Masaru Hiki

Background: Delirium is frequently observed in patients admitted to the intensive care unit, and is associated with mortality and morbidity. Although several studies have reported an association between polyunsaturated fatty acids (PUFAs) and cognitive disorders, the association between PUFA levels and development of delirium in patients with acute cardiovascular disease remains unknown. Objective: This study aimed to clarify the association between PUFA levels and development of delirium in the coronary intensive care unit (CICU). Methods: We enrolled 590 consecutive patients (mean age, 70 ± 14 years) admitted to the CICU of Juntendo University Hospital. Fasting serum PUFA levels were measured within 24 h of admission. Delta-5 desaturase activity was estimated as the ratio of arachidonic acid (AA) to dihomo-gamma-linolenic acid (DGLA). Furthermore, delirium was defined as patients having a delirium score of ≥4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was observed in 55 patients. DGLA levels were significantly lower, and delta-5 desaturase activity was significantly higher in patients with delirium than in those without delirium (both p < 0.001). Conversely, AA alone and omega-3 PUFAs did not differ between the groups. Additionally, DGLA and AA levels, but not omega-3 PUFA levels, were negatively associated; delta-5 desaturase activity was positively associated with the delirium score (both p < 0.001). The duration of delirium was significantly associated with DGLA and AA levels (p = 0.001 and p = 0.004, respectively). Moreover, multivariate analysis showed that decreased DGLA and increased delta-5 desaturase activity remained significant predictors of delirium. Conclusions: Low omega-6 PUFA levels and high delta-5 desaturase activity on admission were significantly associated with the development of delirium in the CICU, indicating that the evaluation of low omega-6 PUFA levels and related enzymes may identify patients at a high risk of developing delirium.

Background/Objectives: Worsening renal function (WRF) during hospitalization for acute decompensated heart failure (ADHF) is associated with poor clinical outcomes. Data on the impact of WRF on clinical outcomes, considering blood urea nitrogen (BUN) level and its changes in patients with ADHF, are scarce. This study aimed to investigate the effects of BUN and its changes during hospitalization on the relationship between WRF during hospitalization and post-discharge clinical outcomes in patients with ADHF. Methods: A total of 509 patients with ADHF, hospitalized between 2007 and 2011, were included. WRF was defined as an absolute increase in serum creatinine level of >0.3 mg/dL, with a >25% increase during hospitalization. The risk of WRF for post-discharge clinical events, including death and rehospitalization, considering BUN levels, was assessed using three multivariable Cox regression models. Results: WRF was observed in 55 (10.8%) patients. The cumulative event-free survival was significantly worse in patients with WRF (p = 0.039). In Model 1 (excluding BUN changes), WRF was associated with a greater risk of post-discharge clinical events. In Model 2, which included both WRF and BUN changes, WRF was not a significant predictor. In Model 3, patients were subdivided according to WRF or BUN increase, and the subgroups were included instead of isolated WRF and BUN changes; only WRF with increased BUN level was associated with an increased risk of post-discharge clinical events. Conclusions: In patients with ADHF, WRF was associated with poor post-discharge clinical outcomes when accompanied by increased BUN levels during hospitalization.

Background: Interactions between the heart and other organs have been a focus in acute decompensated heart failure (ADHF). However, the association between ADHF and pancreatic exocrine insufficiency (PEI), which may lead to malnutrition, remains unclear. We investigated the relationship between exocrine pancreatic enzymes and ADHF. Methods: We enrolled 155 and 46 patients with and without ADHF, respectively. Serum amylase and lipase levels were compared between the two groups. In the ADHF group, factors correlating with serum amylase or lipase levels were assessed using multiple regression analysis, and changes in their levels throughout the hospital course were determined. Results: Patients with ADHF exhibited significantly lower amylase and lipase levels. In the same group, the significant independent correlates of lower amylase levels included a lower blood urea–nitrogen level (partial correlation coefficient, 0.530; p < 0.001), lower albumin level (partial correlation coefficient, 0.252; p = 0.015), and higher uric acid level (partial correlation coefficient, –0.371; p < 0.001). The significant independent correlates of lower lipase levels included coexisting atrial fibrillation (coefficient, 0.287; p = 0.026), lower creatinine level (coefficient, 0.236; p = 0.042), and higher B-type natriuretic peptide level (coefficient, –0.257; p = 0.013). Both amylase and lipase levels significantly increased following the improvement in ADHF. Conclusions: In patients with ADHF, decreased serum amylase and lipase levels were associated with the congestion severity, suggesting that PEI may occur in patients with ADHF, potentially due to ADHF-related congestion.

Background/Objectives: Heart failure (HF) can damage organs because of poor perfusion and/or congestion. The interactions between HF and other organs have recently been studied; however, data on the interaction between HF and pancreatic exocrine function, which may affect fat and protein absorption and malnutrition, are scarce. We previously showed that the serum levels of pancreatic exocrine enzymes, as suggestive of pancreatic exocrine function, were low and associated with malnutrition or congestion in hospitalized patients with acute decompensated HF (ADHF). This study investigated the relationship between the serum levels of pancreatic exocrine enzymes and long-term outcomes in patients with ADHF. Methods: We collected serum levels of pancreatic exocrine enzymes (amylase and lipase) from patients who were admitted to the cardiac intensive care unit due to ADHF. Patients undergoing dialysis and those with neoplasms were excluded. Patients were categorized as having high or low pancreatic exocrine enzyme levels in the first quartile upon admission. The association between low serum pancreatic exocrine enzyme levels at admission and the composite of death and ADHF readmission was assessed. Results: Of the 146 patients, 37 (25.3%) and 36 (24.7%) had low amylase and lipase levels, respectively. Patients with low lipase levels showed worse cumulative event-free survival than those with high lipase levels (p < 0.001). A low lipase level was associated with worse outcomes (hazard ratio: 1.96; p = 0.012). Conclusions: These findings suggest that low serum lipase levels may be a predictor of long-term outcomes in patients with ADHF.

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.

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.

Background:Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and TD (urinary β-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170–871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality.Conclusions:As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

The TCB index (triglycerides × total cholesterol × body weight), a novel simply calculated nutritional index based on serum triglycerides (TGs), serum total cholesterol (TC), and body weight (BW), was recently reported to be a useful prognostic indicator in patients with coronary artery disease. Thus, this study aimed to investigate the relationship between TCBI and long-term mortality in acute decompensated heart failure (ADHF) patients. Patients with a diagnosis of ADHF who were consecutively admitted to the cardiac intensive care unit in our institution from 2007 to 2011 were targeted. TCBI was calculated using the formula TG (mg/dL) × TC (mg/dL) × BW (kg)/1000. Patients were divided into two groups according to the median TCBI value. An association between admission TCBI and mortality was assessed using univariable and multivariable Cox proportional hazard analyses. Overall, 417 eligible patients were enrolled, and 94 (22.5%) patients died during a median follow-up period of 2.2 years. The cumulative survival rate with respect to all-cause, cardiovascular, and cancer-related mortalities was worse in patients with low TCBI than in those with high TCBI. In the multivariable analysis, although TCBI was not associated with cardiovascular and cancer mortalities, the association between TCBI and reduced all-cause mortality (hazard ratio: 0.64, 95% confidence interval: 0.44–0.94, p = 0.024) was observed. We computed net reclassification improvement (NRI) when TCBI or Geriatric Nutritional Risk Index (GNRI) was added on established predictors such as hemoglobin, serum sodium level, and both. TCBI improved discrimination for all-cause mortality (NRI: 0.42, p < 0.001; when added on hemoglobin and serum sodium level). GNRI can improve discrimination for cancer mortality (NRI: 0.96, p = 0.002; when added on hemoglobin and serum sodium level). TCBI, a novel and simply calculated nutritional index, can be useful to stratify patients with ADHF who were at risk for worse long-term overall mortality.