HFpEF is frequent in acute heart failure

Alain COHEN SOLALUMR-S 042 « Biomarkers in Heart Failure » Unit, 

Paris Diderot UniversityCardiology Dpt, Lariboisiere Hospital

Paris

Disclosures I

• Grants or honoraria

– Servier– Pierre Fabre– Amgen– Vifor– Sorin– Novartis– CVRX– Bayer

– GE Healthcare– Actelion– Abbott– Menarini– Roche– Pfizer– ZS– Boehringer Ingelheim

What is heart failure?• Chronic Heart Failure (CHF):

– Heart failure is a complex syndrome in which abnormal heart function results in, or increases the subsequent risk of, clinical symptoms and signs of low cardiac output and/or pulmonary or systemic congestion.

• Acute Heart Failure Syndrome (AHF):– “gradual or rapid change in heart failure

signs and symptoms resulting in the need for urgent therapy”

Heterogeneity of AHF(ESC classification)

high BP, +/- preserved LV systolic fxn; increased sympathetic tone with ↑HR, vasoconstriction; may be euvolaemic or 

only mildly hypervolemic, and frequently with signs of pulmonary or systemic 

congestion 

Severe respiratory distress, ↑RR, orthopnea, rales.  O2 sats <90% RA prior to O2

Clinical and lab evidence of an ACS; ~15% of patients with an ACS have signs and symptoms of HF. Episodes of AHF are frequently assoc w/ or precipitated by arrhythmia (bradycardia, AF, VT).

Usually sys BP <90 mmHg or drop in MAP >30 mmHg and absent/low urine output. Organ hypoperfusion and pulmonary congestion develop rapidly

low output in absence of pulmonary congestion with increased JVP, w/ or w/out HSM, and low LV filling pressures

usually a hx of prog. worsening of known chronic HF on Rx, and evidence of systemic/pulmonary congestion. 

ESC 2008 and 2012A « bouillabaisse » …

The picture of AHF has changed with time …

• Years ago– Younger population– Predominance of unrevascularised AMI– Or old valvular diseases

• Prevalence of LV systolic dysfunction in patients with AHF• Nowadays

– Mean age 80 y– Altered arterial stiffness– Aged heart with low diastolic and systolic reserve – AF– Diabetes rates increase– ..

Epidemiology

– Clinical trials provide a biased wiew of the real incidence of HFpEF in ADHF

• Most of them have excluded pts with pEF• Exclusion of patients with rapide AF, severe renal failure or hypertension, infection, COPD, dementia, ischemia

• Which are frequent in HFpEF

– Registries dealing with patients hospitalized with HF mix pts with AHF and CHF

Clinical trials

PROTECT

CARRESS

DOSE

RELAX-AHF

ParameterPlacebo (N=580)

Serelaxin (N=581)

Age (years) Mean 72.5 71.6

Systolic BP at baseline (mmHg) Mean 142.1 142.2

Heart Rate at Baseline (bpm) Mean 80.4 78.9

Respiratory Rate at baseline (breaths/ min) Mean 22.0 21.8

HF Hospitalization (in the past year) % 31.2 37.2*Most Recent Ejection Fraction Mean 38.7 38.6

< 40% % 54.9 54.7

NYHA (1 month prior to admission) %

III % 46.7 43.7

IV % 17.0 14.4

Medical History

Hypertension % 87.9 85.4

Hyperlipidemia % 54.0 52.3

Stroke or Other Cerebrovascular event % 14.5 12.6

Atrial fibrillation/ atrial flutter at presentation % 42.4 40.1

Diabetes Mellitus % 46.9 48.0

RELAX-AHF : Patient population

Patients in real life often differs from those of clinical trials ..

Registries

The Multinational Observational Cohort on Acute Heart Failure 

(MOCA) study

Lassus J, Cohen-Solal A. Int J Cardiol 2012

5 306 AHF patients, 170 centers, from Finland, Switzerland, USA, Czeck, Holland, France, Austria, Italy, Tunisia, Japan ..

LVEF 40% (26-55%)

- FEVG>40%   51%- FEVG>45%   41%- FEVG>50%   33%

OObservatoire bservatoire FFrançais rançais de lde l’’IInsuffisance nsuffisance CCardiaque ardiaque AAigueigue

(French survey on acute heart failure)(French survey on acute heart failure)

OFICA

(French National WG on HF and cardiomyopathies)

Logeart D et al. Eur J Heart Fail 2012

OFICAA French nationwide survey

Logeart D et al. Eur J Heart Fail 2012

1 654 patients, 170 hospitals

All Pulmonary edema 

Decompensated HF 

Cardiogenic shock 

Isolated right HF 

p

Age (years) 76.3 ± 13.1 77.8 ± 12.0  76.8 ± 12.4  64.5 ± 16.4  74.5 ± 14.7 < 0.001Gender (male) 54.8% 48.0% 56.7% 79.6% 59.4% <0.001Previous AHF 45.1% 39.0% 51.1% 32.7% 49.0% <0.001De novo HF 37.4% 46.9% 31.1% 36.7% 34.3% <0.001Ischemic HD 43.6% 48.9% 40.6% 56.1% 24.0% 0.0003LVEF

   LVEF ≥ 0.50

41.9 ± 16.2

36.2%

43.5

37.2%

41.0

35.5%

29.6

9.0%

50.2

59.2%

<0.001

<0.0001

Diabetes

COPD

BMI  ≥ 30

Severe renal failure

31.1%

20.9%

29.3%

22.1%

31.9%

20.5%

25.1%

21.6%

30.8%

20.7%

32.2%

22.1%

24.5%

19.4%

23.6%

19.7%

33.3%

27.1%

31.0%

24.1%

0.48

0.49

0.13

0.94

Precipitating factors

   STE-ACS

   Infection 

   SV arrhythmia

4.6%

27.2%

23.7%

5.5%

31.4%

22.2%

2.3%

25.2%

26.9%

20.4%

23.4%

11.2%

0

18.7%

19.8%

<0.0001

0.01

0.002

OFICA : the scenarii N = 1 654

EHFS II

LVEF ranged from 29% (ADCHF) to 51% (hypertensive AHF)Mean 38±15%, and 35% > 45%

00

55

1010

1515

2020

2525

3030

3535

4040

%%

Inf Inf   4040yy

40 40 - - 4949yy

50 -50 -5959yy

60 -60 -6969yy

70 70 - 79- 79ansans

Sup  Sup  8080yy

  Age 75 Age 75 yearsyears

  60% pts >75 60% pts >75  y  y 

1%1%3%3%

6%6%

13%13%

38%38%

ETICS39%39%

<40y

40-49y

50-59y

60-69y

70-79y

>=80y

<50%>=50%

72%

58%

78%

54%

40%39%

28%

60%

42%

22%

46%

61%

Relation Relation LVEF/aLVEF/agege ETICS

Preserved LVEF (>50%) n = 507 

Altered LVEF (<50%)n = 893 

p 

LVEF  0.60 ± 0.8  0.32 ± 0.09  <0.0001 

Age (years)  79.1 ± 10.9   73.3 ± 13.8  <0.0001 

Male  40.6 %  66.0%  <0.0001 

Ischemic heart disease  30.4% 54.9% <0.0001

Hypertension  71.8% 55.6% <0.0001

Severe valvulopathy 29.8% 18.1% <0.001

Diabetes 

COPD 

BMI ≥ 30

Severe renal failure

31.7%

23.5%

33.3%

22.8%

32.7%

19.9%

26.4%

19.8%

0.762

0.136

0.069

0.277

Precipitating factors

  STE-ACS

  SV arrhythmia

  Infection

3.0%

27.8%

28.8%

6.2%

20.8%

23.2%

0.012

0.004

0.024

OFICA

In-hospital deaths

Cardiovascular cause

8.2 % (n = 136)

81.2%

Age ≥ 79 years Age < 79 years

10.9 % 6.5 %

LVEF < 50% LVEF ≥ 50%

9.5% 5.9%

Shock No shock

18.1%7.9%

OFICAIn-hospital deaths

Parameters HR 95% CI pAge 1.04 1.02 - 1.05 <0.0001Natriuretic peptides (per quartiles)

1.34 1.09 – 1.65 0.005

Hemoglobin at discharge 0.93 0.83 – 1.03 0.18Previous hospit for AHF 1.50 1.00 – 2.25 0.05Systolic BP at discharge  0.99 0.98 – 1.00 0.19LVEF 0.98 0.93 – 1.04 0.60  

Natremia at discharge 0.97 0.93 – 1.02 0.27

COPD 1.55 1.02 – 2.36 0.04

Cox proportional-hasards regression for mortality after discharge

Mechanisms

First mechanism1) altered/delayed relaxation

.

1

PR

ESS

I ON

VOLUME

Ees

TEM PS

VO

LU

ME

Left BBB, LVH, ischemia …

2) Decreased compliance

Effects of ischemia

Multiple mechanisms …

Exercise as a stress test in HFpEF

Tartiere-Kesri L,…, Cohen-Solal A. J Am Coll Cardiol 2012

Reduced LV compliance response & Excessive Arterial stiffening

       Controls HFpEF

Conclusion

• AHF is frequent and associated with poor outcome

• Epidemiology has changed with time• HFpEF becomes the main cause of AHF hospitalizations

• Phenotype is different : age, BP, comorbities• Less difficult to treat ?• From a « marketing » viewpoint, this population should be the one to target …