Update Medical Therapy in Heart Failure

Curriculum Vitae
Nama : Prof. Dr. dr H. Djanggan Sargowo SpPD,SpJP(K), FIHA, FACC, FCAPC, FESC, FASCC
Tempat/Tgl lahir : Sragen, 21 September 1947

Alamat : Wilis Indah E-10 Malang, Telp. 0341-552395
Pendidikan :
1. Lulus Dokter dari UGM, tahun 1974
2. Lulus Cardiologist dari Univ. Indonesia, tahun 1983
3. Lulus Internist dari Univ. Airlangga, tahun 1986
4. Lulus Doktor, Univ. Airlangga, tahun 1996
5. Advanced Cardiology Course, Univ. Hongkong, tahun 1984
6. Senior Visiting Program, Institut Jantung Negara, Kualalumpur, 1996
7. Fellow American College of Cardiology (FACC), September 2006.
8. Fellow Collage Asia Pacific Society of Cardiology (FCAPC), Desember 2007
9. Fellow European Sociaty of Cardiology (FESC), 2008
10. Fellow Asean Collage of Cardiology (FASCC), 2008
Jabatan :
1. Direktur Program Pascasarjana Universitas Brawijaya
2. Ketua MKEK Ikatan Dokter Indonesia Cabang Malang Raya
3. Ketua PERKI Cabang Malang Raya
4. Anggota Kolegium Kardiovaskuler Indonesia 1
UPDATE OF DIAGNOSIS AND MANAGEMENT IN
HEART FAILURE
Djanggan Sargowo
2
EPIDEMIOLOGY
Europe
The prevalence of symptomatic HF range from 0.4-2%.
10 million HF pts in 900 million total population
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560
USA
nearly 5 million HF pts.
500,000 pts are D/ HF for the 1st time each year.
Last 10 years number of hospitalizations has
increased.
Nearly 300,000 patients die of HF each year.
ACC/AHA Guidelines for the
Evaluation and Management of Chronic Heart Failure in the Adult 2001
3
HEART FAILURE
Heart Failure is complex clinical

syndrome that can result from
any structural or functional
cardiac disorder that impairs the
ability of the ventricle to fill with
or eject blood.
(ACC/AHA Practice Guideline 2001)
4
DEFINITIONS OF HEART FAILURE: WHO(1995)
The WHOs definition of heart failure includes
the pathogenesis and the symptoms and signs.
Pathophysiologically: heart failure means the
incapacity of the heart to transport blood and
therefore oxygen to the organs in amounts
sufficient to meet requirements
Clinically: heart failure means that the cause of the
symptom complex shortness of breath, early
fatigue (these are the typical symptoms) is
contractile dysfunction
Clinical diagnosis of heart failure requires proof of
a significant heart disease and the typical
symptoms of heart failure
5
THE CAUSES OF HEART FAILURE
Population-attributable risk,% - FRAMINGHAM HEART STUDY
70
60 Male Female
60
50
39
40
34
30
20
10 11
8 7
10 4
5 6 5
4
0
Hyper- Myo- Angina Diabetes LV heart Valvular
tension cardial hyper- heart
infaction trophy disease
6
PATHOGENESIS OF HEART FAILURE
Hemodynamic
Symptoms
overload
Ischemia
LV LV Pump
EF Remodeling failure
Genetics
Inflammation Arrhythmias
Asymptomatic
Ventricular remodeling after acute
infarction
Initial infarct Expansion of Global

infarct remodeling
(hours to days) (days to months)
Ventricular remodeling in diastolic and systolic heart
failure
Hypertrophied heart Dilated heart

Normal heart
(diastolic heart failure) (systolic heart failure) 8
CHRONIC HEART FAILURE : NEUROHORMONAL STATUS
SNS
RAAS
Vasopressin
Endothelin-1 DILATATION
Natriuretic peptides
Nitric oxide
CONSTRICTION Vasodilatory PGs
Adrenomedullin
9
FUNCTIONAL AND STRUCTURAL MODIFICATIONS FOLLOWING
NEUROHORMONAL STIMULATION IN HEART FAILURE
Functional modifications Structural modifications

Inotropy Hypertrophy
Heart rate Non-muscular tissue
Vasoconstriction Adult cardiac genes
Water / salt retention expression
Energy demand
Altered loading conditions
Altered vascular / diastolic
properties
Pro-arrhythmogenic effect
ALGORITHM Clinical presentation
HEART Symptoms, physical signs, Diagnosis is obvious :
FAILURE ECG, or Chest x-ray Breathlessness and fatigue

Edema
JVP
Uncertain Third heart sound
BNP Displaced apex beat
Abnormal ECG
< 100 pg/ml > 100 pg/ml CTR on CXR
Echocardiogram
No major cardiac problem

Ejection fraction
> 40 % < 40 %
LV diastolic dysfunction LV systolic dysfunction
No symptoms Symptoms
Asymptomatic
Systolic/ diastolic dysfunction Heart failure syndrome
* Dx. / Rx. Heart Failure, Jones & Barlett Publishers
11
TYPES OF HEART FAILURE
Diastolic dysfunction or
diastolic heart failure
Systolic dysfunction or
systolic heart failure
12
CLUES FOR DIFFERENTIATING BETWEEN SYSTOLIC AND DIASTOLIC
DYSFUNCTION IN PATIENTS WITH HEART FAILURE
Clues from the Systolic Diastolic

evaluation dysfunction dysfunction
History
Hypertension XX XXX
Coronary artery disease* XXX X
Diabetes mellitus XXX XX
Valvular heart disease* XXX --
X = suggestive; the number of Xs reflects the relative weight; -- = not suggestive.
*--Particularly helpful in distinguishing systolic from diastolic dysfunction in heart failure.
Adapted with permission from Young JB. Assessment of heart failure. In: Braunwald E. Atlas of heart disease. Vol 4. Philadelphia: Current Medicine,
1995:7.1-7.2. 13
Clues from the Systolic Diastolic
evaluation dysfunction dysfunction
Physical examination
Third heard sound (S3) gallop* XXX X
Fourth heart sound (S4) gallop* X XXX
Rales XX XX
Jugular venous distention XX X
Edema XX X
Displaced point of maximal XX --
impulse*
Mitral regurgitation* XXX X
14
Adapted with permission from Young JB. Assessment of heart failure. In: Braunwald E. Atlas of heart disease. Vol 4. Philadelphia: Current Medicine, 1995:7.1-7.2.
Clues from the evaluation Systolic Diastolic

dysfunction dysfunction
Chest radiograph
Cardiomegaly* XXX X
Pulmonary congestion XXX XXX
Electrocardiogram
Q wave XX X
Left ventricular hypertrophy* X XXX
Echocardiogram
Decreased ejection fraction* XXX --
Dilated left ventricle* XX --
Left ventricle hypertrophy* X XXX
15
Adapted with permission from Young JB. Assessment of heart failure. In: Braunwald E. Atlas of heart disease. Vol 4. Philadelphia: Current Medicine, 1995:7.1-7.2.
New York Heart Association (NYHA)
Heart Failure Symptom Classification
NYHA CLASS LEVEL of IMPAIREMENT
I No Symptom Limitation With

Ordinary Physical Activity
Ordinary Physical Activity Somewhat
II Limited by Dyspnea (ie. Long distance

Walking, Climbing 2 flights of stairs)
III
Exercise Limited by Dyspnea at Mild Work
Loads (ie. Short Distance Walking,
Climbing One Flight of Stairs)
IV Dyspnea at Rest or
With Very Little Exertion
16
ACC / AHA Classification of CHF 2001
STAGE DESCRIPTION
A
High Risk For Hypertension, Diabetes Mellitus, CAD,
Developing Heart Family History of Cardiomyopathy
Failure
B Previous MI, LV Dysfunction,

Asymptomatic
Valvular Heart Disease
Heart Failure
C Structural Heart Disease, Dyspnea and

Symptomatic Fatigue, Impaired Exercise Tolerance
Heart Failure
D Marked Symptoms at Rest Despite

Refractory End-stage Maximal Medical Therapy
Heart Failure
17
MANAGEMENT OUTLINE
Establish that the patient has HF.
Ascertain presenting features: pulmonary oedema,
exertional breathlessness, fatigue, peripheral oedema
Assess severity of symptoms
Determine aetiology of heart failure
Identify precipitating and exacerbating factors
Identify concomitant diseases
Estimate prognosis
Anticipate complications
Counsel patient and relatives
Choose appropriate management
Monitor progress and manage accordingly
European Heart Journal (2001) 22, 1527-1560 18
AIMS OF TREATMENT
1. Prevention
a) Prevention and/or controlling of diseases
leading to cardiac dysfunction and heart
failure
b) Prevention of progression to heart failure
once cardiac dysfunction is established
2. Morbidity
Maintenance or improvement in quality of life
3. Mortality
Increased duration of life
19
ANCIENT TREATMENT OF HEART FAILURE
TREATMENT OPTIONS
Non-pharmacological management
General advice and measures
Exercise and exercise training
Pharmacological therapy
Angiotensin-converting enzyme (ACE) inhibitors
Diuretics
Beta-adrenoceptor antagonists
Aldosterone receptor antagonists
Angiotensin receptor antagonists
Cardiac glycosides
Vasodilator agents (nitrates/hydralazine)
Positive inotropic agents
Anticoagulation
Antiarrhythmic agents
Oxygen
Devices and surgery
Revascularization (catheter interventions and surgery), other forms of
surgery
Pacemakers
Implantable cardioverter defibrillators (ICD)
Heart transplantation, ventricular assist devices, artificial heart
Ultrafiltration, haemodialysis
NEW THERAPEUTIC OPTIONS
IN THE TREATMENT OF HEART FAILURE
Cardiac resynchronization therapy
(CRT).
CRT + implantable cardioverter
defibrillator (ICD).
Cardiac reparation : rebuilding the
failing heart with new cells, genes, or

blood vessels.
Heart transplantation
22
INTERPLAY BETWEEN DRUGS AND DEVICES
Device/rhythm/arrhythmia logging
function
Sensing function Defibrillation function
Pacing function ATP function
Device
Diuretic PM CRT ICD Class I
-blocker CHF Class III
ACE AAD Class IV
Inhibitors Drug Drug Amiodarone
ARBs
Spironolacto
ne
Digoxin
Rhythm
ST, AF, VE, VT, VF

23
STAGES IN THE EVOLUTION OF HF AND
RECOMMENDED THERAPY BY STAGE
Stage A Stage B Stage C Stage D
Pts with : Pts with : Pts with : Pts who have

Previous MI Struct. HD marked symptoms
Hypertension Refract.
Struct. LV systolic Develop at rest despite
CAD Shortness of
Heart dysfunction Symp.of Symp.of maximal medical
DM breath and fatigue,
Disease Asymptomatic HF HF at rest therapy.
Cardiotoxins reduce exercise
Valvular disease
FHx CM tolerance
THERAPY THERAPY THERAPY THERAPY

Treat Hypertension All measures under
All measures under All measures under
Stop smoking stage A,B and C
stage A stage A
Treat lipid disorders Mechanical assist
ACE inhibitor Drugs for routine use:
Encourage regular
Beta-blockers diuretic device
exercise Heart transplantation
ACE inhibitor
Stop alcohol Continuous IV
Beta-blockers
& drug use
digitalis inotrphic infusions for
ACE inhibition palliation
ACC/AHA Guidelines for the

Evaluation and Management of Chronic Heart Failure in the Adult 2001 24
TREATMENT OF CHF
Normal
Asymptomatic
LV dysfunction
EF <40%
Symptomatic CHF
ACEI + NYHA - II Symptomatic CHF
-Blocker NYHA - III
(post-MI)
ACEI + diuretics Symptomatic CHF
ACEI + diuretics
+ -Blocker NYHA - IV
+/- Digoxin + -Blocker +/-
Digoxin + Spiro
Inotropes + ACEI +
diuretics
+ Digoxin + -
Blocker
Secondary prevention + Spiro
Modification of physical
activity
25
PHARMACOLOGICAL THERAPY
26
A, B, C, D, Es of Heart Failure Therapy
A angiotensin converting enzyme inhibitors

anticoagulants, amiodarone, AICD, assist
devices
B beta blocking drugs
C calcium channel blocking drugs, coronary
revascularization, cardiac transplant,
cardiomyoplasty, cardiac reduction surgery
D diet, diuretics, digitalis, dobutamine
E exercise
27
ACE-I
MECHANISM OF ACTION
VASOCONSTRICTION VASODILATATION
ALDOSTERONE PROSTAGLANDINS
VASOPRESSIN Kininogen tPA
SYMPATHETIC Kallikrein
Angiotensinogen
RENIN
Angiotensin I BRADYKININ
A.C.E. Inhibitor Kininase II
ANGIOTENSIN II Inactive Fragments

28
ACE-Inhibitors
ADVANTAGES IN HEART FAILURE
Inhibit LV remodeling post-MI
Modify the progression of chronic CHF
- Survival
- Hospitalizations
- Improve the quality of life
In contrast to others vasodilators,
do not produce neurohormonal activation
or reflex tachycardia
Tolerance to its effects does not develop
29
ACE INHIBITORS IN HEART FAILURE
TRIALS DRUGS NYHA OUTCOME COMMENTS
Captopril MC Capt II-III improved first MCT to show im-

exercise provement in excerc.
tolerance
CONSENSUS Enal IV improved first CT to show im-

survival provement in survival
SOLVD-T Enal II-III improved first large simple CT

survival in CHF
SOLVD-P Enal I-II better for first CT to show pre-

onset CHF vention of CHF
SAVE Capt LV dysf. better for first CT to test the re-

post M I survival & modelling hypothesis
onset CHF
AIRE Rami HF post improved confirmed the results

MI survival of SAVE
30
IMIDAPRIL proven profile
High Anti-Hypertensive effect
High Selectivity in RA System
Dominant Efficient touching in

in RAA system Kalikrein System
Excellent Produce enough

BP lowering Bradikynin
Very Low Optimal

Optimal BP Control side effect Organ Protection
Very Low Improve

Cough Vascular
Heart
Enjoying Life Renal
31
IMIDAPRIL WELL-TOLERATED
WITH LOWER INCIDENCE OF COUGH
ENALAPRIL SWITCH IMIDAPRIL IMIDAPRIL SWITCH ENALAPRIL COUGH INCIDENCES
33 21 ACE-Is %
47.1% Enalapril 9.6

85 32
Cilazapril 6.8
52.9%
37 0 Lisinopril 7.0
15 11
Benazepril 10.6
WITHDRAW WITHDRAW
Captopril 15.0
25 1 30 31
Quinapril 9.7
20.9%
135 178 Trandolapril 7.6
79.1% Perindopril 5.8
109 117
IMIDAPRIL 4.5
K. Saruta et al., J New Remedies & : cough : no cough

Clinics ; 47 : 249 (1998) 32
IMIDAPRIL proven profile
Patient friendly
Cough incidence lower than other ACE-I
75.0
Hypertension efficacy ()
IMIDAPRIL (TANAPRESS) Benezepril

Antihypertensive Effects
71.3 Perindopril
70.0 0.9 % Cilazapril
Lisinopril Enalapril
Temocapril (66.6 / 9.7)
65.0 Quinapril
Trandorapril
60.0
A Ceronapril
C 55.3 Ramipril
55.0
( )
8.1 %
Anti
50.0
B
0.0 2.0 4.0 6.0 8.0 10.0 12.0
Incidence of Dry Cough ()
M. Sasaguri et al : Biomedicine & Therapeutics 30 : 9231996modified 33
Inhibitory effects on tissue ACE activity
12
ACE Activity in the Thoracic Aorta P < 0.05
10
(nmol/min/mg protein)
0
Control Captopril Enalapril Imidapril
(5 mg/kg/day) (5 mg/kg/day) (5 mg/kg/day)
Subjects : Young male SHRs (n = 7 8)

Method : Inhibition of ACE activity was measured 9 days after stopping
administration of ACEIs for 10 weeks.
Kubo M et al. Jpn J Pharmacol 57(4): 517-26 (1991) 34
Change in Exercise Duration Change in Physical Working Capacity (PWC)
after 12 weeks treatment with IMIDAPRIL after 12 weeks treatment with IMIDAPRIL
60 10
p < 0.05 Vs placebo,
* p < 0.05 Vs placebo
p < 0.05 Vs Imidapril 2,5 mg
50
*
Physical Working Capacity

Exercise duration (soc)
40
5
* *
(Watt)
30 0
20
-5
10
0 -10
Placebo 2,5 mg Imidapril Imidapril Placebo Imidapril Imidapril Imidapril
5 mg 10 mg 2,5 mg 5 mg 10 mg
Veldhuisen, D J, et al. J Am Coll Cardiol 1999;32:1811-1818
35
Change plasma ACE (% from baseline) Change plasma BNP (g/mL)
after 12 weeks treatment with IMIDAPRIL after 12 weeks treatment with IMIDAPRIL
20 15
10
0
5
ACE-activity (%))
BNP (g/ml)
-20 0
-5
-40
-10
-60 **
**** -15 *
**** * <* 0.001
P *
*
-80 -20
Placebo Imidapril Imidapril Imidapril Placebo Imidapril Imidapril Imidapril
2,5 mg 5 mg 10 mg 2,5 mg 5 mg 10 mg
At rest Peak of exercise At rest Peak of exercise
Veldhuisen, D J, et al. J Am Coll Cardiol 1999;32:1811-1818

36
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
Recommended as first-line therapy.

Should be uptitrated to the dosages shown to be
effective in the large, controlled trials, and not
titrated based on symptomatic improvement.
Moderate renal insufficiency and a relatively low blood
pressure (serum creatinine < 250 mol.l-1 and systolic
BP 90 mmHg) are not contraindications.
Absolute contraindications: bilateral renal artery
stenosis and angioedema.

37
ANGIOTENSIN II RECEPTOR ANTAGONISTS
ARBs could be considered in patients who do not
tolerate ACE inhibitors for symptomatic
treatment.
It is unclear whether ARBs are as effective as

ACE inhibitors for mortality reduction.
In combination with ACE inhibition, ARBs may

improve heart failure symptoms and reduce
hospitalizations for worsening heart failure.

38
DIURETICS
Essential for symptomatic
treatment when fluid overload is
present and manifest.
Always be administered in
combination with ACE inhibitors
if possible.

39
ALDOSTERONE RECEPTOR
ANTAGONISTS - SPIRONOLACTONE
Recommended in advanced HF (NYHA III-IV), in
addition to ACE inhibition and diuretics to improve
survival and morbidity
The RALES Mortality Trial

Low dose spironolactone (12.550 mg) on top of
an ACE inhibitor and a loop diuretic improved
survival of patients in advanced heart failure
(NYHA class III or IV).

40
CARDIAC GLYCOSIDES
indicated in atrial fibrillation and any degree
of symptomatic heart failure.
A combination of digoxin and beta-blockade

appears superior than either agent alone.
In sinus rhythm, digoxin is recommended to

improve the clinical status of patients with
persisting heart failure despite ACE inhibitor
and diuretic treatment.

CARDIAC GLYCOSIDES
DIG trial
Long-term digoxin did not improve
survival.
The primary benefit and indication for

digoxin in heart failure is to reduce
symptoms and improve clinical status
decrease the risk of hospitalization for
heart failure without an impact on survival.
42
-Blockade in Heart Failure
43
CARDIOPROTECTIVE MECHANISMS OF
BETA-BLOCKERS
Reduce sympathetic nervous system
activation (heart rate and myocardial
contractility); balance the myocardial oxygen
supply/demand ratio
Increase the threshold for ventricular
fibrillation in the presence of ischemia
May increase the stability of coronary
atherosclerotic plaques
44
WHY BETA-BLOCKERS MAY BE BENEFICIAL IN CHF?
Sympathetic nervous system is activated

earlier than the RAAS in the CHF disease
process
Beta-blockade: more effective suppression of

angiotensin II concentrations than achieved by
ACE-inhibitors alone (Angiotensin II Escape
Phenomenon observed with ACE-inhibitors)
45
BETA - ADRENOCEPTOR ANTAGONISTS
Recommended for the treatment of all pts
with stable, mild, moderate and severe heart
failure on standard treatment, unless there is
a contraindication.
Patients with LV systolic dysfunction, with or

without symptomatic HF, following an AMI
long-term betablockade is recommended
in addition to ACE inhibitor.
46
CIBIS III Trial
1010 patients > 65 years with mild to moderate CHF (NYHA class II or III) and
LV ejection fraction < 35% in 3 months prior to randomization, clinically stable
CHF for 7 days
Randomized
32% female, mean age 72 years, mean follow-up 1.22 years
13% received aldosterone-receptor blocker and 84% diuretic
Monotherapy with beta- Monotherapy with ACE-inhibitor

blocker bisoprolol (first 6 enalapril (first 6 mos)
mos) 10mg B.I.D.
10mg O.D. n=505
n=505
Combination beta-blocker and
ACE-inhibitor therapy (6-24
mos)
Primary Endpoint: Time-to-the-first-event of combined all-cause mortality and all-
cause hospitalization throughout study.
Secondary Endpoint: Combined primary endpoint at end of monotherapy phase;
individual components of primary endpoint at study end and at end of
monotherapy phase.
Presented at ESC 2005
47
CIBIS III Trial: Per-Protocol (PP) Primary Endpoint
PP Analysis of death or rehospitalization (%)

p = 0.046 for non-inferiority
The per-protocol primary endpoint of
death or rehospitalization did not differ
by treatment group (HR 0.97, 95% CL
40% 0.78-1.21), and
32.4% 33.1%
In the per-protocol group , non-inferiority
30% criteria, trended to be significant, but
significance was not met
20% Baseline characteristics were similar

between the two treatment groups:
Ischemic heart disease
present in 62% of patients
10% Mean LVEF of 28.8% NYHA
heart failure classification was
evenly divided by class II and III
0% Adverse even rate was similar
between two treatment groups
Beta-blocker bisoprolol ACE-inhibitor enalapril

48
CIBIS III TRIAL: INTENT-TO-TREAT (ITT)
ITT Analysis of death or rehospitalization
p=0.86 In the intent-to-treat group, non-

200 inferiority criteria was met (HR
n=15 n=15 0.94, 95% CL 0.77-1.16, p=0.019)
150 7
# of patients
1
p=0.44 There was no difference in the
100 individual components of death
n=73
n=65 (n=65 vs n=73, HR 0.88) or
50 hospitalization (n=151 vs n=157,
HR 0.97) among the intent-to-
0 treat group
Death Hospitalization
At the end of the monotherapy
Beta-blocker bisoprolol phase, there was no difference in
ACE-inhibitor enalapril the primary endpoint (HR 1.02,
p=0.90)
49
CIBIS III Trial
Worsening CHF requiring
hospitalization or occuring in-
hospital
p = 0.23
Worsening CHF requiring
75 hospitalization or
n=63 occurring in-hospital was
60 non-significantly higher in
n=51 the bisoprolol group (HR
# of patients
45 1.25)
30 Study drug
discontinuation during the
15 monotherapy arm
occurred in 6.9% of the
0 bisoprolol-first strategy
and 9.7% of the enalapril-
Beta-blocker bisoprolol ACE-inhibitor enalapril first strategy

50
CIBIS III Trial Summary
Among patients with newly diagnosed mild to
moderate heart failure, a strategy of initial treatment
with the beta-blocker bisoprolol did not meet the
criteria for non-inferiority in the per-protocol
population for death or hospitalization compared with
a strategy of initial treatment with the ACE-inhibitor
enalapril.
Non-inferiority was met in the intent-to-treat
population.
Current guidelines recommend first-line therapy with
an ACE-inhibitor after initial heart failure diagnosis,
followed by addition of beta-blocker.
Presented at ESC 2005 51
Survival
US Carvedilol Study
1.0 Carvedilol
(n=696)
-Blockers in CHF - 0.9
Placebo
All-cause Mortality
0.8 (n=398)
0.7 Risk reduction = 65%

P<0.001
0.6
0.5
100 0 50 100 150 200 250 300 350 400
COPERNICUS Days Packer et al (1996)
90 Mortality %
20
MERIT-HF
80 Placebo
% Survival
Carvedilol 15
70 Placebo Metoprolol CR/XL

10
60 P=0.00013 Risk reduction = 34%

5
P=0.0062
0
0
0 3 6 9 12 15 18 21
0 3 6 9 12 15 18 21
Months Months of follow-up
52
The MERIT-HF Study Group (1999)
BISOPROLOL ROLE IN HEART FAILURE
All-Caused Mortality 34% p < 0.0001
Sudden Death 44% p < 0.0011
Hospitalisation Due To Worsening

The Heart Failure p < 0.0001
36%
All-Caused Hospitalization 20% p < 0.0006
Modified from : CIBIS-II, Lancet, Vol. 353, 1999
53
ACTIVATION AND BLOCKADE OF
NEUROHUMORAL SYSTEM IN CHF
RAA System SNS System
Angiotensin II Noradrenalin
ACE-I -Blocker
Hypertrophy, apoptosis, ischemia,

arrhythmia, remodelling, fibrosis
54
RECOMMENDATION FOR PATIENTS IN STAGE A
CLASS I
1. Control of systolic and diastolic HT. (A).
2. Treatment of Lipid disorders.(B).
3. Avoidance behaviours that may increse risk of HF. (C).
4. ACE-I for pts with history of atherosclerotic vascular
disease,DM or HT and associated CV risk factors. (B).
5. Control ventricular rate in pts with SVT. (B).
6. Treatment of Thyroid disorders.(C).
7. Periodic evaluation for sign & symptoms of HF. (C).
55
RECOMMENDATION FOR PATIENTS IN STAGE B
1. ACE-I for post MI patient regardless of EF .(A)

2. ACE-I for pts with reduced EF with/without
previous MI (B).
3. Beta-blockade in pts with recent MI regardless of
EF. (A).
4. Beta-blockade in pts with reduced EF with/without
previous MI. (B).
5. Valve replace or repair for pts with
hemodinamically significant valvular stenosis or
regurgitation.
6. Regular evaluation for sign and symptoms of HF.
7. Measured listed as class I for pts in stage A .
56
Chronic Heart Failure Choice of
A
Pharmacological Therapy
Aldosterone
LV systolic dysfunction ACE inhibitor Diuretic Beta-blocker
Antagonist
Asymptomatic LV
Indicated Not indicated Post MI Not indicated
dysfunction
Symptomatic HF (NYHA Indicated if

Indicated Indicated Not indicated
II) Fluid retention
Worsening HF (NYHA III- Indicated Indicated

Indicated Indicated
IV) comb. diuretic
Indicated Indicated
End-stage HF (NYHA IV) Indicated Indicated
comb. diuretic

57
B Chronic Heart Failure Choice of
Pharmacological Therapy
Angiotensin Vasodilator
(hydralazine/ Potassium -sparing
LV systolic dysfunction II receptor Cardiac glycosides
isosorbide diuretic
antagonists dinitrate)
Asymptomatic LV dysfunction Not indicated With AF Not indicated Not indicated
(a) when AF If ACE

If ACE inhibitors If persisting
inhibitors and
are not tolerated (b) when improved hypokalaemia
Symptomatic HF (NYHA II) from more angiotensin II
and not on beta-
severe HF in antagonists are
blockade
sinus rhythm not tolerated
If ACE inhibitors If ACE
are not tolerated inhibitors and If persisting
Worsening HF (NYHA III-IV) and not on beta- indicated angiotensin II hypokalaemia
blockade antagonists are
not tolerated
If ACE inhibitors If ACE
are not tolerated inhibitors and If persisting
End-stage HF (NYHA IV)
and not on beta- indicated angiotensin II hypokalaemia
blockade antagonists are
not tolerated

RESUME
Pharmacological Treatment :
I. Asymptomatic Systolic LV dysfunction :
ACE Inhibitor
-Blocker (in CAD)
II. Symptomatic Systolic LV dysfunction
A. No fluid retention
ACE Inhibitor
-Blocker
If ischaemia (+) nitrate / revascularization
B. Fluid retention
Diuretic
ACE Inhibitor (ARBs if not tolerated)
-Blocker
Digitalis
59
RESUME
III. Worsening HF
Standard treatment : ACE Inhibitor, -Blocker
Diuretic : doses + loop diuretic
Low dose spironolactone
Digitalis
Consider :
Revascularization
Valve surgery
Heart transplant
IV. End-stage HF
Intermittent inotrophic support
Circulatory support (IABP, Ventr.Assist Devices)
Haemofiltration on dialysis
briddging to heart transplantation
60
CONCLUSION
Management of HF must be
starting from the earlier stage
(AHA/ACC stage A). Treatment at
each stage can reduce morbidity
and mortality.
Before initiating therapy :

Established the correct diagnose.
Consider management outline.
61
CONCLUSION
Non pharmacolgical intervention are helpfull in :
improving quality of life
reducing readmission
lowering cost.
Organize multi-disciplinary care :
HF clinic, HF nurse specialist, pts telemonitoring.
Health care system.
To optimize HF management
Treatment should be according to the Guidelines,
intensive education, and behavioral change
efforts.
62
Thank You 63
ENVOLVING HEARTH FAILURE
64
EVOLVING MODELS OF HEART FAILURE
Cardiorenal Hemodynamic Neurohormonal
Digitalis and Vasodilators or ACE-I, -blockers

Diuretic to Perfuse positive inotropes to and other agents to
kidneys relieve ventricular block neurohormonal
wall stress activation
1940s 1960s 1970s 1990s - 2000
65
CO Preload Afterload Systole Diastole
Hemodynamics
Heart Failure
Paradigms HF Syndrome
(THEN)
Symptoms
Acute / Chronic
Congestion
FTT
Exercise capacity
66
CO Preload Afterload Systole Diastole
Heart Failure
Paradigms (NOW) Hemodynamics Congestion
Endothelin FTT
Exercise
NO
Endothelium Symptoms capacity
Acute / Chronic
ANP
b-AR
Patient Complement
AT1 TNF
AT2 SNS/RAAs SIR
Angiotensin Interleukins
Aldosterone
Cellular / Adhesion
Baroreceptors molecules
Molecular
WBCs
Apoptosis & Necrosis Hypertrophy Energy Signal Transduction Ion channels & pumps
67
STAGE OF CHF
(ACC/AHA guidelines, 2001)
68
TANAPRESS Optimally Control Blood Pressure
With Once Daily Regimen
69
WHY BETA-BLOCKERS MAY BE BENEFICIAL IN CHF?
More effective in reducing sudden

cardiac death than ACE-inhibitors
up to 40-60% of patients with
CHF die from sudden cardiac
death (mainly in early stages of
CHF)
70

Update Medical Therapy in Heart Failure

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Update Medical Therapy in Heart Failure

Hochgeladen von

Copyright:

Verfügbare Formate

Curriculum Vitae

Tempat/Tgl lahir : Sragen, 21 September 1947

Heart Failure is complex clinical

Initial infarct Expansion of Global

Hypertrophied heart Dilated heart

Functional modifications Structural modifications

HEART Symptoms, physical signs, Diagnosis is obvious :

FAILURE ECG, or Chest x-ray Breathlessness and fatigue

No major cardiac problem

LV diastolic dysfunction LV systolic dysfunction

systolic heart failure

Clues from the Systolic Diastolic

Clues from the evaluation Systolic Diastolic

I No Symptom Limitation With

Ordinary Physical Activity Somewhat

II Limited by Dyspnea (ie. Long distance

B Previous MI, LV Dysfunction,

C Structural Heart Disease, Dyspnea and

D Marked Symptoms at Rest Despite

failing heart with new cells, genes, or

ST, AF, VE, VT, VF

Pts with : Pts with : Pts with : Pts who have

THERAPY THERAPY THERAPY THERAPY

ACC/AHA Guidelines for the

A angiotensin converting enzyme inhibitors

A.C.E. Inhibitor Kininase II

ANGIOTENSIN II Inactive Fragments

Captopril MC Capt II-III improved first MCT to show im-

CONSENSUS Enal IV improved first CT to show im-

SOLVD-T Enal II-III improved first large simple CT

SOLVD-P Enal I-II better for first CT to show pre-

SAVE Capt LV dysf. better for first CT to test the re-

AIRE Rami HF post improved confirmed the results

Dominant Efficient touching in

Excellent Produce enough

Very Low Optimal

Very Low Improve

47.1% Enalapril 9.6

79.1% Perindopril 5.8

K. Saruta et al., J New Remedies & : cough : no cough

IMIDAPRIL (TANAPRESS) Benezepril

Subjects : Young male SHRs (n = 7 8)

Physical Working Capacity

Veldhuisen, D J, et al. J Am Coll Cardiol 1999;32:1811-1818

At rest Peak of exercise At rest Peak of exercise

Veldhuisen, D J, et al. J Am Coll Cardiol 1999;32:1811-1818

Recommended as first-line therapy.

Guidelines for the diagnosis and treatment of chronic heart failure

It is unclear whether ARBs are as effective as

In combination with ACE inhibition, ARBs may

Guidelines for the diagnosis and treatment of chronic heart failure

Guidelines for the diagnosis and treatment of chronic heart failure

The RALES Mortality Trial

Guidelines for the diagnosis and treatment of chronic heart failure

A combination of digoxin and beta-blockade

In sinus rhythm, digoxin is recommended to

Guidelines for the diagnosis and treatment of chronic heart failure

The primary benefit and indication for

Sympathetic nervous system is activated

Beta-blockade: more effective suppression of

Patients with LV systolic dysfunction, with or

Monotherapy with beta- Monotherapy with ACE-inhibitor

PP Analysis of death or rehospitalization (%)

20% Baseline characteristics were similar