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.

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.

Background: The prognostic impact of hyperuricemia and the factors that induce hyperuricemia in cardiovascular intensive care patients remain unclear. Methods and results: A total of 3257 emergency department patients were screened, and data for 2435 patients who were admitted to an intensive care unit were analyzed. The serum uric acid level was measured within 15 min of admission. The patients were assigned to a low-uric acid group (uric acid <= 7.0 mg/dl, n=1595) or a high-uric acid group (uric acid >7.0 mg/dl, n=840) according to their uric acid level on admission. Thereafter, the patients were divided into four groups according to the quartiles of their serum uric acid level (Q1, Q2, Q3 and Q4), and uric acid levels and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in a high-uric acid group than in a low-uric acid group, and in Q3 than in Q1 or Q2 and in Q4 than in the other groups. The multivariate logistic regression model for 30-day mortality identified Q4 (odds ratio: 1.856, 95% confidence interval (CI) 1.140-3.022; p=0.013) as an independent predictor of 30-day mortality. The area under the receiver-operating characteristic curve values of the serum uric acid level and APACHE II score for the prediction of 30-day mortality were 0.648 and 0.800, respectively. The category-free net reclassification improvement and integrated discrimination improvement showed that the calculated risk shifted to the correct direction by adding the serum uric acid level to the APACHE II score (0.204, 95% CI 0.065-0.344; p=0.004, and 0.015, 95% CI 0.005-0.025; p=0.004, respectively). The prognosis, including the 365-day mortality, among patients with a high uric acid level and a high APACHE II score was significantly poorer in comparison with other patients. Conclusion: The serum uric acid level, which might be elevated by the various critical stimuli on admission, was an independent predictor in patients who were emergently hospitalized in the intensive care unit. The serum uric acid level is therefore useful as a surrogate biomarker for critical patients in the intensive care unit.

Background: The mechanisms of the increased plasma xanthine oxidoreductase (XOR) activity in outpatients with cardiovascular disease were unclear. Methods and Results: A total of 372 outpatients were screened, and 301 outpatients with cardiovascular disease were prospectively analyzed. Blood samples were collected from patients who visited a daily cardiovascular outpatient clinic. Patients with diabetes mellitus (DM) were significantly more likely to be classified into the high-XOR group (≥100 pg/h/mL; 50%) than the low-XOR group (<100 pmol/h/mL; 28.7%). On multivariate logistic regression analysis, DM (OR, 2.683; 95% CI: 1.441-4.996) was independently associated with high plasma XOR activity in all cohorts. In the diabetic cardiovascular disease patients (n=100), median body mass index (BMI) in the high-XOR group (28.0 kg/m2; IQR, 25.2-29.4 kg/m2, n=32) was significantly higher than in the low-XOR group (23.6 kg/m2; IQR, 21.2-25.7 kg/m2, n=68), and BMI was independently associated with high plasma XOR activity (OR, 1.340; 95% CI: 1.149-1.540). Plasma hydrogen peroxide was significantly higher in DM patients with high plasma XOR activity and obesity (>22 kg/m2) than in other patients. Conclusions: DM with obesity is one of the mechanisms of XOR enhancement in cardiovascular disease. The increase of XOR is a possible pathway for the production of reactive oxygen species in obese cardiovascular disease patients with DM.

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.

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.

AbstractAimsThe 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 resultsA 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.ConclusionsThe 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.

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.

Background: The length of hospital stay (LOHS) after acute heart failure (AHF) is too long in Japan. The clinical approach to shortening LOHS is an urgent issue in the aging Japanese society. Methods and Results: Of 1,473 AHF patients screened, 596 patients >75 years old were enrolled. They were divided by LOHS: <28 days (<28-day group, n=316) and ≥28 days (≥28-day group, n=280). Systolic blood pressure and serum hemoglobin were significantly higher and serum blood urea nitrogen and creatinine significantly lower in the <28-day group than in the ≥28-day group. Non-invasive positive pressure ventilation (NPPV) use was significantly more frequent in the <28-day group than in the ≥28-day group. Furthermore, newly initiated tolvaptan in <12 h was significantly more frequent in the <28-day group than in the ≥28-day group (P=0.004). On multivariate logistic regression analysis, newly initiated tolvaptan in <12 h (OR, 2.574; 95% CI: 1.146-5.780, P=0.022) and NPPV use (OR, 1.817; 95% CI: 1.254-2.634, P=0.002) were independently associated with the <28-day group. The same result was found after propensity score matching for LOHS. Conclusions: LOHS was prolonged in patients with severe HF but could be shortened by early tolvaptan treatment.

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.

Low triiodothyronine (T3) syndrome has recently been evaluated as a prognostic marker of acute heart failure (AHF). However, in which cases low T3 syndrome typically leads to adverse outcomes remain unclear. Of 1,432 AHF patients screened, 1,190 were enrolled. Euthyroidism was present in 956 patients (80.3%), who were divided into 2 groups: the normal group (n = 445, FT3 >= 1.88 mu IU/L) and low-FT3 group (n = 511, FT3 <1.88 mu IU/L). The survival rates and event-free rates within 365 days were significantly lower in the low-FT3 group than in the normal group. A multivariate Cox regression model showed that the low-FT3 group was an independent predictor of 365-day mortality (hazard ratio [HR] 1.429, 95% confidence interval [CI] 1.013 to 2.015) and HF events (HR 1.349, 95% CI 1.047 to 1.739). The multivariate logistic regression analysis revealed that age (per 10year old increase, odds ratio [OR]: 1.186, 95% CI: 1.046 to 1.345) and prognostic nutritional index (PNI; per 1-point increase, OR: 1.067, 95% CI: 1.046 to 1.089) were independently associated with the low-FT3 group. The prognosis in patients with a low PNI and over 75 years old, including all-cause death within 365 days, was significantly poorer in the low-FT3 group than in the normal group. In conclusion, adverse outcomes were predicted by the presence of low T3. AHF patients with low T3 syndrome are strongly associated with aging and malnutrition. Low T3 syndrome complicated with older age and malnutrition is likely to lead to adverse outcomes in patients with AHF. (C) 2019 Elsevier Inc. All rights reserved.

The aim of the present study was to elucidate trends in managing acute heart failure (AHF) patients who require intensive care over a 19-year period. We evaluated a total of 1,475 AHF patients, comparing patient backgrounds, in-hospital management, and prognosis according to the year of admission (2000s group, n = 608 and 2010s group, n = 867). A multivariate logistic regression analysis revealed that age (>= 75 years; odds ratio [OR] 1.334, 95% confidence interval [CI] 1.048 to 1.700), systolic blood pressure (<100 mm Hg; OR 1.934, 95% CI 1.170 to 3.198), left ventricular ejection fraction (>40%; OR 1.441, 95% CI 1.125 to 1.847), and prognostic nutritional index (severe; OR 1.865, 95% CI 1.224 to 2.841) were independently associated with admission in the 2010s group. The use of intra-aortic balloon pumping and noninvasive positive pressure ventilation increased significantly, whereas the need for endotracheal intubation and administration of furosemide and carperitide in the 2010s group decreased significantly compared with the 2000s group. Tolvaptan therapy was introduced from 2010. The duration of intensive care unit admission and total hospitalization in the 2010s group (4 [3 to 6] and 23 [15 to 40] days, respectively) were significantly shorter than in the 2000s group (5 [4 to 8] and 30 [20 to 54] days, respectively). A Kaplan-Meier survival curve analysis showed the survival rate of the 2010s group was significantly poorer compared with the 2000s group (hazards ratio 1.435, 95% CI 1.113 to 1.851). After propensity score matching, the 365-day mortality rates of the 2 groups did not significantly differ. In conclusion, the condition of AHF patients became more critical year by year, leading to poorer long-term prognosis despite improved treatment strategy. These findings will be useful for managing AHF in the next pandemic era. (C) 2019 Elsevier Inc. All rights reserved.

BACKGROUNDS: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. METHODS AND RESULTS: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). CONCLUSIONS:New-onset AF associated with worsening HF increases with age and is independently-associated with adverse outcome in patients with AHF.

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.

Background: The features of sleep-associated acute heart failure (AHF) patients admitted at midnight or early morning (M/E) are unclear.

Background: The relationship between the serum level of uric acid (UA) and the acute kidney injury on admission in patients with acute heart failure (AHF) remain unclear. Methods and results: A total of 1326 AHF patients were screened, and data for 1047 patients who were admitted to the intensive-care unit were analyzed. The patients were assigned to a low-UA group (UA <= 7.0 mg/dl, n = 569) or a high-UA group (UA > 7.0 mg/dl, n = 478) according to their UA level at admission. Acute kidney injury (AKI) at admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value: no-AKI (n = 736) or AKI (n = 311). The patients were therefore assigned to four groups: low-UN/no-AKI (n = 428), high-UA/no-AKI (n = 308), low-UA/AKI (n = 141) and high-UA/AKI (n = 170). The high-UA patients were significantly more frequent in the AKI group than in the non-AKI group among all patients and the non-chronic kidney injury (CKD) cohort. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in the high-UA/AKI group than in the other groups. The multivariate Cox regression model identified only high-UA/AKI as an independent predictor of 365-day mortality (hazard ratio [HR]: 2.511, 95% confidence interval [CI] 1.671-3.772 in all AHF patients, HR: 1.884, 95% CI 1.022-3.473 in non-CKD patients and HR: 3.546, 95% CI 2.136-5.884 in CKD patients). Conclusion: An elevated serum UA level complicated with AKI was an independent predictor of mortality in patients with severely decompensated AHF. (C) 2019 The Authors. Published by Elsevier B.V.

•Whether evaluating plasma volume status (PVS) alone is sufficient remains unclear in acute heart failure.•A multivariate Cox regression model showed that high PVS and high PVS/high Controlling Nutritional Status and high PVS/low prognostic nutritional index were independent predictors of 365-day mortality.•A malnutrition status with a high PVS leads to an adverse outcome.•The simultaneous evaluation of nutrition status and PVS is essential to predict an acute heart failure outcome.