (KD) is a systemic febrile syndrome which causes coronary arteritis. Candida albicans water-soluble fraction (CAWS) is a mannoprotein-β-glucan complex obtained from the culture supernatant of Candida albicans , and frequently used as a murine KD model, because administration ofCAWS induces coronary arteritis. NLRP3 inflammasome is a large multiprotein complex (NLRP3, ASC and caspase-1), and regulates the release of the potent inflammatory cytokine IL-1β. We hypothesized that NLRP3 inflammasome-mediated IL-1β had a pivotal role in the pathogenesis of CAWS-induced vasculitis. Methods and Results: In vivo : The protein level of IL-1β in the hearts was increased by CAWS administration. Activation of caspase-1 was detected around the coronary arteries by FLICA assay. Histological study showed that incidence and severity of CAWS-induced vasculitis, macrophage infiltration, and fibrosis were suppressed in NLRP3-, ASC- and IL-1β-deficient mice (Fig. A). In vitro : Bone marrow-derived dendritic cells (BMDCs) produced IL-1β by CAWS stimulation, which was suppressed by the anti-Dectin-2 antibody or caspase-1 inhibitor. The CAWS-induced IL-1β production was also suppressed in NLRP3-, ASC-, and caspase-1-deficient BMDCs (Fig. B). CAWS induced mitochondrial reactive oxygen species (mtROS) production, and Mito-TEMPO, a mtROS inhibitor, suppressed CAWS-induced caspase-1 activation (Fig. C) and IL-β production. In addition, CAWS-induced mtROS production was suppressed by Syk or JNK inhibitor. Furthermore, Syk or JNK inhibitor suppressed CAWS-induced NF-κB activation and subsequent IL-1β production. Conclusion: These findings demonstrated that NLRP3 inflammasome activation through Dectin-2/Syk/JNK-mediated mtROS plays a pivotal role in CAWS-induced vasculitis. CAWS also induced priming signal through Dectin-2/Syk/JNK/NF-κB pathway. Our finding indicates NLRP3 inflammasome as a new therapeutic target of KD.

Introduction: It has been reported that East Asian people have higher bleeding risks than Western people. The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score was developed to estimate the bleeding risk after percutaneous coronary intervention (PCI). However, the utility of PARIS bleeding score for predicting long-term bleeding risks has not been validated in Japanese population. Methods: Consecutive 1061 patients who underwent PCI and survived to discharge were divided into three groups based on the category of PARIS bleeding risk score: low risk group (0-3 risk points), intermediate risk group (4-7 risk points) and high risk group (8-15 risk points), then we compared patient characteristics and followed bleeding events. Results: The numbers of patients at low, intermediate and high risk groups were 113 (10.7%), 420 (39.6%) and 528 (49.8%), respectively. Clinical characteristics for three groups were as follows: atrial fibrillation (low, intermediate and high risk groups; 8.2%, 8.9% and 21.6%, P &lt 0.001, respectively), peripheral artery disease (3.1%, 9.1% and 22.1%, P &lt 0.001), coronary multi-vessel disease (38.9%, 44.3% and 54.4%, P = 0.001), use of statin (97.3%, 89.6% and 71.7%, P &lt 0.001) and proton-pump inhibitors (69.1%, 72.5%, and 78.9%, P = 0.02). Among 1061 patients, a total of 74 bleeding events were occurred during the follow-up period (mean of 1742 days). In the Kaplan-Meier analysis, the cumulative incidence of bleeding events significantly increased from low risk group to intermediate and high risk group (P &lt 0.001). The risk score showed a significant prognostic value in predicting bleeding events (area under the receiver operating characteristic curve, 0.674; 95% confidence interval, 0.615-0.733). Conclusions: The PARIS bleeding risk score successfully stratified the long-term bleeding risk in patients with coronary artery disease after PCI in Japanese population.

Background: 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 and cardiac mortalities has not been evaluated. Therefore, we aimed to evaluate the predictive value of the PARIS bleeding risk score for all-cause and cardiac mortalities after PCI. Methods and Results: Consecutive 1061 patients, who had admitted to our hospital and performed or undergone PCI, were divided into 3 groups based on PARIS bleeding risk score: low (n = 113), intermediate (n = 420) and high risk groups (n = 528). We compared comorbidities and characteristics of patients among 3 groups. Furthermore, we prospectively followed up all-cause and cardiac mortalities. Clinical characteristics of 3 groups were as follows: mean age (low, intermediate and high risk groups; 56.5, 65.6 and 73.9 years, P < 0.001, respectively), prevalence of chronic kidney disease (2.7%, 24.2% and 67.8%, P < 0.001), atrial fibrillation (8.2%, 8.9% and 21.6%, P < 0.001) and peripheral artery disease (3.1%, 9.1% and 22.1%, P < 0.001). During the mean follow-up period of 1809 days, there were 205 deaths and 64 cardiac deaths. The Kaplan-Meier analysis revealed that both all-cause and cardiac mortalities were highest in high risk group among 3 groups (P < 0.001 and P < 0.001, respectively, Figure). In multivariable Cox proportional hazard analysis adjusted for confounding factors, PARIS bleeding score was an independent predictor of both all-cause and cardiac mortalities (adjusted hazard ratio 1.27 and 1.21 per 1 point increase, P < 0.001 and P = 0.004, respectively). Conclusion: The PARIS bleeding risk score showed significant prognostic values for all-cause and cardiac mortalities in patients after PCI.

Background: It has been known that East Asian people, including Japanese, has a high bleeding risk (HBR) than Western. Therefore, risk stratification is important to detect HBR patients among patients who underwent percutaneous coronary intervention (PCI). The aim of the present study was to investigate the association between serum albumin level and bleeding events in patients who underwent PCI. Methods and Results: Consecutive 1027 patients who underwent PCI and had been discharged from our institution were enrolled. We divided the patients into three groups based on serum albumin levels at discharge: the first tertile (≤3.7 g/dL, n=358), second tertile (3.8-4.1 g/dL, n=308) and third tertile (≥4.2 g/dL, n=361). Clinical characteristics of three groups were as follows: mean age (the first, second and third tertile; 72.9, 69.3 and 63.4 years, P2 , P Conclusion: In patients who underwent PCI, low serum albumin level is independently associated with long-term bleeding events.

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.

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. .

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. .

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-1β-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-1β 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-1β, 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-1β in response to CAWS. In contrast, CAWS induced caspase-1 activation and IL-1β 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-1β expression through a Dectin-2/Syk/JNK/NF-κB pathway, and caspase-1 activation and cleavage of pro-IL-1β 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.

Various types of expanders have been investigated to recover a throttling loss and to improve the performance of CO2 refrigeration cycle. However, the capacity of the expander studied so far is so large that it cannot be used for a small cycle such as a vending machine, since the performance of small expander tends to get worse due to influence of leakage. In this paper, a novel reciprocating expander which can be applied to the small cycle is designed and its performance is examined. The expander has four cylinders and pistons arranged radially, and controls supply and discharge of refrigerant by a reciprocating motion of an adjacent piston. It is found that the developed expander can be operated with a small flow rate and the total efficiency attains to 0.4 over the wide range of rotational speed.