1. Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950 Gregg C. Fonarow MD, FACC, William F. Peacock MD, Christopher O. Phillips MD, MPH, Michael M. Givertz MD, FACC, Margarita Lopatin MS and ADHERE Scientific Advisory Committee and Investigators

2. Admission BNP and In-Hospital Mortality in ADHF Levels of BNP and NT-proBNP have been shown to be elevated in patients with left ventricular (LV) dysfunction and correlate with the New York Heart Association functional classLevels of BNP and NT-proBNP have been shown to be elevated in patients with left ventricular (LV) dysfunction and correlate with the New York Heart Association functional class Clinical investigations of natriuretic peptides have focused on the diagnostic usefulness for heart failure (HF) and LV dysfunction and their prognostic usefulness in chronic HF, acute coronary syndromes, stable coronary artery disease, other medical conditions, and community cohortsClinical investigations of natriuretic peptides have focused on the diagnostic usefulness for heart failure (HF) and LV dysfunction and their prognostic usefulness in chronic HF, acute coronary syndromes, stable coronary artery disease, other medical conditions, and community cohorts Whether plasma levels of BNP are predictive of in-hospital mortality risk in patients hospitalized with acute decompensated HF has not been well studiedWhether plasma levels of BNP are predictive of in-hospital mortality risk in patients hospitalized with acute decompensated HF has not been well studied Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

3. The ADHERE (Acute Decompensated Heart Failure National Registry) Registry Multicenter Observational Open label Electronic web-based Registry of the management of patients treated in hospitals for acutely decompensated heart failure in the US The ADHERE Registry Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

4. Initial BNP Levels in ADHERE Time Period: Q2 2003 – Q4 2004 191 out of 229 ADHERE hospitals (176 BNP only, 15 BNP and pro-BNP, 14 pro-BNP only, 24 none) First BNP result, within 24 hours of admission Results as documented in medical record 48,629 (63%) out of 77,467 pt episodes had BNP assessment Analysis by BNP quartiles, continuous, and log transformed BNP Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

5. Admission BNP and In-Hospital Mortality in ADHF Distribution of BNP Values (pg/mL) 48,629 (63%) out of 77,467 pt episodes had BNP assessment at initial evaluation. Only 3.3% of patients in ADHERE with initial BNP < 100 pg/mL Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

6. Admission BNP and In-Hospital Mortality in ADHF BNP QuartilesBNP Quartiles –Quartile I: < 430 pg/mL –Quartile II: 430 – 839 pg/mL –Quartile III: 840 – 1729 pg/mL –Quartile IV: > 1730 pg/mL Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

7. Patient Characteristics by Quartiles of BNP Levels in the ADHERE Registry Q1 (<430)N=12,161 Q2 (430-839)N=12,146 Q3 (840-1730)N=12,156 Q4 (>1730)N=12,166 P Value Age72.273.974.173.9P<0.0001 Male (%)44.547.249.350.6P<0.0001 White (%)79.579.477.572.4P<0.0001 Hx HF71.373.477.381.7P<0.0001 CAD51.858.762.363.4P<0.0001 Prior MI24.028.933.434.5P<0.0001 HTN76.175.674.775.1P=0.0908 Diabetes50.044.541.340.0P<0.0001 AFib33.836.232.527.8P<0.0001 CRI Hx20.226.432.544.5P<0.0001 Dialysis0.61.22.89.7P<0.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

8. Patient Characteristics by Quartiles of BNP Levels in the ADHERE Registry Q1 (<430) Q2 (430-839) Q3 (840-1730) Q4 (>1730) P Value SOB rest30.333.935.035.1P<0.0001 Rales63.068.770.572.4P<0.0001 SBP145.5145.4142.9141.2P<0.0001 HR87.288.087.987.3P=0.0023 Sodium138.2138.1137.8137.6P<0.0001 BUN26.529.432.738.7P<0.0001 Cr1.31.51.72.3P<0.0001 CXR cong67.874.977.779.2P<0.0001 LVEF46.641.436.031.4P<0.0001 % LVEF <4029.442.557.169.7P<0.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

9. Patient IV Treatments by Quartiles of BNP Levels in the ADHERE Registry Q1 (<430) Q2 (430-839) Q3 (840-1730) Q4 (>1730) P Value Diuretic89.893.593.990.3P<0.0001 Time to Rx7.0 hrs6.9 hrs6.6 hrs6.9 hrsP=0.5311 Vasoactive20.628.136.242.0P<0.0001 Inotrope6.28.311.615.1P<0.0001 Vasodilator16.823.329.533.9P<0.0001 NTG6.47.68.78.4P<0.0001 Nesiritide11.117.122.827.9P<0.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

10. Q1<430N=12,161Q2430-839N=12,146Q3840-1729N=12,156Q4 >1730 N=12,166 P Value Oral Medications ACE Inhibitors (%) 53.656.757.955.4<.0001 ARBs (%) 17.416.114.713.4<.0001 Beta Blockers (%) 60.869.371.873.6<.0001 Calcium Blockers (%) 28.826.822.319.8<.0001 Digoxin (%) 28.833.635.034.4<.0001 Diuretics (%) 76.378.678.074.6<.0001 Peripheral Vasodilators (%) 4.76.78.110.5<.0001 Warfarin (%) 29.731.026.523.8<.0001 Admission BNP and In-Hospital Mortality in ADHF In-hospital Medications Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

11. In-Hospital Mortality Risk by Initial BNP Levels in the ADHERE Registry P<0.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

12. In-Hospital Mortality Risk by Initial BNP Levels in the ADHERE Registry BNP Quartiles CategoryII vs. IIII vs. IIV vs. I Total N12,146 vs. 12,16112,156 vs. 12,16112,166 vs. 12,161 Unadjusted 0 1.50 (1.27-1.79) p<.0001 2.11 (1.80-2.48) p<.0001 3.41 (2.93-3.97) p<.0001 Adjusted 1 1.40 (1.18-1.66) p=.0001 1.94 (1.65-2.29) p<.0001 3.17 (2.72-3.69) p<.0001 Adjusted 2 1.33 (1.12-1.58) p=.0015 1.65 (1.40-1.94) p<.0001 2.34 (2.00-2.74) p<.0001 Adjusted 3 1.46 (1.19-1.78) p=.0003 1.84 (1.51-2.23) p<.0001 2.74 (2.26-3.31) p<.0001 Adjusted 4 1.28 (1.08-1.53) p=.0057 1.58 (1.34-1.86) p<.0001 2.23 (1.91-2.62) p<.0001 0 Area under the ROC curve (AUC)=0.62. 1 Age, gender. AUC=0.66. 2 Age, gender, BUN, systolic BP, creatinine. AUC=0.75. 3 Age, gender, BUN, systolic BP, creatinine, LVEF<.40 or Mod./Sev. AUC=0.75. 4 Age, gender, BUN, systolic BP, creatinine, sodium, pulse, dyspnea at rest. AUC=0.77. Odds Ratios (95% CI), p-value

13. In-Hospital Mortality Risk by Initial BNP Levels Reduced vs. Preserved Systolic Function HF P<0.0001 LVEF < 0.40 LVEF > 0.40 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

14. In-Hospital Mortality Risk by Initial BNP Levels in the ADHERE Registry

15. ADMISSION TO THE ICU STRATIFIED BY BNP QUARTILE % P<.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

16. TOTAL HOSPITAL LENGTH OF STAY STRATIFIED BY BNP QUARTILE Median Days P<.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

17. Patient Outcomes by Quartiles of BNP Levels in the ADHERE Registry Q1 (<430) Q2 (430-839) Q3 (840-1730) Q4 (>1730) P Value Ventilation3.13.73.94.1P=0.0002 CPR0.60.91.21.7P<0.0001 Ultrafiltrat0.60.81.65.0P<0.0001 LOS (days)5.25.75.96.3P<0.0001 ICU admit %12.815.416.619.6P<0.0001 ASx at DC48.849.648.043.6P<0.0001 Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

18. Admission BNP and In-Hospital Mortality in ADHF Study Limitations Data collected from chart review which is dependent on the accuracy and completeness of documentation and abstractionData collected from chart review which is dependent on the accuracy and completeness of documentation and abstraction This “real world” study used results of various commercially available BNP assays vs. results from single central core laboratoryThis “real world” study used results of various commercially available BNP assays vs. results from single central core laboratory Individual hospitalization episodes vs. individual unique patientsIndividual hospitalization episodes vs. individual unique patients –Each hospitalization represents unique opportunity to either survive or not survive. Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

19. Admission BNP and In-Hospital Mortality in ADHF Elevated admission BNP is a significant predictor of in- hospital mortality in ADHF, independent of other risk factorsElevated admission BNP is a significant predictor of in- hospital mortality in ADHF, independent of other risk factors BNP is predictive of mortality in both patients with reduced and those with preserved LVEFBNP is predictive of mortality in both patients with reduced and those with preserved LVEF Further research necessary to determine whether pts with higher admission BNP would benefit from more intensive monitoring and/or aggressive treatment strategiesFurther research necessary to determine whether pts with higher admission BNP would benefit from more intensive monitoring and/or aggressive treatment strategies Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):1943-1950

20. Acknowledgments Acknowledgments The ADHERE Scientific Advisory Committee and Investigators