Effects of NP-1815-PX, a P2X4 Receptor Antagonist, on Contractions in Guinea Pig Tracheal and Bronchial Smooth Muscles.

Administration of a P2X4 receptor antagonist to asthma model mice improved asthma symptoms, suggesting that P2X4 receptor antagonists may be new therapeutics for asthma. However, the effects of these antagonists on tracheal/bronchial smooth muscle (TSM and BSM) have not been investigated. This study examined the effects of NP-1815-PX, a selective P2X4 receptor antagonist, on guinea pig TSM and BSM contractions. In epithelium-intact TSM, NP-1815-PX (10-5 M) strongly suppressed ATP-induced contractions. ATP-induced contractions were strongly suppressed by indomethacin (3 × 10-6 M) and ONO-8130 (a prostanoid EP1 receptor antagonist, 10-7 M). ATP-induced contractions were partially suppressed by SQ 29,548 (a prostanoid TP receptor antagonist, 3 × 10-7 M), although the difference was not significant. In contrast, ATP-induced contractions were not affected by AL 8810 (a prostanoid FP receptor antagonist, 10-5 M) or L-798,106 (a prostanoid EP3 receptor antagonist, 10-8 M). NP-1815-PX (10-5-10-4 M) strongly suppressed U46619 (a TP receptor agonist)- and prostaglandin F2α (PGF2α)-induced epithelium-denuded TSM and BSM contractions, which were largely inhibited by SQ 29,548. Additionally, NP-1815-PX (10-5-10-4 M) strongly suppressed the U46619-induced increase in intracellular Ca2+ concentrations in human TP receptor-expressing cells. However, NP-1815-PX (10-4 M) did not substantially inhibit the TSM/BSM contractions induced by carbachol, histamine, neurokinin A, or 50 mM KCl. These findings indicate that NP-1815-PX inhibits guinea pig TSM and BSM contractions mediated through the TP receptor, in addition to the P2X4 receptor, whose stimulation mainly induces EP1 receptor-related mechanisms. Thus, these findings support the usefulness of NP-1815-PX as a therapeutic drug for asthma.

Docosahexaenoic Acid Selectively Suppresses U46619- and PGF2α-Induced Contractions in Guinea Pig Tracheal Smooth Muscles.

We investigated the potential inhibitory effects of docosahexaenoic acid (DHA) on the contractions of guinea pig tracheal smooth muscles in response to U46619 (a thromboxane A2 (TXA2) mimetic) and prostaglandin F2α (PGF2α) to examine whether this n-3 polyunsaturated fatty acid suppresses prostanoid-induced tracheal contractions. DHA (3 × 10-5 M) significantly suppressed tracheal contractions elicited by lower concentrations of U46619 (10-8 M) and PGF2α (5 × 10-7 M) (vs. control), although it did not suppress the contractions induced by higher concentrations (U46619: 10-7 M; PGF2α: 10-5 M). Supporting these findings, DHA (4 × 10-5 M/6 × 10-5 M) shifted the concentration-response curves for U46619 (10-9-10-6 M) and PGF2α (10-8-10-5 M) to the right. However, the slope of the regression line in the Schild plot of DHA vs. U46619/PGF2α was larger than unity. The tracheal contractions induced by U46619 (10-8 M) and PGF2α (5 × 10-7 M) were significantly suppressed by the prostanoid TP receptor antagonist SQ 29,548 (10-6 M) (vs. ethanol-treated). In contrast, DHA (4 × 10-5 M) did not show significant inhibitory effects on the contractions induced by acetylcholine (10-8-10-4 M), histamine (10-8-10-4 M), and leukotriene D4 (10-11-10-7 M) (vs. ethanol-treated). These findings indicate that DHA selectively suppresses tracheal contractions induced by U46619 and PGF2α. Therefore, DHA may be a useful therapeutic agent against asthma associated with tracheal/bronchial hyper-constriction caused by prostanoids including TXA2 and PGF2α.

Prevalence of Restless Legs Syndrome and Its Effects on Sleep and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. METHODS AND RESULTS: We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (ß=0.211; P = .014) and lower PCS score (ß=-0.177; P = .045). CONCLUSION: In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

Association between C-reactive protein levels at hospital admission and long-term mortality in patients with acute decompensated heart failure.

The C-reactive protein (CRP) levels obtained at hospital admission are associated with the prognosis of several cardiovascular diseases, including acute coronary syndrome. Although the admission CRP level is associated with in-hospital mortality in patients with acute decompensated heart failure (ADHF), there are limited data on the association between the admission CRP level and long-term mortality in patients with ADHF. This study included consecutive ADHF patients admitted to our institution from 2007 to 2011. Eligible patients were divided into four groups based on quartiles of admission CRP levels. The association between the admission CRP level and long-term mortality was assessed by multivariable Cox proportional analysis, including other independent variables with p values < 0.1 in the univariable analyses. Overall, 527 eligible patients were examined. There were 142 deaths (27%) during a median follow-up period of 2.0 years. In the multivariable analysis, the hazard ratio (HR) significantly increased with admission CRP levels in a dose-dependent manner for mortality (p for trend = 0.034). Multivariable analysis also showed a significant association between the admission CRP level, when treated as a natural logarithm-transformed continuous variable, and increased mortality (HR 1.16, p = 0.030). In patients with ADHF, the admission CRP level was associated with an increased risk of long-term mortality.

Relationship between blood urea nitrogen-to-creatinine ratio at hospital admission and long-term mortality in patients with acute decompensated heart failure.

Although elevated blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio at hospital admission has been reported to be associated with poor short-term prognosis, its association to long-term mortality in patients with acute decompensated heart failure (ADHF) remains to be elucidated. Moreover, an additive prognostic value to preexisting renal markers including creatinine and BUN has not been well described. A cohort of 557 consecutive ADHF patients admitted to the cardiac intensive care unit was studied. All cohorts were divided into high and low BUN/Cr ratios according to the median value of BUN/Cr ratio at admission. Association between admission BUN/Cr ratio and long-term all-cause mortality was assessed. There were 145 deaths (27%) observed during the follow-up period of 1.9 years in median. Patients with high BUN/Cr ratio showed with higher mortality compared to low BUN/Cr ratio (log-rank: P = 0.006). In the multivariable analysis, patients with high BUN/Cr ratio at admission were associated with high mortality independently from other covariates including BUN and creatinine (HR 1.81, 95% CI 1.16-2.80, P = 0.009). In patients with ADHF, there is a relationship between admission BUN-to-creatinine ratio and long-term mortality.

Relationship Between Serum Sodium Level Within the Low-Normal Range on Admission and Long-Term Clinical Outcomes in Patients with Acute Decompensated Heart Failure.

Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) is reportedly related with poor prognosis, the available data regarding the impact of serum sodium level within the low-normal range at admission on clinical events in patients with ADHF is limited.We studied eligible patients admitted to our institution in 2007-2011. All the patients were categorized into 3 groups according to the admission serum sodium levels of < 135 mmol/L (hyponatremia), ≥ 135 and < 140 mmol/L (low-normal range), or ≥ 140 mmol/L (normal range). The association between admission serum sodium levels and long-term clinical events, a composite of all-cause deaths and re-hospitalizations for ADHF, was assessed by multivariable Cox proportional analysis.Of the 584 eligible patients, 208 (35.6%) were in the low-normal range and 99 (16.9%) had hyponatremia on admission. On multivariable analysis, compared with those with a sodium level ≥ 140 mmol/L, patients with hyponatremia were at increased risk for clinical events (hazard ratio [HR], 1.53; P = 0.041), whereas the HR of those in the low-normal range was attenuated and insignificant (HR, 1.08; P = 0.625). However, the HR of each category increased significantly as sodium level decreased (P value for HR trend, 0.024). In addition, when serum sodium level was treated as a continuous variable, the lower the serum sodium level, the greater the risk of clinical events (P = 0.012). The cut-off value of serum sodium level to predict mortality was < 138 mmol/L.In conclusion, a low serum sodium level on admission for ADHF, even if low-normal, can increase the risk of long-term mortality and/or re-hospitalization for ADHF.

Low 1,5-anhydroglucitol levels are associated with long-term cardiac mortality in acute coronary syndrome patients with hemoglobin A1c levels less than 7.0.

BACKGROUND: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels. METHODS: The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m2; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded. RESULTS: During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan-Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41-0.98; p = 0.03). CONCLUSION: Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.

Impact on Clinical Outcomes of Periodic Leg Movements During Sleep in Hospitalized Patients Following Acute Decompensated Heart Failure.

BACKGROUND: Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03-4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing. CONCLUSIONS: In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.

Low circulating coenzyme Q10 during acute phase is associated with inflammation, malnutrition, and in-hospital mortality in patients admitted to the coronary care unit.

Coenzyme Q10 (CoQ10) has a potential role in the prevention and treatment of heart failure through improved cellular bioenergetics. In addition, it has antioxidant, free radical scavenging, and vasodilatory effects that may be beneficial. Although critical illness in intensive care unit is associated with decreased circulating CoQ10 levels, the clinical significance of CoQ10 levels during acute phase in the patients of cardiovascular disease remains unclear. We enrolled 257 consecutive cardiovascular patients admitted to the coronary care unit (CCU). Serum CoQ10 levels were measured after an overnight fast within 24 h of admission. We examined the comparison of serum CoQ10 levels between survivors and in-hospital mortalities in patients with cardiovascular disease. Serum CoQ10 levels during the acute phase in patients admitted to the CCU had similar independent of the diagnosis. CoQ10 levels were significantly lower in patients with in-hospital mortalities than in survivors (0.43 ± 0.19 vs. 0.55 ± 0.35 mg/L, P = 0.04). In patients admitted to the CCU, CoQ10 levels were negatively associated with age and C-reactive protein levels, and positively associated with body mass index, total cholesterol, and high-density lipoprotein cholesterol levels. Low CoQ10 levels correlated with low diastolic blood pressure. Multivariate logistic regression analysis demonstrated that low CoQ10 levels were an independent predictor of in-hospital mortality. Low serum CoQ10 levels during acute phase are significantly associated with cardiovascular risk and in-hospital mortality in patients admitted to the CCU.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients.

Medical therapy for severe aortic valve stenosis (AS) is necessary for inoperable patients due to comorbid conditions. Tolvaptan (TLV), unlike other diuretics, resulted in modest changes in filling pressures associated with an increase in urine output, suggesting that TLV improves congestive heart failure (CHF) due to severe AS without hemodynamic instability.We retrospectively investigated 14 consecutive patients ≥ 80 years of age admitted due to decompensated CHF with severe AS at Juntendo University Hospital from April 2014 to November 2015. Seven of the 14 patients were treated with TLV. We examined the safety and efficacy of TLV treatment for severe AS.Mean age was 90.0 ± 6.3 years and mean aortic valve area was 0.57 ± 0.22 cm2. Urine volume at day 1 of TLV treatment was increased and urine osmolality significantly decreased at day 1 of TLV treatment (all P < 0.05). New York Heart Association classification and brain natriuretic peptide levels significantly improved 1 week after treatment and at discharge (all P < 0.05) whereas brain natriuretic peptide levels did not improve in the patients without TLV. Severe adverse events did not occur during TLV treatment. During the first 3 days, blood pressure and heart rate were relatively stable. TLV treatment did not affect serum creatinine, blood urea nitrogen, or the estimated glomerular filtration rate.In elderly patients with severe AS, TLV treatment improved CHF without hemodynamic instability. Further prospective studies are needed to assess the safety and efficacy of TLV in decompensated heart failure due to severe AS.

Multicenter validation study for automated left ventricular ejection fraction assessment using a handheld ultrasound with artificial intelligence.

We sought to validate the ability of a novel handheld ultrasound device with an artificial intelligence program (AI-POCUS) that automatically assesses left ventricular ejection fraction (LVEF). AI-POCUS was used to prospectively scan 200 patients in two Japanese hospitals. Automatic LVEF by AI-POCUS was compared to the standard biplane disk method using high-end ultrasound machines. After excluding 18 patients due to infeasible images for AI-POCUS, 182 patients (63 ± 15 years old, 21% female) were analyzed. The intraclass correlation coefficient (ICC) between the LVEF by AI-POCUS and the standard methods was good (0.81, p < 0.001) without clinically meaningful systematic bias (mean bias -1.5%, p = 0.008, limits of agreement ± 15.0%). Reduced LVEF < 50% was detected with a sensitivity of 85% (95% confidence interval 76%-91%) and specificity of 81% (71%-89%). Although the correlations between LV volumes by standard-echo and those by AI-POCUS were good (ICC > 0.80), AI-POCUS tended to underestimate LV volumes for larger LV (overall bias 42.1 mL for end-diastolic volume). These trends were mitigated with a newer version of the software tuned using increased data involving larger LVs, showing similar correlations (ICC > 0.85). In this real-world multicenter study, AI-POCUS showed accurate LVEF assessment, but careful attention might be necessary for volume assessment. The newer version, trained with larger and more heterogeneous data, demonstrated improved performance, underscoring the importance of big data accumulation in the field.

Impact of sleep-disordered breathing on overnight changes in arterial stiffness in patients with acute heart failure.

Overnight increases in arterial stiffness associated with sleep-disordered breathing may adversely affect patients with acute heart failure. Thus, we investigated overnight changes in arterial stiffness and their association with sleep-disordered breathing in patients hospitalized for acute heart failure. Consecutive patients with acute heart failure were enrolled. All participants underwent overnight full polysomnography following the initial improvement of acute signs and symptoms of acute heart failure. The arterial stiffness parameter, cardio-ankle vascular index (CAVI), was assessed before and after polysomnography. Overall, 60 patients (86.7% men) were analyzed. CAVI significantly increased overnight (from 8.4 ± 1.6 at night to 9.1 ± 1.7 in the morning, P < 0.001) in addition to systolic and diastolic blood pressure (from 114.1 mmHg to 121.6 mmHg, P < 0.001; and from 70.1 mmHg to 78.2 mmHg, P < 0.001, respectively). Overnight increase in CAVI (ΔCAVI ≥ 0) was observed in 42 patients (70%). The ΔCAVI ≥ 0 group was likely to have moderate-to-severe sleep-disordered breathing (i.e., apnea-hypopnea index ≥15, 55.6% vs 80.9%, P = 0.047) and greater obstructive respiratory events (29.4% vs 58.5%, P = 0.041). In multivariable analysis, moderate-to-severe sleep-disordered breathing and greater obstructive respiratory events were independently correlated with an overnight increase in CAVI (P = 0.033 and P = 0.042, respectively). In patients hospitalized for acute heart failure, arterial stiffness, as assessed by CAVI, significantly increased overnight. Moderate-to-severe sleep-disordered breathing and obstructive respiratory events may play an important role in the overnight increase in cardio-ankle vascular index.

Feasibility of self-measurement telemonitoring using a handheld heart sound recorder in patients with heart failure - SELPH multicenter pilot study.

BACKGROUND: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF. METHODS: Ambulatory HF patients recorded their own heart sounds, mono­lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months. RESULTS: In the 77 patients enrolled (63 ±â€¯13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events. CONCLUSIONS: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF.

A case of adult patent ductus arteriosus-associated infective endarteritis who was successfully treated with only antibiotics.

Patent ductus arteriosus-associated infective endarteritis (PDA-IE) is an extremely rare complication of PDA in recent years. In this report, we describe a case of PDA-IE complicated by septic pulmonary embolism who was successfully treated with only antibiotics.

A Case Report of Mixed-type Dyspnoea Diagnosed via Non-invasive and Invasive Cardiopulmonary Exercise Tests.

A gas exchange analysis with the cardiopulmonary exercise test is effective in discriminating non-cardiogenic components of limited exercise tolerance and is important for use in combination with the diastolic stress test. An 80-year-old woman with progressive exertional dyspnoea, hypertension, and untreated bronchial asthma was diagnosed with heart failure with a preserved ejection fraction by invasive testing. Diuretics were initiated, which resulted in partial symptom improvement. A subsequent non-invasive test revealed a reduced breathing reserve, suggesting exertional dyspnoea complications linked to lung disease. Bronchodilators were administered, which further improved the symptoms.

Prognostic Value of Cheyne-Stokes Respiration and Nutritional Status in Acute Decompensated Heart Failure.

Malnutrition frequently coexists with heart failure (HF), leading to series of negative consequences. Cheyne-Stokes respiration (CSR) is predominantly detected in patients with HF. However, the effect of CSR and malnutrition on the long-term prognosis of patients with acute decompensated HF (ADHF) remains unclear. We enrolled 162 patients with ADHF (median age, 62 years; 78.4% men). The presence of CSR was assessed using polysomnography and the controlling nutritional status score was assessed to evaluate the nutritional status. Patients were divided into four groups based on CSR and malnutrition. The primary outcome was all-cause mortality. In total, 44% of patients had CSR and 67% of patients had malnutrition. The all-cause mortality rate was 26 (16%) during the 35.9 months median follow-up period. CSR with malnutrition was associated with lower survival rates (log-rank p < 0.001). Age, hemoglobin, albumin, lymphocyte count, total cholesterol, triglyceride, low-density lipoprotein cholesterol, creatinine, estimated glomerular filtration rate, B-type natriuretic peptide, administration of loop diuretics, apnea-hypopnea index and central apnea-hypopnea index were significantly different among all groups (p < 0.05). CSR with malnutrition was independently associated with all-cause mortality. In conclusion, CSR with malnutrition is associated with a high risk of all-cause mortality in patients with ADHF.

Diurnal Variations in Serum Uric Acid, Xanthine, and Xanthine Oxidoreductase Activity in Male Patients with Coronary Artery Disease.

Hyperuricemia is influenced by diet and can cause gout. Whether it is a potential risk factor for cardiovascular disease (CVD) remains controversial, and the mechanism is unclear. Similar to CVDs, gout attacks occur more frequently in the morning and at night. A possible reason for this is the diurnal variation in uric acid (UA), However, scientific data regarding this variation in patients with CVD are not available. Thus, we aimed to investigate diurnal variations in serum levels of UA and plasma levels of xanthine, hypoxanthine, and xanthine oxidoreductase (XOR) activity, which were measured at 18:00, 6:00, and 12:00 in male patients with coronary artery disease. Thirty eligible patients participated in the study. UA and xanthine levels significantly increased from 18:00 to 6:00 but significantly decreased from 6:00 to 12:00. By contrast, XOR activity significantly increased both from 18:00 to 6:00 and 6:00 to 12:00. Furthermore, the rates of increase in UA and xanthine levels from night to morning were significantly and positively correlated. In conclusion, UA and xanthine showed similar diurnal variations, whereas XOR activity showed different diurnal variations. The morning UA surge could be due to UA production. The mechanism involved XOR activity, but other factors were also considered.

Overnight changes in uric acid, xanthine oxidoreductase and oxidative stress levels and their relationships with sleep-disordered breathing in patients with coronary artery disease.

Serum uric acid (UA) level is associated with the high cumulative incidence or prevalence of coronary artery disease (CAD), and hyperuricemia is considered as an independent risk marker for CAD. Sleep-disordered breathing (SDB) is also associated with an increased risk of CAD. Several studies have shown that SDB is associated with hyperuricemia, but the mechanisms are unclear. We measured serum levels of UA and xanthine oxidoreductase (XOR) activity and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), all of which were assessed at 6 p.m. and the following 6 a.m. in males with CAD. In addition, nocturnal pulse oximetry was performed for the night. Overall 32 eligible patients with CAD were enrolled. Serum UA levels significantly increased overnight. (5.32 ± 0.98 mg/dl to 5.46 ± 1.02 mg/dl, p < 0.001) Moreover, XOR activity and urinary 8-OHdG levels significantly increased from 6 p.m. to 6 a.m. Furthermore, 3% Oxygen desaturation index (ODI) was correlated with the overnight changes in XOR activity (r = 0.36, P = 0.047) and urinary 8-OHdG levels (r = 0.41, P = 0.02). In addition, 3%ODI was independently correlated with the changes in XOR activity (correlation coefficient, 0.36; P = 0.047) and 8-OHdG (partial correlation coefficient, 0.63; P = 0.004) in multivariable analyses. SDB severity was associated with the overnight changes in XOR activity and urinary 8-OHdG, suggesting that SDB may be associated with oxidative stress via UA production. This trial is registered at University Hospital Medical Information Network (UMIN), number: UMIN000021624.

Effectiveness of real-time tele-ultrasound for echocardiography in resource-limited medical teams.

BACKGROUND: Echocardiography is a first-line tool for the screening of patients with cardiac dysfunction. However, the mastery of echocardiography requires significant training, and not all medical teams involve an echocardiography specialist. Telemedicine approaches can potentially improve the quality of echocardiography in resource-limited situations. METHODS: We used a novel tablet-based hand-held ultrasound device that enables tele-ultrasound- a real-time video telecommunication with remote control for ultrasound images. A trainee scanned patients with various cardiovascular diseases and interpreted the images. Subsequently, the same trainee re-scanned the same patients and re-interpreted the same images using tele-ultrasound with an echocardiography specialist. An examination on the same patients by a blinded specialist was considered the gold standard. RESULTS: We included 31 patients (median 77 [interquartile range 68-84] years old, 42% women). Mean absolute errors in left ventricular (LV) end-diastolic and end-systolic diameters, visual LV ejection fraction, and tricuspid annular plane systolic excursion decreased significantly after tele-ultrasound advice (5.9 mm, 5.8 mm, 8.6%, and 4.5 to 1.6 mm, 2.8 mm, 0.7%, and 1.8 mm, respectively, all p < 0.001), and intra-class correlation coefficients improved (0.76, 0.84, 0.68, and 0.44 to 0.96, 0.93, 0.99, and 0.90, respectively). Notably, with tele-advice, the trainee's examination showed perfect agreement with that of the specialist in classifying LV ejection fraction (> 50%, 50-35%, or > 35%) and identifying significant valvular heart diseases. CONCLUSION: Real-time tele-ultrasound improved a trainee's echocardiography results to those of a specialist-level examination. This approach might be helpful in resource-limited medical teams where echocardiographic specialists are not readily available.