1. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. Characteristics, Treatments, and Outcomes of Patients With Preserved Systolic Function Hospitalized for Heart Failure: A Report From the OPTIMIZE- HF Registry (Organized Program To Initiate life-saving treatMent In hospitaliZEd patients with Heart Failure) Gregg C. Fonarow MD, FACC, Wendy Gattis Stough PharmD, William T. Abraham MD, FACC, Nancy M. Albert PhD, RN, Mihai Gheorghiade MD, FACC, Barry H. Greenberg MD, FACC, Christopher M. O'Connor MD, FACC, Jie Lena Sun MS, Clyde W. Yancy MD, FACC, James B. Young MD, FACC and OPTIMIZE-HF Investigators and Hospitals

2. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 2 Disclosures Funding Support –GlaxoSmithKline funded the OPTIMIZE-HF registry under the guidance of the OPTIMIZE-HF Steering Committee and funded data collection and management by Outcome Sciences, Inc (Cambridge, MA) and analysis of registry data at Duke Clinical Research Institute (Durham, NC) Individual author disclosures are listed in the manuscript

3. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 3 Heart Failure and Preserved Systolic Function A substantial portion of patients with heart failure (HF) have relatively normal or preserved systolic function (PSF) Heart failure with PSF has been defined as the presence of HF symptoms in patients with a documented left ventricular ejection fraction (EF) of >40% or >50%, depending on the study Few data are available in patients with HF and PSF that describe outcomes or guide management strategies

4. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 4 Study Objective The objective of this study was to evaluate the characteristics, treatments, and outcomes of patients with preserved and reduced systolic function heart failure in a large, representative population of patients from all regions of the country.

5. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 5 OPTIMIZE-HF Program Objectives OPTIMIZE-HF is a national performance improvement initiative to improve guidelines adherence in patients hospitalized with HF Overall OPTIMIZE-HF program objectives: –Improve medical care and education of patients hospitalized with HF –Accelerate initiation of HF evidence-based, guideline- recommended therapies by starting these therapies before hospital discharge in appropriate patients without contraindications –Increase understanding of barriers to use of ACEIs,  -blockers, and other guideline-recommended therapies in eligible HF patients

6. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 6 OPTIMIZE-HF Process-of-Care Intervention and Registry “Process-of-care” intervention –Enhanced inpatient HF care and education –Enhanced discharge planning –Care maps, pathways, and standardized order sets that encouraged adoption of evidence-based therapies ACEI and  -blocker initiation before discharge JCAHO performance indicators –Educational programs to encourage adoption by providers Web-based registry –Tracks treatment rates and changes following performance interventions –Captures JCAHO/ORYX Quality of Care indicators –Benchmarks comparisons between institutions –Enhances understanding of barriers to uptake

7. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 7 OPTIMIZE-HF Performance Improvement Registry Protocol Eligibility –Adults hospitalized for episode of new or worsening HF as primary cause of admission, or with significant HF symptoms that develop during hospitalization when the initial reason for admission was not HF –Includes patients with systolic dysfunction and/or isolated diastolic dysfunction (HF with preserved systolic function) –Any admission satisfying JCAHO HF core measure criteria Prespecified subgroup (10%) with 60–90-day follow-up data –Survival, readmissions, and medical regimen –Informed consent required for follow-up The registry coordinating center was Outcome Sciences, Inc

8. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 8 OPTIMIZE-HF Hospital Characteristics Total Hospitals (N=259), n (%) Follow-Up Hospitals (N=91), n (%) Bed size: 0 to 9931 (12)9 (10) 100 to 24958 (22)21 (23) 250 to 499103 (40)40 (44) 500 to 74938 (15)13 (14)  750 13 (5)4 (4) Unknown16 (6)4 (4) Academic*118 (48)48 (55) Transplant program*34 (14)9 (10) Interventional † (CABG/PCI)163 (67)62 (70) Region ‡ : Midwest68 (27)27 (30) Northeast44 (17)14 (16) South87 (34)34 (38) West56 (22)15 (17) * N=246, n=88; † N=245, n=88; ‡ N=255, n=90. CABG/PCI = coronary artery bypass graft/percutaneous coronary intervention.

9. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 9 OPTIMIZE-HF Patient Characteristics Hospital Cohort (N=48,612) Follow-Up Cohort (N=5,791) Age, mean (years)73.172.0 Male (%)4851 Caucasian (%)7478 Ischemic etiology (%)4642 LVEF, mean (%)39.036.9 LVSD (% of those assessed)48.853.2 Insulin-treated diabetes (%)17 Non–insulin-treated diabetes (%)2526 Hypertension (%)7172 Rales (%)6462 Mean SBP (mmHg)143140 Mean heart rate (bpm)8786 Mean sodium (mEq/L)136.7136.8 Mean serum creatinine (mg/dL)1.81.7 Mean hemoglobin (g/dL)12.112.2

10. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 10 0- 5 6- 10 11- 15 16- 20 21- 25 26- 30 31- 35 36- 40 41- 45 46- 50 51- 55 56- 60 61- 65 66- 70 71- 75 76- 80 81- 85 86- 90 91- 95 96- 100 Distribution of LVEF in Patients Hospitalized With Primary Discharge Diagnosis of HF Left Ventricular Ejection Fraction (%) Documented LVEF Measured Prior to or During Hospitalization

11. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 11 Patient Characteristics at Hospital Admission by LVSD vs PSF Characteristic LVSD (n=20,118) 40%≤ EF ≤50% (n=7,321) EF >50% (n=10,072) P Value* Age, mean (years)70.474.375.6<.0001 Male (%)624832<.0001 African American (%)2115.880 Atrial arrhythmia (%)283332.179 Ischemic etiology (%)544932<.0001 Insulin-treated diabetes (%)151816.013 Non  insulin-treated diabetes (%) 242625.418 Hypertension (%)667477<.0001 Mean LVEF %24.34561<.0001 *P value (40%≤ EF ≤50% vs EF >50%). PSF = preserved systolic function.

12. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 12 Patient Physical Exam Findings at Hospital Admission by LVSD vs PSF Characteristic Patients With LVSD (n=20,118) Patients With PSF (n=21,149) P Value Dyspnea at rest (%)44.194 Dyspnea on exertion (%)6362.206 Rales (%)6365.001 Jugular venous distension (%)3326 .0001 Mean SBP (mmHg)135149 .0001 Mean heart rate (bpm)8985 .0001 Mean sodium (mEq/L)138 .0001 Mean BNP (pg/mL)1635977 .0001 Mean troponin I (ng/mL)1.600.74 .0001 Mean serum creatinine (mg/dL)1.701.73 .0001 Mean hemoglobin (g/dL)12.5311.86 .0001 PSF = LVEF  40%.

13. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 13 HF Treatments Applied at Discharge by LVSD vs PSF P<.0001 Eligible Patients Treated (%) P<.0001 P=.0003 P<.0001 P=.004 P=.0009 *Statin use among patients with CAD, cerebrovascular accident/transient ischemic attack, diabetes, hyperlipidemia, or peripheral vascular disease. PSF = LVEF  40%.

14. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 14 In-Hospital Outcomes by LVSD vs PSF P=.237 P .0001 LVSDPSF Length of Stay, Mean (days) Length of Stay, Median (days) In-Hospital Mortality (%) 6.0 5.7 4.0 3.9 2.9 PSF = LVEF  40%.

15. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 15 Patient Outcomes by LVSD vs PSF Outcome LVSD (n=20,118) 40%≤ EF ≤50% (n=7,321) EF >50% (n=10,072) P Value* In-hospital mortality: all patients 3.93.02.9.647 Follow-Up Cohort Post-discharge mortality9.89.29.3.887 Rehospitalization29.929.030.9.366 Post-discharge mortality/ rehospitalization 36.135.136.8.436 *P value (40%≤ EF ≤50% vs EF >50%).

16. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 16 LVSD2,2942,1881,994469 No LVSD2,6042,4712,195441 60- to 90-Day Survival by LVSD vs PSF Survival Time in Days Since Discharge LVSDNo LVSD Survival Function 0.75 0.80 0.85 0.90 0.95 1.00 0102030405060708090 P=.459 *P value (40%≤ EF ≤50% vs EF >50%).

17. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 17 ACEI/ARBs and Post-Discharge Outcomes in PSF (Unadjusted) No ACEI/ARBACEI/ARB Survival Function 0102030405060708090 P=.052 Survival Time in Days Since Discharge 0.75 0.80 0.85 0.90 0.95 1.00 ACEI/ARB1,2881,2491,138269 No ACEI/ARB595560515149

18. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 18 β-Blockers and Post-Discharge Outcomes in PSF (Unadjusted) No β-blockerβ-blocker Survival Function 0.75 0.80 0.85 0.90 0.95 1.00 0102030405060708090 P=.7741 Survival Time in Days Since Discharge β-blocker1,4251,3651,245292 No β-blocker543525484119

19. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 19 Risk- and Propensity-Adjusted Analysis of Discharge Medication Use in Patients with PSF Post-discharge Mortality Hazard Ratio 95% Hazard Ratio Confidence Limits P Value ACEI/ARB vs no ACEI/ARB 1.1410.8121.603.447 β-Blocker vs no β-Blocker 1.2090.8721.675.255 Post-discharge Death and/or Hospitalization Odds Ratio 95% Odds Ratio Confidence Limits P Value ACEI/ARB vs no ACEI/ARB 0.9090.6921.196.497 β-Blocker vs no β-Blocker 0.9230.7231.179.523 PSF = LVEF  40%.

20. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 20 Limitations The present observations include only hospitalized patients with HF, a population known to be at increased risk of adverse outcomes Left ventricular function was not assessed in 7,345 patients (15%), and these patients were excluded Follow-up data were collected only from a pre-specified subset of patients and extended only 60 to 90 days after hospital discharge Despite extensive covariate and propensity adjustment, residual confounding cannot be excluded, thus may only be demonstrating associations, rather than cause-and- effect relationships

21. Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768  777. 21 Conclusions Data from the OPTIMIZE-HF reveal a high prevalence of HF with PSF These patients have a similar post-discharge mortality risk and equally high rates of rehospitalization as patients with HF and LVSD No differences in clinical outcomes were seen with different definitions for PSF Despite the burden to patients and health care systems, data are lacking on effective management strategies for patients with HF and PSF Large well designed clinical trials are critically needed to identify effective management strategies for this population