Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

A mature liquid fertilizer derived from cattle urine promotes Arabidopsis thaliana growth via hormone-like responses.

To understand the fertilization effects of liquid fertilizer (LF) produced by aerobic microbial processing of cattle urine, we investigated the influence of LF on growth and shoot genetic responses of the model plant Arabidopsis thaliana. LF significantly enhanced both shoot and root growth under aseptic conditions. Although filtrate from ultrafiltration (molecular weight cutoff: 10 000) also promoted shoot growth and root elongation, the concentrate only promoted root growth. Multiple growth-promoting factors were therefore associated with the growth promotion. Transcriptome analysis of shoots following LF addition identified 353 up-regulated and 512 down-regulated genes. According to gene ontology and KEGG enrichment analyses, signal transduction of a phytohormone cytokinins was influenced by LF addition. Cytochrome P450 induction triggered the following signal transitions, and would introduce the growth promotion for shoot. Primary auxin responses and abscisic acid signaling responses were also observed in the presence of the LF. Ethylene signaling seemed to be insensitive.

High-intensity interval training versus moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis.

The effects of high-intensity interval training (HIIT) in patients with heart failure (HF) remain controversial. This systematic review and meta-analysis aimed to examine the efficacy of HIIT versus moderate-intensity continuous aerobic training (MCT) on exercise tolerance in patients with HF. We searched for studies published up to 4 March 2022 in Embase, MEDLINE, PubMed, and the Cochrane Library with no limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. We identified 15 randomized controlled trials with 557 patients. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; participants = 557; studies = 15; I2 = 65.7%; very low-quality evidence). The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the difference in peak VO2 between HIIT and MCT was inversely associated with body mass index (r = - 0.508, p = 0.028, 95% confidence interval - 0.95 to - 0.07). Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with HF. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

Artificial intelligence-assisted analysis reveals amino acid effects and interactions on Limosilactobacillus fermentum growth.

To understand the growth of lactic acid bacteria (LAB), Limosilactobacillus fermentum, in response to medium compositions, a deep neural network (DNN) was designed using amino acids (AAs) as explanatory variables and LAB growth as the objective variable. Sixty-four different patterns of free AAs were set using an orthogonal array. The best DNN model had high accuracy with low mean square errors and predicted that Asp would affect LAB growth. Bayesian optimization (BO) using this model recommended an optimal growth media comprising maximum amounts of Asn, Asp, Lys, Thr, and Tyr and minimum amounts of Gln, Pro, and Ser. Furthermore, this proposed media was empirically validated to promote LAB growth. The absence of Gln, Ser, and Pro indicates that the different growth trends among the DNN-BO-optimized media were likely caused by the interactions among the AAs and the other components.

Clinical impact of left ventricular systolic dysfunction in patients undergoing dialysis access surgery.

BACKGROUND: An arteriovenous fistula (AVF) is the most frequently used dialysis access for haemodialysis. However, it can cause volume loading for the heart and may induce circulatory failure when performed in patients with low cardiac function. This study aimed to characterise patients with low cardiac function when initiating dialysis and determine how cardiac function changes after the dialysis access surgery. METHODS: We conducted a retrospective observational study at two centres incorporating 356 patients with end-stage kidney disease who underwent echocardiography before the dialysis access surgery. RESULTS: An AVF and a subcutaneously fixed superficial artery were selected in 70.4% and 23.5% of 81 patients with reduced/mildly reduced (< 50%) left ventricular ejection fraction (LVEF), respectively, and in 94.2% and 1.1% of 275 patients with preserved (≥ 50%) LVEF (p < 0.001), respectively. Follow-up echocardiography was performed in 70.4% and 38.2% of patients with reduced/mildly reduced and preserved LVEF, respectively, which showed a significant increase in LVEF (41 ± 9-44 ± 12%, p = 0.038) in patients with reduced/mildly reduced LVEF. LVEF remained unchanged in 12 patients with reduced/mildly reduced LVEF who underwent subcutaneously fixed superficial artery (30 ± 10-32 ± 15%, p = 0.527). Patients with reduced/mildly reduced LVEF had lower survival rates after surgery than those with preserved LVEF (p = 0.021 for log-rank). CONCLUSION: The LVEF subcategory was associated with dialysis access selection. After the dialysis access surgery, LVEF was increased in patients with reduced/mildly reduced LVEF. These results may help select dialysis access for patients initiating dialysis.

A Simple Risk Score to Differentiate Between Coronary Artery Obstruction and Coronary Artery Spasm of Patients With Acute Coronary Syndrome Without Persistent ST-Segment Elevation.

BACKGROUND: The aim of this study was to create a risk scoring model to differentiate obstructive coronary artery (CA) from CA spasm in the etioology of acute coronary syndrome (ACS).Methods and Results: We included 753 consecutive patients with ACS without persistent ST-segment elevation (p-STE). The exclusion criteria were: (1) out-of-hospital cardiac arrest; (2) cardiogenic shock; (3) hemodialysis; (4) atrial fibrillation/flutter; (5) severe valvular disease; (6) no coronary angiography; (7) non-obstructive coronary artery without "definite" vasospastic angina definition; and/or (8) missing data. From the multivariate logistic regression analysis for prediction of obstructive CA, an integer score of 2 to each 0.5 increment in odds ratio was given, and values were divided into quartiles according to the total score. The scores were as follows: age >70 years (6 points), non-STE myocardial infarction (9 points), diabetes mellitus (5 points), B-type natriuretic peptide >90 pg/mL (7 points), neutrophil to lymphocyte ratio >2 (5 points), and high-density lipoprotein cholesterol <50 mg/dL (5 points). CA spasm-induced ACS occurred in 50.0% in Quartile 1 (total score: 0-13), 20.5% in Quartile 2 (total score: 14-19), 4.9% in Quartile 3 (total score: 20-26), and 2.2% in Quartile 4 (total score: 27-37) (P<0.001), indicating that a total score of <20 was a potential clinical indicator of CA spasm-induced ACS. CONCLUSIONS: CA spasm-induced ACS should be suspected if a total score of <20, and a spasm provocation test was being considered.

Sex differences in the prevalence and prognostic impact of physical frailty and sarcopenia among older patients with heart failure.

BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

Impact of grip strength and gait speed on exercise tolerance in patients with pulmonary hypertension without left heart disease.

Patients with pulmonary hypertension (PH) suffer from poor exercise tolerance due to impaired oxygenation and/or reduced cardiac output. However, the relationship between exercise tolerance and physical function remains unclear. The purpose of this study was to investigate the relationship between exercise tolerance and physical function in patients with PH. A total of 94 patients without left heart disease (61.3 ± 14.7 years old, 69.1% females, 22/8/60/4 patients with Group 1/3/4/5 PH) were retrospectively analysed. Physical function was measured using muscle strength (grip strength, knee extension muscle strength), balance function (one-leg standing time), and gait speed within 7 days of cardiac catheterization. Exercise tolerance was measured using the 6-min walking distance (6-MWD). A total of 194 6-MWD measurements and the corresponding physical function were evaluated in 94 patients. Multivariable linear regression analysis using adaptive-LASSO methods indicated that the World Health Organization functional classification, pulmonary vascular resistance, mixed venous oxygen saturation, grip strength, and gait speed were independently associated with the 6-MWD. Low grip strength (< 28 kg for males and < 18 kg for females; adjusted odds ratio and 95% confidence interval: 2.06 [1.30-3.26], p = 0.002), and slow gait speed (< 1.0 m/s for both sexes; 13.33 [3.61-49.19], p < 0.001) were independent predictors of poor exercise tolerance (6-MWD < 440 m) in a logistic regression analysis. Grip strength and gait speed as measures of physical function, pulmonary vascular resistance, and mixed venous oxygen saturation were associated with exercise tolerance in patients with PH without left heart disease.

Admission free-fatty acid level is a predictor of the mid-term worsening renal function in patients with ST-segment elevation myocardial infarction.

Whether free fatty acids (FFAs), which are generators of reactive oxygen species and substrates of cytotoxic lipid peroxidation products in proximal tubules of the kidney, can be a predictor of worsening renal function (WRF) is not fully elucidated. A total of 110 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h after symptom onset were included. The exclusion criteria were out-of-hospital cardiac arrest, vasospastic angina, hemodialysis, and/or lack of data. FFAs and serum cystatin C were measured on admission, and urinary liver-type fatty acid-binding protein (L-FABP) was measured 3 h after admission. WRF, defined as an increase in serum creatinine by ≥ 0.3 mg/dL for 2-year follow-up, was observed in 16 patients (15%). A multivariate logistic regression analysis (a stepwise algorithm) revealed that the FFA level was an independent predictor of WRF (P = 0.024). The FFA level was associated with WRF adjusted after serum cystatin C (odds ratio [OR]: 1.378 per 1 mEq/L, P = 0.017), L-FABP (OR: 1.370 per 1 mEq/L, P = 0.016), or the Mehran contrast-induced nephropathy (CIN) risk score (OR: 1.362 per 1 mEq/L, P = 0.021). The FFA level was inversely associated with the change in estimated glomerular filtration rate level for 2 years (R2 = 0.051, P = 0.018). The FFA level on admission was associated with the mid-term WRF in patients with STEMI.

Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan.

BACKGROUND: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear. METHODS: This study was a multicenter retrospective observational cohort study of COVID-19 patients, diagnosed by polymerase chain reaction. We retrospectively analyzed 500 COVID-19 patients (mean age: 51 ± 19 years) admitted to eight hospitals in Japan. Kidney dysfunction was defined as a reduced estimated glomerular filtration rate (< 60 mL/min/1.73 m2) or proteinuria (≥ 1 + dipstick proteinuria) on admission. The primary composite outcome included in-hospital death, extracorporeal membrane oxygenation, mechanical ventilation (invasive and noninvasive methods), and intensive care unit (ICU) admission. RESULTS: Overall, 171 (34.2%) patients presented with on-admission kidney dysfunction, and the primary composite outcome was observed in 60 (12.0%) patients. Patients with kidney dysfunction showed higher rates of in-hospital death (12.3 vs. 1.2%), mechanical ventilation (13.5 vs. 4.0%), and ICU admission (18.1 vs. 5.2%) than those without it. Categorical and multivariate regression analyses revealed that kidney dysfunction was substantially associated with the primary composite outcome. Thus, on-admission kidney dysfunction was common in COVID-19 patients. Furthermore, it correlated significantly and positively with COVID-19 severity and mortality. CONCLUSIONS: On-admission kidney dysfunction was associated with disease severity and poor short-term prognosis in patients with COVID-19. Thus, on-admission kidney dysfunction has the potential to stratify risks in COVID-19 patients.

Sarcopenic obesity is associated with impaired physical function and mortality in older patients with heart failure: insight from FRAGILE-HF.

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

Skeletal muscle mass is associated with glycemic variability in patients with ST-segment elevation myocardial infarction.

Skeletal muscle function has been studied to determine its effect on glucose metabolism; however, its effect on glycemic variability (GV), which is a significant glycemic marker in patients with coronary artery disease, is unknown. The aim of the present study was to elucidate the association between skeletal muscle mass and GV. Two hundred and eight consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent continuous glucose monitoring to evaluate mean amplitude of glycemic excursion (MAGE) as GV and a dual-energy X-ray absorptiometry (DEXA) to evaluate skeletal muscle mass were enrolled. Skeletal muscle index (SMI) level was calculated as skeletal muscle mass divided by height squared (kg/m2). SMI level in men had a weak inverse correlation with Log MAGE level by the linear regression model in diabetes mellitus (DM) patients (R2 = 0.139, P = 0.004) and even in non-DM patients (R2 = 0.068, P = 0.004). Multivariate linear regression analysis with a stepwise algorithm (age, male sex, body mass index [BMI], hemoglobin A1c [HbA1c], fasting glucose, HOMA-IR, and SMI; R2 = 0.203, P < 0.001) demonstrated that HbA1c level (B = 0.077, P < 0.001) and SMI level (B = - 0.062, P < 0.001) were both independently associated with Log MAGE level. This association was also confirmed in limited non-DM patients with a subgroup analysis. SMI level was associated with Log MAGE level (B = - 0.055, P = 0.001) independent of BMI or HbA1c level. SMI level was inversely associated with MAGE level independent of glucose metabolism in STEMI patients, suggesting the significance of skeletal muscle mass as blood glucose storage for glucose homeostasis to reduce GV.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92 ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92 ng/mg creatinine. The patients were followed up for a median period of 34 months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

Multidomain Frailty in Heart Failure: Current Status and Future Perspectives.

PURPOSE OF REVIEW: With a worldwide aging population, frailty and heart failure (HF) have become issues that need to be addressed urgently in cardiovascular clinical practice. In this review, we outline the clinical implications of frailty in HF patients and the potential therapeutic strategies to improve the clinical outcomes of frail patients with HF. RECENT FINDINGS: Frailty has physical, psychological, and social domains, each of which is a prognostic determinant for patients with HF, and each domain overlaps with the other, although there are no standardized criteria for diagnosing frailty. Frailty can be targeted for treatment with various interventions, and recent studies have suggested that multidisciplinary intervention could be a promising option for frail patients with HF. However, currently, there is limited data, and further research is needed before its clinical implementation. Frailty and HF share a common background and are strongly associated with each other. More comprehensive assessment and therapeutic interventions for frailty need to be developed to further improve the prognosis and quality of life of frail patients with HF.

Characteristics and Prognosis of Patients with Vasospastic Angina Diagnosed by a Provocation Test with Secondary Prevention Implantable Cardioverter Defibrillator.

This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

In-Hospital Mortality in Acute Myocardial Infarction According to Population Density and Primary Angioplasty Procedures Volume.

BACKGROUND: Low population density may be associated with high mortality in acute myocardial infarction (AMI) patients. The purpose of this study was to investigate the effect of population density and hospital primary percutaneous coronary intervention (PCI) volume on AMI in-hospital mortality in Japan.Methods and Results:This is a retrospective study of 64,414 AMI patients transported to hospital by ambulances. The main outcome measure was in-hospital mortality. The median population density was 1,147 (interquartile range, 342-5,210) persons/km2. There was a significant negative relationship between population density and in-hospital mortality (OR for a quartile down in population density 1.086, 95% CI 1.042-1.132, P<0.001). Patients in less densely populated areas were more often transported to hospitals with a lower primary PCI volume, and they had a longer distance to travel. By using multivariable analysis, primary PCI volume was found to be significantly associated with in-hospital mortality, but distance to hospital was not. When divided into the low- and high-volume hospitals, using the cut-off value of 115 annual primary PCI procedures, the increase in in-hospital mortality associated with low population density was observed only in patients hospitalized in the low-volume hospitals. CONCLUSIONS: Increased in-hospital mortality related to low population density was observed only in AMI patients who were transported to the low primary PCI volume hospitals, but not in those who were transported to high-volume hospitals.

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (ß=0.29, P=0.0006) and poor initial TIMI flow (ß=0.37, P<0.0001) as independent determinants of AUCCK. CONCLUSIONS: T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

Prognostic role of bronchial asthma in patients with heart failure.

There are few reports investigating the relationship between bronchial asthma (BA) and heart failure (HF). We hypothesized BA may have impact on prognosis in patients with HF. Among 323 consecutive outpatients with HF, 191 patients without chronic obstructive pulmonary disease were analyzed. Twenty patients had BA, most of whom (80.0%) had preserved left ventricular ejection fraction (LVEF ≥ 50%). The use of ß-blockers was less frequent (55.0% vs 83.0%. p = 0.01), systolic blood pressure (133 ± 22 vs 120 ± 17 mmHg, p = 0.003), and heart rate (83 ± 14 vs 74 ± 15 bpm, p = 0.02) were higher in patients with BA than those without BA. During median follow up of 24 months, 45 (23.6%) experienced primary outcome defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unexpected hospitalization due to HF. Multivariate Cox regression analysis revealed that the presence of BA was independently associated with the occurrence of primary outcome (hazard ratio 3.08, 95% CI 1.42-6.71, p = 0.004). In the subgroup analysis of patients with preserved LVEF, patients with BA exhibited worse outcomes (p = 0.03 by log-rank). Patients with HF complicated by BA, most of whom had preserved LVEF, exhibited worse outcomes than those without BA.

Randomized controlled trial of landiolol, a short-acting beta-1 adrenergic receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention.

Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI (N = 35) or control group (N = 35). The primary endpoint was serum APN and HMW-APN level 3 days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81 µg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13 µg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1 day after PCI [-0.55 ± 0.92 µg/mL (9.87-9.32 µg/mL), p < 0.001 and -0.20 ± 0.45 µg/mL (3.89-3.69 µg/mL), p < 0.001, respectively]. Additionally, the absolute change in HMW-APN was significantly smaller in the landiolol group compared to the control group (-0.08 ± 0.27 vs. -0.31 ± 0.55 µg/mL, p = 0.031). Multiple linear regression analysis showed that use of landiolol was an independent predictor of change in HMW-APN (ß = 0.276, p = 0.014). Serum APN and HMW-APN level 3 days after PCI were similar between patients treated with and without landiolol. APN and HMW-APN decreased 1 day after PCI in the SAP and landiolol mitigated decrease in HMW-APN.

Conversion and Hydrothermal Decomposition of Major Components of Mint Essential Oil by Small-Scale Subcritical Water Treatment.

Thermal stabilities of four major components (l-menthol, l-menthone, piperitone, and l-menthyl acetate) of Japanese mint essential oil were evaluated via subcritical water treatment. To improve experimental throughput for measuring compound stabilities, a small-scale subcritical water treatment method using ampoule bottles was developed and employed. A mixture of the four major components was treated in subcritical water at 180-240 °C for 5-60 min, and then analyzed by gas chromatography. The results indicated that the order of thermal resistance, from strongest to weakest, was: l-menthyl acetate, l-menthol, piperitone, and l-menthone. In individual treatments of mint flavor components, subsequent conversions of l-menthyl acetate to l-menthol, l-menthol to l-menthone, l-menthone to piperitone, and piperitone to thymol were observed in individual treatments at 240 °C for 60 min. As the mass balance between piperitone and thymol was low, the hydrothermal decomposition of the components was considered to have occurred intensely during, or after the conversion. These results explained the degradation of mint essential oil components under subcritical water conditions and provided the basis for optimizing the extraction conditions of mint essential oils using subcritical water.