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Eur J Cardiothorac Surg 2005;27:899-905
© 2005 Elsevier Science NL

Natriuretic peptides and E-selectin as predictors of acute deterioration in patients with inotrope-dependent heart failure

Evgenij V. Potapova,*, Felix Henniga, Frank D. Wagnera, Hans-Dieter Volkb, Ralf Sodiana, Harald Hausmanna, Hans B. Lehmkuhla, Roland Hetzera

a Deutsches Herzzzentrum Berlin, Department of Cardiothoracic and Vascular Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
b Charité, Humboldt University Berlin, Campus Mitte, Berlin, Germany

Received 27 December 2004; received in revised form 20 January 2005; accepted 21 January 2005.

* Corresponding author. Tel.: +49 304 5932065; fax: +49 304 5932079. (E-mail: potapov{at}dhzb.de).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
 References
 
Objective: In patients with inotrope-dependent end-stage heart failure the timely application of the most suitable treatment, i.e. heart transplantation, implantation of a ventricular assist device or conservative treatment, is a key issue for therapeutic success. Methods: Seventy-six inotrope-dependent patients with end-stage heart failure were enrolled. Measurements of hemodynamics, routine laboratory parameters, and clinical examination were performed daily. Additionally, natriuretic peptides (BNP and NT-proBNP) and E-selectin were measured at the end of the study. The patients were retrospectively divided into groups with regard to the following end-points: Group I—deterioration into cardiogenic shock after an initially stable clinical course (n=26); Group II—stable clinical course without deterioration into cardiogenic (n=41); Group III—weaning from inotropic support (n=9). Results: One day before cardiogenic shock occurred, BNP, NT-proBNP and E-selectin were significantly elevated in group I compared with group II. A logistic regression model showed that only BNP and E-selectin were independent predictors of clinical deterioration on the following day. The odds ratio (OR) for E-selectin using a cut-off point of 65ng/ml was 8.7 and for BNP using a cut-off of 500pg/ml it was 4.8. In combination, the OR increased to 11.1. Continuous decrease of NT-proBNP predicted patients in whom weaning from inotropes was possible. Conclusions: While routine parameters did not predict the clinical course, elevated BNP and E-selectin independently predicted cardiogenic shock on admission and 1 day before its occurrence. The combination showed increased predictive value.

Key Words: BNP • NT-proBNP • E-selectin • Ventricular assist device • Heart transplantation • Cardiogenic shock • Heart failure


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
 References
 
Chronic heart failure is a growing problem in developed countries. Approximately 40% of patients die within 1 year after acute exacerbation of the disease [1] has occurred. In patients with inotrope-dependent end-stage congestive heart failure the application of the most suitable treatment—heart transplantation (HTx), implantation of a ventricular assist device (VAD) or conservative treatment at the right point in time—is a key issue for therapeutic success. The prediction of clinical course in these patients is still an unsolved problem [2]. So far, results of physical examination and parameters of organ function, infection and hemodynamics are used for judgment of the clinical situation, based on individual experience. There is growing evidence that the neurohumoral and immune systems play an important role in the progression of congestive heart failure [3–9]. B-type natriuretic peptide (BNP) and the aminoterminal part of the proB-type natriuretic peptide (NT-proBNP) have gained most interest. Soluble E-selectin is an integrative marker of vascular inflammation and has been shown to be elevated in patients with advanced heart failure [10,11].

The aim of the present study was to evaluate the value of BNP, NT-proBNP, ultrasensitive C-reactive protein (CrP), and E-selectin for the prediction of hemodynamic deterioration into cardiogenic shock, which would impair outcome after both HTx and VAD implantation, and of the clinical course in patients with inotrope-dependent end-stage congestive heart failure.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
 References
 
The Institutional Ethics Committee approved the study and informed consent was obtained from all patients or, if they were unable to sign, from their relatives.

Between May 2001 and December 2002, 86 adult patients with inotrope-dependent end-stage congestive heart failure referred from other hospitals to our institution for further evaluation were enrolled in the study. Inotrope dependency was considered to be present if the level of inotropic support was >3, calculated using a modified inotropic score [12]. Briefly, the doses of dopamine, dobutamine and enoximone in micrograms per kg body weight per minute were added; the doses of epinephrine and norepinephrine were multiplied by 100 and then added.

The exclusion criteria were absence of written consent, age under 16 years, myocardial infarction within the last 4 weeks and impending surgical therapy other than VAD or HTx. Patients presenting in profound cardiogenic shock on admission (n=10) requiring salvage VAD placement were excluded from the analysis.

Daily measurements of hemodynamic parameters were performed in all patients in supine position for at least 30min, including data from pulmonary catheterization. Additionally, the patients underwent clinical examination and the medication administered was recorded. At the same time as daily measurements of hemodynamic parameters and routine laboratory blood analysis, blood for study purposes was drawn and stored for further analysis, which was performed at the end of the study.

On admission and during follow-up transesophageal echocardiography was performed routinely in all patients.

VAD implantation was considered an emergency operation if performed as a life-saving procedure in patients with deterioration into cardiogenic shock during hospital stay. Deterioration into cardiogenic shock after an initially stable clinical course was defined at the beginning of the study and considered to have occurred if one of the following happened:

1. Onset of lung edema requiring mechanical ventilation
2. Doubling of the inotropic support during a 24-h period
3. Life threatening arrhythmia (e.g. pulseless ventricular tachycardia or fibrillation)
4. Cardiopulmonary resuscitation
5. Death due to cardiogenic shock

VAD implantation was considered an urgent procedure if it was scheduled for the next day in order to minimize the risk of further deterioration in accordance with the definitions used in the STS Database Report 2000–2002.

The patients were retrospectively divided into three groups with regard to the end-points:

– Group I consisted of patients who developed deterioration into cardiogenic shock after an initially stable clinical course (decompensation group, n=26).
– Group II comprised patients who had stable clinical course without deterioration into cardiogenic shock during hospital stay allowing ‘high urgency’ heart transplantation or scheduled implantation of a VAD (stable group, n=41). Some patients in group II received a VAD, not being listed for HTx due to advanced age, significant comorbidity or their own wishes (VAD as a definitive therapy). Scheduled VAD implantation was also performed if pulmonary vascular resistance was high or if a prolonged waiting period for HTx was likely because of such factors as positive panel reactive antibodies or donor-recipient size or weight mismatch. The decision to continue to wait for a suitable donor organ or to proceed with VAD implantation to forestall decompensation was made on an individual basis.
– Group III consisted of patients who were weaned from inotropic support and discharged home (weaning group, n=9).

The sequence of study events is represented schematically in Fig. 1.



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  		Fig. 1. Sequence of study events and clinical course of patients enrolled in the study. CHF, congestive heart failure; HU HTx, high urgency heart transplantation; VAD, ventricular assist device.

 
2.1. Laboratory measurements at the end of the study
Each day blood samples were taken for routine laboratory procedures and hemodynamic parameters measured. At the same time, blood samples for the measurement of neurohumoral and inflammatory markers were drawn into prechilled standard tubes (no anticoagulant for serum and sodium citrate for plasma) and immediately centrifuged at 4°C and 3000rpm and stored at –80°C. The samples were analyzed at the end of the study.

BNP was measured in plasma using commercially available immune radiometric assays (IRMA, Shionogi Co., Osaka, Japan, catalog no. 38K634). The sensitivity of the tests was 2pg/ml; the intra- and interassay coefficient of variance (CV) was less than 6%. The reference level was less than 19.0pg/ml.

The aminoterminal part of the pro-B-type natriuretic peptide (NT-proBNP) was measured in serum using a commercially available kit based on electrochemiluminescence technique (Roche Diagnostics, Mannheim, Germany, catalog no. 03121640). The sensitivity of the test was 5pg/ml; the intraassay CV was <3% and the interassay CV <3.5%. The reference level for males was 150pg/ml and for females 80pg/ml.

E-selectin was measured in serum by means of an enzyme-linked immunosorbent assay using a commercially available kit (R&D Systems Inc., Minneapolis, MN, catalog no. BBE 2B). The sensitivity of the test was less than 0.1ng/ml; the intraassay CV was 5% and the interassay CV 8.8%. The reference level was 46.3ng/ml.

Ultrasensitive C-reactive protein (CrP) was measured in plasma by means of an automated immunofluorescence assay using a commercially available kit (B.R.A.H.M.S., Germany). The sensitivity of the test was 0.06µg/ml; the intraassay CV was 5.1% and the interassay CV 14.2%. The reference level is less than 5µg/ml.


   3. Statistical analysis
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
 References
 
The data obtained on admission were compared among the three groups.

During follow-up the data obtained on days 1, 2 and 3 before profound cardiogenic shock occurred in group I (decompensation) were compared day by day with the data obtained in group II (stable) 1, 2 and 3 days before urgent HTx or VAD implantation was performed. The courses of the study parameters in group III (weaning) were analyzed separately. The analyses were performed for the last 5 days before inotropic support was stopped (day 0).

Statistical analysis was performed using SPSS 10.0.5 for Windows. For quantitative data median and quartiles or mean and standard deviation have been calculated. Qualitative data are reported as relative frequencies and percentages. The Kruskall–Wallis or {chi}2-test was applied to test differences among groups at admission and the Wilcoxon rank-sum test was used for comparisons between groups I (decompensation) and II (stable) at different time points. Logistic regression analysis was performed to identify risk factors for development of profound cardiogenic shock on admission and 1 day before clinical deterioration. For BNP and E-selectin the areas under the curve of the receiver-operating characteristics (ROC) were calculated to identify the cut-off with the best predictive value for calculation of the odds ratios. Briefly, ROC represents a trade-off between the false negative and false positive rates for every possible cut off value.

The Friedman test was employed to analyze changes over time in group III (weaning).

A P value of less than 0.05 was considered statistically significant.


   4. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
5. Discussion
 6. Conclusion
 7. Limitations
 References
 
4.1. Comparison among the groups at admission
Of 76 patients (mean age 52.7±12.5, range 16–77 years) 68 were men.

The demographics and selected results of clinical, laboratory and echocardiographic examination as well as medication and hemodynamics on admission in all groups are presented in Table 1.


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  		Table 1. Demographics, data from clinical and echocardiographic examination and medication and hemodynamics on admission
 
There were no significant differences among the groups for the hemodynamic parameters measured except for heart rate and systemic blood pressure.

The BNP levels were significantly higher in group I (decompensation) as compared to group III (weaning) (P=0.032) and to group II (stable) (P=0.016) and are given in Fig. 2(A).



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  		Fig. 2. Levels of BNP (A) and E-selectin (B) on admission in all three groups. The horizontal lines represent medians, the box plots 25 and 50 percentiles and the vertical lines the ranges.

 
The levels of NT-proBNP showed no significant differences among the groups (P=0.081).

The levels of E-selectin were significantly lower in group II (stable) compared to group I (decompensation) (P<0.0001) and are shown in Fig. 2(B).

There were no significant differences among the groups for CRP.

There was no correlation between BNP and E-selectin 1 day before occurrence of end-points (r=–0.207, P=0.1), as shown in Fig. 3.



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  		Fig. 3. No correlation between BNP and E-selectin on admission.

 
The odds ratio (OR) for the occurrence of profound cardiogenic shock during follow-up calculated for an E-selectin level of >65ng/ml was 7.2 (95% CI 2.1–25.1, P=0.002). Specificity was 58.9%, sensitivity was 83.3%. The OR for BNP level of >500pg/ml was 2.9 (95% CI 0.96–9.1, P=0.06). Specificity was 52.5%; sensitivity was 72.7%. In combination, if one or both markers were elevated, the OR was 9.5 (range 2.8–32.0, P=0.001). Specificity was 82% and sensitivity 68%.

4.2. Comparison between decompensation and stable groups during hospital stay
The mean time from admission to end-point was 2.7±3.5 days in group I (decompensation) and 5.9±5.1 days in group II (stable).

In group I (decompensation) emergency VAD implantation was performed in 19 patients (LVAD n=14 and BVAD n=5). Ten patients (53%) were alive after 30 days. Seven patients did not meet the criteria for emergency VAD implantation (e.g. sepsis, advanced age or family decision) and subsequently expired from cardiogenic shock.

In the stable group (group II) urgent LVAD implantation was performed after 5±3 days in 28 patients. ‘High urgency’ HTx was performed after a mean waiting time of 10±7 days in 11 patients. Two further patients refused surgical treatment and were transferred back to the referring hospitals in stable condition. Thirty days after VAD implantation the survival rate was 71%. In group I (decompensation) fewer patients were alive after VAD implantation than in group II (stable) (P=0.19).

Thirty days after one of the study end-points had been reached, survival in group I (decompensation) was significantly lower than in group II (stable) (38.5 vs. 73%, P=0.005).

There were no differences for most of the parameters listed in Table 1 between group I (decompensation) and group II (stable) compared day by day 1, 2 and 3 days before end-points occurred (data not shown). Three days before profound cardiogenic shock occurred creatinine levels were significantly elevated in group I (decompensation) compared to group II (stable) (2.29±1.38 vs. 1.45±0.82mg/dl; P=0.039). Two days before profound cardiogenic shock occurred aspartate aminotransferase was significantly lower in group I (decompensation) than in group II (stable) (27.72±20.64 vs. 68.89±275.63U/l; P=0.027).

One day before profound cardiogenic shock occurred heart rate, systolic blood pressure and mixed venous oxygen saturation differed significantly between group I (decompensation) and group II (stable) (107±20 vs. 91±18min–1, P=0.001; 92±17 vs. 100±15mmHg, P=0.025 and 58.1±12.6 vs. 63.4±7.9%; P=0.026, respectively).

The levels of BNP (Fig. 4(A)) and NT-proBNP (Fig. 4(B)) were significantly elevated in group I (decompensation) as compared to group II (stable) 1 day before the event (P=0.016 and 0.026, respectively).



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  		Fig. 4. Levels of BNP (A), NT-proBNP (B), and E-selectin (C) in group I (decompensation) 1, 2 and 3 days before profound cardiogenic shock occurred compared day by day to those of group II (stable) 1, 2 and 3 days before HTX or VAD implantation was performed. The horizontal lines represent medians, the box plots 25 and 50 percentiles and the vertical lines the ranges.

 
The levels of E-selectin were significantly elevated 1, 2 and 3 days before the end-point in group I (decompensation) as compared to group II (stable) (P<0.0001, 0.0001 and 0.001, respectively, Fig. 4(C)).

There were no differences for CRP between group I and group II compared day by day.

On multivariate analysis only two parameters, BNP and E-selectin, were found to be independent predictors of hemodynamic deterioration on the following day (P=0.033 and 0.001, respectively). The area under the ROC curves for BNP was 0.714 (95% CI 0.588–0.840), P=0.005 and for E-selectin 0.791 (95% CI 0.668–0.913), P<0.0001.

There were no correlations between these two parameters on days 1, 2 and 3 before profound cardiogenic shock occurred in group I, or VAD implantation or HTx was performed in group II (r=0.04, 0.24 and 0.19 and P=0.21, 0.08 and 0.19, respectively). Also no correlations were found if the groups were analyzed separately.

One day before clinical deterioration occurred the OR for E-selectin using a cut-off point of 65ng/ml was 8.7 (95% CI 2.2–34.9, P=0.002). Specificity was 60%, whereas sensitivity was 85%. The OR for BNP using a cut-off of 500pg/ml was 4.8 (95% CI 1.5–15.3, P=0.008). Specificity was 66% and sensitivity was 71.1%.

After both parameters were combined using the above cut-off points, the OR increased to 11.1 (95% CI 3.1–40.0, P<0.001). For this combination specificity was 86.8% and sensitivity was 65%.

4.3. Weaned patients
The mean time from admission to end-point was 6.9±3.3 days in patients weaned from inotropic support.

All nine weaned patients were discharged home and survived longer than 1 year. In two patients emergency VAD implantations were performed 6 and 10 months after discharge home. The remaining patients present good myocardial function.

Of the study parameters only NT-proBNP showed a significant decrease (P=0.046) during the last 7 days of weaning from inotropic support (Fig. 5). The serum creatinine levels showed a decreasing tendency (P=0.056). One patient with dialysis-dependent renal failure was excluded from this analysis.



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  		Fig. 5. Levels of NT-proBNP in group III during weaning from inotropic support. Day 0 indicates first day without i.v. inotropes. The horizontal lines represent medians, the box plots 25 and 50 percentiles and the vertical lines the ranges.

 

   5. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
6. Conclusion
 7. Limitations
 References
 
Hemodynamic deterioration significantly affects outcome after both HTx and VAD implantation; therefore, the study focused on prediction of the time point of deterioration and not on the type of treatment that followed (HTx, VAD or medical).

The study showed significant correlation between neurohumoral and inflammatory markers and hemodynamic deterioration in patients with end-stage heart failure. In their contribution to the development of profound cardiogenic shock, neurohumoral and inflammatory mechanisms seem to be independent of each other.

Furthermore, measurement of natriuretic peptides and E-selectin may assist in predicting the clinical course of patients with inotrope-dependent congestive heart failure. The combined measurement of both BNP and E-selectin leads to an improved predictive value.

The role of natriuretic peptides for the diagnosis of heart failure and the prediction of long-term outcome in patients with chronic heart failure has been evaluated in numerous studies [13–15]. Recently, Gardner et al. demonstrated that a single measurement of NT-proBNP in patients with advanced CHF can help to identify patients at highest risk of death and is a better prognostic marker than the LVEF, peak VO2 or Aaronson score [6]. Furthermore, measurement of BNP may optimize treatment of patients with end stage heart failure [16–18].

The inflammatory processes substantially contribute to the development of congestive heart failure [8,9,11]. E-selectin facilitates adhesion of inflammatory components to the activated endothelium. An increased level of the soluble isoform reflects enhanced expression and/or shedding and indicates increased leukocyte activity and endothelial permeability. Consequently, soluble E-selectin is an integrative marker of inflammation. In our previous studies E-selectin was elevated in patients with cardiogenic shock requiring VAD implantation [11]. A recent study showed prognostic value of soluble cell adhesion molecules in patients with heart failure [10].

Our study showed better 30-day survival after VAD implantation or HTx if surgery was performed under stable clinical conditions. Moreover, stable patients were supported with an implantable LVAD only, while one third of patients suffering from decompensation required an extracorporeal BVAD with subsequent limitations in quality of life. Therefore, VAD implantation before profound cardiogenic shock occurs would improve the outcome. Aaronson showed a superior survival rate until a donor organ is found in patients bridged with a VAD and significantly better survival after HTx than in patients bridged with inotropes [19]. In our center it is routine policy to implant a VAD in patients with severe end-stage heart failure who are on inotropic support as a bridge to transplantation.

In our study over one third of patients presented with or developed profound cardiogenic shock during their hospital stay. Prediction of clinical course in these patients remains difficult, since the established parameters, such as peak VO2, cannot be obtained. As yet, neurohormonal and inflammatory markers have not been adequately investigated in this relatively small but highly unstable cohort of patients with high 30-day mortality and the probability of deterioration requiring VAD implantation in over 50% of cases [2,20]. The importance of the group is underlined by the fact reported by the United Network for Organ Sharing that, in 2002 in the UNOS area, of 2155 donated hearts 857 (39.8%) were allocated to ‘1A’ recipients. A similar situation has been reported by Eurotransplant.

In our study the hemodynamic parameters heart rate, blood pressure and mixed venous oxygen saturation were worse in patients presenting cardiogenic shock the next day. The differences were small, although significant, with large standard deviations.

Our study has demonstrated that patients who developed cardiogenic shock during the study period presented elevated levels of BNP and E-selectin at hospital admission. The fact that BNP and E-selectin showed no correlations at admission or during follow-up may indicate two different mechanisms leading to clinical deterioration: neurohormonal activation represented by elevated BNP and over-activated inflammatory processes, represented by elevated E-selectin. This hypothesis is supported by the fact that BNP and E-selectin in combination showed a higher OR than each parameter alone 1 day before profound cardiogenic shock occurred. Furthermore, multivariate analysis showed that only these two parameters are independent predictors of clinical deterioration 1 day before its occurrence. This theory is also supported by the fact that the circulating TNF-{alpha}, which substantially contributes to primary progression of heart failure [21], is elevated in only 30–40% of patients with heart failure [22]. Numerous studies have shown a lack of correlation between neurohumoral and proinflammatory cytokine levels [8,23]. Thus, these data and our own suggest that the neurohormonal activation is independent of the inflammatory processes, with both independently contributing to deterioration of heart failure. This should be taken into consideration in developing new treatment concepts employing recombinant natriuretic peptides [24] and inhibitors of selectin-mediated leukocyte-endothelial adhesion [25]. Although each of these mechanisms explains some aspects of heart failure, none of them is sufficient to explain it in total. In our opinion, the future of prognosis and treatment of heart failure lies in a combination of strategies based on different heart failure models.

Weaning from inotropic support in our study was performed using echocardiographic and hemodynamic parameters (e.g. pulmonary pressure, PCWP) to monitor myocardial recovery during inotropic therapy. However, in two patients recurrence of myocardial failure 6 and 10 months later required emergency VAD implantation. In these patients NT-proBNP levels decreased during the treatment (from 40,082 to 2193 and 4556 to 1811pg/ml, respectively), but remained high at the end of weaning. Based on this limited experience we would suggest more frequent outpatient checks for patients with elevated NT-proBNP level on discharge.


   6. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
7. Limitations
 References
 
Neurohumoral and inflammatory mechanisms are activated independently of each other in patients with severe heart failure. This fact should be taken into account in predicting and monitoring the clinical course of these patients.

While routine parameters did not predict clinical course, elevated BNP and E-selectin independently predicted clinical deterioration on admission and 1 day before its occurrence.

The combination of these parameters if at least one parameter was elevated showed increased predictive value. Serial decrease of NT-proBNP predicts weaning from inotropes without the necessity of urgent HTx or implantation of mechanical circulatory support.

Based on the results of this study we have changed our strategy in favor of earlier implantation of the VAD—before profound cardiogenic shock occurs. Daily measurement of NT-proBNP is now included in our routine laboratory check-up as an additional parameter for the decision-making process. However, it should be remembered that BNP and NT-proBNP levels rise with age and are affected by gender, obesity, comorbidity, renal function and drug therapy. Therefore, these parameters should not be used in isolation from the clinical context [7]. BNP and NT-pro BNP assays are commercially available; routine clinical laboratory measurement of E-selectin is not.

In this pilot study BNP and E-selectin were distinguished as possessing predictive value for clinical deterioration in patients with end-stage heart failure. These data open the way for prospective studies to further investigate this potentially important phenomenon.


   7. Limitations
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
References
 
The predictive values of the study parameters were calculated retrospectively. Although the study employed a large patient cohort, prospective randomized studies based on commercially available diagnostic tests will be necessary to confirm the presented results. However, large ranges of the selected parameters led to low sensitivity and specificity of these markers.

Several other neurohumoral and inflammatory markers may also have predictive value in these patients. These markers should be investigated in further studies.


   Acknowledgments
 
Ms Julia Stein, M.S., for statistical advice and Ms Anne Gale, Editor in the Life Sciences, for editorial assistance. This article contains data from the doctoral thesis of F. Hennig and S. Ignatenko. The study was supported by a research grant from the Humboldt University, Berlin, Germany. We are thankful for study support to Roche Diagnostics, Bayer and B.R.A.H.M.S., Germany.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Conclusion
 7. Limitations
 References
 

  1. Jaagosild P, Dawson NV, Thomas C, Wenger NS, Tsevat J, Knaus WA, Califf RM, Goldman L, Vidaillet H, Connors Jr AF. Outcomes of acute exacerbation of severe congestive heart failure: quality of life, resource use, and survival. SUPPORT Investigators. The study to understand prognosis and preferences for outcomes and risks of treatments. Arch Intern Med 1998;158(10):1081-1089.[Abstract/Free Full Text]
  2. MacGowan GA, Kormos RL, McNamara DM, Alvarez RJ, Rosenblum WD, Pham S, Feldman AM, Murali S. Predicting short-term outcome in severely ill heart failure patients: implications regarding listing for urgent cardiac transplantation and patient selection for temporary ventricular assist device support. J Card Fail 1998;4(3):169-175.[CrossRef][Medline]
  3. Sharma R, Anker SD. Immune and neurohormonal pathways in chronic heart failure. Congest Heart Fail 2002;8(1):23-28and 48.[Medline]
  4. Sodian R, Loebe M, Schmitt C, Potapov EV, Sinawski H, Müller J, Hausmann H, Zurbrügg H, Weng Y, Hetzer R. Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory systems. J Am Coll Cardiol 2001;38(7):1942-1949.[Abstract/Free Full Text]
  5. Maisel A. B-type natriuretic peptide levels: a potential novel ‘white count’ for congestive heart failure. J Card Fail 2001;7(2):183-193.[CrossRef][Medline]
  6. Gardner RS, Ozalp F, Murday AJ, Robb SD, McDonagh TA. N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 2003;24(19):1735-1743.[Abstract/Free Full Text]
  7. Cowie MR, Jourdain P, Maisel A, Dahlstrom U, Follath F, Isnard R, Luchner A, McDonagh T, Mair J, Nieminen M, Francis G. Clinical applications of B-type natriuretic peptide (BNP) testing. Eur Heart J 2003;24(19):1710-1718.[Abstract/Free Full Text]
  8. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the studies of left ventricular dysfunction (SOLVD). J Am Coll Cardiol 1996;27(5):1201-1206.[Abstract]
  9. Tsutamoto T, Hisanaga T, Fukai D, Wada A, Maeda Y, Maeda K, Kinoshita M. Prognostic value of plasma soluble intercellular adhesion molecule-1 and endothelin-1 concentration in patients with chronic congestive heart failure. Am J Cardiol 1995;76(11):803-808.[CrossRef][Medline]
  10. Yin WH, Chen JW, Jen HL, Chiang MC, Huang WP, Feng AN, Lin SJ, Young MS. The prognostic value of circulating soluble cell adhesion molecules in patients with chronic congestive heart failure. Eur J Heart Fail 2003;5(4):507-516.[Abstract/Free Full Text]
  11. Hasper D, Hummel M, Kleber FX, Reindl I, Volk HD. Systemic inflammation in patients with heart failure. Eur Heart J 1998;19(5):761-765.[Abstract/Free Full Text]
  12. Kormos RL, Gasior TA, Kawai A, Pham SM, Murali S, Hattler BG, Griffith BP. Transplant candidate's clinical status rather than right ventricular function defines need for univentricular versus biventricular support. J Thorac Cardiovasc Surg 1996;111(4):773-782discussion 782–3.[Abstract/Free Full Text]
  13. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347(3):161-167.[Abstract/Free Full Text]
  14. Berger R, Strecker K, Huelsmann M, Moser P, Frey B, Bojic A, Stanek B, Pacher R. Prognostic power of neurohumoral parameters in chronic heart failure depends on clinical stage and observation period. J Heart Lung Transplant 2003;22(9):1037-1045.[CrossRef][Medline]
  15. Monge JC. Neurohormonal markers of clinical outcome in cardiovascular disease: is endothelin the best one?. J Cardiovasc Pharmacol 1998;32(Suppl. 2):S36-S42.
  16. Nicholls MG, Lainchbury JG, Richards AM, Troughton RW, Yandle TG. Brain natriuretic peptide-guided therapy for heart failure. Ann Med 2001;33(6):422-427.[Medline]
  17. Richards M. Outpatient management of heart failure. Heart Fail Rev 2003;8(4):345-348.[CrossRef][Medline]
  18. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355(9210):1126-1130.[CrossRef][Medline]
  19. Aaronson KD, Eppinger MJ, Dyke DB, Wright S, Pagani FD. Left ventricular assist device therapy improves utilization of donor hearts. J Am Coll Cardiol 2002;39(8):1247-1254.[Abstract/Free Full Text]
  20. Aaronson KD, Schwartz JS, Chen TM, Wong KL, Goin JE, Mancini DM. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation 1997;95(12):2660-2667.[Abstract/Free Full Text]
  21. Packer M. Is tumor necrosis factor an important neurohormonal mechanism in chronic heart failure?. Circulation 1995;92(6):1379-1382.[Free Full Text]
  22. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323(4):236-241.[Abstract]
  23. Dutka DP, Elborn JS, Delamere F, Shale DJ, Morris GK. Tumour necrosis factor alpha in severe congestive cardiac failure. Br Heart J 1993;70(2):141-143.[Abstract/Free Full Text]
  24. Maisel AS. Nesiritide: a new therapy for the treatment of heart failure. Cardiovasc Toxicol 2003;3(1):37-42.[CrossRef][Medline]
  25. Schon MP, Krahn T, Schon M, Rodriguez ML, Antonicek H, Schultz JE, Ludwig RJ, Zollner TM, Bischoff E, Bremm KD, Schramm M, Henninger K, Kaufmann R, Gollnick HP, Parker CM, Boehncke WH. Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation. Nat Med 2002;8(4):366-372.[CrossRef][Medline]



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R. Hetzer, E. V. Potapov, B. Stiller, Y. Weng, M. Hubler, J. Lemmer, V. Alexi-Meskishvili, M. Redlin, F. Merkle, F. Kaufmann, et al.
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