1. Heart Failure with Normal Systolic Function: Better or Worse Prognosis? Maria Rosa Costanzo, M.D., F.A.C.C, F.A.H.A. Medical Director, Midwest Heart Specialists Heart Failure and Pulmonary Arterial Hypertension Programs Medical Director, Edward Hospital Center for Advanced Heart Failure Naperville, Illinois, U.S.A.

2. Characteristics of Patients with Heart Failure and Normal or Reduced Ejection Fraction CharacteristicReduced EF (n=2429) Normal EF (n=2167) P Value Age (yr)71.7 ± 12.174.4 ± 14.4< 0.001 Male Sex (%)65.444.3< 0.001 BMI28.6 ± 7.029.7 ± 7.80.002 Obesity (%)35.541.40.007 sCr on adm. (mg/dl)1.6 ± 1.0 0.31 Hgb on adm. (g/dl)12.5 ± 2.011.8 ± 2.1< 0.001 HTN (%)48.062.7< 0.001 CAD (%)63.752.9< 0.001 AF (%)28.541.3< 0.001 DM (%)34.333.10.42 Significant VHD (%)6.52.6<0.001 EF (%)29 ± 1061 ± 7<0.001 Owan TE et al. NEJM 2006; 355:251-9

3. Owan T et al. N Engl J Med 2006;355:251-259 Secular Trends in the Prevalence of Heart Failure with Normal Ejection Fraction

4. Secular Trends in Survival among Patients with Heart Failure and Normal or Reduced EF Owan T et al. NEJM 2006;355:251-259 Survival Improved Over Time in Patients with Reduced EF, But Not in Patients with Normal EF

5. Association of Clinical Characteristics with Mortality in Patients with Normal versus Reduced EF VariableNormal EFReduced EF AgeYES Female SexYES sCr on AdmissionYES Hgb on AdmissionYES HTNYES CADNOYES AFNO DMYES Significant VHDNO Year of AdmissionNOYES Owan T et al. NEJM 2006;355:251-259

6. Jones, R.C. et al. J Am Coll Cardiol 2004;44:1025-1029 Predictors of Mortality in Patients with HF and Normal Systolic Function in the DIG Trial GFR NYHA III/IV Male gender Age Diuretics BMI CR Ratio DM Vasodilators K-Sparing Diur. DBP

7. Lee, D. S. et al. Circulation 2009;119:3070-7 Survival of Patients with HFNEF and HFREF by Cause HFNEF HFREF

8. Tribouilloy C et al. EHJ 2008;29:339-47 Survival Curves by Etiology of HF with Normal EF

9. Impact of EF on Outcomes after PCI in HF Patients-NHLBI PTCA Registry Holper EM et al. AHJ 2006; 151: 69-75

10. Kaplan–Meier Analysis of the Probability of Survival among 3166 Patients with a Recent AMI Divided by No In-Hospital CHF, HFNEF (CHF+WMI>1.3), and HFREF (CHF+WMI<1.3), and Stratified According to Age. Møller J E et al. EJHF 2003;5:811-9 *No CHF vs. HFNEF p= 0.00001  No CHF vs. HFREF p= 0.00001

11. Prognostic Importance of Pulmonary Hypertension in Patients with HF Kjaergaard J et al. AJC 2007; 99: 1146-50

12. Danciu Sc et al. AJC 2006; 97: 256-9

13. Racial Differences in the O utcomes of Patients with Diastolic HF CAD NO CAD white AA white AA P = 0.488 P = 0.002 East MA et al. AHJ 2004; 148: 151-6

14. Survival Kapoor JR et al. AHJ 2010; 159: 75-80

15. Anemia and Survival in Patients with Reduced and Normal EF Felker MG et al. AHJ 2006; 151: 457-62

16. Risk of Different Outcomes Associated with Diabetes in HFREF and HFNEF MacDonald M R et al. EHJ 2008;29:1377-85

17. Effect of Severe Autonomic Failure on Outcomes after MI in Patients with Normal LVEF Bauer A et al. EHJ 2009; 30:576-83 Severe autonomic failure (SAF): combination of severely impaired baroreflex function with abnormal autonomic tone, assessed by Heart Rate Turbulence (HRT) and cardiac Deceleration Capacity (DC).

18. BNP Predicts Medium-Term Risk in Patients with Acute HF and Normal EF BNP Levels Pg/mL 80 278 434 P< 0.05 Valle R et al. JCF 2005; 11: 498-503

19. % P < 0.0001 P = 0.0003 P < 0.004 P < 0.0009 Fonarow GC et al. JACC2007; 50: 767-77

20. Massie B et al. N Engl J Med 2008;359:2456-2467 Effects of Ibersartan in Patients with HFNEF

21. EF % of Patients * * * * * P = 0.001 vs. prior year Massie BM et al. AJC 2007; 99: 1263-8

22. Dobre D et al. EJHF 2007;9:280-6 VariableN (%)Adjusted HR 95% CIP value BB227(51)0.570.37-0.880.01 GFR ≤ 40 ml/min 247(56)2.141.37-3.340.001 COPD126(28)1.601.04-2.450.03 Male sex197(44)1.481.00-2.190.05 Digoxin98(22)1.581.006-2.470.05 VariableN(%)Adjusted HR 95% CiP value BB Low Dose93(41)0.740.45-1.210.2 BB High Dose134(59)0.510.30-0.860.01 Effect of Beta Blockers on Survival in Patients with Advanced HF and Normal EF

23. Conclusions The prevalence of HFNEF is increasing Hospitalizations for ADHF in patients with HFNEF are increasing The outcomes of HFNEF and HFREF are similar The outcomes of patients with HFNEF are determined by the presence and severity of comorbidities With the exception of BB, other therapies which improve the outcomes of patients with HFREF do not significantly alter morbidity and mortality of patients with HFNEF