[Admission and predischarge levels of NT pre brain natriuretic peptide in patients hospitalized because of worsening heart failure. relation to risk of death in the next 6-12 months].

UNLABELLED: Inhospital treatment of patients with heart failure (HF) can cause changes of N-terminal pro-brain natriuretic peptide (NT proBNP) levels. It has not been established yet which NT proBNP value (before or at height of treatment activation) is closer related to prognosis of unfavorable outcome after discharge. AIM: To compare relation to risk of post discharge unfavorable outcome of patients with HF of NT proBNP levels measured close to hospital admission and discharge. MATERIAL AND METHODS: We studied 69 patients (64% men) aged 66.6 +/- 11.0 years with coronary heart disease or hypertension hospitalized because of worsening HF. Median left ventricular ejection fraction was 28%. NT-proBNP was measured during first 3 days of hospitalization (admission level) and in 2 weeks after first measurement (predischarge level). Duration of follow-up was 6-12 (mean 11.6 +/- 1.3) months. RESULTS: Admission NT-proBNP level (median 13.23, interquartile range 5.95-25.89 ng/ml) exceeded upper limit of normal (ULN) in 67 patients (97.1%). Predischarge NT-proBNP became significantly lower (median 6.02 ng/ml, interquartile range 2.52-12.23 ng/ml; p=0.012), but remained above ULN in 62 patients (89.8%). During follow-up 27 patients (39.1%) died. Median NT-proBNP in the group of patients who later died compared with those who survived was insignificantly higher at admission (15.03 vs. 9.9 ng/ml, respectively, p=0.09) and significantly higher at predischarge (8.65 vs. 3.60 ng/ml, respectively, p=0.012). Analysis of receiver operating characteristic curves identified predischarge NT-proBNP level 3.5 ng/ml as cut - off value for increased risk of death. Multivariate regression analysis selected predischarge NT-proBNP more or equal 3.5 ng/ml as independent predictor of death during follow-up. CONCLUSION: In this group of patients hospitalized because of worsening HF predischarge but not admission NT-proBNP level was independently related to risk of death during next 6-12 months.

[Heart fatty acid binding protein in patients hospitalized because of worsening heart failure. Relation to prognosis of death].

PURPOSE: We tested the hypothesis that serum heart fatty-acid binding protein (FABP), an early marker of myocardial necrosis, is related to prognosis of patients hospitalized because of worsening heart failure (HF). METHODS: Sixty nine patients (64% men, age 66.6 +/- 11.0 years) with NYHA class II, III, IV HF (1, 18, and 50 patients, respectively) at hospital admission were followed for 6-12 (mean 11.6 +/- 1.3) months. Forty seven patients (68.1%) had history of myocardial infarction (MI), 56 (81.2%) - hypertension, 15 (21.7%) -- diabetes, and 17 (24.6%) had echocardiographical signs of aortic stenosis. Median left ventricular ejection fraction was 28%. Serum FABP, cardiac troponin I (Tn I) and N-aminoterminal pro brain natriuretic peptide (NT proBNP) were measured within 3 days after admission ( " admission " levels) and 2 weeks later (minimal hospital stay). Manufacturer recommended upper limits of norm (ULN) were 4.0 ng/ml for FABP, 0.35 ng/ml for Tn I, 0.1 ng/ml for NT proBNP. RESULTS: Median admission FABP was insignificantly higher than level measured 2 weeks later (4.17 vs 4.03 ng/ml, p=0.069). FABP exceeded ULN in 38 (55.1%) patients and in 35 (50.7%) patients at admission and in 2 weeks, respectively (p=0.65). Median admission NT proBNP was significantly higher than 2 weeks level (13.23 vs 6.02 ng/ml, p < 0.0001). Median admission and 2-weeks levels of Tn I were similar and greatly lower than ULN. There were 27 all cause deaths (39.1%) during follow up. Median admission levels of TnI, FABP and NT proBNP were similar in patients who died and survived. Two weeks NT proBNP was significantly higher in patients who died (8.65 vs 3.62 ng/ml, p=0.012). ROC curve derived cut-off levels of FABP and NT proBNP (3.31 ng/ml and 3.5 ng/ml, respectively) were used in univaritate regression analysis. According to this analysis FABP >or= 3.31 ng/ml was related to occurrence of death (OR 3.54; 95% CI 1.03-12.17, p=0.044). FABP and variables with p > 0.1 (age, history of MI and diabetes, regular treatment with nitrates, signs of aortic stenosis, pulmonary rales at admission, and 2 weeks level of NT proBNP >or = cut-off) were included into multivariate logistic regression model. Independent predictors of death were aortic stenosis (OR 31.67; 95% CI 6.11-164.00) and NT proBNP >or= 3.5 ng/ml (OR 5.75; 95%CI 1.69- 19.52). CONCLUSION: In this group of patients hospitalized due to worsening of HF admission values of neither FABP nor other biomarkers studied were predictors of death during about 1 year of follow up. FABP level after 2 weeks of hospital stay was related to occurrence of death but as predictor was inferior to NT-proBNP measured at the same time point.

[Levels of fatty acid binding protein before and after direct current cardioversion of atrial fibrillation or flutter in patients without acute coronary syndrome].

UNLABELLED: It is not known whether FABP suggested as an early marker of myocardial necrosis increases after direct current cardioversion (DCC). Moreover there are no data on FABP levels in patients with atrial fibrillation (AF) and flutter. AIM: To find out whether DCC induces acute changes of FABP levels in patients with AF or flutter without acute coronary syndrome. METHODS: Serum FABP and troponin I (TnI) were measured in 63 pts treated with DCC (monophasic shocks) because of AF (n=45, 71.4%) or atrial flutter (n=18, 28.6%). Initial energy was 50J for atrial flutter and 200J for AF. Median total energy was 200J, max 660J. Blood was sampled before DCC and in 30, 60 min, 3, 6 h after first shock. TnI and FABP were measured with single-step sandwich method ("Hytest" Finland). Upper limit of normal range (ULN) for TnI was 0.4 ng/ml (recommended by manufacturer). Serum FABP was measured in healthy volunteers and 95th percentile was used as ULN (4.67 ng/ml). RESULTS: Most pts (n=40, 63.5%) had baseline FABP > ULN (median for all pts--5.55 ng/ml). In 11 pts (17.4%) baseline FABP was > 2 ULN. No relationship was found between baseline FABP and age, sex, duration of arrhythmia, concomitant ECG changes, and presence of overt coronary heart disease or clinical signs of heart failure. Median FABP level increased after DCC (p for trend 0.00014). FABP levels after DCC correlated with total delivered energy. Delivery of > or = 2 shocks compared with 1 shock was associated with higher FABP (median 60 min--9.65 and 5.24 ng/ml, p=0.009; 3 h--12.41 and 5.84 ng/ml, p=0.01, respectively). Median TnI levels were below ULN at each study point. After DCC TnI did not exceed ULN in 61 pts and remained unchanged in 2 pts with baseline TnI above ULN. CONCLUSION: Unexpectedly most pts with AF and atrial flutter had elevated FABP at baseline. After DCC FABP increased in proportion with total delivered energy. Elevations of FABP levels were not associated with rapid increases of TnI so skeletal muscle damage can be a likely cause of elevated FABP. AF, atrial flutter and DCC for these arrhythmias should be considered as sources of false positive results when FABP is used for diagnosis of acute myocardial infarction.

[Prognostic significance of heart fatty acid binding protein in patients with non-ST elevation acute coronary syndrome: results of follow-up for twelve months].

UNLABELLED: Value of heart fatty acid binding protein (FABP) for medium term prognosis in patients with non-ST elevation acute coronary syndrome (NSTEACS) is not well established. AIM: To compare prognostic value of FABP levels with those of troponin I (TnI) and creatine kinase MB (CK MB) activity in patients with NSTEACS. METHODS: Serum FABP and TnI levels (HyTest), CK MB activity (Biocon) were measured in 203 patients with NSTEACS (mean age 63.9+/-11.5 years, 52.2% male). Blood was sampled at admission within 12 (median 3.83) hours and in 6 and 12 hours after onset of pain. Upper limits of normal range (ULN) for TnI and CK MB were 0.4 ng/ml and 25 U/l, respectively. Serum FABP was measured in 53 healthy volunteers (mean age 44.3+/-13.3) and 95th percentile was used as ULN (4.67 ng/ml). Deaths and nonfatal MIs (events) were registered during one year follow-up. RESULTS: There were 47 events (23%, 23 deaths and 24 nonfatal MIs). Patients with events compared with those without events had significantly higher TnI and CK MB 12 hours after onset of pain and significantly higher FABP at all time points of blood sampling. Multivariate (step-up) analysis selected the following independent predictors of events: elevated FABP 6 hours after pain onset (OR 2.45, 95% CI 1.14-5.24; p=0.021), T-wave inversion on admission ECG, age >65 and regular use of nitrates before hospitalization. Sensitivity of elevated FABP 6 hours after pain onset was 78.4%, specificity -- 45.1%. After exclusion from analysis of all or just admission and 6 hours FABP data elevated TnI 12 hours after onset of pain became an independent predictor of events. CONCLUSION: In this group of patients with NSTEACS among markers of myocardial necrosis (FABP, TnI, MB CK) obtained serially during first 12 hours after pain onset elevated FABP was the best predictor of events during 1 year follow up for subjects in whom blood sample could be done 6 hours after pain onset.

[Diagnostic value of heart fatty-acid binding protein in early hospitalized patients with non ST elevation acute coronary syndrome]. / Ostryi koronarnyi sindrom bez pod"emov segmenta ST na EKG: diagnosticheskoe znachenie serdechnogo belka, sviazyvaiushchego zhirnye kisloty.

BACKGROUND: Heart fatty-acid-binding protein (FABP) is supposed to be the most sensitive biomarker of myocardial necrosis in patients with Q-wave myocardial infarction (MI) and non-diagnostic ECG during first hours after onset of symptoms. However, diagnostic value of FABP in patients with non-ST elevation acute coronary syndrome (NSTEACS) is not well established. AIM: To elucidate diagnostic value of FABP in patients with NSTEACS hospitalized within time interval considered to be too early for a majority of biochemical tests. MATERIAL AND METHODS: FABP levels were measured by immunofluorometry (HyTest, Finland) in 44 patients (26 men, mean age 69+/-8.9 years) at admission within 6 hours (median - 2 h) from onset of index attack of angina and in 6, 12, 24 hours after onset of pain. Cut off FABP level was 12 ng/ml. Serum cardiac troponin I was measured for diagnosis of MI on admission and twice during first 24 hours of hospital stay. Cut off TnI level was 0.4 ng/ml. RESULTS: Acute MI was diagnosed by TnI above cut off in 31 patients (70.5%). There were no new-Q-wave MIs. Average ratio of observed serum FABP level to diagnostic cut off value on admission and in 6, 12, 24 hours after onset of pain was higher in patients with MI than in patients with unstable angina (1.01, 1.53, 0.81, 0.66 and 0.78, 0.51, 0.65, 0.56, respectively). The difference was maximally significant in 6 hours after onset of pain (p=0.018). Among patients with MI admission FABP compared with admission TnI more frequently exceeded diagnostic level (in 18 vs 9 patients, respectively, p=0.009). Sensitivity and specificity of admission levels of FABP and TnI for diagnosis of MI were 58 and 85%, 29% and 100%, respectively. CONCLUSION: In patients with NSTEACS during first 6 hours after pain onset FABP compared with TnI has greater sensitivity for detection of MI and sufficient specificity. FABP can be used as additional diagnostic tool for MI detection in early admitted patients with NSTEACS.

[Heart fatty acid binding protein in patients with ST-elevation acute coronary syndrome hospitalized within 6 hours after onset of pain]. / Serdechnyi belok, sviazyvaiushchii zhirnye kisloty, u bol'nykh ostrym koronarnym sindromom s pod"emami segmenta ST, gospitalizirovannykh v pervye 6 ch zabolevaniia.

AIM: To compare diagnostic value of a novel marker of myocardial necrosis heart fatty acid binding protein (FABP) with that of troponin I (TnI) and total creatine kinase (CK) in patients admitted early after onset of ST-elevation acute coronary syndrome. MATERIAL: Fifty seven patients with ST-segment elevations justifying thrombolytic therapy admitted within 6 hours (29/57 within 3 and 12/57 - 2 hours) after onset of chest pain. In all patients myocardial infarction (MI) was eventually confirmed by development of Q waves and/or diagnostic increase of CK. METHODS: Samples of blood were taken at admission to coronary care unit. Cut-off values for an elevated level of FABP was 12 ng/ml, TnI - 1.2 and 0.4 ng/ml, CK - 400 IU/l. RESULTS: Overall FABP was elevated in 47 (83%), TnI - in 16 (28.1%), CK in 7 (12.3%) patients. Among patients admitted within first 3 and 2 hours FABP was elevated in 23/29 (79.3%) and 11/12 (91%), TnI - in 9/29 (31%) and 5/12 (41.7%), CK in 3/29 (10.3%) and 1/12 (8.3%) patients, respectively. The use of lower cut-off of abnormality (0.4 ng/ml) increased proportion of patients with elevated TnI up to 56.1% in the group as a whole, to 48.3% and 50% among patients admitted within first 3 and 2 hours, respectively. Nevertheless proportion of patients with elevated FABP remained higher with difference being significant for the whole group and patients admitted within first 3 hours (p=0.004 and 0.016, respectively). CONCLUSION: Most patients with ST-elevation acute coronary syndrome hospitalized within 2-6 hours after onset of pain had elevated levels of heart FABP.

Degradation of cardiac troponin I: implication for reliable immunodetection.

We have analyzed by different immunological methods the proteolytic degradation of cardiac troponin I (cTnI) in human necrotic tissue and in serum. cTnI is susceptible to proteolysis, and its degradation leads to the appearance of a wide diversity of proteolytic peptides with different stabilities. N- and C-terminal regions were rapidly cleaved by proteases, whereas the fragment located between residues 30 and 110 demonstrated substantially higher stability, possibly because of its protection by TnC. We conclude that antibodies selected for cTnI sandwich immunoassays should preferentially recognize epitopes located in the region resistant to proteolysis. Such an approach can be helpful for a much needed standardization of cTnI immunoassays and can improve the sensitivity and reproducibility of cTnI assays.