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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 ProgramsMedical Director, Edward Hospital Center for
Advanced Heart FailureNaperville, Illinois, U.S.A.
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Characteristics of Patients with Heart Failure and Normal or Reduced Ejection Fraction
Characteristic Reduced EF (n=2429)
Normal EF (n=2167)
P Value
Age (yr) 71.7 ± 12.1 74.4 ± 14.4 < 0.001
Male Sex (%) 65.4 44.3 < 0.001
BMI 28.6 ± 7.0 29.7 ± 7.8 0.002
Obesity (%) 35.5 41.4 0.007
sCr on adm. (mg/dl) 1.6 ± 1.0 1.6 ± 1.0 0.31
Hgb on adm. (g/dl) 12.5 ± 2.0 11.8 ± 2.1 < 0.001
HTN (%) 48.0 62.7 < 0.001
CAD (%) 63.7 52.9 < 0.001
AF (%) 28.5 41.3 < 0.001
DM (%) 34.3 33.1 0.42
Significant VHD (%) 6.5 2.6 <0.001
EF (%) 29 ± 10 61 ± 7 <0.001
Owan TE et al. NEJM 2006; 355:251-9
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Owan T et al. N Engl J Med 2006;355:251-259
Secular Trends in the Prevalence of Heart Failurewith Normal Ejection Fraction
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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
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Association of Clinical Characteristics with Mortality in Patients with Normal versus Reduced EF
Variable Normal EF Reduced EF
Age YES YES
Female Sex YES YES
sCr on Admission YES YES
Hgb on Admission YES YES
HTN YES YES
CAD NO YES
AF NO NO
DM YES YES
Significant VHD NO NO
Year of Admission NO YES
Owan T et al. NEJM 2006;355:251-259
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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
GFRNYHA III/IVMale genderAgeDiureticsBMICR RatioDMVasodilatorsK-Sparing Diur.DBP
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Lee, D. S. et al. Circulation 2009;119:3070-7
Survival of Patients with HFNEF and HFREF by CauseHFNEF
HFREF
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Tribouilloy C et al. EHJ 2008;29:339-47
Survival Curves by Etiology of HF with Normal EF
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Impact of EF on Outcomes after PCI in HF Patients-NHLBI PTCA Registry
Holper EM et al. AHJ 2006; 151: 69-75
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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
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Prognostic Importance of Pulmonary Hypertension in Patients with HF
Kjaergaard J et al. AJC 2007; 99: 1146-50
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69%
53%
66%
40%
22%
10%
16%
6%
47%
51%
42%
17%17%
4%7% 5%
4%2%2% 0%
0%
10%
20%
30%
40%
50%
60%
70%
6 mo readmand mort.
6 mo mort. 2 mo readm.and mort.
2 mo mort. Hosp. Mort.
Outcomes by Presence or Absence of IVCD
HFREF+IVCD
HFREF-IVCD
HFPEF+IVCD
HFPEF-IVCD
Danciu Sc et al. AJC 2006; 97: 256-9
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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
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56%
38%
26% 25%
17% 19%
25%
0%
10%
20%
30%
40%
50%
60%
< 20 20-25 26-30 31-35 36-40 41-45 > 45
BMI
Obesity and Survival in HFPEF
Su
rviv
al
Kapoor JR et al. AHJ 2010; 159: 75-80
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Anemia and Survival in Patients with Reduced and Normal EF
Felker MG et al. AHJ 2006; 151: 457-62
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Risk of Different Outcomes Associated with Diabetes in HFREF and HFNEF
MacDonald M R et al. EHJ 2008;29:1377-85
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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).
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BNP Predicts Medium-Term Risk in Patients with Acute HF and Normal EF
Impaired Ps eudonormal Res tr ic tiv e
0
50
100
150
200
250
300
350
400
450
BNP Levels
Pg
/mL
80
278
434
P< 0.05
Valle R et al. JCF 2005; 11: 498-503
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75
58
912
83
70
21
9
4440
60
53
6662
5652
0
10
20
30
40
50
60
70
80
90
ACEI ARB BB Ald. Ant. Statin D/C Instr. SmokingCess.
Couns.
Warfarinfor AF
Treatments and Performance Measures Applied at Discharge
LVSD
PSF
%
P < 0.0001
P < 0.0001
P < 0.0001
P < 0.0001
P < 0.0001
P = 0.0003
P < 0.004
P < 0.0009
Fonarow GC et al. JACC2007; 50: 767-77
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Massie B et al. N Engl J Med 2008;359:2456-2467
Effects of Ibersartan in Patients with HFNEF
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0
5
10
15
20
25
30
35
40
<21 21-30 31-40 >40
Hospitalizations before and after BB, by EF
HF Hosp. prior yr
HF Hosp. 1 yr f/u
EF
% o
f P
atie
nts
* **
*
* P = 0.001 vs. prior year
Massie BM et al. AJC 2007; 99: 1263-8
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Dobre D et al. EJHF 2007;9:280-6
Variable N (%) Adjusted HR
95% CI P value
BB 227(51) 0.57 0.37-0.88 0.01
GFR ≤ 40 ml/min
247(56) 2.14 1.37-3.34 0.001
COPD 126(28) 1.60 1.04-2.45 0.03
Male sex 197(44) 1.48 1.00-2.19 0.05
Digoxin 98(22) 1.58 1.006-2.47 0.05
Variable N(%) Adjusted HR
95% Ci P value
BB Low Dose 93(41) 0.74 0.45-1.21 0.2
BB High Dose 134(59) 0.51 0.30-0.86 0.01
Effect of Beta Blockers on Survival in Patients with Advanced HF and Normal EF
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Conclusions
The prevalence of HFNEF is increasingHospitalizations for ADHF in patients with HFNEF are increasingThe outcomes of HFNEF and HFREF are similarThe outcomes of patients with HFNEF are determined by the presence and severity of comorbiditiesWith 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