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7/29/2019 Heart Failure Fk Upn 2010
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HEART FAILURE,THE CLINICAL EVIDENCE
Prof.DR.dr. Zainal Musthafa, SpJP, MSi, FS, FIHA
Gatot Soebroto Military Hospital
Dept. of Cardiology, FKUPNV
2010
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Evolution of the Concept of Heart Failure 1950 to 2000
1950 2000Aetiology Hypertension CHD
Valvheart dis HypertensionDilated CMP
Natural Course Slowly progressive Slowly progressive(remodeling) or unpredictable and rapid
( coronary event )
Understanding Hemodynamic model Neurohormonalmodel
Common cause Pulmonary infection Sudden death
of death Pump failure
Arrhythmia Atrial Ventricular
Treatment goal Control edema Improve quality of life+ reduce mortality
+ reduce hospitalization
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FraminghAnnual incidence
0
5
10
15
20
25
30
35
45-54 55-64 65-74 75-84 85-94
Female
Male
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Heart Failure Classification N Y H A
Class Definition Terminology
I. Patients with cardiac disease
but without resulting
limitation of physicalactivity
Asymptomatic
II. Patients with cardiac disease
resulting in slight limitationof physical activity
Mild
III. Patient with cardiac disease
resulting in marked
limitation of physical
activity
Moderate
IV. Patient with cardiac diseaseresulting in ability to carryon any physical activity
without discomfort
Severe
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Treatment of Heart Failure:Objectives
Identify and, if possible correct the
underlying cause
Correct aggravating factors:
Hypertension, arrhytmia, severe anemia
Correct salt and water overload
Correct major symptoms:
Dyspnoea, fatigue and edema
Improve prognosis
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Framingham Study 5 Year
Mortality of Heart Failure
010
20
30
40
50
60
70
80
5 years
mortality (%)
I II III IV
NYHA
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Coronary arterydisease
Hypertension
Cardiomyopathy
Valvular disease
Left
ventricular
dysfunction
Low
ejection
fraction
Non-cardiac
factors
Remodeling
Symptoms
Arrhythmia
Death
Pump
failure
Cohn, N Engl J Med, 1996;335
ChronicHeart
failure
catecholamine
RAASendothelin
natriuretic peptide
cytokine
growth factor
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Hypertrophy, apoptosis, ischaemia,
arrhythmia, remodeling, fibrosis
Activation and Blockade of Neurohumoral
System in CHF
RAA SystemRAA System SNS SystemSNS System
AngiotensinAngiotensin IIII NoradrenalinNoradrenalin
ACEACE--II --BlockerBlocker
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Renin Angiotensin Aldosteron System
CHYMASE
ANGIOTENSIN I
ANGIOTENSINOGEN(LIVER)
AT1 AT2
ANGIOTENSIN II
ACE
INHIBITOR
AT1 RECEPTOR BLOCKER
RENIN
INHIBITOR
BRADYKININ
PEPTIDES
Other enzymes
e.g.
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RAS: SCIENTIFIC RATIONALE
INCREASED VASCULAR TONEVASCULAR PROLIFERATIONNA+ RETENTIONALDOSTERONE SECRETIONCARDIAC MYOCYTE PROLIFERATIONINCREASED SYMPATHETIC TONE
N OVASODILATIONGROWTH INHIBITIONAPOPTOSIS
AT1 AT2
ANGIOTENSIN II
EFFECTS OF ANGIOTENSIN II ON AT1 AND AT2 RECEPTORS
(-) effects : (+) effects :
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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 Rena HF post improved confirmed the results
M I survival of SAVE
ACE Inhibitors in Heart Failure
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ACE inhibitors in heart failure
Approximately 7,000 patients evaluatedin placebo-controlled clinical trials
Consistent improvement in cardiacfunction, symptoms and clinical status
Decrease in all-cause mortality by 20-25% (p
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1 receptors 2 receptors
Myocyte hypertrophy & death,
dilatation, ischaemia & arrhythmia's
1 receptors
Cardiac
sympathetic activitySympathetic
activity to kidneys& blood vessels
Vasoconstriction
Sodium retention
CNS sympathetic
outflow
Adrenergic Activation
Packer, AHA 2000
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Mortality in Long-term-Blocker TrialsTrial No of Death/Pts Reduction
Control -Blocker (%)
Norwegian (Timolol) 152/939 98/945 36
BHAT (Propanolol) 188/1921 138/1916 26
Gteborg (Metoprolol) 62/697 40/698 36
Multicenter (Proctolol) 127/1520 102/1520 20
US (Sotalol) 52/583 64/873 18
All Others (18 studies) 584/6482 568/7024 10
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Sudden Deaths in -Blocker Trials
Trial No of Death/Pts Reduction
Control -Blocker (%)
Norwegian (Timolol) 95/939 47/945 51
BHAT (Propanolol) 89/1921 64/1916 28
All Metoprolol (5 studies) 104/2721 62/2753 41
UK (Sotalol) 27/583 41/873 -7
All Others (7 studies) 156/2968 113/3102 30
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Carvedilol
(n=696)
Placebo
(n=398)
Survival
Days0 50 100 150 200 250 300 350 400
1.0
0.9
0.8
0.7
0.6
0.5
Risk reduction = 65%
p
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All patients with stable class II or III
heart failure due to left ventricular
systolic dysfunction should receive a -
blocker
(in addition to an ACE inhibitor) unless
they have a contraindication to its use or
cannot tolerate treatment with the drug
Beta-Blockade inHeart Failure
Consensus recommendations
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-Blockade in Patients with Severe HFTrials Agent Pts with NYHA Overall placebo Effect on mor-
Class IV HF mortality rate tality in NYHAN (%) IV patients
US Carvedilol Carvedilol 32 (2.9) 11.1% N/S
CIBIS II Bisoprolol 445 (16.8) 13.2% N/S
MERIT-HF Metoprolol 145 (3.6) 11.0% N/S
BEST Bucindolol 216 (8.0) 16.6% PossibleAEs
COPERNICUS Carvedilol 2289 (100) 18.5% 35% riskreduction
(p < 0.0002)
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TERIMA KASIHTERIMA KASIH