Current treatment of acute heart failure

Department of Cardiology of the University Medical Center Belgrade, Serbia

Prof. Petar M. Seferović, MD, PhD, FESC, FESCMember of the Board, Heart Failure Association of the ESC

Natural history of congestive heart Natural history of congestive heart failurefailure

Initial phaseInitial phase Last yearLast year

Normal heartNormal heart Chronic heart failureChronic heart failure5 million in the US5 million in the US

10 million in Europe10 million in Europe

DeathDeath

Initial Initial myocardial myocardial

injuryinjury

First ADHF episode:First ADHF episode:Pulmonary edemaPulmonary edema

ER admissionER admission

Later ADHF episodes:Later ADHF episodes:Rescue therapyRescue therapyICU admissionICU admission

Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G.Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G.

Hea

rt V

iab

ility

Hea

rt V

iab

ility

Acute heart failure is heterogeneous Acute heart failure is heterogeneous syndromesyndrome

CardiogenicCardiogenic

shockshock

PULMONARYPULMONARY

EDEMAEDEMA

Right Heart FailureRight Heart Failure

High Output FailureHigh Output Failure

Hypertensive HFHypertensive HF

Acute Acute Decompensated Decompensated

CHFCHF

Filippatos 2005Filippatos 2005

Diagnostic approach to acute heart failure

Diagnostic approach to acute heart failure

EVIDENCE

Applying guidelines in acute heart failure: Facts or fancy?

ACCF/AHA Practice Guideline

40 pages

Canadian Cardiovascular Society Consensus Recomendations

Australia/New Zealand Heart Failure Guidelines

The etiology of acute heart failure can vary significantlly

• Primary dilated cardiomyopathy

• Acute coronary syndrom

• Arterial hypertension, diabetes mellitus

• Toxic cardiomyopathy (cocaine, alchohol)

Clinical and pathophysiological classification of acute heart failure

More than 90% of patients hospitalized with heart failure have congestion (wet) and show elevated PCWP1,2

References: 1. Stevenson LW. Tailored therapy to hemodynamic goals for advanced heart failure. Eur J Heart Fail. 1999;1:251-257. Available at: http://www.sciencedirect.com/science/journal/13889842. 2. Fonarow GC. The treatment targets in acute decompensated heart failure. Rev Cardiovasc Med. 2001;2(suppl 2):S7-S12.

Warm & Dry

PCWP* normal

CI† normal(compensated)

Warm & Wet

PCWP elevated

CI normal

Cold & Dry

PCWP low/normal

CI decreased

Cold & Wet

PCWP elevated

CI decreased

Congestion at rest

Low perfusionat rest

Vasodilators,diuretics

No

No

Yes

Yes

Normal SVR High SVR

4%

37%

39%

7%

12%

1%

AdHF Pulmonary oedema Cardiogenic shock Hypertensive HF Right HF High cardiac output failure

Clinical presentations of acute heart failure in EHFS II and ALARM-HF studies

Clinical presentations of acute heart failure in EHFS II and ALARM-HF studies

ALARM-HFEHFS II

Pulmonary oedema (16% vs 37%) and cardiogenic shock (4% vs 12%) are significantly different between the two studies.

ESC treatment algorithm for acute heart failure

ESC treatment algorithm for acute heart failure

ADHERE registry: Treatment of acute heart failure

• ADHERE (Acute Decompensated HEart Failure National REgistry)

• Data from >100.000 patients

• Database of demographic and clinical parameters of hospitalized patients with decompensated heart failure

Clinical presentation of acute heart Clinical presentation of acute heart failure in major clinical studiesfailure in major clinical studies

Diuretics in acute heart failure: Proven and effective

Diuretics in acute heart failure: Proven and effective

CLINICALLYCLINICALLY proven, proven, pathophysiologically pathophysiologically UNCLEARUNCLEAR

SYMPTOMATICSYMPTOMATICimprovement improvement

HEMODYNAMICHEMODYNAMIC improvementimprovement

To increase To increase DIURESISDIURESIS To improve To improve OXYGEN OXYGEN

SATURATIONSATURATION

CLINICALLYCLINICALLY proven, proven, pathophysiologically pathophysiologically UNCLEARUNCLEAR

SYMPTOMATICSYMPTOMATICimprovement improvement

HEMODYNAMICHEMODYNAMIC improvementimprovement

To increase To increase DIURESISDIURESIS To improve To improve OXYGEN OXYGEN

SATURATIONSATURATION

Increasing mortality with intravenous furosemide in acute heart failure?

Increasing mortality with intravenous furosemide in acute heart failure?

Ahmed et al. European Heart Journal 2006 27, 1431–1439Hasselblad V, et al. HFSA, 2005.

ESCAPE Trial

Vasodilatators in acute heart failure

Vasodilatators in acute heart failure

Intravenous nitrate/SNP (caution if SBP <110mmHg)Intravenous nitrate/SNP (caution if SBP <110mmHg)

Class I/level BClass I/level B

The VMAC Investigators. JAMA. 2002; 287: 1531

Subjects Improved (%)

Subjects Worse (%)

p values are based on Van Elteren test with 7 - point ordinal scale

0

10

20

30

40

50

60

70

80

10

90

100

NTGNesiritide Placebo

No Change

p = 0.034

p = 0.191

30 days Readmissions 20% 23%

Acute heart failure: VMAC primary endpoint: Dyspnea at 3 hours.

Acute heart failure: VMAC primary endpoint: Dyspnea at 3 hours.

Sackner-Bernstein JD, et al. JAMA. 2005;293:1900-1905.

0

2

4

6

8

10

0 10 20 30

Mor

talit

y, %

Days

Nesiritide(n = 485)

Control(n = 377)

Unadjusted: hazard ratio 1.86 (95% CI, 1.02-3.41), P=0.04Adjusted for study: hazard ratio 1.80 (95% CI 0.98-3.31), P=0.057

Meta-Analysis of 3 Nesiritide Trials*

*NSGET, VMAC, and PROACTION trials

Neseritide is associated with increasing mortality in acute heart failure

Neseritide is associated with increasing mortality in acute heart failure

Treatment of acute heart failure according to blood pressure at presentation

Treatment of acute heart failure according to blood pressure at presentation

Left ventricular filling pressures as the guide for the treatment of acute heart failure

Inotropes in the treatment of acute heart failure

Inotropes in the treatment of acute heart failure

Inotropes should be considered in patients with low output states

Most class IIa or IIb and level B!

ADHERE registry: Inotropic agents and mortality in acute heart failureADHERE registry: Inotropic agents and mortality in acute heart failure

Abraham WT, et al. JACC 2005;46(1):57–64.

4,7

7,1

12,3

13,9

0

2

4

6

8

10

12

14

16

Hos

pita

l Mor

talit

y (%

)

NTG Nesiritide Milrinone Dobutamine

0

0.25

0.50

0.75

1.00

0 0.25 0.75 1.25 1.50

Fra

ctio

n S

urvi

ved

Follow-Up, year

No Dobutamine(n = 391)

Dobutamine(n = 80)

P=0.0001*

*For NYHA III-IV patients. O’Connor CM, et al. Am Heart J. 1999;138:78-86.

FIRST Trial: Adjusted Survival

EFFECT OF DOBUTAMINE EFFECT OF DOBUTAMINE ON SURVIVALON SURVIVAL

OPTIME-CHF Trial: Sub-Group Survival

MilrinoneNon-ischemic

Milrinone Ischemic

Placebo Ischemic

Placebo Non-ischemic

100

98

96

94

92

90

88

860 10 20 30 40 50 60

Days

Su

rviv

al,

%

Felker GM, et al. J Am Coll Cardiol. 2003;41:997-1003.Cuffe MS, et al. JAMA. 2002;287:1541-1547.

EFFECT OF MILRINONE ON SURVIVALEFFECT OF MILRINONE ON SURVIVALKaplan-Meier survival curves (at 60 days, by Kaplan-Meier survival curves (at 60 days, by

heart failure etiology and treatment) heart failure etiology and treatment)

Ca2+

Levosimendan

Diastole Systole

Pollesello P, et al. J Biol Chem. 1994;269:28584-28590.Sorsa T, et al. Mol Cell Biochem. 2004;266:87-107.

Levosimendan Binding to Troponin C

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 30 60 90 120 150 180

Days Since Start of Study Drug Infusion

Pro

babi

lity

of S

urvi

ving

LevosimendanDobutamine

180 day all-cause mortality180 day all-cause mortalitySURVIVESURVIVE

Levosimendan (n = 664)Levosimendan (n = 664) 173 (26%)173 (26%)

Dobutamine (n = 663)Dobutamine (n = 663) 185 (28%)185 (28%)

Hazard Ratio (CI)Hazard Ratio (CI) 0.91 (0.74-1.13)0.91 (0.74-1.13)

PP-Value-Value 0.4010.401

∆ Deaths - 12

5d

31d

180d

Treatment of acute heart failure Balancing RISKS AND BENEFITS

for individual patients!

CHF

ESC ACC/AHA Canadian

Oxygen I C I C -

Loop diuretic I B I B I B

Vasodilators I B IIa C I B

Non-invasive ventilation IIa B - IIa B

Inotropes IIa B I C/IIb C I B

Invasive monitoring IIa B/IIa C I C/IIa C I B

Ultrafiltration IIa B IIa B None

Coronary reperfusion I C IIa C None

No class of drugs has reccomendation level of evidence A !

Treatment of acute heart failureComparison of various treatment modalities in different guidelines

FAST FACTS

Experts from five leading European associationsAgreed on cosensus document on the treatment of acute heart failure in

Europe

Medical decisions were always tough to make