NT-proANP and NT-proBNP as prognostic markers in patients with acute decompensated heart failure of different etiologies

Background and purpose

Peak NT-proANP and NT-proBNP plasma levels after hospital admission may be of additional prognostic value in patients with acute decompensation of heart failure. The time-course of natriuretic plasma levels after hospital admission, and a possible influence of the underlying etiology on the time-course have not been sufficiently investigated.

Methods and results

Natriuretic peptide plasma levels of 85 patients with decompensated heart failure from ischemic and non-ischemic origins were measured at baseline and at 12 h after hospital admission. NT-proBNP plasma levels on admission were lower compared to 12-hour-plasma levels, whereas NT-proANP plasma levels on admission were higher compared to 12-hour-plasma levels. Twenty-six patients (31%) died within the first 30 days. In patients who died within the first 30 days after admission NT-proANP and NT-proBNP plasma levels on admission and 12 h later were significantly higher compared to survivors. Irrespective of different etiologies NT-proANP on admission and NT-proBNP 12 h after admission were highest and demonstrated superior impact with respect to the prediction of 30-day-mortality.

Conclusions

NT-proANP and NT-proBNP are powerful markers of 30-day-mortality in patients with acute heart failure of ischemic and non-ischemic origins. With respect to the prediction of 30-day-mortality, NT-proBNP plasma levels at 12 h after admission are comparable with NT-proANP plasma levels on admission. These data underline the fact that with regard to etiology-dependent hemodynamic changes and plasma half-time, the determination of peak plasma levels is of highest importance for the estimation of the impact of natriuretic peptides on the prognosis of patients with decompensated heart failure.     

心功能不全患者血浆BNP、NT-proBNP检测分析

目的探讨血浆脑钠肽（BNP）和氨基末端B型尿钠肽前体（NT-proBNP）变化与心功能不全患者血管病变的关系。方法108例心功能不全患者发病后2周内采静脉血分离血清,28例非心脏病患者作为正常对照组,用电化学发光法测定BNP和NT-proBNP。结果对照组、心功能Ⅰ级组、Ⅱ级组、Ⅲ级组、Ⅳ级组血浆BNP水平分别是（51．34±11．27）、（155．06±39．12）、（247．05±68．34）、（513．17±127．88）（612．34±155．87）。NT—proBNP（μg／L）水平分别是（25．78±14．49）、（177．86±143．65）、（299．81±166．09）、（608．17±123．14）、（979．04±176．45）,组间比较差异均有统计学意义（P〈0．01）。结论血浆BNP水平升高与冠脉病变的严重程度有关,NT-proBNP可用于早期评价心脏收缩功能不全,早期评价舒张功能不全和心室壁节段运动协调性。     

NH2 terminal pro-brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients

OBJECTIVE: To investigate N-terminal pro-brain natriuretic peptide (NT-proBNP) level as a prognostic factor and a marker of myocardial dysfunction in patients with septic shock. DESIGN: Prospective observational study. SETTING: Intensive care unit. SUBJECTS: A total of 39 patients diagnosed with septic shock and requiring mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, respiratory, and biological data (notably NT-proBNP, lactate, and cardiac troponin I) were collected at inclusion and every 12 hrs. The independent factors for death were higher Sequential Organ Failure Assessment score in the 24-hr period after inclusion (odds ratio, 4.7; 95% confidence interval, 1.15-19.3) and the highest NT-proBNP level in the 24-hr period after inclusion (odds ratio, 1.12 per 1000 pg/mL increase; 95% confidence interval, 1.05-1.26). An NT-proBNP of >13,600 pg/mL predicted intensive care unit mortality with an accuracy of 77%. Area under the receiver operating characteristic curve was 0.8 (p = .002; 95% confidence interval, 0.66-0.93). NT-proBNP levels were over the accepted normal range in all patients. Values were highest between 24 and 36 hrs after onset of septic shock and were significantly higher in nonsurvivors at each time between inclusion and day 7. The lowest left ventricular stroke work index of the first 24-hr period after inclusion was the only factor that independently influenced higher NT-proBNP levels at the same time (odds ratio, 0.91; 95% confidence interval, 0.84-0.98). CONCLUSION: NT-proBNP seems to be an early factor of prognosis and myocardial dysfunction in patients with septic shock.     

Increased plasma histamine levels in migraine patients

Whole blood and plasma histamine levels, peripheral basophil and eosinophil counts and serum immunoglobulins have been measured in a group of eighteen patients with migraine in remission and in twelve of these patients during a headache attack. Plasma histamine levels were significantly elevated (P less than 0.0005) in patients with migraine both during headache attacks and symptom-free periods.     

D-erythro-neopterin plasma levels in intensive care patients with and without septic complications

The activation of macrophages is accompanied by release of 2-amino-4-oxo-6(D-erythro-1',2',3'-trihydroxypropyl)-dihydropterid ine (D-erythro-neopterin). The neopterin levels of 21 patients were measured with radioimmunoassay. The patients were classified according to the clinical course and outcome. We found highly significant differences between survivors and nonsurvivors for each of the evaluated days of the observation period. In addition to a sustained increase, patients with fatal outcome always showed a higher percentage of neopterin levels (88.2 +/- 28 [SD]%) exceeding the upper confidence limit (27.4 nmol/L) than survivors (31.8 +/- 29.9%). We conclude that the assessment of D-erythro-neopterin might be an easily available aid for an early evaluation of the immunologic status of a patient at risk for septic complications.     

Increased circulating levels of plasma ATP in cystic fibrosis patients

Recent studies have shown that the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP‐binding cassette (ABC) transporter whose mutations are responsible for cystic fibrosis (CF), permeates ATP. However, little information is available concerning extracellular ATP concentrations in CF patients. Thus, the goal of this preliminary study was to determine the circulating levels of plasma ATP in CF patients. Circulating levels of plasma ATP were determined by the luciferin‐luciferase assay in both CF patients and healthy volunteer control subjects. The two groups were compared using an analysis of variance. CF genotype and age, which ranged from 7 to 56 years, were also used to compare data by single‐blind analysis. With comparable sample numbers, CF patients had statistically higher levels of circulating ATP (34%, P<0·01) when compared by analysis of covariance with the age of the subjects as the cofactor. The CF patients bearing the ΔF508 genotype had a 54% (n=33, P<0·01) higher plasma ATP concentration compared to controls, while patients bearing other CF genotypes were similar to controls (n=10, P<0·4). We conclude that CF patients have higher circulating levels of ATP when compared to controls. Increased levels of plasma ATP, which is an important autocrine/paracrine hormone in many cell types, may be associated with chronic manifestations of the disease.     

Altered levels and molecular forms of granzyme k in plasma from septic patients

Granzyme K (GrK) is a member of a highly conserved group of potent serine proteases specifically found in the secretory granules of cytotoxic T lymphocytes and natural killer cells. Based on the report indicating that inter-alpha inhibitor proteins are the physiological inhibitors of GrK and on previous findings that showed a significant decrease in plasma inter-alpha inhibitor proteins in patients with sepsis, it was our aim to determine whether increased levels of uninhibited GrK would contribute to the development of sepsis. To test this hypothesis, a competitive enzyme-linked immunosorbent assay system was developed; and the levels of GrK were measured in plasma samples obtained from healthy controls and 2 sets of patients with sepsis: patients admitted to the emergency department with a putative diagnosis of sepsis and patients with severe sepsis enrolled in a clinical trial. In addition, the molecular form(s) of GrK present in these samples was analyzed by Western blot. The levels of GrK were significantly increased in emergency department patients compared with healthy controls and significantly decreased in patients with severe sepsis enrolled in a clinical trial compared with healthy controls. GrK was detected as high-molecular-weight protein complexes in healthy controls but as complexes of lower molecular weight in the septic patients. The decrease in complex size correlated with the appearance of a band at 26 kDa similar to the size of free GrK. Our results indicate that plasma levels of GrK could serve as a useful diagnostic marker to stage sepsis, permitting better classification of septic patients and enabling targeting of specific treatments, and may play a functional role in the development of sepsis.     

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19).The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.     

脓毒症心功能障碍研究进展

脓毒症在急诊有着高发病率和致死率,临床上发现脓毒症患者发生心功能障碍的程度不同,这可能与不同的免疫状态及基因型相关.目前已证明体内心肌抑制的潜在病理生理学机制,但有心功能障碍的脓毒血症患者的死亡率并没有明显下降.因此,深入研究脓毒血症引起心功能障碍的机制十分重要,本文主要总结目前脓毒症心肌损伤分子机制、临床监测及治疗手段的最新进展,试图对将来临床及基础研究有所启发.     

Increased levels of glycosaminoglycans during septic shock: relation to mortality and the antibacterial actions of plasma

Glycosaminoglycans (GAGs) are structurally heterogeneous negatively charged polysaccharides. Endothelial GAGs, also known as glycocalyx, are involved in capillary permeability. In rat venules stimulated with proinflammatory substances ex vivo, the GAG-containing proteoglycan, syndecan-1, is shed from the endothelium. We wanted to investigate if we could trace the same response during septic shock as reflected in the circulating GAG levels. Arterial plasma samples were collected from 18 consecutive septic shock patients admitted to our intensive care unit. Plasma GAGs were measured with an Alcian blue slot binding assay, and syndecan-1 levels were measured with enzyme-linked immunosorbent assay. Effects of GAGs on the antibacterial activity of plasma were assessed by a radial diffusion assay. The median plasma GAG level was significantly higher in the septic shock patients than in matched controls (median [interquartile range], 2.7 microg/mL [1.9 - 4.8 microg/mL] vs. 1.8 microg/mL [1.7 - 2.0 microg/mL]). Furthermore, the GAG levels were significantly higher in nonsurvivors (4.6 microg/mL [3.1 - 8.8 microg/mL], n = 8) than survivors (1.8 microg/mL [1.6 - 2.6 microg/mL], n = 10). The syndecan-1 levels were also increased in the patients compared with controls (246 ng/mL [180 - 496 ng/mL] vs. 26 ng/mL [23 - 31 ng/mL]) and correlated to the cardiovascular Sequential Organ Failure Assessment (SOFA) score. The GAGs inhibited the endogenous antibacterial activity of plasma as well as isolated antimicrobial peptides. The concentrations required were in the same range as the GAG levels measured in the patients. These results show that the GAG levels are increased in septic shock patients, possibly reflecting peripheral endothelial cell damage. We also found that GAGs in relevant concentrations neutralize antimicrobial peptides in plasma.     

Microparticles and acute renal dysfunction in septic patients

Purpose

The role of microparticles (MPs) in the pathogenesis of sepsis is not completely elucidated. We aimed to assess changes in the number of MPs during severe sepsis to follow the effect of sepsis-related organ failures, particularly renal impairment, an independent mortality factor of sepsis.

Materials and Methods

Thirty-seven severe septic patients and 20 controls were enrolled. Patient status as well as organ failure–related laboratory markers was followed up to 5 consecutive days. Microparticles (annexin V + events in MP size gate) of platelet (CD41, CD42a, and PAC1), monocyte (CD14), and myeloid cell line (CD13) origin were measured using flow cytometry.

Results

Significantly increased total MP and CD41-, CD42a-, and PAC1-positive particle numbers were found in septic patients compared with controls. Actual number of organ dysfunctions on sample collection showed no correlation with MP numbers. Septic patients with renal dysfunction showed an increase in total MP, CD41⁺, and CD13⁺ particle numbers on admission. Amounts of platelet-derived CD42a⁺ particles from patients with sepsis-related renal injury correlated negatively with actual blood urea nitrogen and creatinine concentrations.

Conclusion

The increased numbers of platelet-derived MPs in severe septic patients emphasize the possible contribution of the hemostasis system in the development of sepsis-related renal impairments.     

Transpulmonary thermodilution-derived cardiac function index identifies cardiac dysfunction in acute heart failure and septic patients: an observational study

Introduction  

There is limited clinical experience with the single-indicator transpulmonary thermodilution (pulse contour cardiac output, or PiCCO) technique in critically ill medical patients, particularly in those with acute heart failure (AHF). Therefore, we compared the cardiac function of patients with AHF or sepsis using the pulmonary artery catheter (PAC) and the PiCCO technology.     

Right ventricular dysfunction in septic patients.

OBJECTIVE: To compare right ventricular ejection fraction in trauma and septic patients during the hyperdynamic circulatory phase of these states. DESIGN: Prospective, consecutive study. SETTING: University hospital ICU. PATIENTS: Eleven trauma patients (group 1) and ten septic patients (group 2) were studied. Patients with circulatory shock were excluded from the study. INTERVENTIONS: Right ventricular ejection fraction was measured with a modified pulmonary artery catheter using the thermodilution method. Patients requiring catecholamines to maintain a systolic BP greater than 90 mm Hg were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Both groups 1 and 2 had high mean cardiac output values (cardiac indices 4.7 +/- 0.9 [SD] and 4.6 +/- 1.4 L/min/m2, respectively). Right ventricular ejection fraction was significantly (p less than .005) reduced in septic patients (47 +/- 7.0% vs. 36 +/- 9.7%; group 1 vs. group 2) and end-diastolic volume index was significantly (p less than .01) increased (101 +/- 34 vs. 122 +/- 40 mL/m2; group 1 vs. group 2) in comparison with the trauma patients. However, there were no significant differences in afterload between the two groups. CONCLUSIONS: Hemodynamic measurements comparing septic and trauma patients showed increased cardiac output in both groups and no differences in the pulmonary resistance. Right ventricular ejection fraction in the septic patients was significantly reduced compared with the trauma patients. Therefore, we concluded that right ventricular contractility may be decreased in septic patients.