HEART FAILURE

HEART FAILURE

Braunwald : gagalnya jantung memompa darah

pada kecepatan yang sesuai dengan
kebutuhan metabolisme jaringan

ACC/AHA : sindroma klinik akibat gangguan

struktur atau fungsional jantung yang berakibat
terganggunya kemampuan ventrikel untuk
memompa darah

Cardiac Performance (Kemampuan ?)

PREDIKTOR :
Preload : - a change in initial length
- tegangan ventrikel akhir diastole
dipengaruhi - Venous Return
- Total volume
- Distribusi volume
Posisi tubuh
Tekanan intrathorak
Tekanan intrapericard
Tonus vena
Kontraksi atrium

 After load : Force / Stress pada ventrikel segera

sesudah pemendekan otot ventrikel.
Dipengaruhi - Pressure Venous Return
- Fisik arteri

- Volume pada ejeksi

Kontraktilitas : performance
Saraf simpatis
Catecholamin
Inotropik agent
Depressant
Mass lost
Intrinsic myocardial depression

LV Size
PVR
Preload

Contractility

Stroke
Volume
Myocard
fiber short

COP
HR

Afterload

B.P

MEKANISME
Circulatory Failure & Overload :
1. Circulatory Failure :
a. Heart failure
b. Non cardiac (peripheral) circul. Failure
Venous return (volume )
Kapasitas vaskular bed
Gangguan vaskular perifer
Oxyhemoglobin

2. Circulatory Congestion :
a. Cardiac gagal jantung
b. Non cardiac :
Volume darah
Venous return (vask. Resistance )

TERMINOLOGI

Congestive heart failure (acute chronic)

cardiac origin
Myocardial dysfunction / failure sistolik,
diastolik
Forward failure backward failure
Left VS Right Heart Failure
Latent Heart Failure
Compensated heart failure

Mekanisme Kompensasi pada Heart Failure

Autonomic nervous system

a. Jantung
: HR, kontraktilitas , kecepatan
relaxasi
b. Circ. Perifer : Vasokonstriksi arterial (after load )
Vasokonstriksi venous (preload )
Ginjal R.A.A
a. Vasokonstriksi arterial (afterload )
b. Retensi Na H20 (PRG & afterload )
c. Kontraktilitas
Frank Starling Law of the Heart
Pemanjangan sarcomerg pada akhir diastole
Kenaikan volume, tekanan

 Hipertrofi

- Paralel (konsentris)
- Seri (eksentris)
Oksigen Perifer
a. Redistribusi cardiac output
b. Kurva disosiasi oxygen hemoglobin
c. Ekstraksi O2 jaringan
Metabolisme Anaerob

The Heart Failure Milieu :

Compensatory Mechanisms

Disease
process

Ventricular
dysfunction

Renal
Renin-angiotensin-aldosterone
Salt/water retention

Ventricular
Dilation
Hypertrophy

Hemodynamic
abnormalities

Compensatory
mechanisms

Sympathetic
Increased contractility
Tachycardia
Increased venous tone
Increased arterial tone

Renal Considerations in Heart Failure

The

Angiotensinogen
(liver)

Renin
release
Angiotension I

Angiotension II

Thirst

Sodium
retention
(direct tubular
effect)

Vasoconstriction

Angiotensinconverting
enzyme

Aldosterone
secretion

Kidney

Diuretic
therapy
Distal tubular
sodium load

In

Renal perfusion
pressure

Heart

Other K+, Ca2+,

prostaglandins

Failure

Atrial natriuretic
factor

Vasopressin

 Stress mekanik (after load / pre load)

Pressure over load
Volume overload
Pressure overload
Kontraksi > kuat : lebih lambat
Hipertrofi konsentris (replikasi sarcomer
paralel)
Chamber tetap (<<)
Kontraksi perunit ( ttp total mass )
LV diastolic filling
Bukan OK HF
LV compliance / distensibility

 Volume Over Load

Hipertrofi eksentris (replikasi sarcomere seri)
Replikasi paralel (+) (o.k. wall stress)
Pengosongan LV > cepat wall tension <<
Chamber >> ; tanpa kenaikan tekanan diastole
Bila compliance tekanan diastole

Responses to Hemodynamic Overload

Pressure overload

Volume overload

Systolic wall stress

Diastolic wall stress

Mechanical transducers
Intracellular signals
Ventricular remodeling

Paralel sarcomeres

Concentric hypertrophy

Series sarcomeres
Normal

Eccentric hypertrophy

PENYEBAB OVERALL HEART PUMP

FAILURE
I.

Kelainan Mekanis :
a. Beban tekanan
b. Beban volume regurgitasi,
preload
c. Obstruksi vent. Filling MS. TS
d. Konstriksi pericard
e. Endokard miokard restriksi
f. Ventric. Aneurysm
g. Ventric. Disinergi

II.

III.

Kelainan otot ( miokard )

a. Primer :

Miopati

Miokarditis

Metabolik (DM)

Toxic (alcohol, etc)

Presbycardia
b. Sekunder :

Disdinamik (sekunder o.k. mekanik)

Iskhemia

Kelainan systemik

PPOM

Obat
Gangguan Ritme / Konduksi
a. Standstill
b. Fibrilasi
c. Takhikardi Bradikardi berat
d. Gangguan konduksi

Overall Heart Failure tanpa Myocardial

Failure
1.

2.

3.

4.

Acute mechanical overload

Acute Cor Pulmonale
Hipertensi
Acute Volume Overload
Chronic severe overload
High COP (beri-beri, Pagets disease)
Value & Congenital Heart Disease
Gangguan pengisian (Impaired Cardiac Filling)
Pericardial Restruction
Restrictive Myocardial Disease
Obstruksi mekanik (MS TS Tumor)
Tachycardi
Low Cardiac output Heart block / bradicardy

Aetiology of Heart Failure

In the Framingham study, CAD increased
from 22% in 1950 to 67% 1980, in contrast
RHD declined
In developed country, degeneratif CAD,
hypertension, either singly or together,
myopathy, Infection
In Indonesia (?) probably hypertension, CAD,
infection (RHD), etc

KLASIFIKASI
(Toleransi terhadap Latihan Jasmani)
Menurut NYHA (New York Heart Association )
I. Aktifitas fisik tidak terbatas
II. Aktifitas fisik sedikit terbatas
III. Aktifitas fisik sangat terbatas
IV. Istirahat sesak
Subjektif Anamnese
Objektif uji latih dengan beban

DIAGNOSIS IN CLINICAL
PRACTICE

Symptoms and signs

Hematologi, biochemistry
Brain Natriuretic peptide,
Other neuroendocrine, nor adrenalin, Ang II,
aldosteron, endothelin-1, adrenomedulin
ECG, Holter, Chest X ray,Echo/stress echo
Nuclear cardiology, MRI
Lung Function, Treadmill exercise test

The Heart Failure Milieu :

Clinical Presentation

Physical findings
Disease
process

Ventricular
dysfunction

Physical findings
Azotemia
Hyponatremia
Hypocalemia
Hypomagnesemia
Hyperuricemia
Acidosis/alkalosis
Hypoxia/O2 desaturatuion
Decreased MVO2

Hemodynamic
abnormalities

Peripheral edema
Ascites
Vascular congestion
Jugular venous distension
Rales
Tachycardia
Hypotension
Cachexia
Disease-specific findings

Metabolic
changes
Compensatory
mechanisms Symtoms and
physical findings

Symptoms
Fatique and weakness
Dyspnea and fluid retention
syndromes
Nocturia
Gastrointestinal symptoms
Diminished mentation

Diagnosis
A. Gagal Jantung Kiri
Dyspnea deffort
Orthopnea
Paroxysmal nocturnal dyspnea
Edema paru
Pernapasan cheyne stokes
Hemoptisis
Berdebar debar
Pembesaran jantung
Takikardi
S3 gallop
P2 mengeras
Ronkhi basah kedua basal paru

CIRCULATORY CIRCUIT

PARU

Kanan

Kiri

B. Gagal Jantung Kanan

Lelah
Mual, anorexia, rasa penuh pada perut
Sesak nafas tidak menyolok
JVP
Hepar >>, nyeri tekan, ikterus (+)
Splenomegali
Ascites
Edema tungkai bawah
Hidrothorak

TREATMENT OF HEART FAILURE

Not only symptomatic improvement
Prevention disease leading to cardiac
dysfunction/failure
Prevention of progression to heart
failure
Morbidity, improvement of quality of life
Mortality, increased duration of life

Gagal Jantung
Perbaikan daya pompa jantung
Pengurangan beban jantung
Mengurangi retensi Na & air

Myocardial Failure

Inotropic

Pump Failure
COP

COP on demand

Tekanan Vena

Vasodilator
Vasokonstriksi simpatis

Renin release

Resistensi Perifer

Edema
Perifer

Edema
Pulm.

Diuretik
Retensi Na / H2O

Angiotensin I

CEI
Angiotensin II

Aldosterone

Management Of Chronic
Heart Failure
Non Pharmacological management
Pharmacological therapy
Devices and surgery

PHARMACOLOGICAL THERAPY

Angiotensin converting enzym inhibitor

Diuretic
B-blockade
Angotensin receptor blockade
Cardiac glycoside
Vasodilator
Positive inotropic

ACE INHIBITOR
ACEI recommend as first line therapy
Should be uptitrated to the dosage
shown to be effective in the large,
controlled trial in heart failure, not based
on symptomatic improvement alone

PHARMACOLOGICAL THERAPY (Continued)

DOSES OF ACEI
STUDIES OF MORTALITY
Target dose
Mean daily dose

Drug
Studies in chronic heart failure
Consensus Trial Study Group, 1978
Cohn et al. (V-HeFT II, 1991)
The SOLVD Investigators, 1991
ATLAS

Enalapril
Enalapril
Enalapril
Lisinopril

Studies after MI LV dysfunction with or without HF

Pfeffer et al (SAVE, 1992)
Captopril
AIRE
Ramipril
TRACE
Trandolapril

20 mg b.i.d.
10 mg b.i.d.
10 mg b.i.d
High dose :
Low dose :

50 mg t.i.d.
5 mg b.i.d.
4 mg daily

18.4 mg
15.0 mg
16.6 mg
32.5 35 mg daily
2.5 5 mg daily

(not available)
(not available)
(not available)

PHARMACOLOGICAL THERAPY (Continued)

RECOMMENDED ACEI
Drug
Benazepril
Captopril
Enalapril
Lisinopril
Quinapril
Perindopril
Ramipril
Cilazapril
Fosinopril
Trandolapril

Initiating dose
2.5 mg
6.25 mg t.i.d.
2.5 mg daily
2.5 mg daily
2.5 5 mg daily
2 mg daily
1.25 2.5 mg daily
0.5 mg daily
10 mg daily
1 mg daily

Maintenance dose
5 10 mg b.i.d.
25 50 mg t.i.d.
10 mg b.i.d.
5 20 mg daily
5 10 mg daily
4 mg daily
2.5 5 mg b.i.d.
1 2.5 mg daily
20 mg daily
4 mg daily

* Manufactures or regulatory recommendations

PHARMACOLOGICAL THERAPY (Continued)

DIURETIC
Essential for symptomatic, when fluid
overload, pulm congestion, peripheral
edema
Should be in combination with ACEI
loop diuretic, thiazides, Potassium
sparing

PHARMACOLOGICAL THERAPY (Continued)

DIURETIC

Loop diuretics
Furosemide
Bumetanide
Torasemide

Initial dose (mg)

Maximum
recommended
daily dose (mg)

Major side effects

20 40
0.5 1.0
5 10

250 500
5 10
100 - 200

Hypokalemia,
hypomagnesaemia, hyponatremia
Hyperuricaemia, glucose
intolerance
Acid-base disturbance

25
2.5
2.5

50 75
10
2.5

Hypokalemia,
hypomagnesaemia, hyponatremia
Hyperuricaemia, glucose
intolerance
Acid-base disturbance

Thiazides
Hydrochlorothiazide
Metolazone
Indapamide

Potassium-sparing
diuretic
Amiloride
Triamterene
Spironolactone

+
ACEI
2.5
25
26

ACEI
5
50
50

+ ACEI
20
100
50

ACEI
40
200
100200

Hyperkalemia, rash
Hyperkalaemia
Hyperkalaemia, gynaecomastia

Chodilawati,R., ghanie,A. Pola etiologi gagal jantung di RSMH Palembang. Kopapdi Menado 2003

Pemakaian dan dosis dari spironolactone

1.

2.

3.
4.
5.
6.

Pertimbangkan apabila gagal jantung berat (NYHA III IV)

meskipun telah menggunakan penyekat enzym konversi
angiotensin/diuretik
Periksa potasium serum (<5.0 mmol.l-1) dankreatini ( <250
mol.l-1 )
Tambahkan 25 mg spironolactone perhari
Periksa serum potassium dan kreatinine setelah 4 6 days
Jika serum potassium > 5 5.5 < mmol.l-1, kurangi dosis sampai
50%, dan hentikan bila serum potassium > 5.5 mmol.l-1.
Jika setelah 1 bulan keluhan menetap tanpa kenaikan serum
potasium, naikkan dosis sampai
50 mg perhari. Ulangi
pemeriksaan serum potassium / kreatinine sesudah 1 minggu.

BETA-ADRENOCEPTOR
ANTAGONISTS
Recommended for all patient with
stable,mild, moderate and severe heart
failure, whatever the cause
In LV dysfunction with or without
symptom of heart failure, following MCI,
long term b-blocker is recommended in
addition to ACEI to reduce mortality
Carvedilol, bisoprolol, metoprolol
PHARMACOLOGICAL THERAPY (Continued)

Cara pemakaian penyekat beta berdasarkan uji coba

klinis yang besar
Beta-blocker

First
dose
(mg)

Increments
(mg.day-1)

Target
dose
(mg.day-1)

Titration
period

1.25

2.5, 3.75, 5, 7.5, 10

10

Weeks
Month

10, 15, 30, 50, 75,

100

150

Weeks
Month

Carvedilol

12.5/25

25, 50, 100, 200

200

Weeks
Month

Nebivolol

3.125

6.25, 12.5, 25, 50

50

Weeks
Month

Bisoprolol

Metoprolol succinate
CR

Daily frequency of administration as in the trials referenced above

Guidelines for the diagnosis and treatment of chronic heart failure.

The European society of cardiology 2005

ANGIOTENSIN II RECEPTOR
ANTAGONIS
Could be consider in whom do not
tolerate ACEI
It is unclear whether ARBs are as
effective as ACEI for mortality reduction
In combination with ACEI, improve
symptom and reduce hospitalization

PHARMACOLOGICAL THERAPY (Continued)

ANGIOTENSINOGEN
RENIN

TISSUE
RENIN

ANGIOTENSIN I

BRADYKININ

ACE

INACTIVE
FRAGMENTS

TISSUE ACE
CHYMASE
CATHEPSIN G

CATHEPSIN G
ELASTASE
TPA

ANGIOTENSIN II
ARBs

VASOCONSTRICTION
RENAL NA+
REABSORPTION
ALDOSTERONE
SECRETION
SYMPATHETIC ACTION
VASOPRESSIN SECTION
CELL GROWTH AND
PROLIFERATION

AT1

AT2

VASODILATION
ANTIPROLIFERATION
APOPTOSIS

PHARMACOLOGICAL THERAPY (Continued)

Currently available Angiotensin II

receptor antagonis
Drug
Losartan
Valsartan
Irbesartan
Candesartan cilexetil
Telmisartan
Eprosartan

Daily dose (mg)

50 100
80 320
150 300
4 16
40 80
400 800
PHARMACOLOGICAL THERAPY (Continued)

CARDIAC GLYCOSIDE
Indicated in Atrial fibrillation, and any
degree of symptomatic heart failure
Combination of digoxin and b-blockade
appear superior than either agent
alone

PHARMACOLOGICAL THERAPY (Continued)

VASODILATOR AGENTS
There no specific role of vasodilator,
although may be used as adjunctive for
angina or hypertension
Hydralazine-isosrbide dinitrate
In case of Intolerance to ACEI, ARBs
are preferred to the combination of
hydralazine-nitrat
PHARMACOLOGICAL THERAPY (Continued)

POSITIVE INOTROP
Only for short time period, as a bridge to
heart transplantation
Repeated or prolonged oral inotropic,
increase mortality
Currently no sufficient data available to
recommend dopaminergic agents for
heart failure
PHARMACOLOGICAL THERAPY (Continued)

Petunjuk pilihan obat pada gagal jantung kronik pada disfungsi sistolik
ACEInhibitor

Angiotensin
receptor blocker

Diuretic

Beta blocker

Aldosterone
antagonists

Cardiac
glycosides

Asymptomatic
LV
dysfunction

Indicated

If ACE intolerant

Not indicated

Post MI

Recent MI

With atrial
fibrillation

Symptomatic
HF (NYHA II)

Indicated

Indicated with or
without ACEinhibitor

Indicated if
fluid retention

Indicated

Recent MI

a. when

Worsening HF
(NYHA IIIIV)

Indicated

Indicated with or
without ACE
inhibitor

Indicated,
combination
of diuretics

Indicated
(under
specialist
care)

Indicated

Indicated

End-stage-HF
(NYHA IV)

Indicated

Indicated with or
without ACEinhibitor

Indicated,
combination
of diuretics

Indicated
(under
specialist
care)

Indicated

Indicated

atrial
fibrillation
b.when
improved
from more
severe HF
in sinus
rhythm

Guidelines for the diagnosis and treatment of chronic heart failure . The European society of cardiology 2005

Terapi penderita disfungsi sistolik yang simtomatik menurut derajat

gagal jantung
For survival/morbidity

NYHA I

Continue ACE inhibitor / ARB if ACE

inhibitor intolerant, continue aldosterone
antagonist if post MI
add beta blocker if post MI.

NYHA II

Ace inhibitor as first-line treatment / ARB if

ACE inhibitor intolerant
add beta-blocker
and aldosterone antagonist if post MI

NYHA III

ACE inhibitor plus ARB or ARB

alone if ACE intolerant
beta-blocker
add aldosterone
antagonist

NYHA IV

Continue ACE inhibitor / ARB

beta-blocker
Aldoesterone antagonist

For symptoms

Reduce / stop diuretic

+/- diuretic depending on fluid

retention

+ diuretic + digitalis if still

symptomatic

+ diuretic + digitalis + consider

temporary inotropic support

Guidelines for the diagnosis and treatment of chronic heart failure . The European society of cardiology 2005

DEVICES AND SURGERY

Revascularization, LV dysfunction of ischemic origin

Valve surgery
Cardiomyoplasty, not recommend
Partial left ventriculotomy (Batista) ?
Pacemaker, biventricular resynchronization
Implantable cardioverter defibrillators
Heart transplantation, end stage heart failure
Ventricular assist devices, Arteficial Heart
Ultrafiltration, severe refractory congestive failure

REMODELING
Remodeling dikaitkan dengan perubahan
struktural pada miosit jantung dan matriks
ekstraseluler
Melibatkan berbagai mediator seperti faktor
neurohormonal, sitokin growth factor, enzim,
kanal ion, stres oksidtif dan stres mekanis.
ACE, ARB dan penyekat beta memiliki efek
inhibisi pada proses remodeling jantung

 Terapi resinkronisasi Jantung

Exercise terapi

TERIMA KASIH

Left Ventricular Function Curve

End diastolic Pressure

Stroke volume

End diastolic volume

End diastolic volume

Stroke Volume

Left Ventricular Function Curve

End diastolic volume

CONTRACTILE STATE
OF MYOCARD

EDV

Posisi
Tekanan Intrathoracal
Atrial Contrib
Venous Return

Ventrikel Performance

Blood Volume

Otot Seklet
STRETCHING

EDV

The Heart Failure Milieu :

From Molecular Biodynamics to a Clinical Syndrome
DNA

Contractile proteins

Molecular
Genetic

Heritable disorders

Cellular,
Organelle

Volume overload/
pressure overload
Hormone signal transduction

Contraction

CELL

Pump

HEART

Physiologic milieu

Compensation

Integrated
Organism:
Man
Prevention
Treatment

Necrosis
Toxins
Remodeling
Compensatory responses
Decompensation

Heart Failure Milieu : Disease Process

Mechanical Dysfunction
Pressure Overload
Hypertension
Aortic/pulmonic
valve stenosis
Pulmonary hypertension
Volume overload
Aortic, mitral, tricuspid
valve insufficiency

Impaired Heart Filling

Pericardial disease
Ventricular hypertrophy
Myocardial restriction
Mitral/tricuspid stenosis

Disease
Process

Mechanical Dysfunction
Myocardial infarction
Cardiomyopathy
Myocarditis
Drug/toxin-induced
Systemic disease effects

The Heart Failure Milieu :

Disease
process

End-Organ Failure and Death

Systemic organ failure
Renal failure
Hepatic failure
Respiratory failure
Multi-organ failure
Pulmonary embolism
Peripheral (cerebral embolism)

Ventricular
dysfunction

Hemodynamic
abnormalities
Metabolic
changes
Compensatory
mechanisms
End-Organ
Failure

Lethal arrhythmia
Electrolyte abnormalities
Elevated catecholamine levels
Ischemia
Drug-proarrhythmia

Symtoms and
physical findings

Death
Sudden
Death