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Context: Cardiorenal biomarkers (CBs) predict outcome in acute heart failure (AHF). Objective: To evaluate CBs in early follow-up prognostication. Methods: In 124 AHF patients, levels of CystatinC, NT-proBNP and Troponinl measured five weeks from admission (W5) and relative change from day 2 (D2) were assessed for 6-month prognosis (mortality/HF hospitalization). Results: The combined end-point occurred in 33 patients (27%). D2-, W5-cystatin≥ median, and lack of ≥30%decrease in NT-proBNP were independent predictors of outcome. Additionally, a risk score established from W5 CBs identified patients with very high event rate. Conclusions: CBs at early follow-up of AHF may guide risk stratification. [ABSTRACT FROM AUTHOR]

Background: Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed. Methods and results: Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-αα [TNF-αα], IL-10) were measured in consecutive patients ( n == 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-αα had the strongest relation with renal function (ββ == 0.39, P < 0.0001). Elevated TNF-αα levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (ββ == 0.26, P < 0.0001) and IL-10 (ββ == 0.15, P < 0.01), but not TNF-αα, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2--2.9, P == 0.003). TNF-αα was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP. Conclusion: Levels of TNF-αα in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-αα. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart--kidney interactions. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. DESIGN AND SETTING:: Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). PATIENTS:: A total of 254 patients with severe sepsis or septic shock. MEASUREMENTS:: After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. MAIN RESULTS:: NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. CONCLUSION:: NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis. [ABSTRACT FROM AUTHOR]

Objective: Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs.Design: The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured.Results: Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values (p < 0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups.Conclusions: In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signsof positive outcome, even though statistical significance could not be reached. [ABSTRACT FROM AUTHOR]

Objective: To compare the prognostic significance of bactericidal/permeability-increasing protein (BPI), group II phospholipase A2 (PLA2-II), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF), interleukin-8 (IL-8) and interferon-gamma (IFN) in terms of predicting severity of sepsis and outcome.Design: A prospective study.Setting: Medical intensive care unit (ICU) of a university hospital.Patients: Thirty-four patients with severe sepsis requiring ICU treatment.Measurements and Results: The levels of BPI, PLA2-II, CRP, TNF, IL-8 and IFN were measured in these 34 patients. High levels of BPI were associated particularly with Gram-negative sepsis. BPI and BPI/neutrophil ratios correlated positively with PLA2-II, CRP, TNF and IL-8 and negatively with blood pressure. At 24 h, BPI/neutrophil ratios, IL-8 and Simplified Acute Physiology Scores II (SAPS II) scores were higher in non-survivors than in survivors. No such associations were noted in the levels of CRP, PLA2-II, TNF or IFN. The areas under the curve (AUC(ROC)s) of SAPS II scores and IL-8 were higher than AUC(ROC) of BPI/neutrophil ratio.Conclusion: The BPI and BPI/neutrophil ratios may serve as adjunctive tools to illustrate the severity of sepsis. However, their predictive power for sepsis-related death was not comparable to that of SAPS II scores and IL-8. [ABSTRACT FROM AUTHOR]

Purpose: Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group).Results: Insulin sensitivity index (ISI) increased by 33% (P<0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2+/-11.5 to 81.7+/-10.7 ml/min/kg (mU/l), P<0.05]. No change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated with maximal oxygen uptake (r=0. 65, P<0.0001) and body mass index (r=-0.55, P<0.001). The change in ISI correlated weakly with the improvement in muscle exercise capacity (r=0.53, P<0.05).Conclusions: Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta1- selective adrenoceptor antagonist, potentiates this effect. [ABSTRACT FROM AUTHOR]

Aims The classification of an acute ischaemic cardiac event is traditionally based on cardiac enzymes, electrocardiography (ECG) and clinical symptoms. The impact of new specific cardiac markers on the diagnostic classification of suspected acute myocardial infarction remains poorly studied. We therefore set out to compare the diagnostic and prognostic information provided by the MONICA code and a patient classification based on the maximal level of creatine kinase MB isoenzyme. The significance of typical pain and various ECG algorithms were separately analysed.Methods and Results The study population consisted of 311 consecutive patients who were evaluated for suspected acute myocardial infarction in a regional referral hospital. Patients were retrospectively classified according to the MONICA criteria, by a simplified code combining symptoms and creatine kinase MB, and solely using the maximal creatine kinase MB concentration. Total mortality was followed for 1 and 5 years. The creatine kinase MB based classification was shown to be the strongest predictor of mortality (OR=2·8–3·7, p<0·001) for outcome both at 1 and 5 years. Typical pain and a positive Minnesota ECG had no prognostic relevance. However, an analysis algorithm of the admission ECG was predictive of 1- and 5-year survival.Conclusions The epidemiological classification of suspected acute myocardial infarction could be based solely on a specific cardiac marker, such as creatine kinase MB mass. This approach contains prognostic information and is accurate enough for the structured diagnosis of acute myocardial infarction. Other outcome predictors could be used to identify patient subgroups and assess therapy. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to investigate the applicability of computerized electrocardiogram interpretation in classifying patients with suspected acute myocardial infarction. Computerized acquisition and analysis of the 12-lead electrocardiogram can increase the consistency and reduce the workload of patient classification. The serial electrocardiograms of 311 consecutive patients with suspected myocardial infarction were studied and a new computerized myocardial infarction (CMI) electrocardiographic classification was developed and compared with one commercially available and two manual codes. Statistically, there was almost no correlation between the four ECG codes. Compared with the WHO enzymatic criteria, the sensitivity of the CMI code toward detecting definite and possible infarction was 69.2% and 29.8% with a specificity of 62.1% and 79.7%, respectively. In subjects without previous infarction (n = 214) the sensitivity of the CMI code for definite enzymatic infarction was 71.9% and specificity 77.6%. Substituting the CMI for the Minnesota code had no effect on patient classification by the WHO MONICA criteria in 78% of patients with first infarction. Judged by cardiac macromolecular leakage, all electrocardiographic classifications of possible infarction were poorly correlated with myocardial tissue injury. We have developed a new computerized coding system to detect electrocardiographic myocardial infarction. The structure of the code allows interactive redefinition of criteria to meet user-defined needs. However, because of the weak relationship between electrocardiographic and biochemical criteria of myocardial injury, the role of ECG in the diagnostic classification of acute ischemic syndromes should be re-evaluated. [ABSTRACT FROM AUTHOR]