gagal jantung upn 2010

7/29/2019 Gagal Jantung 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 Conc ept of Heart Failure 1 950 to 2000

1 950 2000Aetiology Hypertens ion CHD

Valv heart dis Hypertens ionDilated CMP

Natural Cours e S lowly progres s ive S lowly progres s ive

(remodeling) or unpredictable and rapid

( coronary event )

Unders tanding Hemodynamic model Neurohormonal model

Common caus e Pulmonary infec tion S udden death

of death Pump failure

Arrhythmia Atrial Ventricular

Treatment goal Control edema Improve quality of life+ reduce mortality

+ reduc e hos pitalization


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Framingham Heart StudyAnnual incidence of new cases heart failure

0

5

10

15

20

25

30

35

45-54 55-64 65-74 75-84 85-94

Female

Male

Age (years)

Averages

annualincidence/1000people


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Heart Failure Classification N Y H A

Class Definition Terminology

I. Patients with cardiac diseasebut 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 physicalactivity

Moderate

IV. Patient with cardiac disease

resulting 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 YearMortality of Heart Failure

0

10

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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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 Trials

Trial 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


18/19

-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

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