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 A.; Halushka, Marc; Hare, Joshua M.; Kasper, Edward K.; Russell, Stuart D.

doi:10.1016/j.healun.2009.04.019

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 28, Issue 7 , Pages 704-709, July 2009

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

Michelle M. Kittleson, MD, PhD
- Department of Medicine, Division of Cardiology, University of California at Los Angeles, Los Angeles, California
Diane V. Skojec, CRNP
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Ilan S. Wittstein, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Hunter C. Champion, MD, PhD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Daniel P. Judge, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Lili A. Barouch, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Marc Halushka, MD, PhD
- Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland
Joshua M. Hare, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Edward K. Kasper, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
Stuart D. Russell, MD
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland
- Reprint requests: Stuart D. Russell, MD, Johns Hopkins Hospital, Carnegie 568, 600 N Wolfe St, Baltimore, MD 21287. Telephone: 410-955-5708. Fax: 410-955-3478

Received 19 February 2007; received in revised form 23 February 2009; accepted 10 April 2009.

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.