Disclosures

1. 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. 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. 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. 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. 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. 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. 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. OPTIMIZE-HF Hospital Characteristics * N=246, n=88; † N=245, n=88; ‡ N=255, n=90. CABG/PCI = coronary artery bypass graft/percutaneous coronary intervention.

9. OPTIMIZE-HF Patient Characteristics

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 Documented LVEF Measured Prior to or During Hospitalization Left Ventricular Ejection Fraction (%)

11. Patient Characteristics at Hospital Admission by LVSD vs PSF *P value (40%≤ EF ≤50% vs EF >50%). PSF = preserved systolic function.

12. Patient Physical Exam Findings at Hospital Admission by LVSD vs PSF PSF = LVEF 40%.

13. HF Treatments Applied at Discharge by LVSD vs PSF P<.0001 P<.0001 P=.004 P<.0001 P=.0009 P=.0003 Eligible Patients Treated (%) P<.0001 P<.0001 *Statin use among patients with CAD, cerebrovascular accident/transient ischemic attack, diabetes, hyperlipidemia, or peripheral vascular disease. PSF = LVEF 40%.

14. In-Hospital Outcomes by LVSD vs PSF LVSD PSF P=.237 6.0 5.7 P=.237 P.0001 4.0 4.0 3.9 2.9 Length of Stay,Mean (days) Length of Stay,Median (days) In-Hospital Mortality(%) PSF = LVEF 40%.

15. Patient Outcomes by LVSD vs PSF *P value (40%≤ EF ≤50% vs EF >50%).

16. 60- to 90-Day Survival by LVSD vs PSF 1.00 P=.459 0.95 0.90 Survival Function 0.85 0.80 No LVSD LVSD 0.75 0 10 20 30 40 50 60 70 80 90 Survival Time in Days Since Discharge LVSD 2,294 2,188 1,994 469 No LVSD 2,604 2,471 2,195 441 *P value (40%≤ EF ≤50% vs EF >50%).

17. ACEI/ARBs and Post-Discharge Outcomes in PSF (Unadjusted) 1.00 P=.052 0.95 0.90 Survival Function 0.85 0.80 No ACEI/ARB ACEI/ARB 0.75 0 10 20 30 40 50 60 70 80 90 Survival Time in Days Since Discharge ACEI/ARB 1,288 1,249 1,138 269 No ACEI/ARB 595 560 515 149

18. β-Blockers and Post-Discharge Outcomes in PSF (Unadjusted) 1.00 P=.7741 0.95 0.90 Survival Function 0.85 0.80 No β-blocker β-blocker 0.75 0 10 20 30 40 50 60 70 80 90 Survival Time in Days Since Discharge β-blocker 1,425 1,365 1,245 292 No β-blocker 543 525 484 119

19. Risk- and Propensity-Adjusted Analysis of Discharge Medication Use in Patients with PSF PSF = LVEF 40%.

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. 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