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.

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.

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.

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.

One-pot enzymatic synthesis of 2-deoxy-scyllo-inosose from d-glucose and polyphosphate.

2-Deoxy-scyllo-inosose (2DOI, [2S,3R,4S,5R]-2,3,4,5-tetrahydroxycyclohexan-1-one) is a biosynthetic intermediate of 2-deoxystreptamine-containing aminoglycoside antibiotics, including butirosin, kanamycin, and neomycin. In producer microorganisms, 2DOI is constructed from d-glucose 6-phosphate (G6P) by 2-deoxy-scyllo-inosose synthase (DOIS) with the oxidized form of nicotinamide adenine dinucleotide (NAD+). 2DOI is also known as a sustainable biomaterial for production of aromatic compounds and a chiral cyclohexane synthon. In this study, a one-pot enzymatic synthesis of 2DOI from d-glucose and polyphosphate was investigated. First, 3 polyphosphate glucokinases (PPGKs) were examined to produce G6P from d-glucose and polyphosphate. A PPGK derived from Corynebacterium glutamicum (cgPPGK) was found to be suitable for G6P production under ordinary enzymatic conditions. Next, 7 DOISs were examined for the one-pot enzymatic reaction. As a result, cgPPGK and BtrC, the latter of which is a DOIS derived from the butirosin producer Bacillus circulans, achieved nearly full conversion of d-glucose to 2DOI in the presence of polyphosphate.

Epimerization at C-3'' in butirosin biosynthesis by an NAD(+) -dependent dehydrogenase BtrE and an NADPH-dependent reductase BtrF.

Butirosin is an aminoglycoside antibiotic consisting two epimers at C-3'' of ribostamycin/xylostasin with a unique 4-amino-2-hydroxybutyrate moiety at C-1 of the aminocyclitol 2-deoxystreptamine (2DOS). To date, most of the enzymes encoded in the biosynthetic gene cluster for butirosin, from the producing strain Bacillus circulans, have been characterized. A few unknown functional proteins, including nicotinamide adenine dinucleotide cofactor-dependent dehydrogenase/reductase (BtrE and BtrF), are supposed to be involved in the epimerization at C-3'' of butirosin B/ribostamycin but remain to be characterized. Herein, the conversion of ribostamycin to xylsostasin by BtrE and BtrF in the presence of NAD(+) and NADPH was demonstrated. BtrE oxidized the C-3'' of ribostamycin with NAD(+) to yield 3''-oxoribostamycin. BtrF then reduced the generated 3''-oxoribostamycin with NADPH to produce xylostasin. This reaction step was the last piece of butirosin biosynthesis to be described.