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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 © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Emergency Medicine (EM) was established as a speciality in Finland in the beginning of 2013. The training period of six years conforms to the principles of the European Curriculum for EM. We present here the first-year training in Kanta-Häme Central Hospital, located in Southern Finland. Training is not only based on "learning by doing". Lunchtime lectures covering a wide variety of topics in EM are an essential part of our weekly education day. This day also offers to the residents small group sessions with abstracts, case reports, focused lectures and ultrasound training. A successful training program of EM is achievable by good collaboration with other specialities.

Alcohol withdrawal delirium (AWD) is often refractory to conventional medication. We report a prospective series of patients treated with α2-agonist dexmedetomidine added to conventional sedation. Eighteen patients with AWD were diagnosed by Confusion assessment method for ICU score. Treatment, complications, length of stay (LOS) in ICU and hospital were recorded. In addition, hospital and 1-year mortality were assessed. Dexmedetomidine was given for 23.9 (18.4) h [mean (SD)]. All the patients also received benzodiazepines but three patients were given haloperidole. No patient was intubated. The maximum infusion rate of dexmedetomidine was 1.5 (1.2) µg/kg/h. Time to resolution of AWD was 3.8 (1.3) days. The ICU LOS was 7.1 (2.7) days and in-hospital LOS 12.1 (4.5) days. No adverse events were observed although one patient died from acute pancreatitis. The use of dexmedetomidine in AWD seems safe but warrants further studies.

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

Aim: This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF)., Methods and Results: Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60 mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality)., Conclusion: In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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 12 months), 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 © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aims: To examine the use of the treatments for acute heart failure (AHF) recommended by ESC guidelines in different clinical presentations and blood pressure groups., Methods: The use of intravenous diuretics, nitrates, opioids, inotropes, and vasopressors as well as non-invasive ventilation (NIV) was analysed in 620 patients hospitalized due to AHF. The relation between AHF therapies and clinical presentation, especially systolic blood pressure (SBP) on admission, was also assessed., Results: Overall, 76% of patients received i.v. furosemide, 42% nitrates, 29% opioids, 5% inotropes and 7% vasopressors, and 24% of patients were treated with NIV. Furosemide was the most common treatment in all clinical classes and irrespective of SBP on admission. Nitrates were given most often in pulmonary oedema and hypertensive AHF. Overall, only SBP differed significantly between patients with and without the studied treatments. SBP was higher in patients treated with nitrates than in those who were not (156 vs. 141 mmHg, p<0.001). Still, only one-third of patients presenting acute decompensated heart failure and SBP over 120 mmHg were given nitrates. Inotropes and vasopressors were given most frequently in cardiogenic shock and pulmonary oedema, and their use was inversely related to initial SBP (p<0.001). NIV was used only in half of the cardiogenic shock and pulmonary oedema patients., Conclusions: The management of AHF differs between ESC clinical classes and the use of i.v. vasoactive therapies is related to the initial SBP. However, there seems to be room for improvement in administration of vasodilators and NIV.

Background: The aim of the present pilot study was to determine if pulse photoplethysmography amplitude (PPGA) could be used as an indicator of critical illness and as a predictor of higher need of care in emergency department patients., Methods: This was a prospective observational study. We collected vital signs and one minute of pulse photoplethysmograph signal from 251 consecutive patients admitted to a university hospital emergency department. The patients were divided in two groups regarding to the modified Early Warning Score (mEWS): > 3 (critically ill) and ≤ 3 (non-critically ill). Photoplethysmography characteristics were compared between the groups., Results: Sufficient data for analysis was acquired from 212 patients (84.5%). Patients in critically ill group more frequently required intubation and invasive hemodynamic monitoring in the ED and received more intravenous fluids. Mean pulse photoplethysmography amplitude (PPGA) was significantly lower in critically ill patients (median 1.105 [95% CI of mean 0.9946-2.302] vs. 2.476 [95% CI of mean 2.239-2.714], P = 0.0257). Higher variability of PPGA significantly correlated with higher amount of fluids received in the ED (r = 0.1501, p = 0.0296)., Conclusions: This pilot study revealed differences in PPGA characteristics between critically ill and non-critically ill patients. Further studies are needed to determine if these easily available parameters could help increase accuracy in triage when used in addition to routine monitoring of vital signs.

Background: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR)., Methods and Results: The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR., Conclusions: The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.

Background: We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin., Methods and Results: The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups., Conclusions: Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

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 © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular dysfunction (RVD) in acute pulmonary embolism (APE) can be assessed with helical computerized tomography (CT) and transthoracic echocardiography (TTE). Signs of RVD and elevated natriuretic peptides like NT-proBNP and cardiac troponin (TnT) are associated with increased risk of mortality. However, the prognostic role of both initial diagnostic strategy and the use of NT-proBNP and TnT for screening for long-term probability of RVD remains unknown. The aim of the study was to determine the role of helical CT and NT-proBNP in detection of RVD in the acute phase. In addition, the value of NT-proBNP for ruling out RVD at long-term follow-up was assessed., Methods: Sixty-three non-high risk APE patients were studied. RVD was assessed at admission in the emergency department by CT and TTE, and both NT-proBNP and TnT samples were taken. These, excepting CT, were repeated seven months later., Results: At admission RVD was detected by CT in 37 (59 %) patients. RVD in CT correlated strongly with RVD in TTE (p < 0.0001). NT-proBNP was elevated (≥ 350 ng/l) in 32 (86 %) patients with RVD but in only seven (27 %) patients without RVD (p < 0.0001). All the patients survived until the 7-month follow-up. TTE showed persistent RVD in 6 of 63 (10 %) patients who all had RVD in CT at admission. All of them had elevated NT-proBNP levels in the follow-up compared with 5 (9 %) of patients without RVD (p < 0.0001)., Conclusions: TTE does not confer further benefit when helical CT is used for screening for RVD in non-high risk APE. All the patients who were found to have RVD in TTE at seven months follow-up had had RVD in the acute phase CT as well. Thus, patients without RVD in diagnostic CT do not seem to require further routine follow-up to screen for RVD later. On the other hand, persistent RVD and thus need for TTE control can be ruled out by assessment of NT-proBNP at follow-up. A follow-up protocol based on these findings is suggested.

The cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidneys. Evaluating renal function is an essential part of the assessment of every cardiac patient. It has become clear that serum creatinine is not an accurate enough marker of glomerular filtration rate (GFR) and should not be used to evaluate kidney dysfunction. Creatinine-based estimates of GFR are preferred, but require renal function to be stable and are not suitable when changes in kidney function occur. Cystatin C (CysC) has been the target of much interest in the search for an alternative measure of GFR. As an endogenous biomarker, CysC possesses many of the properties required of a good marker of renal function. Compared with that of creatinine, plasma concentrations of CysC are less influenced by factors other than GFR. Consequently, CysC correlates with true GFR more accurately than creatinine. Equations for estimating GFR from CysC values have also been developed, which makes values easier to interpret and facilitates the clinical use of this new marker. The use of CysC in acute kidney injury has also shown promising results. CysC has been studied as a risk marker for prognosis in cardiovascular disease. This effect is attributed to the strong impact of renal dysfunction on progressive cardiovascular disease and impaired survival. Higher levels of CysC have consistently been predictive of incident or recurrent cardiovascular events and adverse outcomes. CysC is a predictor of the development of heart failure and increased levels of CysC have an independent association with higher mortality in both chronic and acute heart failure. In conclusion, CysC appears to be an interesting marker of renal function and is useful for risk stratification in heart failure.

Aims: Several models for predicting the prognosis of heart failure (HF) patients have been developed, but all of them focus on a single outcome variable, such as all-cause mortality. The purpose of this study was to develop a multistate model for simultaneously predicting survival and HF-related hospitalization in patients discharged alive from hospital after recovery from acute HF., Methods and Results: The model was derived in the COACH (Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) cohort, a multicentre, randomized controlled trial in which 1023 patients were enrolled after hospitalization because of HF. External validation was attained with the FINN-AKVA (Finish Acute Heart Failure Study) cohort, a prospective, multicentre study with 620 patients hospitalized due to acute HF. The observed vs. predicted 18-month survival was 72.1% vs. 72.3% in the derivation cohort and 71.4% vs. 71.2% in the validation cohort. The corresponding values of the c statistic were 0.733 [95% confidence interval (CI) 0.705-0.761] and 0.702 (95% CI 0.663-0.744), respectively. The model's accuracy in predicting HF hospitalization was excellent, with predicted values that closely resembled the values observed in the derivation cohort., Conclusion: The COACH risk engine accurately predicted survival and various measures of recurrent hospitalization in (acute) HF patients. It may therefore become a valuable tool in improving and personalizing patient care and optimizing the use of scarce healthcare resources.

The maturation of emergency medicine (EM) as a specialty has coincided with dramatic increases in emergency department (ED) visit rates, both in the United States and around the world. ED crowding has become a public health problem where periodic supply and demand mismatches in ED and hospital resources cause long waiting times and delays in critical treatments. ED crowding has been associated with several negative clinical outcomes, including higher complication rates and mortality. This article describes emergency care systems and the extent of crowding across 15 countries outside of the United States: Australia, Canada, Denmark, Finland, France, Germany, Hong Kong, India, Iran, Italy, The Netherlands, Saudi Arabia, Catalonia (Spain), Sweden, and the United Kingdom. The authors are local emergency care leaders with knowledge of emergency care in their particular countries. Where available, data are provided about visit patterns in each country; however, for many of these countries, no national data are available on ED visits rates or crowding. For most of the countries included, there is both objective evidence of increases in ED visit rates and ED crowding and also subjective assessments of trends toward higher crowding in the ED. ED crowding appears to be worsening in many countries despite the presence of universal health coverage. Scandinavian countries with robust systems to manage acute care outside the ED do not report crowding is a major problem. The main cause for crowding identified by many authors is the boarding of admitted patients, similar to the United States. Many hospitals in these countries have implemented operational interventions to mitigate crowding in the ED, and some countries have imposed strict limits on ED length of stay (LOS), while others have no clear plan to mitigate crowding. An understanding of the causes and potential solutions implemented in these countries can provide a lens into how to mitigate ED crowding in the United States through health policy interventions and hospital operational changes., (© 2011 by the Society for Academic Emergency Medicine.)

Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (DL,CO), but data on the mechanisms involved are inconsistent. We wanted to investigate whether reduction in diffusing capacity of alveolo-capillary membrane (DM) and pulmonary capillary blood volume (Vc) is associated with the extent of PE or the presence and severity of right ventricular dysfunction (RVD) induced by PE and how the possible changes are corrected after 7-month follow-up. Forty-seven patients with acute non-massive PE in spiral computed tomography (CT) were included. The extent of PE was assessed by scoring mass of embolism. DL,CO, Vc, DM and alveolar volume (VA) were measured by using a single breath method with carbon monoxide and oxygen both at the acute phase and 7 months later. RVD was evaluated with transthoracic echocardiography and electrocardiogram. Fifteen healthy subjects were included as controls. DL,CO, DL, CO/VA, DM, vital capacity (VC) and VA were significantly lower in the patients with acute PE than in healthy controls (P < 0.001). DM/Vc relation was significantly lower in patients with RVD than in healthy controls (P = 0.004). DM correlated inversely with central mass of embolism (r = -0.312; P = 0.047) whereas Vc did not. DM, DL,CO, VC and VA improved significantly within 7 months. In all patients (P = 0.001, P = 0.001) and persistent RVD (P = 0.020, P = 0.012), DM and DL,CO remained significantly lower than in healthy controls in the follow-up. DM was inversely related to central mass of embolism. Reduction in DM mainly explains the sustained decrease in DL,CO in PE after 7 months despite modern treatment of PE., (© 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objectives: Oral levosimendan improves ventricular function in short-term clinical trials. The effects of long-term treatment with oral levosimendan were investigated on echocardiographic parameters of left ventricular function in patients with chronic heart failure., Design: Twenty-nine patients with NYHA III-IV congestive chronic HF were prospectively enrolled in a randomised, double-blind, placebo controlled study. Oral levosimendan was administered on top of existing medication over a treatment period of at least 180 days. Echocardiographic measurements estimating pulmonary capillary wedge pressure (PCWP) and tissue Doppler mitral basal myocardial velocities (Sm, Em) were performed at baseline and 90 and 180 days after randomisation., Results: Estimated PCWP at baseline was elevated in both groups and decreased by 13% in the levosimendan group compared to an increase of 9% in the placebo group (p = 0.035). Sm was decreased in both groups at baseline and improved by 0.9 cm/s in the levosimendan group and decreased by 0.1 cm/s in the placebo group (p = 0.035). Levosimendan did not significantly alter heart rate or systolic blood pressure., Conclusions: Oral levosimendan improved hemodynamic function in chronic heart failure patients and the effect was sustained over the 180-day follow-up period.

Aims: Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. However, definitions and prognostic impact of AKI in AHF have been variable. Cystatin C is a prospective new marker of AKI. The objective of this study was to investigate the use of cystatin C as a marker of early AKI in AHF., Methods and Results: Patients (n = 292) hospitalized for AHF had measurements of cystatin C on admission and at 48 h. We assessed the incidence of a rise in cystatin C between the two measurements and evaluated the effect of an increase in cystatin C on outcomes up to 12 months. The population was on average 75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L (interquartile range 0.99-1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48 h after hospitalization (AKI(cysC)) occurred in 16% of patients and resulted in 3 days (P = 0.01) longer hospital stay and was associated with significantly higher in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3-11.7, P = 0.01]. During follow-up, AKI(cysC) was an independent predictor of 90 days mortality, adjusted odds ratio 2.8 (95% CI 1.2-6.7, P = 0.02)., Conclusion: Cystatin C appears to be a useful marker of early AKI in patients hospitalized for AHF. A decline in renal function detected by cystatin C during the first 48 h after hospitalization occurs frequently in AHF and has a detrimental impact on prognosis.

Encephalitis has been described as a rare complication of pandemic 2009 (H1N1) influenza A infection in children and adolescents. This report is on two adult patients who presented with encephalitis in relation to acute H1N1 influenza. Encephalitis is therefore also a potential complication of pandemic 2009 (H1N1) influenza infection in adults.

Aims: Acute heart failure (AHF) has a poor prognosis. We evaluated 3- and 12-month mortality in different clinical classes of AHF patients from 30 European countries who were included in the EuroHeart Failure Survey (EHFS) II., Methods and Results: Follow-up data were available for 2981 AHF patients, of these 62% had a history of chronic HF. One-year mortality after discharge was lower in patients with de novo AHF when compared with acutely decompensated chronic HF (ADCHF), 16.4 vs. 23.2% (P < 0.001). Cardiogenic shock conferred the highest cumulative 1-year mortality (52.9%) as a result of in-hospital mortality of 39.3%. Long-term prognosis in decompensated AHF was also dismal. Hypertensive HF was associated with the lowest mortality (13.7% at 1 year). Age, prior myocardial infarction, creatinine level, and low plasma sodium were independently associated with mortality during the whole follow-up period. Diabetes, anaemia, and history of chronic HF were associated with worse and hypertension with better long-term survival. History of cerebrovascular disease was associated with worse short-term outcome., Conclusion: Early and late mortality differ between de novo AHF and ADCHF and between clinical classes of AHF. EHFS II identifies clinical risk markers and demonstrates the importance of a thorough characterization of AHF populations according to history and clinical presentation.

The determination of troponin from a blood sample is the most sensitive means to prove a recent myocardial injury. An elevating troponin level associated with acute coronary syndrome indicates an increased risk of death and reinfarction, serving as an indication for an invasive investigation of coronary anatomy. Troponin is also frequently elevated in injuries not caused by cardiac infarction. The use of troponin should be focused on situations involving a suspicion of myocardial ischemia on clinical grounds. We analyzed the causes of an elevated troponin level from the emergency discharge diagnoses of 301 patients referred to internal medicine emergency.

Aims: International guidelines are frequently not implemented in the elderly population with heart failure (HF). This study determined the management of octogenarians with HF enrolled in Euro Heart Failure Survey II (EHFS II) (2004-05)., Methods and Results: We compared the clinical profile, 12 month outcomes, and management modalities between 741 octogenarians (median age 83.7 years) and 2836 younger patients (median age 68.4 years) hospitalized for acute/decompensated HF. Management modalities were also compared with those observed in EHFS I (2000-01). Female gender, new onset HF (de novo), hypertension, atrial fibrillation, co-morbidities, disabilities, and low quality of life were more common in the elderly (all P < 0.001). Mortality rates during hospital stay and during 12 months after discharge were increased in octogenarians (10.7 vs. 5.6% and 28.4 vs. 18.5%, P < 0.001). Underuse and underdosage of medications recommended for HF were observed in the elderly. However, a significant improvement was observed when compared with EHFS I both in the overall HF octogenarian population and in the subgroup with ejection fraction < or =45% for prescription rates of ACE-I/ARBs, beta-blockers, and aldosterone antagonists at discharge (82 vs. 71%; 56 vs. 29%; 54 vs. 18.5%, respectively, all P < 0.01), as well as for recommended combinations and dosage. Prescription rates remained stable for 12 months after discharge in survivors., Conclusion: Our study confirms that the contemporary management of very elderly patients with HF remains suboptimal but that the situation is improving.

Background: Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF)., Aims: To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF., Methods: FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed., Results: Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2-3.5, p=0.01) and cTnT (OR 2.6, 95% CI 1.5-4.4, p=0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2-13, p<0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0-1.8, p=0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8-0.9, p=0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality., Conclusions: cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.

Background: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF)., Aim: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF., Methods: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated., Results: Elevated levels of IL-6 and TNF-alpha were strongly associated with increased 12-month mortality (P<0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P<0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years' increase and TNF-alpha were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome., Conclusions: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-alpha, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.

Aims: This analysis evaluates the gender differences in patients hospitalised for acute heart failure (AHF) in the EuroHeart Failure Survey II (EHFS)., Results: Of the 3580 patients included in EHFS II, 1384 (39%) were women, mean age 73 years. 2196 (61%) were men, mean age 68 years. Women more frequently had new-onset AHF, hypertension and valvular disease and less frequently coronary heart disease or dilated cardiomyopathy compared with men. Smoking, chronic obstructive pulmonary disease, peripheral arterial disease and renal failure were less common, but diabetes and anaemia significantly more frequent in women. Atrial fibrillation and preserved left ventricular function were more common in women. Men were more often non-compliant with medication. After adjustment for indications and age, there were no significant gender differences in prescription of HF medication. All-cause readmission rate during the one-year follow-up was lower in women. However, the proportion of HF hospitalisation and one-year mortality after discharge (20%) were similar in both genders., Conclusion: Women frequently present with new-onset AHF. A significant gender difference exists in aetiology, ventricular function and co-morbidities. Women's use of HF medication has improved. These findings emphasize the importance of individualised management and need for more comprehensive recruitment of women in clinical trials.

Background: Although weakly supported by scientific evidence, according to guidelines the use of inotropes in acute heart failure is indicated in the presence of hypoperfusion refractory to fluid resuscitation., Aims: We examined the characteristics of the inotrope-treated patients, as well as, their in-hospital mortality. The frequency and dosing of inotropic infusions in patients admitted with acute heart failure was assessed in detail., Methods: We included 620 consecutive patients with acute heart failure who were admitted to hospital during three months during spring 2004 in an observational multi-centre study., Results: Of the patients 84 (14%) were treated with inotropes. Dopamine was used in 46 (7%), dobutamine 22 (4%), epinephrine 5 (1%), norepinephrine in 33 (5%), and levosimendan in 44 (7%) cases. The in-hospital mortality was 21% in the inotrope-treated group, and 5% in the control group. The mortality was 7% if only one inotrope was used. The mortality increased in proportion to the number of inotropes used. Lower blood pressure at admission, low ejection fraction, elevated C-reactive protein and cardiac markers correlated with the inotrope administration., Conclusion: Inotrope administration is a marker of increased mortality in patients with acute heart failure. Still, the use of a single inotrope during hospital stay seems rather safe.

Guideline recommendations for the prehospital and early in-hospital (first 6-12 hrs after presentation) management of acute heart failure syndromes are lacking. The American College of Cardiology/American Heart Association and European Society of Cardiology guidelines direct the management of these acute heart failure patients, but specific consensus on early management has not been published, primarily because few early management trials have been conducted. This article summarizes practical recommendations for the prehospital and early management of patients with acute heart failure syndromes; the recommendations were developed from a meeting of experts in cardiology, emergency medicine, and intensive care medicine from Europe and the United States. The recommendations are based on a unique clinical classification system considering the initial systolic blood pressure and other symptoms: 1) dyspnea and/or congestion with systolic blood pressure >140 mm Hg; 2) dyspnea and/or congestion with systolic blood pressure 100-140 mm Hg; 3) dyspnea and/or congestion with systolic blood pressure <100 mm Hg; 4) dyspnea and/or congestion with signs of acute coronary syndrome; and 5) isolated right ventricular failure. These practical recommendations are not intended to replace existing guidelines. Rather, they are meant to serve as a tool to facilitate guideline implementation where data are available and to provide suggested treatment approaches where formal guidelines and definitive evidence are lacking.

Aims: Cystatin C, a novel marker of renal function, has been implicated as a prognostic marker in cardiovascular disease. We investigated the prognostic value of cystatin C in acute heart failure (AHF) in comparison to other markers of renal function and NT-proBNP., Methods and Results: Patients with cystatin C measurements (n = 480) from a prospective multicentre study on AHF were included. All-cause mortality at 12 months was 25.4%. Cystatin C, creatinine, age, gender, and systolic blood pressure on admission were identified as independent prognostic risk factors. Cystatin C above median (1.30 mg/L) was associated with the highest adjusted hazard ratio, 3.2 (95% CI 2.0-5.3), P < 0.0001. Mortality increased significantly with each tertile of cystatin C. Combining tertiles of NT-proBNP and cystatin C improved risk stratification further. Moreover, in patients with normal plasma creatinine, elevated cystatin C was associated with significantly higher mortality at 12 months: 40.4% vs. 12.6% in patients with both markers within normal range, P < 0.0001., Conclusion: Cystatin C is a strong and independent predictor of outcome at 12 months in AHF. Furthermore, cystatin C identifies patients with poor prognosis despite normal plasma creatinine. Cystatin C seems to be a promising risk marker in patients hospitalized for AHF.

Background and Objectives: Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It increases myocardial contractility, reduces the filling pressure and dilates both the peripheral and coronary vessels. The circulating metabolites of levosimendan, OR-1855 and OR-1896, are formed and eliminated slowly after intravenous administration of levosimendan. The aim of this study was to investigate the effect of impaired renal function and haemodialysis on the pharmacokinetics of levosimendan, OR-1855 and OR-1896., Study Design: This study was an open-label, nonrandomised, phase I pharmacokinetic study. Levosimendan was administered as a single-dose infusion of 0.1 microg/kg/minute for 24 hours. The follow-up period lasted 3 weeks., Study Setting: Twenty-fivepatients were included:12 patients with severe chronic renal failure (CRF) with creatinine clearance of < 30 mL/minute/1.73 m(2) and 13 patients with end-stage renal disease (ESRD) undergoing haemodialysis. A group of 12 healthy subjects served as controls., Results: Levosimendan, the parent drug, was eliminated rapidly from the plasma after discontinuation of its infusion, with an elimination half-life (t(1/2)) [mean +/- standard error of mean] of 1.5 +/- 0.09 hours in ESRD patients undergoing haemodialysis, 1.0 +/- 0.2 hours in patients with severe CRF and 0.91 +/- 0.03 hours in healthy subjects. The t(1/2) of levosimendan was significantly longer (p < 0.001) in ESRD patients undergoing haemodialysis than in healthy subjects. The t(1/2) of OR-1855 and OR-1896 were 94.0 +/- 20.4 hours and 96.5 +/- 19.5 hours, respectively, in ESRD patients undergoing haemodialysis compared with 60.8 +/- 5.2 and 61.6 +/- 5.2 hours, respectively, in healthy subjects (p = not significant). The t(1/2) of OR-1855 was significantly longer (85.0 +/- 13.6 hours) in patients with severe CRF than in healthy subjects (60.8 +/- 5.2 hours, p < 0.05). The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (C(max)) of the metabolites were approximately 2-fold in patients with ESRD undergoing haemodialysis and patients with severe CRF compared with healthy subjects. The mean unbound fraction (f(u)) of levosimendan in plasma was approximately 2% in each study group, whereas the f(u) of the metabolites was considerably higher (63-70%). In contrast to levosimendan, the metabolites were dialysable, with dialysis clearance of approximately 100 mL/minute. The haemodynamic responses and adverse event profiles were similar in the study groups, with headache, palpitations and dizziness being the most frequently recorded adverse events., Conclusion: The t(1/2) of the levosimendan metabolites was prolonged 1.5-fold and their AUC and C(max) were 2-fold in patients with severe CRF and ESRD patients undergoing haemodialysis as compared with healthy subjects. These results suggest that the dose should be reduced when levosimendan is used for the treatment of congestive heart failure in patients with severe renal insufficiency.

Aims: Acute heart failure (AHF) is associated with poor prognosis and requires recurrent hospitalizations. However, studies on AHF characteristics, treatment, and prognostic factors are few. Our aim was to investigate the characteristics, treatment, and 1-year prognosis of AHF and identify prognostic factors in different clinical groups., Methods and Results: We conducted a prospective multicentre study with 620 patients hospitalized due to AHF; mean age 75.1 (10.4) years, 50% male. Half of the patients had new-onset heart failure. Acute congestion (63.5%) and pulmonary oedema (26.3%) were the most common clinical presentations. Left ventricular ejection fraction (LVEF) was reported in two-thirds of patients. Half of these had preserved systolic function (LVEF> or =45%). At discharge, 86% of patients had beta-blockers and 76% either ACE-inhibitors or angiotensin receptor blockers in use. The 12-month all-cause mortality was 27.4%. We identified several clinical and biochemical prognostic risk factors in univariate analysis. Independent predictors of 1-year mortality were older age, male gender, lower systolic blood pressure (SBP) on admission, C-reactive protein, and serum creatinine >120 micromol/L., Conclusion: We present the characteristics and prognosis of an unselected population of AHF patients. One-year mortality is high, and independent clinical risk factors include age, male gender, lower SBP on admission, C-reactive protein, and renal dysfunction.

Aims: The objective of the EuroHeart Failure Survey II (EHFS II) was to assess patient characteristics, aetiology, treatment, and outcome of acute heart failure (AHF) in Europe in relation to the guidelines on the diagnosis and treatment of AHF published by the European Society of Cardiology., Methods and Results: Patients hospitalized for AHF were recruited by 133 centres in 30 European countries. Three thousand five hundred and eighty patients were entered into the database by the end of August 2005. Mean age was 70 years, and 61% of patients were male. New-onset AHF (de novo AHF) was diagnosed in 37%, of which 42% was due to acute coronary syndromes (ACS). Clinical classification according to the guidelines divided AHF patients into (i) decompensated HF (65%), (ii) pulmonary oedema (16%), (iii) HF and hypertension (11%), (iv) cardiogenic shock (4%), and (v) right HF (3%). Coronary heart disease, hypertension, and atrial fibrillation were the most common underlying conditions. Arrhythmias, valvular dysfunction, and ACS were each present as precipitating factor in one-third of cases. Preserved left ventricular ejection fraction (> or =45%) was observed in 34%. Valvular disorders were common, especially mitral regurgitation (MR) which was reported on echocardiography in 80% of patients. Median length of stay was 9 days, and in-hospital mortality 6.7%. At discharge, 80% of patients were on angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, whereas 61% were taking beta-blocker medication., Conclusion: Decompensated HF is the most common clinical presentation of AHF patients. More than one-third of AHF patients do not have a previous history of HF, and new-onset HF is often caused by ACS. Preserved systolic function is found in a substantial proportion of the patients. The prevalence of valvular dysfunction is strikingly high and contributes to the clinical presentation. The EHFS II on AHF verified that the use of evidence-based HF medication was well adopted to clinical practice.

Background: 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.

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 < or =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.

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.

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.

Aims: Acute heart failure (HF) is a common but ill-defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an unfavourable outcome., Methods and Results: We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty-eight percent had de-novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV-EF was <35%, 35-50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU-treatment was necessary in 39% of the patients. Thirty-day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve-month all-cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age., Conclusions: This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high.