Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease.

BACKGROUND: The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI. METHODS: One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint. RESULTS: Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97). CONCLUSION: Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.

Impact of mannose-binding lectin deficiency on radiocontrast-induced renal dysfunction: a post-hoc analysis of a multicenter randomized controlled trial.

BACKGROUND: Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort. METHODS: 246 patients with advanced non-dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥ 0.5 mg/dL or ≥ 25% within 48 hours) or cystatin C-based (increase of ≥ 10% within 24 hours) CIN. RESULTS: The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥ 10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193-4471) vs. 1997 (IQR 439-3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels ≤ 500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥ 10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01). CONCLUSION: MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

OBJECTIVES: Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). DESIGN: Prospective cohort study. SETTING: University hospital, emergency department. PATIENTS: 632 consecutive patients presenting with acute dyspnoea. MAIN OUTCOME MEASURES: MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. RESULTS: AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, p<0.001 and 4916 (2169-10285) versus 1177 (258-5166) pg/ml, p<0.001 for NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90, 95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off levels in AF patients were significantly higher compared with the optimal cut-off levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500 pg/ml respectively). After adjustment in multivariable Cox proportional hazard analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13 (1.09-1.17), per 100 pmol/l increase, p<0.001). CONCLUSION: In AF patients, NT proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

Pathophysiology of lower extremity edema in acute heart failure revisited.

BACKGROUND: The pathophysiology and key determinants of lower extremity edema in patients with acute heart failure are poorly investigated. METHODS: We prospectively enrolled 279 unselected patients presenting to the Emergency Department with acute heart failure. Lower extremity edema was quantified at predefined locations. Left ventricular ejection fraction, central venous pressure quantifying right ventricular failure, biomarkers to quantify hemodynamic cardiac stress (B-type natriuretic peptide), and the activity of the arginine-vasopressin system (copeptin) also were recorded. RESULTS: Lower extremity edema was present in 218 (78%) patients and limited to the ankle in 22%, reaching the lower leg in 40%, reaching the upper leg in 11%, and was generalized (anasarca) in 3% of patients. Patients in the 4 strata according to the presence and extent of lower leg edema had comparable systolic blood pressure, left ventricular ejection fraction, central venous pressure, and B-type natriuretic peptide levels, as well as copeptin and glomerular filtration rate (P=NS for all). The duration of dyspnea preceding the presentation was longer in patients with more extensive edema (P=.006), while serum sodium (P=.02) and serum albumin (P=.03) was lower. CONCLUSION: Central venous pressure, hemodynamic cardiac stress, left ventricular ejection fraction, and the activity of the arginine-vasopressin system do not seem to be key determinants of the presence or extent of lower extremity edema in acute heart failure.

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure.

INTRODUCTION: The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. METHODS: A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. RESULTS: Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P<0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P<0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P=0.04) in multivariable regression analysis. CONCLUSIONS: Plasma NGAL levels do not adequately predict AKI in patients with AHF.

Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial.

AIMS: The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN. METHODS AND RESULTS: We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48 h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference -3.9 [95% confidence interval (CI), -6.8 to -1] mL/min/1.73 m2, P = 0.009} and similar between groups C and B [mean difference 1.3 (95% CI, -1.7-4.3) mL/min/1.73 m(2), P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9). CONCLUSION: Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT00130598.

A combined cardiorenal assessment for the prediction of acute kidney injury in lower respiratory tract infections.

BACKGROUND: The accurate prediction of acute kidney injury (AKI) is an unmet clinical need. A combined assessment of cardiac stress and renal tubular damage might improve early AKI detection. METHODS: A total of 372 consecutive patients presenting to the Emergency Department with lower respiratory tract infections were enrolled. Plasma B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in a blinded fashion at presentation. The potential of these biomarkers to predict AKI was assessed as the primary endpoint. AKI was defined according to the AKI Network classification. RESULTS: Overall, 16 patients (4%) experienced early AKI. These patients were more likely to suffer from preexisting chronic cardiac disease or diabetes mellitus. At presentation, BNP (334 pg/mL [130-1119] vs 113 pg/mL [52-328], P <.01) and NGAL (269 ng/mL [119-398] vs 96 ng/mL [60-199], P <.01) levels were significantly higher in AKI patients. The predictive accuracy of presentation BNP and NGAL levels was comparable (BNP 0.74; 95% confidence interval [CI], 0.64-0.84 vs NGAL 0.74; 95% CI, 0.61-0.87). In a combined logistic model, a joint BNP/NGAL approach improved the predictive accuracy for early AKI over either biomarker alone (area under the receiver operating characteristic curve: 0.82; 95% CI, 0.74-0.89). The combined categorical cut point defined by BNP >267 pg/mL or NGAL >231 ng/mL correctly identified 15 of 16 early AKI patients (sensitivity 94%, specificity 61%). During multivariable regression analysis, the combined BNP/NGAL cutoff remained the independent predictor of early AKI (hazard ratio 10.82; 95% CI, 1.22-96.23; P = .03). CONCLUSION: A model combining the markers BNP and NGAL is a powerful predictor of early AKI in patients with lower respiratory tract infection.

Increasing B-type natriuretic peptide levels predict mortality in unselected haemodialysis patients.

AIMS: Cardiac disease is the major cause of death in patients undergoing chronic haemodialysis. Recent studies have found that B-type natriuretic peptide (BNP) levels accurately reflect the cardiovascular burden of dialysis patients. However, the prognostic potential of BNP measurements in dialysis patients remains unknown. METHODS AND RESULTS: The study included 113 chronic dialysis patients who were prospectively followed up. Levels of BNP were measured at baseline and every 6 months thereafter. The potential of baseline BNP and annual BNP changes to predict all-cause and cardiac mortality were assessed as endpoints. Median follow-up was 735 (354-1459) days; 35 (31%) patients died, 17 (15%) of them from cardiac causes. Baseline BNP levels were similar among survivors and non-survivors, and failed to predict all-cause and cardiac death. Cardiac death was preceded by a marked increase in BNP levels. In survivors BNP levels remained stable [median change: +175% (+20-+384%) vs. -14% (-35-+35%) over the 18 months preceding either death or the end of follow-up, P< 0.001]. Hence, annual BNP changes adequately predicted all-cause and cardiac death in the subsequent year {AUC(all-cause) = 0.70 [SD 0.05, 95% CI (0.60-0.81)]; AUC(cardiac) = 0.82 [SD 0.04, 95%CI (0.73-0.90)]}. A BNP increase of 40% provided the best cut-off level. Cox regression analysis confirmed that annual increases over 40% were associated with a seven-fold increased risk for all-cause and cardiac death. CONCLUSIONS: Annual BNP increases above 40% predicted all-cause and cardiac death in the subsequent year. Hence, serially measuring BNP levels may present a novel tool for risk stratification and treatment guidance of end-stage renal disease patients on chronic dialysis.

Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.

Central venous pressure and impaired renal function in patients with acute heart failure.

AIMS: To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department. METHODS AND RESULTS: Central venous pressure was determined non-invasively using compression sonography in 140 patients with AHF at presentation. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥ 0.3 mg/dL during hospitalization. In the study cohort [age 77 ± 12 years, B-type natriuretic peptide 1862 ± 1564 pg/mL, left ventricular ejection fraction 40 ± 15%, estimated glomerular filtration rate (eGFR) 58 ± 28 mL/min, and CVP 13.2 ± 6.9 cmH(2)O], 51 patients (36%) developed WRF. No significant association between CVP at presentation or discharge and concomitant eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed. However, in patients with systolic blood pressure (SBP) <110 mmHg and concomitant high CVP (>15 cmH(2)O), eGFR was significantly lower at presentation and discharge (29 ± 17 vs. 47 ± 19 mL/min/1.73 m(2), P = 0.039 and 26 ± 10 vs. 53 ± 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at presentation and at discharge did not differ between patients with or without in-hospital WRF (12.6 ± 7.2 vs. 13.5 ± 6.7 cmH(2)O, P = 0.503 and 7.4 ± 6.5 vs. 7.7 ± 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively). However, patients with CVP in the lowest tertile (<10 cmH(2)O) at presentation were more likely to develop WRF within the first 24 h than patients with CVP in the highest tertile (>15 cmH(2)O) (18 vs. 4%, P = 0.046). CONCLUSION: In AHF, combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may also be associated with short-term WRF. The pathophysiology of WRF and the role of CVP seem to be more complex than previously thought.

Diagnostic and prognostic value of uric acid in patients with acute dyspnea.

BACKGROUND: Uric acid was shown to predict outcome in patients with stable chronic heart failure. Its impact in patients admitted in the Emergency Department with acute dyspnea, however, remains unknown. METHODS: We prospectively investigated the diagnostic and prognostic value of uric acid in 743 unselected patients presenting to the Emergency Department with acute dyspnea. RESULTS: Uric acid at admission was higher in patients with acute decompensated heart failure (51% of the cohort) as compared with patients with noncardiac causes of dyspnea (median, 447 micromol/L vs 340 micromol/L, P <.001). The area under the receiver operating characteristic curve for the accuracy to detect acute decompensated heart failure was inferior for uric acid (0.70) than for B-type natriuretic peptide (area under the receiver operating characteristic curve 0.91, P <.001). Patients in the highest uric acid tertile more often required admission to the hospital (92% vs 74% in the first tertile, P <.001) and had higher in-hospital mortality (13% vs 4% in the first tertile, P <.001). Cumulative 24-month mortality rates were 28% in the first, 31% in the second, and 50% in the third tertile (P <.001). After adjustment in multivariable Cox proportional hazard analysis, uric acid predicted 24-month mortality independently of B-type natriuretic peptide (P=.003). CONCLUSIONS: Our study first shows that uric acid, measured at Emergency Department admission or hospital discharge, is a powerful predictor of long-term outcome in dyspneic patients.

Incidence of contrast-induced nephropathy with volume supplementation--insights from a large cohort.

OBJECTIVE: The present study was performed to determine the effect of combined intravenous and oral volume supplementation on the incidence of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: Consecutive patients (n = 958) receiving iomeprol 350 during PCI were evaluated prospectively for the development of CIN. All patients received protocol-defined intravenous and oral volume supplementation. CIN was defined as an increase in serum creatinine of at least 44 micromol/l within 48 h. RESULTS: Of the 958 patients enrolled in the study, 147 (15%) were diabetic and 107 (11%) had stage III renal disease. The average baseline glomerular filtration rate was 88 +/- 25 ml/min/1.73 m(2). During the intervention an average of 238 +/- 86 ml of contrast medium was administered. CIN developed in 13 of 958 (1.4%; 95% confidence interval 0.6-2.1%) patients. The incidence of CIN was low even in predefined risk subgroups (women: 2.4%, diabetics: 2.7%, patients with stage III kidney disease: 6.5%). CONCLUSIONS: The incidence of CIN is low when preprocedural fluid volume supplementation is used.

Impact of body temperature on in-hospital and long-term mortality in patients with acute heart failure.

OBJECTIVES: Body temperature (BT) was shown to have impact on outcome in several medical conditions. This study investigated the prognostic impact of BT in patients with acute heart failure (HF). DESIGN AND PATIENTS: The B-type natriuretic peptide for Acute Shortness of breath EvaLuation (BASEL) study prospectively enrolled 452 consecutive patients presenting with acute dyspnoea to the emergency department. Among these, 170 patients had a final discharge diagnosis of acute HF and a documented BT on presentation. The primary endpoint was cardiovascular mortality during long-term follow-up. Morbidity was documented as secondary endpoint. RESULTS: BT on presentation was 37.2 degrees C (SD 0.9) and ranged from 34.8-40.4 degrees C. Patients were divided into quartiles of BT. Initial morbidity as reflected by intensive care unit admission rate was significantly higher among patients in the highest quartile (38% versus 13% in the first quartile, p <0.05). Length of stay in hospital was significantly increased by 2.7 days per one degree rise in BT. A total of 64 cardiovascular deaths occurred (38%). Kaplan-Meier analysis showed no apparent difference in long-term cardiovascular mortality among quartiles of BT. Cardiovascular mortality rate was 47% in the first (<36.6 degrees C), 26% in the second (36.7-37.2 degrees C), 44% in the third (37.3-37.8 degrees C) and 35% in the fourth quartile ( 37.9 degrees C; P = 0.31) at 720 days. In addition, Cox regression analysis adjusted for age and sex showed no association between BT and either in-hospital (HR 0.59, 95% CI 0.26-1.35; P = 0.21) or long-term cardiovascular mortality (HR 0.91, 95% CI 0.67-1.24; P = 0.55). CONCLUSION: In patients with acute HF, BT on presentation is not associated with in-hospital or long-term cardiovascular mortality, but is associated with short-term morbidity. However, it is important to stress that our findings relate to central BT and do not negate the undisputed value of assessing peripheral BT, which reflects peripheral hypoperfusion.

Multimarker strategy for risk prediction in patients presenting with acute dyspnea to the emergency department.

BACKGROUND: Multimarker approaches improve risk prediction in patients presenting with acute coronary syndrome. We hypothesized that simultaneous assessment of B-type natriuretic peptide (BNP), cardiac troponin I (cTNI) and C-reactive protein (CRP) enables clinicians to better predict risk among patients with acute dyspnea presenting to the emergency department. METHODS AND RESULTS: In this post-hoc analysis of the B-Type natriuretic peptide for Acute Shortness of Breath Evaluation (BASEL) study, above biomarkers were available in 305 patients. Death occurred in 123 (40%) patients within 24 months of follow-up. Using prospectively defined cut-off points (BNP>100 pg/mL; cTNI>0.8 microg/L; CRP>5 mg/L) and categorizing patients by the number of elevated cardiac biomarkers, the 24 months risk of death increased in proportion to the number of cardiac biomarkers elevated (p<0.001 for trend). Elevated biomarkers significantly predicted increased risk of death at 24 months of follow-up in univariate Cox models (BNP: RR 4.78, 95%CI: 2.51-9.14; p<0.001; cTNI: RR: 2.29, 95%CI: 1.61-3.26, p<0.001; CRP: RR 1.98, 95%CI: 1.28-3.08; p=0.002). Multivariable Cox regression analysis revealed that elevated levels of BNP (p<0.001) and TNI levels (p<0.002) indicated increased risk of death during long-term follow-up, while only a statistical trend was seen for elevated CRP (p=0.09). Comparably, risk of death or rehospitalization significantly increased with the number of elevated biomarkers. CONCLUSIONS: Our findings suggest that a simple multimarker approach with simultaneous assessment of BNP, and cTNI demonstrates potential to assist clinicians in predicting risk of death and/or rehospitalization in patients presenting with acute dyspnea in the emergency department.

QRS and QTc interval prolongation in the prediction of long-term mortality of patients with acute destabilised heart failure.

OBJECTIVES: To quantify the prognostic utility of QRS and QTc interval prolongation in patients presenting with acute destabilised heart failure (ADHF) to the emergency department (ED). DESIGN: Prospective cohort study among patients enrolled in the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study. QRS and QT intervals were measured in 173 consecutive patients with ADHF. QT interval was corrected using the Bazett formula. The primary end point was all-cause mortality during the 720-day follow-up. RESULTS: QRS interval was prolonged (> or =120 ms) in 27% of patients, and QTc interval was prolonged (> or =440 ms) in 72% of patients. Baseline demographic and clinical characteristics were comparable in patients with normal and prolonged QRS or QTc intervals. A total of 78 patients died during follow-up. Interestingly, the 720-day mortality was similar in patients with prolonged and normal QTc (44% vs 42%, p = 0.546), but was significantly higher in patients with prolonged QRS interval than in those with normal QRS (59% vs 37%, p = 0.004). In Cox proportional hazards analysis, prolonged QRS interval was associated with a nearly twofold increase in mortality (HR 1.94, 95% CI 1.22 to 3.07; p = 0.005). This association persisted after adjustment for variables routinely available in the ED. CONCLUSIONS: Prolonged QRS interval, but not prolonged QTc interval, is associated with increased long-term mortality in patients with ADHF.

Gender-specific risk stratification with B-type natriuretic peptide levels in patients with acute dyspnea: insights from the B-type natriuretic peptide for acute shortness of breath evaluation study.

OBJECTIVES: We examined whether B-type natriuretic peptide (BNP) levels allow gender-specific risk stratification in patients with acute dyspnea. BACKGROUND: B-type natriuretic peptide levels determined in patients with heart failure correlate with the severity of disease and prognosis. Gender differences in risk prediction are poorly examined. METHODS: The BASEL (B-type natriuretic peptide for Acute Shortness of Breath Evaluation) Study enrolled 190 female and 262 male patients presenting with acute dyspnea. RESULTS: At 24 months, cumulative mortality was comparable in women and men (38% vs. 35%, p = 0.66). Cox regression analyses revealed that BNP levels >500 pg/ml indicated a 5.1-fold increase in mortality for women (95% confidence interval [CI] 3.0 to 8.5, p < 0.001) versus a 1.8-fold increase in men (95% CI 1.2 to 2.6; p = 0.007). The area under the receiver-operating characteristic curve (AUC) for BNP to predict death was significantly higher in female (AUC: 0.80, 95% CI 0.73 to 0.86) than in male patients (AUC: 0.64, 95% CI 0.57 to 0.71; p = 0.001 for the comparison of AUC(women) versus AUC(men)). Women with BNP >500 pg/ml displayed a higher mortality as compared with men with BNP >500 pg/ml (68% vs. 46%, p = 0.015). Interaction analysis showed that BNP is a stronger predictor of death in women than in men (p = 0.008). CONCLUSIONS: B-type natriuretic peptide plasma levels seem to be stronger predictors of death in women than in men.

Incidence, risk factors, and outcome of aspiration pneumonitis in ICU overdose patients.

OBJECTIVE: To assess the incidence and outcome of clinically significant aspiration pneumonitis in intensive care unit (ICU) overdose patients and to identify its predisposing factors. DESIGN: Retrospective cohort study. SETTING: Medical ICU of an academic tertiary care hospital. PATIENTS: A total of 273 consecutive overdose admissions. MEASUREMENTS AND RESULTS: Clinically significant aspiration pneumonitis was defined as the occurrence of respiratory dysfunction in a patient with a localised infiltrate on chest X-ray within 72 h of admission. In our cohort we identified 47 patients (17%) with aspiration pneumonitis. Importantly, aspiration pneumonitis was associated with a higher incidence of cardiac arrest (6.4 vs 0.9%; p = 0.037) and an increased duration of both ICU stay and overall hospital stay [respectively: median 1 (interquartile range 1-3) vs 1 (1-2), p = 0.025; and median 2 (1-7) vs 1 (1-3), p < 0.001]. In multivariate logistic regression analysis, Glasgow Coma Scale (GCS) score [odds ratio (OR) for each point of GCS 0.8; 95% confidence interval (CI) 0.7-0.9; p = 0.001], ingestion of opiates (OR 4.5; 95% CI 1.7-11.6; p = 0.002), and white blood cell count (WBC) (OR for each increase in WBC of 10(9)/l 1.05; 95% CI 1.0-1.19; p = 0.049) were identified as independent risk factors. CONCLUSIONS: Clinically relevant aspiration pneumonitis is a frequent complication in overdose patients admitted to the ICU. Moreover, aspiration pneumonitis is associated with a higher incidence of cardiac arrest and increased ICU and total in-hospital stay.

Gender differences in acute congestive heart failure.

BACKGROUND: Little is known about sex differences in baseline characteristics and outcomes in patients with acute congestive heart failure (CHF). METHODS AND RESULTS: This prospective observational study evaluated gender differences among 217 consecutive patients (124 men and 93 women) presenting with acute CHF to the emergency department. The primary endpoint was all-cause mortality. Women were older, and had less pulmonary comorbidity, but more noticeable jugular venous distension, as well as higher diastolic blood pressure and troponin level at presentation. Among contributing causes of acute CHF, myocardial ischaemia and anaemia were more frequent in women. Adequate medical CHF therapy was initiated more rapidly in women. Initial resource utilisation, time to discharge, and mortality were similar. Important differences to the disadvantage of women were noted during long-term follow-up. Mean cumulative survival was 619 (95% CI, 533-705) days in women as compared with 669 (95% CI, 601-737; p = 0.0663) in men. However, after multivariate adjustment female sex was not an independent predictor of long-term mortality (hazard ratio 1.14, 95% CI, 0.68-1.90; p = 0.619). Total spending for treatment cost was 11,858 US dollars University of Basel, University Hospital, Department of Internal Medicine, Switzerland (95% CI, 8921-14794) in women compared to 15,965 US dollars (95% CI, 12328-18003; p = 0.115) in men after 1 year. Functional status was similar in women and men at 6 and 12 months. CONCLUSIONS: The trend towards lower survival in women seems primarily related to higher age and other factors rather than gender itself. Female sex is not an independent predictor of long-term mortality in acute CHF.

Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea.

BACKGROUND: B-type natriuretic peptide (BNP) is a quantitative marker of heart failure that seems to be helpful in its diagnosis. METHODS: We performed a prospective randomized study (B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation) including 452 patients who presented to the emergency department with acute dyspnea to estimate the long-term cost-effectiveness of BNP guidance. Participants were randomly assigned to a diagnostic strategy involving the measurement of BNP levels (n = 225) or assessment in a standard manner (n = 227). Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane during 180 days of follow-up. RESULTS: Testing of BNP induced several important changes in management of dyspnea, including a reduction in the initial hospital admission rate, the use of intensive care, and total days in the hospital at 180 days (median, 10 days [interquartile range, 2-24 days] in the BNP group vs 14 days [interquartile range, 6-27 days] in the control group; P = .005). At 180 days, all-cause mortality was 20% in the BNP group and 23% in the control group (P = .42). Total treatment cost was significantly reduced in the BNP group (7930 dollars vs 10,503 dollars in the control group; P = .004). Analysis of incremental 180-day cost-effectiveness showed that BNP guidance resulted in lower mortality and lower cost in 80.6%, in higher mortality and lower cost in 19.3%, and in higher or lower mortality and higher cost in less than 0.1% each. Results were robust to changes in most variables but sensitive to changes in rehospitalization with BNP guidance. CONCLUSION: Testing of BNP is cost-effective in patients with acute dyspnea.