The Change in B-Type Natriuretic Peptide Levels Over Time Predicts Significant Rejection in Cardiac Transplant Recipients

Michelle M. Kittleson, Diane V. Skojec, Ilan S Wittstein, Hunter C. Champion, Daniel P. Judge, Lili Barouch, Marc K Halushka, Joshua M. Hare, Edward K Kasper, Stuart D. Russell

Research output: Contribution to journalArticle

Abstract

Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

Original languageEnglish (US)
Pages (from-to)704-709
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume28
Issue number7
DOIs
StatePublished - Jul 2009

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Brain Natriuretic Peptide
Odds Ratio
Confidence Intervals
Cross-Sectional Studies
Heart-Lung Transplantation
Pulmonary Wedge Pressure
pro-brain natriuretic peptide (1-76)
Transplant Recipients
Heart Failure
Hemodynamics
Biopsy
Pressure

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

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The Change in B-Type Natriuretic Peptide Levels Over Time Predicts Significant Rejection in Cardiac Transplant Recipients. / Kittleson, Michelle M.; Skojec, Diane V.; Wittstein, Ilan S; Champion, Hunter C.; Judge, Daniel P.; Barouch, Lili; Halushka, Marc K; Hare, Joshua M.; Kasper, Edward K; Russell, Stuart D.

In: Journal of Heart and Lung Transplantation, Vol. 28, No. 7, 07.2009, p. 704-709.

Research output: Contribution to journalArticle

Kittleson, Michelle M. ; Skojec, Diane V. ; Wittstein, Ilan S ; Champion, Hunter C. ; Judge, Daniel P. ; Barouch, Lili ; Halushka, Marc K ; Hare, Joshua M. ; Kasper, Edward K ; Russell, Stuart D. / The Change in B-Type Natriuretic Peptide Levels Over Time Predicts Significant Rejection in Cardiac Transplant Recipients. In: Journal of Heart and Lung Transplantation. 2009 ; Vol. 28, No. 7. pp. 704-709.
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abstract = "Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95{\%} confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95{\%} CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95{\%} CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95{\%} for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.",
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T1 - The Change in B-Type Natriuretic Peptide Levels Over Time Predicts Significant Rejection in Cardiac Transplant Recipients

AU - Kittleson, Michelle M.

AU - Skojec, Diane V.

AU - Wittstein, Ilan S

AU - Champion, Hunter C.

AU - Judge, Daniel P.

AU - Barouch, Lili

AU - Halushka, Marc K

AU - Hare, Joshua M.

AU - Kasper, Edward K

AU - Russell, Stuart D.

PY - 2009/7

Y1 - 2009/7

N2 - Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

AB - Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

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