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Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS).Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-150h level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-1512h cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-1512h >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality.Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS. [ABSTRACT FROM AUTHOR]

Background Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. Methods and Results Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF ( P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF ( P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07–3.79; P = .03). Conclusions Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality. [ABSTRACT FROM AUTHOR]

Abstract: Backround: The myosin heavy chain (MHC) is altered in chronic heart failure (CHF), but the effect of exercise on MHC expression in CHF patients is not understood. The aim of the present study was to show the effect of aerobic exercise on MHC distribution in patients with CHF. Methods: Patients (n =17) with stable NYHA class I–III CHF were randomised into training and control groups. For a period of three months, the training group cycled on an ergometric cycle 3 times a week for 30 min, the control group continued as they did previously. Both a baseline and a final 3 month graded maximal exercise test and exercise endurance test with constant submaximal work load were performed. Muscle samples, obtained from vastus lateralis muscle at baseline and after 3 months from the 8 patients in the training group and the 9 in the control group, were analysed for MHC distribution using SDS-polyacrylamide gel electrophoresis. Results: Baseline MHC distributions were similar in both groups and training did not alter the MHC distribution. Exercise duration, at constant submaximal work load, improved from 14.9±7.1 to 26.9±9.6 min (p <0.01 for the change between the groups). Training did not improve peak oxygen consumption. Conclusion: No correlation between the change in exercise capacity and MHC distribution appeared despite the significant improvement of exercise duration. [Copyright &y& Elsevier]

Heart failure (HF) has emerged as a major public health issue and is among the most significant causes of morbidity and mortality for older adults in Western countries. Acute HF syndromes (AHFS) encompass many important etiologies and comorbidities. There are several different clinical definitions and classifications of AHFS that are based on their clinical picture and pathophysiology. These definitions and classifications should, at best, serve to individually tailor diagnostics and therapy. Another important application of these definitions and classifications is to help guide future clinical trials in AHFS. The epidemiology of AHFS has been studied in large and small registries and surveys in both North America and Europe. The properties of the population of patients with acute HF are discussed in light of these data. [Copyright &y& Elsevier]

Objective: Levosimendan is a new calcium sensitizer with inodilatory properties. There is growing clinical experience with levosimendan given to cardiac surgical patients. The aim of this report was to evaluate the effects of perioperative use of levosimendan in surgical patients with high perioperative risk, compromised left ventricular (LV) function, or difficulties in weaning from cardiopulmonary bypass (CPB). Design: Case series. Setting: Single-institution, university hospital. Participants: Patients undergoing cardiac surgery. Measurements and Main Results: Sixteen cardiac surgical patients received levosimendan infusion with a maximum duration of 29 hours. Eight were initiated preoperatively and 8 postoperatively. Coronary artery disease was the main operative indication in 10 of 16 cases, and 75% of the patients were high-risk patients. Results: Continuous levosimendan infusion increased cardiac index significantly in both groups compared with preoperative baseline. Pulmonary capillary wedge pressure and systolic blood pressure did not change significantly. Norepinephrine and epinephrine were the most common concomitant vasoactive medications. Most importantly, weaning from CPB was successful in all patients even after failure to wean the patient with catecholamines. One high-risk patient in the preoperative group and 2 patients in the postoperative group died in the hospital. Another patient died during the 1-year follow-up. Conclusion: Levosimendan can be used for postoperative rescue therapy for patients difficult to wean from CPB. Also, elective preoperative initiation of levosimendan seems applicable to patients with high perioperative risk or compromised LV function. [Copyright &y& Elsevier]

Levosimendan, a new calcium sensitizer, was administered orally to 10 patients with severe congestive heart failure (CHF), who had a mean baseline pulmonary capillary wedge pressure (PCWP) of 22 mm Hg and a left ventricular ejection fraction of 23%. Each patient received 3 escalating doses of 1 mg, 2 mg, and 4 mg of levosimendan within 18-24 hours in an open-label pilot study. After administration of a 1-mg dose of levosimendan, PCWP decreased by 18% (p = 0.002) and cardiac output increased by 22% (p = 0.005). Diastolic blood pressure was decreased by about 5 mm Hg. Plasma catecholamine levels were unaffected. Plasma concentrations of levosimendan were unexpectedly Iow after administration of the 2-mg dose, and responses were weak. This was probably due to delayed drug absorption and altered baseline hemodynamics caused by ingestion of a meal before drug intake. The 4-mg dose of levosimendan was associated with a 27% increase in cardiac output (p = 0.009). PCWP showed only a small decrease, probably a result of relatively Iow baseline values (carryover from previous doses). Right atrial pressure decreased substantially by 40%. Heart rate increased by only 1-8 beats/min after administration of the 1- and 4-mg doses of levosimendan. It is concluded that oral levosimendan has favorable cardiac and hemodynamic effects in patients with severe CHF, and that these effects are similar to those seen after intravenous dosing with levosimendan in this patient group. [ABSTRACT FROM AUTHOR]

Abstract: Background: The costs of different classes of acute HF (AHF) are not known. Methods: AHF patients (N =620) were divided in a national, prospective, observational study into five clinical classes: cardiogenic shock, pulmonary oedema, congestive HF, hypertensive HF, and right HF. Index episode and 6-month readmissions were assessed and hospitalization costs were evaluated. Results: The length of index episode, ICU/CCU stay and costs of index episode and cumulative 6-month costs differed significantly between the clinical classes. The highest cumulative 6-month hospitalization costs, 25,963 (15,053–44778) € (mean, 95% confidence interval) incurred in cardiogenic shock, followed by pulmonary oedema, 12,912 (11,006–15,148) €, and congestive HF, 9475 (8550–10,500) €. Conclusions: AHF leads to significant need for hospital care and high costs which differ significantly between clinical classes of AHF. [ABSTRACT FROM AUTHOR]

Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0−120 h) from 183 patients in the CardShock study. The study population was dichotomized by PCT max ≥ and < 0.5 μg/L, and IL-6 and CRP max above/below median. PCT peaked already at 24 h [median PCT max 0.71 μg/L (IQR 0.24–3.4)], whereas CRP peaked later between 48 and 72 h [median CRP max 137 mg/L (59–247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCT max ≥ 0.5 μg/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRP max. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCT max ≥ 0.5 μg/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRP max showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. • Inflammatory marker levels are considerably elevated during the first days of CS. • PCT peaks early at 24 h, while CRP continues to rise until 48 to 72 h in CS. • High levels of PCT and IL-6 are strongly associated with systemic hypoperfusion in CS. • High inflammatory marker levels are associated with increased mortality in CS. [ABSTRACT FROM AUTHOR]

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. • Inotropes increase cardiac output mainly by enhancing cardiac contractility. • Inotropes indicated for heart failure are beta-agonists, milrinone, levosimendan. • Inotropes should only be used in low-output acute or advanced heart failure. • Identifying patients with low-output heart failure is often challenging. • Inotrope selection should be individually tailored. [ABSTRACT FROM AUTHOR]

Background: Vasopressor agents could have certain specific effects in patients with cardiogenic shock (CS) after myocardial infarction, which may influence outcome. Although norepinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and intervention data are lacking.Objectives: The goal of this paper was to compare in a prospective, double-blind, multicenter, randomized study, the efficacy and safety of epinephrine and norepinephrine in patients with CS after acute myocardial infarction.Methods: The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyperlactatemia, and high inotrope and vasopressor doses.Results: Fifty-seven patients were randomized into 2 study arms, epinephrine and norepinephrine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epinephrine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remaining unchanged with norepinephrine (p < 0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double product (p = 0.0002) and lactic acidosis from H2 to H24 (p < 0.0001).Conclusions: In patients with CS secondary to acute myocardial infarction, the use of epinephrine compared with norepinephrine was associated with similar effects on arterial pressure and cardiac index and a higher incidence of refractory shock. (Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock [OptimaCC]; NCT01367743). [ABSTRACT FROM AUTHOR]

Background: The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA).Objectives: A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population.Methods: A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release.Results: Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively).Conclusions: Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T. [ABSTRACT FROM AUTHOR]

Background: Mortality in cardiogenic shock (CS) remains high. Early risk stratification is crucial to make adequate treatment decisions.Objectives: This study sought to develop an easy-to-use, readily available risk prediction score for short-term mortality in patients with CS, derived from the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock) trial.Methods: The score was developed using a stepwise multivariable regression analysis.Results: Six variables emerged as independent predictors for 30-day mortality and were used as score parameters: age >73 years, prior stroke, glucose at admission >10.6 mmol/l (191 mg/dl), creatinine at admission >132.6 μmol/l (1.5 mg/dl), Thrombolysis In Myocardial Infarction flow grade <3 after percutaneous coronary intervention, and arterial blood lactate at admission >5 mmol/l. Either 1 or 2 points were attributed to each variable, leading to a score in 3 risk categories: low (0 to 2), intermediate (3 or 4), and high (5 to 9). The observed 30-day mortality rates were 23.8%, 49.2%, and 76.6%, respectively (p < 0.0001). Validation in the IABP-SHOCK II registry population showed good discrimination with an area under the curve of 0.79. External validation in the CardShock trial population (n = 137) showed short-term mortality rates of 28.0% (score 0 to 2), 42.9% (score 3 to 4), and 77.3% (score 5 to 9; p < 0.001) and an area under the curve of 0.73. Kaplan-Meier analysis revealed a stepwise increase in mortality between the different score categories (0 to 2 vs. 3 to 4: p = 0.04; 0 to 2 vs. 5 to 9: p = 0.008).Conclusions: The IABP-SHOCK II risk score can be easily calculated in daily clinical practice and strongly correlated with mortality in patients with infarct-related CS. It may help stratify patient risk for short-term mortality and might, thus, facilitate clinical decision making. (Intraaortic Balloon Pump in Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036). [ABSTRACT FROM AUTHOR]

Background Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. Objectives This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. Results In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. Conclusions Amiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. Background: Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. Methods: We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. Results: Normal-weight patients (BMI 18.5 to 25 kg/m2) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m2; p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the “protective” association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004). Conclusions: A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The “obesity paradox” is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox. [Copyright &y& Elsevier]

Objectives: The aim of this study was to evaluate the prognostic value of high-sensitivity troponin T (hs-TnT) in addition to clinical risk factors and the CHA2DS2VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) risk score in patients with atrial fibrillation (AF). Background: The level of troponin is a powerful predictor of cardiovascular events and mortality. Methods: A total of 14,897 patients with AF were randomized to treatment with apixaban or warfarin in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial. The associations between baseline hs-TnT levels and outcomes were evaluated using adjusted Cox regression models. Results: Levels of hs-TnT were measurable in 93.5% of patients; 75% had levels >7.5 ng/l, 50% had levels >11.0 ng/l, and 25% had levels >16.7 ng/l. During a median 1.9-year period, the annual rates of stroke or systemic embolism ranged from 0.87% in the lowest hs-TnT quartile to 2.13% in the highest hs-TnT quartile (adjusted hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.35 to 2.78; p = 0.0010). The annual rates in the corresponding groups ranged from 0.46% to 4.24% (adjusted HR: 4.31; 95% CI: 2.91 to 6.37; p < 0.0001) for cardiac death and from 1.26% to 4.21% (adjusted HR: 1.91; 95% CI: 1.43 to 2.56; p = 0.0001) for major bleeding. Adding hs-TnT levels to the CHA2DS2VASc score improved the C statistic from 0.620 to 0.635 for stroke or systemic embolism (p = 0.0226), from 0.592 to 0.711 for cardiac death (p < 0.0001), and from 0.591 to 0.629 for major bleeding (p < 0.0001). Apixaban reduced rates of stroke, mortality, and bleeding regardless of the hs-TnT level. Conclusions: Levels of hs-TnT are often elevated in patients with AF. The hs-TnT level is independently associated with an increased risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc risk score. The benefits of apixaban as compared with warfarin are consistent regardless of the hs-TnT level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984) [Copyright &y& Elsevier]

Abstract: Aims: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart failure. Methods: Patients with AHF (n=620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined. Results: The overall mortality was 60.3% (n=374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p<0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4–2.2; p<0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome. Conclusion: The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF. [Copyright &y& Elsevier]

Objective: The aim of this analysis was to assess the association between elevated blood glucose level and mortality in acute heart failure (AHF). Background: Elevated blood glucose has been reported to be prognostically meaningful in patients with cardiac diagnoses, such as coronary artery disease. The short-term prognostic impact of hyperglycemia in AHF is unknown, however. Methods: In a multinational cohort of AHF, we examined the ability of blood glucose concentrations at presentation to predict all-cause mortality by 30 days. Fully adjusted models for prognosis included a previous diagnosis of diabetes mellitus as a covariate. Results: A total of 6,212 subjects with AHF (mean age, 72 years; 52.5% male) were studied; the median blood glucose concentration on arrival at the hospital was 7.5 mmol/l (135 mg/dl), and 41% had a previous diagnosis of diabetes mellitus (DM). After 30 days, 618 patients (10%) had died. Compared with survivors, decedents had significantly higher median blood glucose concentrations (8.9 mmol/l vs. 7.4 mmol/l; p < 0.0001). In the fully adjusted model, an elevated blood glucose level was an independent predictor of 30-day mortality in AHF (odds ratio: 2.19; 95% confidence interval: 1.69 to 2.83; p < 0.001). The risk associated with an elevated blood glucose level appeared consistent across all subgroups of patients, including patients with preserved (hazard ratio: 5.41; 95% confidence interval: 2.44 to 12.0; p < 0.0001) and impaired systolic function (hazard ratio: 2.37; 95% confidence interval: 1.57 to 3.59; p < 0.0001). Furthermore, in reclassification analyses, elevated blood glucose added significant prognostic information to clinical parameters alone (4.4% net reclassification improvement; p = 0.01). Conclusions: Among patients with AHF, blood glucose concentrations at presentation are powerfully prognostic for 30-day mortality, independent of a diagnosis of diabetes mellitus or other clinical variables. Because blood glucose is easily modifiable, it may represent a valid target for therapeutic intervention. [Copyright &y& Elsevier]

Abstract: Introduction: Normal concentrations of D-Dimer can be used to exclude venous thromboembolism (VTE). However, methods for sensitive and quantitative D-Dimer measurements at the point-of-care (POC) are still limited. Materials and methods: We developed a 10-min, non-competitive immunofluorometric assay for D-Dimer in citrated whole blood and plasma using pre-dispensed reagents dried in single assay wells. The simple, automated assay procedure comprises a 1:50 sample dilution, one-step incubation, washing, and time-resolved fluorometric measurement directly from the wet well surface. Results: The limits of detection (background+3SD) and quantification (CV <15%) were 0.05 and 0.2 mg/L D-Dimer, respectively, and the assay was linear up to 400 mg/L. Correlations to Roche TinaQuant (r =0.726, n =200) and Biopool Auto·Dimer (r =0.190, n =149) were carried out using citrated plasma. Diagnostic sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values were 98.7%, 64.4%, 99.1% and 55.1%, and 92.2%, 81.0%, 95.9% and 68.3%, respectively, using cut-off values of 0.6 and 1.0 mg/L, respectively, in outpatients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) (n =77) compared with outpatients with various other diseases (n =174). The within- and between-run CVs near the cut-off values were ≤10% in both whole blood and plasma. The 95th percentile upper range in apparently healthy individuals was 0.68 mg/L of whole blood (n =101). Conclusions: The high sensitivity and NPV suggest that the rapid immunofluorometric assay could be valuable for rapid exclusion of VTE in outpatients. With appropriate cut-offs, the assay could potentially be used as a stand-alone test or combined with clinical probability assessment, but further studies are required. [Copyright &y& Elsevier]