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.

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

Owan T et al. N Engl J Med 2006;355:251-259

Secular Trends in the Prevalence of Heart Failurewith Normal Ejection Fraction

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

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

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

Lee, D. S. et al. Circulation 2009;119:3070-7

Survival of Patients with HFNEF and HFREF by CauseHFNEF

HFREF

Tribouilloy C et al. EHJ 2008;29:339-47

Survival Curves by Etiology of HF with Normal EF

Impact of EF on Outcomes after PCI in HF Patients-NHLBI PTCA Registry

Holper EM et al. AHJ 2006; 151: 69-75

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

Prognostic Importance of Pulmonary Hypertension in Patients with HF

Kjaergaard J et al. AJC 2007; 99: 1146-50

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

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

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

Anemia and Survival in Patients with Reduced and Normal EF

Felker MG et al. AHJ 2006; 151: 457-62

Risk of Different Outcomes Associated with Diabetes in HFREF and HFNEF

MacDonald M R et al. EHJ 2008;29:1377-85

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).

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

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

Massie B et al. N Engl J Med 2008;359:2456-2467

Effects of Ibersartan in Patients with HFNEF

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

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

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