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ACUTE HEART FAILURE

Venice Chairiadi, MD, FIHA

JANTUNG SEBAGAI POMPA

Kanan

Kiri

Heart Failure: Significant Clinical


and Economic Burden

Persons with HF in the US


4.9 million
Overall prevalence
2.3%
Incidence
550,000/year
Death rate in 2003
286,700
Five-year mortality rate
50%
Cost-2006
$29.6 billion

American Heart Association. Heart Disease and Strok Statisti 2006 Update.

Estimated Direct and Indirect Costs of


Heart Failure in the US-2006
Lost productivity/
mortality*
Home healthcare $2.8
$2.4

Total cost:
$29.6 Billion

Drugs/other
medical durables
$3.1

Physicians/other
professionals
$2.0

Hospitalization
$15.4

Nursing home
$3.9
* Lost future earnings of persons who will die in 2006, discounted
by 3%.
American Heart Association. Heart Disease and Stroke Statistics 2006 Update.

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Patofisiologi

CRITICAL LV
DETERIORATION

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Diagnosis

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Current Treatments for ADHF


Diuretics

Reduce
Fluid
Volume

Vasodilators

Decrease
Preload
and
Afterload

Inotropes

Augment
Contractility

Natriuretic
Peptide
Decrease
Decrease
Preload
Preload
and
and
Afterload;
Afterload;
Reduce
Reduce
Fluid
Fluid
Volume
Volume

Most Common IV Medications


ADHERE Registry
All Enrolled Discharges (n=105,388)
October 2001-January 2004
100
90

88%

Patients (%)

80
70
60
50
40
30
20

6%

10
0

IV Diuretic

Dobutamine

6%
Dopamine

3%
Milrinone

10%

10%
1%

Nesiritide

IV Vasoactive Meds

Nitroglycerin

Nitroprusside

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Wide-spread use of
Nesiritide

It is a natural product
First new drug in many years
Its Natural
Use after current therapy fails
But became a first-line therapy
Out of control! Inpatient and
outpatient
Whats wrong with nitroglycerin and
furosemide?

Effects of Nesiritide
Venous, arterial, coronary
VASODILATION
HEMODYNAMIC

NATRIURESIS
DIURESIS

CARDIAC
INDEX

rhBNP

R I SS
D
S
M
S
K
G
R
L
G
H
G
F
R
C
R
S
S
C
K V L
G
S P K MV
QGS

Preload
Afterload
PCWP
Dyspnea

RENAL

Fluid volume
Preload
Diuretic
usage

Aldosterone
Endothelin
Norepinephrine

CARDIAC
No increase in HR
Not proarrhythmic

SYMPATHETIC AND
NEUROHORMONAL SYSTEMS

Nesiritide
Advantages
Rapid symptomatic improvement
Theoretical antagonism of RAAS activation

Disadvantages
Minimal indirect effect in increasing cardiac
output
Incompatibilities; cannot be infused through same
IV catheter as heparin (no heparin-coated
catheters), insulin, bumetanide, enalaprilat,
hydralazine, or furosemide
Associated with clinically significant hypotension
Associated with increased serum creatinine
concentrations
Impact on hospitalization and mortality remains
uncertain
Cost > effect?

Mean Change in PCWP (mm Hg)

VMAC Trial:
Hemodynamics
PCWP

0
1
2
3

*
*

5
6
BL

0.5

0.25

Placebo

*
3

Hours
Nitroglycerin

Nesiritide

Added to standard therapy; N = 242


*P<0.05 vs placebo plus standard care
Publication Committee for the VMAC Investigators. JAMA. 2002;287:1531

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

The Future of ADHF


Pharmacotherapy
Management
Other natriuretic peptides (ie,

ularitide, carperitide)
Levosimendan (inotrope/vasodilator)
Vasopressin Receptor Antagonists
IV Conivaptan (dual vasopressin
blocker)
Adenosine-1 receptor antagonists
(diuretic and renal protection in
ADHF)

Levosimendan
A novel compound for the treatment

of heart failure
Unique dual mechanism of action
Increases calcium myofilament
responsiveness through binding to
cardiac troponin C (calcium sensitizer)
Opens ATP-sensitive potassium channels
in vascular smooth muscle cells and in
cardiac myocytes (vasodilator)

Levosimendan Trial MetaAnalysis


Meta-analysis of 4 Phase III trials, a total of

1004 patients
Levosimendan was found to be safe and
well tolerated
Mild headache and hypotension were the
most common adverse events
Levosimendan patients had a 48% reduction
in the risk of death compared with control
patients (placebo or dobutamine)
Hazard ratio 0.52 (95% CI 0.33-0.82) P=.005

Sandell EP, et al. Eur J Heart Fail 2004;3(suppl 1):86 (abstract 341).

Levosimendan Results:Late Breaking


Session AHA Nov. 05 (REVIVE II)

RCT in 600 patients of Levo vs placebo


Primary endpoint achieved-Clinical

composite endpoint at 6, 24, 48 hrs, 5 days


33% more patients in the levosimendan
group had improved and 30% fewer of them
had worsened compared to controls
90-day all-cause mortality: 15.1% with
levosimendan vs 11.6% in controls (NSD)
Higher incidence of hypotension and
arrhythmias (a. fib and v. tach)

Levosimendan Results:Late
Breaking Session AHA Nov. 05
(SURVIVE)

RCT Levosimendan vs dobutamine, N

= 1327
No effect on mortality in 5, 31, and
180 days (trend in early timeframe)
ADEs similar except increased cardiac
failure in the dobutamine arm and
atrial fibrillation in the levosimendan
arm
Will have to see what the future holds

TERIMA KASIH