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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: The importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF. Methods and results: Two hundred eighty‐one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non‐WRF (n = 168), pseudo‐WRF (n = 56), or true‐WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan–Meier curve showed that the survival and heart failure event rate of the true‐WRF group within 1000 days was significantly lower than that of the non‐WRF and pseudo‐WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466–7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893–4.243, P ≤ 0.001, respectively]. The serum heart‐type fatty acid‐binding protein (s‐HFABP) levels were significantly higher in the true‐WRF group than in the non‐WRF and pseudo‐WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true‐WRF group was the s‐HFABP level (odds ratio: 5.472, 95% CI: 2.729–10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s‐HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non‐chronic kidney disease (CKD) patients, respectively. Conclusions: Cardiac biomarkers, especially the s‐HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD. [ABSTRACT FROM AUTHOR]

Aims: Plasma xanthine oxidoreductase (XOR) activity during the acute phase of acute heart failure (AHF) requires further elucidation. Methods and results: One hundred eighteen AHF patients and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analysed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Plasma XOR activity was compared between the two groups, and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the AHF group (median, 104.0 pmol/h/mL; range, 25.9–423.5 pmol/h/mL) was significantly higher than that in the control group (median, 45.2 pmol/h/mL; range, 19.3–98.8 pmol/h/mL). The multivariate logistic regression model showed that serum uric acid (per 1.0 mg/dL increase, odds ratio: 1.280; 95% confidence interval: 1.066–1.536; P = 0.008) and lactate levels (per 1.0 mmol/L increase, odds ratio: 1.239; 95% confidence interval: 1.040–1.475; P = 0.016) were independently associated with high plasma XOR activity (>300 pg/h/mL) during the acute phase of AHF. Conclusions: Plasma XOR activity was extremely high in patients with severely decompensated AHF. This would be associated with a high lactate value and would eventually lead to hyperuricaemia in patients with AHF. [ABSTRACT FROM AUTHOR]

The optimum method of managing anemia during the acute phase of acute heart failure (AHF) remains to be elucidated. The data from 1109 AHF patients were enrolled in present study. The hemoglobin (Hb) levels were evaluated in all patients at admission (day 1) and 3 days after admission (day 3), and in survival discharge patients (n = 998) before discharge (pre-discharge). The serum hemoglobin levels were significantly lower on day 3 (11.2 (9.6–12.9) g/dl) than on day 1 (12.4 (10.4–14.2) g/dl) and at pre-discharge (11.6 (10.1–13.2) g/dl). A multivariate Cox regression model showed that mild anemia (11.0 ≤ Hb ≤ 12.9 g/dl, n = 316) and severe anemia (Hb ≤ 10.9 g/dl, n = 517) on day 3 were independent predictors of HF event (hazard ratio (HR) 1.542, 95% confidence interval (CI)1.070–2.221, HR 2.026, 95% CI 1.439–2.853), and severe anemia on day 3 were independent predictors of 365-day mortality (HR 2.247, 95% CI 1.376–3.670). The prognosis, including all-cause death and HF events, in patients with non-anemia on day 1 was significantly poorer in severe new-anemia patients on day 3 (n = 44) than in mild new-anemia patients on day 3 (n = 153) and non-anemia patients on day 3 (n = 252). In patients with anemia on day 1, the prognosis was significantly poorer in patients with severe anemia on day 3 (n = 190) than in those with non-anemia or mild anemia on day 3 (n = 482). The hemoglobin level after the initial treatment might be easily influenced by clinical decongestion. Successfully treated decongestion can help maintain the hemoglobin levels. It, therefore, leads to a prognostic benefit in patients with AHF. These findings might underscore the importance of hemoglobin management of the acute phase of AHF. [ABSTRACT FROM AUTHOR]

The prevalence of atrial fibrillation (AF) has been increasing in aging societies. The prognostic impact of AF associated with worsening heart failure (HF) remains obscure. We analyzed 1170 acute heart failure (AHF) patients who required intensive care. Patients were assigned to two groups according to the prevalence of AF: no episode of AF (n = 940) and pre-existing AF (Group-1, n = 230). Patients with no episode of AF (n = 940) were further divided into two groups according to presence of new-onset of AF after admission (Group-2a, n = 258) or not (Group-2b, n = 682). Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-1 compared to the Group-2b. However, a multivariate Cox regression model showed that the Group-1 was not an independent predictor of 1000-day mortality and HF-events. Furthermore, Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-2a than in the Group-2b. A multivariate Cox regression model revealed that the Group-2a was an independent predictor of 1000-day mortality (HR: 1.403, 95% CI: 1.018–1.934) and HF-events (HR: 1.352, 95% CI: 1.071–1.708). A multivariate logistic regression model showed that only age (≥75 years old) was independently associated with new-onset of AF after admission (odds ratio: 1.556, 95% CI: 1.130–2.143). New-onset AF associated with worsening HF increases with age and is independently-associated with adverse outcome in patients with AHF. • The prognostic impact of AF associated with worsening heart failure (HF) is not obscured. • A multivariate Cox regression model showed that the pre-AF was not an independent predictor of 1000-day mortality and HF event. • A multivariate Cox regression model revealed that the new-onset AF group was an independent predictor of 1000-day mortality. • A multivariate logistic regression model showed that only age was independently associated with new onset of AF after admission. [ABSTRACT FROM AUTHOR]

Background: Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure (AHF) is unclear. The biomarker for the prediction of true WRF, which is associated with a poor prognosis, is also obscured. Methods and Results: The total 1,083 patients with AHF were analyzed. A WRF, indicated by a change in serum creatinine ≥ 0.3 mg/ml within the first 5 days, occurred in 360 patients, while no WRF, indicated by a change < 0.3 mg/dl in 723 patients. Acute kidney injury (AKI) on admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value, and placed into groups based on the degree of AKI: no-AKI (n=751), Class R (risk; n=193), Class I (injury; n=41), or Class F (failure; n=98). The patients were assigned to another four groups: no-WRF/no-AKI (n=512), no-WRF/AKI (n=211), WRF/no-AKI (n=239) and WRF/AKI (n=121). A multivariate Cox regression model found that no-WRF/AKI and WRF/AKI were independently associated with 365-days mortality (hazard ratio [HR]: 1.916; 95%confidence interval [CI]: 1.234-2.974, and HR: 3.622; 95%CI: 2.332-5.624). Kaplan-Meier survival curves showed that the rate of 365-days mortality was significantly poorer in the no-WRF/AKI and WRF/AKI groups than in the WRF/No-AKI and no-WRF/no-AKI group, and in Class I and Class F than in Class R and the no-AKI group. We next analyzed 283 AHF patients. Their biomarkers were measured within 30 minutes of admission. Patients were assigned to the non-WRF (n=143), no-WRF/AKI (n=38), WRF/no-AKI (n=53) and WRF/AKI (n=47) groups. The multivariate logistic regression model indicated that the predictive biomarker for the WRF/AKI group was the serum heart-type fatty acid-binding protein (s-HFABP) level (odds ratio: 9.235; 95%CI: 3.101-27.509). S-HFABP demonstrated the optimum balance between sensitivity and specificity (80.9%, 76.5%; area under the curve=0.831) at 22.4 ng/ml for the WRF/AKI group. Conclusions: The presence of AKI on admission, especially Class I and Class F status, is associated with a poor prognosis despite the lack of an WRF within the first 5 days. Cardiac biomarkers, the s-HFABP, might predict the development of true WRF (WRF/AKI) in AHF patients. [ABSTRACT FROM AUTHOR]