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American Heart Association. Heart Disease and Strok Statisti 2006 Update.
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.
Patofisiologi
CRITICAL LV
DETERIORATION
Diagnosis
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
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
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?
VMAC Trial:
Hemodynamics
PCWP
0
1
2
3
*
*
5
6
BL
0.5
0.25
Placebo
*
3
Hours
Nitroglycerin
Nesiritide
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)
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
(SURVIVE)
= 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