Late Kidney Injury After Admission to Intensive Care Unit for Acute Heart Failure.

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

Clinical Significance of the Triglyceride-Glucose Index in Patients Requiring Nonsurgical Intensive Care.

The evaluation of triglyceride-glucose (TyG) index has not been sufficient in patients requiring nonsurgical intensive care.A total of 3,906 patients who required intensive care were enrolled. We computed the TyG index using the value on admission by the following formula: ln [triglyceride (mg/dL) × glucose (mg/dL) /2]. Patients were divided into three groups according to the TyG index quartiles: low (quartile 1 [Q1]; TyG index ≤ 8.493, n = 977), middle (Q2/Q3; 8.494 ≤ TyG index ≤ 9.536, n = 1,953), and high (Q4; TyG index > 9.537, n = 976). The median (interquartile range) TyG index was 9.00 (8.50-9.54); acute coronary syndrome (ACS) had the highest TyG index among all etiologies at 9.12 (8.60-9.68). A multivariate logistic regression model showed that ACS (odds ratio [OR], 2.133; 95% confidence interval [CI], 1.783-2.552) were independently correlated with high TyG index. A Cox proportional hazards regression model revealed that, in ACS, the Q2/Q3 and Q4 groups were independent predictors of 30-day all-cause mortality (hazard ratio [HR], 1.778; 95% CI, 1.014-3.118; HR, 2.986; 95% CI, 1.680-5.308; respectively) and that in acute heart failure [AHF], the Q4 group was a converse independent predictor of 30-day all-cause mortality (HR, 0.488; 95% CI, 0.241-0.988).High TyG index was linked to ACS and negative outcomes in the ACS group; in contrast, low TyG index was associated with adverse outcomes in the AHF group.

Timing and Degree of Acute Kidney Injury in Patients Requiring Non-Surgical Intensive Care.

BACKGROUND: The degree and timing of acute kidney injury (AKI) on admission and during hospitalization in patients requiring non-surgical intensive care remain unclear.Methods and Results: In this study, 3,758 patients requiring intensive care were analyzed retrospectively. AKI was defined based on the ratio of serum creatinine concentrations recorded at each time point (i.e., on admission and during the first 5 days in the intensive care unit and during hospitalization) to those measured at baseline. Patients were grouped by combining AKI severity (RIFLE class) and timing (i.e., from admission to 5 days [A-5D]; from 5 days to hospital discharge [5D-HD]) as follows: No-AKI; New-AKI (no AKI to Class R [risk; ≥1.5-fold increase in serum creatinine], I [injury; ≥2.0-fold increase in serum creatinine], and F [failure; ≥3.0-fold increase in serum creatinine or receiving dialysis during hospitalization]); Stable-AKI (Class R to R; Class I to I); and Worsening-AKI (Class R to I or F; Class I to F). Multivariate logistic regression analysis indicated that 730-day mortality was independently associated with Class R, I, and F on admission; Class I and F during the 5D-H period; and New-AKI and Worsening-AKI during A-5D and 5D-HD. CONCLUSIONS: AKI on admission, even Class R, was associated with a poor prognosis. An increase in RIFLE class during hospitalization was identified as an important factor for poor prognosis in patients requiring intensive care.

Time-Dependent Changes in N-Terminal Pro-Brain Natriuretic Peptide and B-Type Natriuretic Peptide Ratio During Hospitalization for Acute Heart Failure.

The time-dependent changes in the simultaneous evaluation of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels during hospitalization for acute heart failure (AHF) remain obscure.A total of 356 AHF patients were analyzed. Blood samples were collected within 15 minutes of admission (Day 1), 48-120 hours (Day 2-5) and between days 7 and 21 (Before-discharge). Plasma BNP and serum NT-proBNP were significantly decreased on Days 2-5 and Before-discharge in comparison to Day 1, but the NT-proBNP/BNP ratio was not changed. Patients were divided into 2 groups according to the median NT-proBNP/BNP (N/B) ratio on Day 2-5 (Low-N/B versus High-N/B). A multivariate logistic regression model showed that age (per 1-year increase), serum creatinine (per 1.0-mg/dL increase), and serum albumin (per 1.0-mg/dL decrease) were independently associated with High-N/B (odds ratio [OR]: 1.071, 95%confidence interval [CI]: 1.036-1.108, OR: 1.190, 95%CI: 1.121-1.264 and OR: 2.410, 95%CI: 1.121-5.155, respectively). Kaplan-Meier curve analysis showed that the High-N/B group had a significantly poorer prognosis than the Low-N/B group, and a multivariate Cox regression model revealed that High-N/B was an independent predictor of 365-day mortality (hazard ratio [HR]: 1.796, 95%CI: 1.041-3.100) and HF events (HR: 1.509, 95%CI: 1.007-2.263). The same trend in prognostic impact was significantly observed in both low and high delta-BNP cohorts (< 55% and ≥ 55% BNP value on the start date/BNP value at 2-5-days).A high NT-proBNP/BNP ratio on Day 2-5 was associated with non-cardiac conditions and was associated with adverse outcomes even if BNP was adequately decreased by the treatment of AHF.

Evaluation of Plasma Xanthine Oxidoreductase (XOR) Activity in Patients with Cardiopulmonary Arrest.

Plasma xanthine oxidoreductase (XOR) activity in patients with cardiopulmonary arrest (CPA) has not yet been studied.A total of 1,158 patients who required intensive care and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analyzed. Blood samples were collected within 15 minutes of admission from patients in intensive care patients, which were divided into a CPA group (n = 1,053) and a no-CPA group (n = 105). Plasma XOR activity was compared between the 3 groups and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the CPA group (median, 1,030.0 pmol/hour/mL; range, 233.0-4,240.0 pmol/hour/mL) was significantly higher than in the no-CPA group (median, 60.2 pmol/hour/mL; range, 22.5-205.0 pmol/hour/mL) and control group (median, 45.2 pmol/hour/mL; range, 19.3-98.8 pmol/hour/mL). The regression model showed that out-of-hospital cardiac arrest (OHCA) (yes, odds ratio [OR]: 2.548; 95% confidence interval [CI]: 1.098-5.914; P = 0.029) and lactate levels (per 1.0 mmol/L increase, OR: 1.127; 95% CI: 1.031-1.232; P = 0.009) were independently associated with high plasma XOR activity (≥ 1,000 pmol/hour/mL). Kaplan-Meier curve analysis indicated that the prognosis, including all-cause death within 30 days, was significantly poorer in high-XOR patients (XOR ≥ 6,670 pmol/hour/mL) than in the other patients.Plasma XOR activity was extremely high in patients with CPA, especially in OHCA. This would be associated with a high lactate value and expected to eventually lead to adverse outcome in patients with CPA.

Trends in Sudden Death Following Admission for Acute Heart Failure.

Few studies on sudden death (SD) after admission for acute heart failure (AHF) have been published. A total of 1,664 patients with AHF were enrolled in this study, and 1,261 patients who were successfully followed up during the first year after admission were analyzed. The primary end point was SD, which was defined as out-of-hospital cardiac arrest. The median follow-up period from admission was 1,008 days (range 408 to 2,132). In total, 505 patients (40.0%) died: 341 (67.5%) died of cardiovascular causes and 55 (10.9%) died of other causes. Of the 505 who died, 80 (15.8%) experienced SD. The proportion of SDs increased in the later phases of follow-up (0 to 1 year, 10.3%; 1 to 2 years, 18.0%; 2 to 5 years, 18.8%; ≥5 years, 28.2%; p <0.001). A multivariate logistic regression model showed that younger age was independently associated with SD (60 to 69 years: odds ratio 2.249, 95% confidence interval 1.060 to 4.722; <60 years: odds ratio 3.863, 95% confidence interval 1.676 to 8.905). Kaplan-Meier curves showed that the incidence of cardiovascular death was highest during the acute phase, whereas the incidence of SD increased gradually over the entire follow-up period. In conclusion, the incidence of SD was surprisingly high in patients with AHF, accounting for 16% of long-term mortality. The proportion of SDs increased during the very late follow-up phases.

Type III procollagen peptide level can indicate liver dysfunction associated with volume overload in acute heart failure.

AIM: The role of serum type III procollagen peptide (P3P) level in the acute phase of acute heart failure (AHF) requires clarification. We hypothesized that serum P3P level is temporarily higher during the acute phase, reflecting liver dysfunction due to congestion. METHODS AND RESULTS: A total of 800 AHF patients were screened, and data from 643 patients were analysed. Heart failure was diagnosed by the treating physician according to the European Society of Cardiology (ESC) guidelines, and included patients being treated with high-concentration oxygen inhalation (including mechanical support) for orthopnea, inotrope administration, or mechanical support for low blood pressure, and various types of diuretics for peripheral or pulmonary oedema. In all cases, diuretics or vasodilators were administered to treat AHF. The patients were divided into three groups according to their quartile (Q) serum P3P level: low-P3P (Q1, P3P ≤ 0.6 U/mL), mid-P3P (Q2/Q3, 0.6 < P3P <1.2 U/mL), and high-P3P (Q4, P3P ≥ 1.2 U/mL). The plasma volume status (PVS) was calculated using the following formula: ([actual PV - ideal PV]/ideal PV) × 100 (%). The primary endpoint was 365 day mortality. A Kaplan-Meier curve analysis showed that prognoses, including all-cause mortality and heart failure events within 365 days, were significantly (P < 0.001) worse in the high-P3P group when compared with the mid-P3P and low-P3P groups. A multivariate logistic regression analysis showed that high PVS (Q4, odds ratio [OR]: 4.702, 95% CI: 2.012-20.989, P < 0.001), high fibrosis-4 index (Q4, OR: 2.627, 95% CI: 1.311-5.261, P = 0.006), and low estimated glomerular filtration rate per 10 mL/min/1.73 m2 decrease (OR: 1.996, 95% CI: 1.718-2.326, P < 0.001) were associated with high P3P values. The Kaplan-Meier curve analysis demonstrated a significantly lower survival rate, as well as a higher rate of heart failure events, in the high-P3P and high-PVS groups when compared with the other groups. A multivariate Cox regression model identified high P3P level and high PVS as an independent predictor of 365 day all-cause mortality (hazard ratio [HR]: 2.249; 95% CI: 1.081-3.356; P = 0.026) and heart failure events (HR: 1.586, 95% CI: 1.005-2.503, P = 0.048). CONCLUSION: A high P3P level during the acute phase of AHF served as a comprehensive biomarker of liver dysfunction with volume overload (i.e. liver congestion) and renal dysfunction. A high P3P level at admission may be able to predict adverse outcomes in AHF patients.

Successful treatment of a patient with type-A acute aortic dissection with emergent percutaneous coronary intervention and thoracic endovascular aortic repair under percutaneous cardiopulmonary support: a case report.

Background: Type-A acute aortic dissection (AAD) with acute coronary involvement can be instantly fatal. The patient's haemodynamics can easily collapse, so rapid decisions regarding treatment strategy are essential. Case summary: A 76-year-old man requested an ambulance because of sudden back pain and paraplegia. He was admitted to the emergency room with cardiogenic shock due to acute myocardial infarction with ST-segment elevation. Computed tomography angiography revealed a thrombosed AAD from the ascending to the distal aorta after the renal artery bifurcation, suggesting a retrograde DeBakey type IIIb (DeBakey IIIb + r, Stanford type-A) dissection. He suddenly developed ventricular fibrillation with cardiac arrest and haemodynamic collapse. We thus performed percutaneous coronary intervention (PCI) and thoracic endovascular aortic repair under percutaneous cardiopulmonary support (PCPS). Percutaneous cardiopulmonary support and respiratory support were withdrawn 5 and 12 days after admission, respectively. The patient was transferred to the general ward on Day 28; he was eventually discharged to a rehabilitation hospital on Day 60, having recovered completely. Conclusion: Immediate decisions regarding treatment strategy are essential. Non-invasive emergent treatment strategies (such as PCI and TEVAR under PCPS) may be options for critically ill patients with type-A AAD.

The Prognostic Impact of Hospital Transfer after Admission due to Acute Heart Failure.

The prognostic impact of transfer to another hospital among acute heart failure (AHF) patients has not been well elucidated.Of the 800 AHF patients analyzed, 682 patients were enrolled in this study for analysis. The subjects were divided into two groups according to their discharge location: discharge home (Group-H, n = 589) or transfer to another hospital for rehabilitation (Group-T, n = 93). The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and heart failure (HF) events (death, readmission-HF), in Group-T than that in Group-H (P < 0.001, respectively). A multivariate Cox regression model showed that Group-T was an independent predictor of 365-day all-cause death (hazard ratio: 2.618, 95% confidence interval [CI]: 1.510-4.538, P = 0.001). The multivariate logistic regression analysis showed that aging (per 1-year-old increase, odds ratio [OR]: 1.056, 95% CI: 1.028-1.085, P < 0.001), female gender (OR: 2.128, 95% CI: 1.287-3.521, P = 0.003), endotracheal intubation during hospitalization (OR: 2.074, 95% CI: 1.093-3.936, P = 0.026), and increased Controlling Nutritional Status score on admission (per 1.0-point increase, OR: 1.247, 95% CI: 1.131-1.475, P < 0.001) were associated with transfer to another hospital after AHF admission. The prognosis, including all-cause death, was determined to be significantly poorer in patients who were transferred to another hospital, as their activities of daily living were noted to lessen before discharge (n = 11) compared to others (n = 82).Elderly AHF patients suffering from malnutrition were difficult to discharge home after AHF admission, and transfer to another hospital only led to adverse outcomes. Appropriate rehabilitation during definitive hospitalization appears necessary for managing elderly patients in the HF pandemic era.

Successful Treatment of Thrombocytopenia, Anasarca, Fever, Reticulin Myelofibrosis/Renal Insufficiency, and Organomegaly Syndrome Using Plasma Exchange Followed by Rituximab in the Intensive Care Unit.

Thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal insufficiency, and organomegaly (TAFRO) syndrome is treated using corticosteroids and/or immunosuppressive agents as first-line therapy. We report the case of a 69-year-old female with TAFRO syndrome in which the patient presented multiple organ failure and steroid resistance, which was successfully treated using plasma exchange (PE) followed by rituximab. Decisions regarding the next treatment, including PE, are urgent for patients with steroid-resistant TAFRO syndrome. Since it is considered that immunosuppressive agents may be removed by PE, the performance of PE before treatment with immunosuppressive agents might be an option for steroid-resistant TAFRO syndrome.

Clinical Significance of Low-Triiodothyronine Syndrome in Patients Requiring Non-Surgical Intensive Care　- Triiodothyronine Is a Comprehensive Prognostic Marker for Critical Patients With Cardiovascular Disease.

Background: Low-triiodothyronine (T3) syndrome is a known complication in intensive care unit (ICU) patients, but the underlying mechanisms and prognostic impact are unclear. Methods and Results: This study retrospectively enrolled 2,976 patients who required care in the ICU. Of these patients, 2,425 were euthyroid and were divided into normal (n=1,666; free T3 [FT3] ≥1.88 µIU/L) and low-FT3 (n=759; FT3 <1.88 µIU/L) groups. Multivariate logistic regression analysis revealed that prognostic nutritional index >46.03 (odds ratio [OR] 2.392; 95% confidence interval [CI] 1.904-3.005), age (per 1-year increase; OR 1.022; 95% CI 1.013-1.031), creatinine (per 0.1-mg/dL increase; OR 1.019; 95% CI 1.014-1.024), and C-reactive protein (per 1-mg/dL increase; OR 1.123; 95% CI 1.095-1.151) were independently associated with low FT3. Survival rates (within 365 days) were significantly lower in the low-FT3 group. A multivariate Cox regression model showed that low FT3 was an independent predictor of 365-day mortality (hazard ratio 1.785; 95% CI 1.387-2.297). Low-T3 syndrome was significantly more frequent in patients with non-cardiovascular than cardiovascular diseases (73.5% vs. 25.8%). Prognosis was significantly poorer in the low-FT3 than normal group for patients with cardiovascular disease, particularly those with acute coronary syndrome and acute heart failure. Conclusions: Low-T3 syndrome was associated with aging, inflammatory reaction, malnutrition, and renal insufficiency and could lead to adverse outcomes in patients admitted to a non-surgical ICU.

Clinical significance of the N-terminal pro-brain natriuretic peptide and B-type natriuretic peptide ratio in the acute phase of acute heart failure.

AIMS: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels are rarely evaluated simultaneously in the acute phase of acute heart failure (AHF). METHOD AND RESULTS: A total of 1207 AHF patients were enrolled, and 1002 patients were analysed. Blood samples were collected within 15 min of admission. Patients were divided into two groups according to the median value of the NT-proBNP/BNP ratio [low-NT-proBNP/BNP group (Group L) vs. high-NT-proBNP/BNP group (Group H)]. A multivariate logistic regression model showed that the C-reactive protein level (per 1-mg/dL increase), Controlling Nutrition Status score (per 1-point increase), and estimated glomerular filtration rate (eGFR, per 10-mL/min/1.73 m2 increase) were independently associated with Group H [odds ratio (OR) 1.049, 95% confidence interval (CI) 1.009-1.090, OR 1.219, 95% CI 1.140-1.304, and OR 1.543, 95% CI 1.401-1.698, respectively]. A Kaplan-Meier curve analysis showed that the prognosis was significantly poorer in Group H than in Group L, and a multivariate Cox regression model revealed Group H to be an independent predictor of 180-day mortality [hazard ratio (HR) 3.084, 95% CI 1.838-5.175] and HF events (HR 1.963, 95% CI 1.340-2.876). The same trend in the prognostic impact was significantly observed in the low-BNP (<810 pg/mL, n = 501), high-BNP (≥810 pg/mL, n = 501), and low-eGFR (<60 mL/min/1.73 m2, n = 765) cohorts, and tended to be observed in normal-eGFR (≥60 mL/min/1.73 m2, n = 237) cohort. CONCLUSION: A high NT-proBNP/BNP ratio was associated with a non-cardiac condition (e.g. inflammatory reaction, nutritional status, and renal dysfunction) and is independently associated with adverse outcomes in AHF.

Clinical Significance of the Fibrosis-4 Index in Patients with Acute Heart Failure Requiring Intensive Care.

The Fibrosis-4 (FIB4) index could indicate the liver fibrosis in patients with chronic hepatic diseases. It was calculated using the following formula: (age × aspartate aminotransferase [U/L]) / (platelet count [103/µL] × âˆšalanine aminotransferase [U/L]). However, the clinical impact of the FIB4 index in the acute phase of acute heart failure (AHF) has not been sufficiently investigated.A total 1,468 AHF patients were analyzed. The median FIB4 index was 2.71 [1.85-4.22]. The patients were divided into three groups according to the quartiles of their FIB4 index (low-FIB4 [Q1, ≤ 1.847], middle-FIB4 [Q2/Q3, 1.848-4.216], and high-FIB4 [Q4, ≥ 4.216] groups). A Kaplan-Meier curve analysis showed that the prognosis, such as all-cause mortality and HF events within 365 days, was significantly poorer in the high-FIB4 group than in the middle-FIB4 and low-FIB4 groups. A multivariate Cox regression model identified high FIB4 index as an independent predictor of 365-day all-cause death (hazard ratio (HR): 1.660, 95% CI: 1.136-2.427) and HF events (HR: 1.505, 95% CI: 1.145-1.978). The multivariate logistic regression analysis showed that the high plasma volume status (PVS) (Q4, odds ratio [OR]: 2.099, 95% CI: 1.429-3.082), low systolic blood pressure (SBP) (< 100 mmHg, OR: 3.825, 95% CI: 2.504-5.840), and low left ventricular ejection fraction (< 40%, OR: 1.321, 95% CI: 1.002-1.741) were associated with a high FIB4 index.A high FIB4 index can predict adverse outcomes in AHF patients, which indicate that congestive liver and liver hypoperfusion occur due to low cardiac output in the acute phase of AHF.

The prognostic impact of the serum heart-type fatty acid-binding protein level in patients with sepsis who were admitted to the non-surgical intensive-care unit.

Ongoing myocardial damage at the acme of the sepsis status has not been sufficiently evaluated. The clinical data of 160 sepsis patients who require intensive care and 127 outpatients with chronic heart failure (HF) were compared as a retrospective cohort study. Thereafter, the sepsis patients were divided into 3 groups according to the serum heart-type fatty acid-binding protein (H-FABP) quartiles [low H-FABP = Q1 (n = 39), middle H-FABP = Q2/Q3 (n = 81), and high H-FABP = Q4 group (n = 40)]. The H-FABP level was measured within 15 min of admission. The serum H-FABP levels in the sepsis patients [26.6 (9.3-79.0) ng/ml] were significantly higher than in the choric HF patients [6.6 (4.6-9.7) ng/ml]. A Kaplan-Meier curve showed that the survival rate of the high-H-FABP group was significantly lower than that of the middle- and low-H-FABP groups. The multivariate Cox regression analysis for the 365-day mortality showed that the high-H-FABP group (hazard ratio: 6.544, 95% confidence interval [CI] 2.026-21.140; p = 0.002) was an independent predictor of the 365-day mortality. The same trend in the prognostic impact was significantly (p = 0.015) observed in the cohort that had not been suffering from the cardiac disease before admission. The serum H-FABP level was an independent predictor of the 365-day mortality in the patients who were emergently hospitalized in the intensive-care unit due to sepsis. Ongoing myocardial damage was detected in the majority of patients with sepsis, suggesting that ongoing myocardial damage might be a candidate predictor of adverse outcomes in sepsis patients.

Time-dependent changes in plasma xanthine oxidoreductase during hospitalization of acute heart failure.

AIMS: The aim of present study is to evaluate the clinical significance of the time-dependent changes in xanthine oxidoreductase (XOR) activity during hospitalization for acute heart failure (AHF). METHODS AND RESULTS: A total of 229 AHF patients who visited to emergency room were prospectively enrolled, and 187 patients were analysed. Blood samples were collected within 15 min of admission (Day 1), after 48-72 h (Day 3), and between Days 7 and 21 (Day 14). The AHF patients were divided into two groups according to the XOR activity on Day 1: the high-XOR group (≥100 pmol/h/mL, n = 85) and the low-XOR group (<100 pmol/h/mL, n = 102). The high-XOR patients were assigned to two groups according to the rate of change in XOR from Day 1 to Day 14: the decreased group (≥50% decrease; n = 70) and the non-decreased group (<50% decrease; n = 15). The plasma XOR activity significantly decreased on Days 3 and 14 [23.6 (9.1 to 63.1) pmol/h/mL and 32.5 (10.2 to 87.8) pmol/h/mL, respectively] in comparison with Day 1 [78.5 (16.9 to 340.5) pmol/h/mL]. A Kaplan-Meier curve indicated that the prognosis, including heart failure (HF) events (all-cause death and readmission by HF) within 365 days, was significantly poorer in the low-XOR patients than in the high-XOR patients and was also significantly poorer in the non-decreased group than in the decreased group. CONCLUSIONS: The plasma XOR activity was rapidly decreased by the appropriate treatment of AHF. Although high-XOR activity on admission was not associated with increased HF events in AHF, high-XOR activity that was not sufficiently reduced during appropriate treatment was associated with increased HF events.

Systolic blood pressure and cardiac mortality related to serum total bilirubin levels at admission in patients with acute heart failure.

The impact of elevated total bilirubin (Tbil) levels on adverse clinical outcomes in patients with acute heart failure (HF) has not been fully established, although liver damage is common among these patients. We therefore examined the associations between Tbil levels at admission and systolic blood pressure (SBP) in patients with acute HF in an emergency setting and to evaluate clinical outcomes related to elevated Tbil, particularly in patients with SBP < 100 mmHg. Clinical data and outcomes in acute HF patients (n = 877) were compared according to Tbil quartiles. SBP values < 100 mmHg were more prevalent among patients in the highest quartile (Tbil ≥ 1.0 mg/dL) vs. others (15.4% vs. 3.1%, p < 0.001). Tbil levels were inversely and significantly correlated with SBP at admission (Spearman's ρ, - 0.243; p < 0.001). Kaplan-Meier estimate survival curves showed that event-free survival was worse among patients in the highest Tbil quartile vs. others (78.5% vs. 90.4%, p < 0.001). When comparing survival rates among patients in SBP < 100 mmHg (n = 50), the difference of survival rate became larger for the patients in the highest quartile (n = 29) vs. others (n = 21) (41.4% vs. 77.7%, p < 0.001). Multivariate Cox proportional hazard analysis showed that Tbil ≥ 1.3 mg/dL, not SBP or B-type natriuretic peptide, independently and significantly predicted cardiac death within 180 days in acute HF patients with SBP < 100 mmHg (hazard ratio 3.74; 95% confidence interval 1.39-10.05; p < 0.001). In conclusion, Tbil levels were inversely correlated with SBP at admission in patients with acute HF. Tbil levels independently predicted the risk of 180-day cardiac mortality, especially in acute HF patients with SBP < 100 mmHg.

Characteristics of Patients with an Abnormally Decreased Plasma Xanthine Oxidoreductase Activity in Acute Heart Failure Who Visited the Emergency Department.

BACKGROUND: The factors associated with a low plasma xanthine oxidoreductase (XOR) activity were not elucidated in patients with acute heart failure (AHF). METHODS: Two-hundred and twenty-nine AHF patients who visited the emergency department were prospectively analyzed. AHF patients were divided into 3 groups according to the plasma XOR quartiles (Q1 = low-XOR group [n = 57], Q2/Q3 = middle-XOR group [n = 115], and Q4 = high-XOR group [n = 57]). The prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) score were evaluated. RESULTS: The multivariate logistic regression model showed that the nutritional status (PNI: OR 1.044, 95% CI 1.000-1.088; CONUT: OR 3.805, 95% CI 1.158-12.498), age, and serum creatinine level were independently associated with a low plasma XOR activity. The Kaplan-Meier curve showed a significantly lower incidence of heart failure events in the low-XOR group than in the middle + high-XOR group (hazard ratio, HR 1.648, 95% CI 1.061-2.559). In particular, a low XOR activity with an increased serum creatinine level (>1.21 mg/dL) was independently associated with heart failure events (HR 1.937, 95% CI 1.199-3.130). CONCLUSION: A low plasma XOR activity was associated with malnutrition, renal dysfunction, and aging in AHF. A low XOR activity complicated with renal dysfunction leads to adverse long-term outcomes.

Plasma xanthine oxidoreductase (XOR) activity in patients who require cardiovascular intensive care.

Hyperuricemia is known to be associated with adverse outcomes in cardiovascular intensive care patients, but its mechanisms are unknown. A total of 569 emergency department patients were prospectively analyzed and assigned to intensive care (ICU group, n = 431) or other departments (n = 138). Uric acid (UA) levels were significantly higher in the intensive care patients (6.3 [5.1-7.6] mg/dl vs. 5.8 [4.6-6.8] mg/dL). The plasma xanthine oxidoreductase (XOR) activity in the ICU group (68.3 [21.2-359.5] pmol/h/mL) was also significantly higher than that in other departments (37.2 [15.1-93.6] pmol/h/mL). Intensive care patients were divided into three groups according to plasma XOR quartiles (Q1, low-XOR, Q2/Q3, normal-XOR, and Q4, high-XOR group). A multivariate logistic regression model showed that lactate (per 1.0 mmol/L increase, OR 1.326; 95%, CI 1.166-1.508, p < 0.001) and the Acute Physiology and Chronic Health Evaluation II score (per 1.0 point increase, OR 1.095, 95% CI 1.034-1.160, p = 0.002) were independently associated with the high-XOR group. In-hospital mortality was significantly higher in the high-XOR group (n = 28, 26.2%) than in the normal- (n = 11, 5.1%) and low- (n = 9, 8.3%) XOR groups. The high-XOR group (vs. normal-XOR group) was independently associated with the in-hospital mortality (OR 2.934; 95% CI 1.170-7.358; p = 0.022). Serum UA levels and plasma XOR activity were high in patients admitted to intensive care. The enhanced XOR activity may be one of the mechanisms under which hyperuricemia was associated with adverse outcomes in patients requiring cardiovascular intensive care.

Mechanisms of Urgently Presenting Acute Heart Failure.

The mechanisms of urgently presenting acute heart failure (AHF) are not clear. We evaluated the serum catecholamine values of AHF patients immediately after admission. A total of 1,475 AHF patients were screened, and 484 who were admitted from their homes and in whom serum catecholamine could be evaluated immediately after admission were analyzed. The patients were divided into three groups according to the time interval from the onset of symptoms to admission (OA): < 3 hours (early-OA group; n = 283), 3-24 hours (middle-OA group; n = 142), and ≥24 hours (late-OA group; n = 59). In the early-OA group, the systolic blood pressure (SBP) was significantly higher, orthopnea was more frequent, the pH value was significantly decreased, and the use of noninvasive positive-pressure ventilation was required significantly more often than in the other groups. The serum noradrenaline level was significantly increased in the early-OA group (1.96 [1.02-3.60] ng/mL) than in the middle-OA (1.49 [0.73-3.41] ng/mL) and late-OA (1.40 [0.91-2.42] ng/mL) groups, and the adrenaline level was significantly increased in the early-OA group (0.36 [0.13-1.17] ng/mL) than in the late-OA (0.22 [0.09-0.52] ng/mL) group. A multivariate logistic regression model indicated the early-OA group was independently associated with the SBP > 140 mmHg (odds ratio [OR]: 2.219, 95% CI: 1.375-3.581), midnight/early morning admission (OR: 3.158, 95% CI: 2.048-4.868), and high serum catecholamine value (adrenaline > 0.96 ng/mL, noradrenaline > 3.39 ng/mL, and dopamine > 0.21 ng/mL) (OR 2.091, 95% CI: 1.161-3.767). In conclusion, urgently presented AHF might be induced by an endogenous catecholamine surge, which causes an excessive rise in blood pressure leading to increased after-overload and volume-shift lung congestion.