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
Slide 8
A number of barriers to implementing risk factor modification, including lipid lowering therapy, in patients with coronary heart disease where identified at the 27th American College of Cardiology Bethesda Conference. These barriers included physicians being focused on acute problems, time constraints and lack of incentives, lack of training, and limited resources and outpatient facilities. It has more recently been recognized that the setting in which treatment is initiated may be a very import factor influencing treatment rates. Conventional treatment guidelines such as the NCEP ATP-I and ATP-II, had recommended delaying baseline lipid assessment and treatment until 6 weeks after acute presentation in recognition that the acute phase response triggered by acute myocardial infarction and coronary artery bypass grafting can substantially lower total and LDL-cholesterol. As a result, the first opportunity for beginning treatment was delayed to a time when the patient and their physician may be no longer focused on addressing the patient’s underlying atherosclerotic disease process. By recommending a delay in the assessment of lipid levels and the initiation of lipid-lowering treatment in patients presenting with coronary heart disease, inadvertently, an important treatment opportunity was missed. Thus the guidelines themselves may have been contributing to the treatment gap.

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.
Slide 8
A number of barriers to implementing risk factor modification, including lipid lowering therapy, in patients with coronary heart disease where identified at the 27th American College of Cardiology Bethesda Conference. These barriers included physicians being focused on acute problems, time constraints and lack of incentives, lack of training, and limited resources and outpatient facilities. It has more recently been recognized that the setting in which treatment is initiated may be a very import factor influencing treatment rates. Conventional treatment guidelines such as the NCEP ATP-I and ATP-II, had recommended delaying baseline lipid assessment and treatment until 6 weeks after acute presentation in recognition that the acute phase response triggered by acute myocardial infarction and coronary artery bypass grafting can substantially lower total and LDL-cholesterol. As a result, the first opportunity for beginning treatment was delayed to a time when the patient and their physician may be no longer focused on addressing the patient’s underlying atherosclerotic disease process. By recommending a delay in the assessment of lipid levels and the initiation of lipid-lowering treatment in patients presenting with coronary heart disease, inadvertently, an important treatment opportunity was missed. Thus the guidelines themselves may have been contributing to the treatment gap.

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
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
Total Hospitals
(N=259), n (%)
Follow-Up Hospitals (N=91), n (%)
Bed size: 0 to 99
31 (12)
9 (10)
100 to 249
58 (22)
21 (23)
250 to 499
103 (40)
40 (44)
500 to 749
38 (15)
13 (14)
750
13 (5)
4 (4)
Unknown
16 (6)
Academic*
118 (48)
48 (55)
Transplant program*
34 (14)
Interventional† (CABG/PCI)
163 (67)
62 (70)
Region‡: Midwest
68 (27)
27 (30)
Northeast
44 (17)
14 (16)
South
87 (34)
34 (38)
West
56 (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. OPTIMIZE-HF Patient Characteristics
Hospital Cohort
(N=48,612)
Follow-Up Cohort (N=5,791)
Age, mean (years)
73.1
72.0
Male (%) 48 51
Caucasian (%) 74 78
Ischemic etiology (%) 46 42
LVEF, mean (%)
39.0
36.9
LVSD (% of those assessed)
48.8
53.2
Insulin-treated diabetes (%) 17
Non–insulin-treated diabetes (%) 25 26
Hypertension (%) 71 72
Rales (%) 64 62
Mean SBP (mmHg)
143
140
Mean heart rate (bpm) 87 86
Mean sodium (mEq/L)
136.7
136.8
Mean serum creatinine (mg/dL)
1.8
1.7
Mean hemoglobin (g/dL)
12.1
12.2

10. Distribution of LVEF in Patients Hospitalized With Primary Discharge Diagnosis of HF0- 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
Documented LVEF Measured Prior to or During Hospitalization
Left Ventricular Ejection Fraction (%)

11. Patient Characteristics at Hospital Admission by LVSD vs PSF
LVSD (n=20,118)
40%≤ EF ≤50% (n=7,321)
EF >50% (n=10,072)
P Value*
Age, mean (years)
70.4
74.3
75.6
<.0001
Male (%) 62 48 32
African American (%) 21 15
.880
Atrial arrhythmia (%) 28 33
.179
Ischemic etiology (%) 54 49
Insulin-treated diabetes (%) 18 16
.013
Noninsulin-treated diabetes (%) 24 26 25
.418
Hypertension (%) 66 74 77
Mean LVEF %
24.3 45 61
*P value (40%≤ EF ≤50% vs EF >50%).
PSF = preserved systolic function.

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 (%) 63 62
.206
Rales (%) 65
.001
Jugular venous distension (%) 33 26
.0001
Mean SBP (mmHg)
135
149
Mean heart rate (bpm) 89 85
Mean sodium (mEq/L)
138
Mean BNP (pg/mL)
1635
977
Mean troponin I (ng/mL)
1.60
0.74
Mean serum creatinine (mg/dL)
1.70
1.73
Mean hemoglobin (g/dL)
12.53
11.86
PSF = LVEF 40%.

13. HF Treatments Applied at Discharge by LVSD vs PSF
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
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
LVSD (n=20,118)
40%≤ EF ≤50% (n=7,321)
EF >50% (n=10,072)
P Value*
In-hospital mortality: all patients
3.9
3.0
2.9
.647
Follow-Up Cohort
Post-discharge mortality
9.8
9.2
9.3
.887
Rehospitalization
29.9
29.0
30.9
.366
Post-discharge mortality/ rehospitalization
36.1
35.1
36.8
.436
*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 10 20 30 40 50 60 70 80 90
Survival Time in Days Since Discharge
LVSD 2,294 2,188 1,
No LVSD 2,604 2,471 2,
*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 10 20 30 40 50 60 70 80 90
Survival Time in Days Since Discharge
ACEI/ARB 1,288 1,249 1,
No ACEI/ARB

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 10 20 30 40 50 60 70 80 90
Survival Time in Days Since Discharge
β-blocker 1,425 1,365 1,
No β-blocker

19. 95% Hazard Ratio Confidence Limits 95% Odds Ratio Confidence Limits
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
1.141
0.812
1.603
.447
β-Blocker vs no β-Blocker
1.209
0.872
1.675
.255
Post-discharge Death and/or Hospitalization
Odds Ratio
95% Odds Ratio Confidence Limits
P Value
ACEI/ARB vs no ACEI/ARB
0.909
0.692
1.196
.497
β-Blocker vs no β-Blocker
0.923
0.723
1.179
.523
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