Acute Heart Failure: Venice Chairiadi, MD, FIHA

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 Total cost:
$2.4
$29.6 Billion
Drugs/other
medical durables
$3.1
Hospitalization
Physicians/other $15.4
professionals
$2.0
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
Patofisiologi
CRITICAL LV
DETERIORATION

Diagnosis

Current Treatments for ADHF
Natriuretic
Diuretics Vasodilators Inotropes Peptide
Decrease
Preload
Decrease and
Reduce Augment
Preload Afterload;
Fluid Contractility
and Reduce
Volume
Afterload Fluid
Volume
Most Common IV Medications
ADHERE Registry
All Enrolled Discharges (n=105,388)
October 2001-January 2004
100 88%
90
80
70
Patients (%)
60
50
40
30
20 10% 10%
6% 6%
10 3% 1%
0
IV Diuretic Dobutamine Dopamine Milrinone Nesiritide Nitroglycerin Nitroprusside
IV Vasoactive Meds
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 RENAL
HEMODYNAMIC NATRIURESIS
DIURESIS
CARDIAC
INDEX
Fluid volume
rhBNP R I SS
Preload
M
D S
S
Diuretic
Preload K
R
G
usage
L
G
Afterload F
C S S
C
G
R
R
H
K V L
PCWP S P K MV
QGS
G
Dyspnea
Aldosterone
Endothelin
Norepinephrine
CARDIAC
No increase in HR SYMPATHETIC AND
Not proarrhythmic 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
Mean Change in PCWP (mm Hg)

0 PCWP
1
3 *
*
4
*
5 * *
*
6
BL 0.5 1 2 3
0.25
Hours
Placebo 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
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 Meta-Analysis
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

Acute Heart Failure: Venice Chairiadi, MD, FIHA

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ACUTE HEART FAILURE

Venice Chairiadi, MD, FIHA

Persons with HF in the US 4.9 million

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Acute Heart Failure ESC Guideline, Eur Heart J 2005

Mean Change in PCWP (mm Hg)

Placebo Nitroglycerin Nesiritide

Added to standard therapy; N = 242

Other natriuretic peptides (ie, ularitide,

Meta-analysis of 4 Phase III trials, a total of 1004

RCT in 600 patients of Levo vs placebo

RCT Levosimendan vs dobutamine, N =

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