Study definitions:

1. Correlation of Brain Natriuretic Peptide (BNP) Levels with Clinical Outcomes in Hospitalized Patients with Community-Acquired Pneumonia: Results from the Rapid Empiric Treatment with Oseltamivir Study (RETOS) Sridivya Peddapalli, MD;Srinivas Uppatla, MD; Johnson Britto, MD; Tiffany Lindeman, Jaimini Jodhani, MD; Mark Burns, MD; Timothy Wiemken, PhD. Division of Infectious Diseases, University of Louisville RESULTS (Cont’d) ABSTRACT INTRODUCTION (Cont’d) RESULTS (Cont’d) • In the ROC analysis, the area under curve (AUC) for both BNP levels and PSI was 0.66 and the AUC for CURB-65 was 0.62 (Figure 1). • Results from Kaplan-Meier curve show median LOS for patients with BNP levels <148 as 4 days, and median LOS for patients with BNP levels >148 as 5 days, p=0.045 (Figure 2) and median TCS in patients with BNP <148 and >148 was 3 days, p=0.810 (Figure 3). • There are limited data available in the literature regarding the ability of BNP to predict clinical outcomes in hospitalized patients with CAP. • The objective of this study was to determine the diagnostic accuracy of serum BNP at the time of admission on the clinical outcomes in hospitalized patients with CAP. Background: Community-acquired pneumonia (CAP) is the eighth leading cause of death in the United States and the leading cause of hospitalization due to an infectious disease. For patients hospitalized with CAP, mortality is traditionally predicted using the pneumonia severity index (PSI) or CURB-65 scores. Recently, there is a growing interest in using biomarkers as predictors of clinical outcomes. The objective of this study was to correlate the biomarker, serum BNP, at the time of admission with clinical outcomes in hospitalized patients with CAP. Methods: This was a secondary analysis of the RETOS database, an on going, randomized, prospective clinical trial to evaluate the impact of rapid empiric treatment with oseltamivir on the outcomes of hospitalized patients with lower respiratory tract infections (LRTIs). All patients admitted to eight hospitals in Louisville, Kentucky from December 2010 to March 2012 with a diagnosis of LRTI were invited to participate in the study. Patients diagnosed with CAP who had BNP levels available within 48 hours of admission were included. A rreceiver operating characteristic (ROC) curve was used to determine the accuracy of BNP for predicting 30-day mortality in comparison to PSI and CURB-65. Results: A total 243 patients with CAP were enrolled. In the ROC, the area under curve (AUC) for both BNP levels and PSI was 0.66 and the AUC for CURB-65 was 0.62. Conclusions: Our results show that serum BNP alone is comparable to PSI and CURB-65 for predicting 30-day mortality in hospitalized patients with CAP. Physicians should consider obtaining serum BNP levels for CAP patients upon admission to the hospital in an attempt to define severity of disease. MATERIALS AND METHODS Study design and Study population: All patients were analyzed from the Rapid Empiric Treatment with Oseltamivir Study (RETOS) database. These patients were admitted to eight hospitals in Louisville, Kentucky from December 2010 to March 2012 with a diagnosis of LRTI. Patients diagnosed with CAP who had BNP levels available within 48 hours of admission were included in the present analysis. Figure 2: Kaplan-Meier curves showing for serum BNP levels by length of stay (LOS) • Study definitions: • CAPwas defined as the presence of a new pulmonary infiltrate on a chest radiograph at the time of hospitalization that was associated with at least one of the following: • New or increased cough •  An abnormal temperature (<35.6˚C or > 37˚C) •  Leukocytosis, leukopenia, or left shift • Study variables: • Predictor Variable: The primary predictor variable for this study was serum BNP collected at the time of hospital admission. The PSI and CURB-65 scores were also used as predictor variables for comparison to serum BNP. • Outcome Variables: The primary outcome variable for this study were: • Mortality during hospitalization • Mortality at 30 days • Secondary outcome variables included: • Time to reach clinical stability (TCS), defined as the day that the following four criteria were met. • 1. Cough and Shortness of breath (Normal or improving) • 2. Afebrile for at least 8 hours (<38 ˚C or <100 F) • 3. WBC improving (1>10%) • 4. Intake and absorption adequate • Length of hospital stay (LOS), defined as the number of days between hospital admission and hospital discharge. • Laboratory Methods: • Serum BNP was detected in ethylenediamine tetra-acetic acid plasma from all patients with a fluorescence immunoassay (Biosite Diagnostics). • Statistical Analysis: • Chi squared and Mann-Whitney U-tests were used to compare patient characteristics and clinical outcomes between those with a BNP ≥148 versus <148. A receiver operating characteristic (ROC) curve was used to determine the accuracy of BNP for predicting 30-day mortality in comparison to PSI and CURB-65. Kaplan-Meier curves were used to evaluate the association of serum BNP levels with LOS and TCS. A p-value ≤ 0.05 was considered statistically significant. R v2.14.0 was used for all analysis. Figure 3: Kaplan-Meier curves for serum BNP levels by time to clinical stability (TCS) CONCLUSIONS INTRODUCTION • Our results show that serum BNP alone is comparable to PSI and CURB-65 for predicting 30-day mortality in hospitalized patients with CAP. • Physicians should consider obtaining serum BNP levels for CAP patients upon admission to the hospital in an attempt to define severity of disease. • In hospitalized elderly patients with CAP with elevated BNP levels, physicians need to have a low threshold for ICU admission. • Community-acquired pneumonia (CAP) is the eighth leading cause of death in the US and the leading cause of hospitalization due to an infectious disease.1 • For patients hospitalized with CAP, mortality can be predicted using a number of different severity scores. The most commonly used severity scores are the pneumonia severity index (PSI) and CURB-65. These scores have been shown to have a wide variability in their ability to accurately predict mortality for patients with CAP, and in some instances, can be very difficult to compute at the bedside.2 • Recently, there has been a growing interest in using biomarkers as predictors of clinical outcomes of patients with CAP. Some biomarkers have shown very good accuracy in predicting mortality in patients with CAP, and they are relatively easy to obtain.3,4 • One such marker is B-type natriuretic peptide (BNP), a 32–amino-acid polypeptide, which is released by the left and right cardiac ventricles and regulates physiologic effects like natriuresis, diuresis, and vasodilatation.4 Cardiac stress has been shown to be the main stimulus for the secretion of BNP which, in turn, is reflected by myocardial stretch and pressure or volume overload. More recently, proinflammatory cytokines, the activation of the sympathetic nervous system, and hypoxia have also been identified as additional triggers that induce BNP secretion.5 REFERENCES • Heron M, Hoyert DL, Murphy SL, et al National Vital Statistics Reports. Deaths: Final Data for 2006. April 17, 2009. • Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(suppl):S27-S72 • Smith RP, Lipworth BJ, Cree IA, et al . C-reactive protein A clinical marker in community-acquired pneumonia. Chest 1995;108:1288–91. • McIvor RA . Plasma d-dimer for outcome assessment in patients with CAP: not a replacement for PSI. Chest2004;126:1015–16. • Breidthardt T, Laule K, Strohmeyer AH et al. Medical and economic long-term effects of B-type natriuretic peptide testing in patients with acute dyspnea. ClinChem2007; 53: 1415–22. • WeinfeldMS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart • failure. Am Heart J 1999; 138: 285–90. RESULTS A total 243 patients with CAP and BNP levels were enrolled. Patient characteristics are shown in Table 1 below. Figure 1: Receiver Operating Characteristic curve for BNP predicting 30-day mortality versus PSI and CURB-65