All About CHF

CHRONIC CONGESTIVE HEART
FAILURE
A Comprehensive Overview on Diagnosis and Treatment
Dr. Cholid Tri Tjahjono,

Tjahjono, MKes, SpJP
Faculty of Medicine
Brawijaya University Malang
Introduction
Definition :
The situation when the heart is incapable of
maintaining a cardiac output adequate to
accommodate metabolic requirements and the
venous return. E. Braunwald
Pathophysiological state in which an

abnormality of cardiac function is responsible
for the failure of the heart to pump blood at a
rate commensurate with the requirements of
the metabolizing tissues. Euro Heart J; 2001. 22: 1527-1560
DEFINITION OF HEART FAILURE.

Criteria 1 and 2 should be fulfilled in all cases
1. Symptoms of heart failure

(at rest or during exercise)
And
2. Objective evidence of cardiac dysfunction
(at rest)
And
(in cases where the diagnosis is in doubt)
3. Response to treatment directed towards heart

failure
Task Force Report. Guidelines for the diagnosis and treatment of chronic heart failure.
European Society of Cardiology.2001
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
DESCRIPTIVE TERMS in HEART FAILURE

Acute vs Chronic Heart Failure
Systolic vs Diastolic Heart Failure

Right vs Left Heart Failure
Mild , Moderate, Severe Heart Failure
European Heart Journal (2001) 22, 1528
New York Heart Association (NYHA)

Classification of Heart Failure
Class I
No limitation : ordinary physical exercise does

not cause undue fatigue, dyspnoea or palpitations.
Class II
Slight limitation of physical activity : comfortable at rest but ordinary activity results in
fatigue, dyspnoea, or palpitation.
Class - III
Marked limitation of physical activity : comfortable at rest but less than ordinary activity
results in symptoms.
Class - IV
Unable to carry out any physical activity without discomfort : symptoms of heart failure are
present even at rest with increased discomfort
with any physical activity.
European Heart Journal (2001) 22, 1531
(Adapted from Williams JF et al., Circulation. 1995; 92 : 2764-2784)
ACC/AHA A New Approach To The Classification of HF

Stage
Descriptions
Examples
Patient who is at high risk for

developing HF but has no
structural disorder of the heart.
Hypertension; CAD; DM;

rheumatic fever; cardiomyopathy.
Patient with a structural disorder

of the heart but who has never
developed symptoms of HF.
LV hypertrophy or fibrosis;
LV dilatation; asymptomatic VHD;
MI.
Patient with past or current

symptoms of HF associated with
underlying structural heart
disease.
Dyspnea or fatigue ec LV systolic

dysfunction; asymptomatic
patients with HF.
Patient with end-stage disease
Frequently hospitalized pts ; pts

awaiting heart transplantation etc

Stages in the evolution of HF and recommended therapy by stage
Stage A
Stage B
Pts with :
Hypertension
CAD
DM
Cardiotoxins
FHx CM
Pts with :
Previous MI
LV systolic
dysfunction
Asymptomatic
Valvular disease
Struct.
Heart
Disease
THERAPY
Treat Hypertension
Stop smoking
Treat lipid disorders
Encourage regular
exercise
Stop alcohol
& drug use
ACE inhibition
THERAPY
All measures under
stage A
ACE inhibitor
Beta-blockers
Stage C
Stage D
Pts with :
Develop
Symp.of
HF
Struct. HD
Refract.
Shortness of
Symp.of
breath and fatigue,
HF at rest
reduce exercise
tolerance
THERAPY
All measures under
stage A
Drugs for routine use:
diuretic
ACE inhibitor
Beta-blockers
digitalis
Pts who have

marked symptoms
at rest despite
maximal medical
therapy.
THERAPY
All measures under
stage A,B and C
Mechanical assist
device
Heart transplantation
Continuous IV
inotrphic infusions for
palliation

EVOLUTION OF
CLINICAL STAGES
NORMAL
Asymptomatic
LV Dysfunction
No symptoms
Compensated
Normal exercise
CHF
Abnormal LV fxn
No symptoms
Decompensated
Exercise
CHF
Abnormal LV fxn
Symptoms
Refractory
Exercise
CHF
Abnormal LV fxn
No symptoms
Normal exercise
Normal LV fxn
Symptoms not controlled

with treatment
Evolution of the Concept of Heart Failure

1950 1950 to 2000
2000
Aetiology
Hypertension
Valvular heart dis
CHD
Hypertension
Dilated CMP
Natural Course
Slowly progressive
Understanding
Hemodynamic model
Slowly progressive (remodelling)

or unpredictable and rapid
( coronary event )
Neurohormonal model
Common cause
of death
Pulmonary infection
Sudden death
Pump failure
Arrhythmia
Atrial
Ventricular
Treatment goal
Control edema
Slowing Heart Rate
Improve quality of life

+ reduce mortality + reduce
hospitalization
Patophysiology of C H F
AO
Aortic
closure
Aortic
pressure
Ventricular
pressure
Crossover
Heart
sounds
A2
P2 S
3
M1
T1
S4
MO
Atrial
pressure
Cardiologic
systole
c
v
Opie (2001)
JVP
P
ECG
800 msec
The Wiggers cycle

g
f
e
a
b
iso
iso
PULMONARY VENOUS
PRESSURE
Input
Filling
Emptying
Stroke
EF
ED volume x
effective = volume
LV Distensibility
x
Contractility
Relaxation
Afterload
Heart
Left atrium
Preload
rate
Mitral valve
Pericardium
Structure
Diastolic function Systolic function

Output
CARDIAC OUTPUT
Block diagram of left ventricular pump performance

(Little, 2001)
PRESSURE VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILURE
DIASTOLIC FAILURE
Normal
Normal
diastolic
chamber
distensibility
Left Ventricular Volume
Left Ventricular Pressure
Left Ventricular Pressure
SYSTOLIC FAILURE
Decreased
diastolic
chamber
distensibility
Left Ventricular Volume
(Zile & Brutsaert 2002)
Left ventricular pressure
Abnormal
relaxation
Pericardial
restraint
Chamber
dilation
Increased
chamber stiffness
D
Left ventricular volume
Mechanisms that cause diastolic dysfunction.
(Zile, 1990)
DETERMINANTS OF
VENTRICULAR FUNCTION
CONTRACTILITY
PRELOAD
AFTERLOAD
STROKE
VOLUME
- Synergistic LV contraction
- LV wall integrity
- Valvular competence
CARDIAC OUTPUT
HEART
RATE
Frank-Starling Law
Normal
Cardiac Output
Compensated
Normal C.O.
CHF
LVEDP
Ventricular Function Curve:

Frank-Starlings
Normal
SV
LVEDV
Congestion
Factors That Influence Ventricular

Function Curves:
Ventricular Performance
Catecholamines
Cardiac
Glycosides
Contractile State of
the Myocardium
Ca Channel
Blockers (?)
LVEDV
Loss of
Myocardium
ETOH
The Pathophysiology of Heart Failure
Hurst. The Heart. Diagnosis and Management of Heart Failure.10 th ed. 688
Pathophysiological Sequence of
CHF
Heart Failure
Inadequate Cardiac Output

( ) O2 Delivery (rest and/or exercise)
Systemic Vasoconstriction
SAS (NE))
RAAS (A-II)
() Flow to Skin, Gut,
and Renal Circulations
Neurohormonal Activation
Activation of
RAS and ANS
Hurst. The Heart. Diagnosis and Management of Heart Failure.10 th ed. 688
Frank-Starling Effect
Ventricular dilatation
Wall stress
O2 consumption
Coronary
perfusion
SNS
Preload
Afterload
Renin release
Angiotensin II
Growth
factors
ALDO
Vasoconstriction
Hypertrophy
Apoptosis
Fluid
accumulation
Collagen
deposition
Myofibril
necrosis
Perfusion of Vital Organs

RBF
Na filtered
Renin release
Angiotensin II
Growth
factors
ALDO
Vasoconstriction
Hypertrophy
Apoptosis
Fluid accumulation
Afterload
Collagen deposition
Myofibril necrosis
Sympathetic nervous system up-regulation

Increased
Norepinephrine levels
Activation of the
RAA system
Increased
Angiotensin II &
Aldosteron
Na+
& water
retention
Vasoconstriction
Direct
Myocardial toxicity
Decreased
Renal blood
flow
Myocyte dysfunction
Increased HR, PVR &
arteriolar vasoconstriction
Increased myocardial
oxygen demand
Cardiac remodeling
Myocyte
necrosis
Intracellular
Ca2+ overload/
Energy depletion
Apoptosis
Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002
Causes of Heart Failure

Myocardial Damage or Disease
Infarction (Acute) / Ischemia
Myocarditis
Hypertrophic Cardiomyopathy
Excess Load on Ventricle
Volume/ Pressure Overload
Resistance to Flow into Ventricle

Cardiac Arrhythmias
Primary Changes in CHF

Site of
Failure
Backward
Failure
Right Heart () Systemic

Failure
Venous
Pressure
Left Heart
Failure
Forward
Failure
() ejection
into
Pulmonary
Artery
() Pulmonary () ejection
Venous
into aorta
Pressure
MI-INDUCED HEART FAILURE

Myocardial Damage
Contractility
Pump Performance
() Systolic Work Load
Vasoconstriction
RAAS SYSTEM
FLUID RETENTION
() SAS Drive
Diagnosis of C H F
IDENTIFICATIONS OF HF PATIENTS
With a Syndrome of Decrease Exercise

Tolerance
With a Syndrome of Fluid Retention
With No Symptoms or Symptoms of

Another Cardiac or Non Cardiac
Disorder
(MI, Arrythmias, Pulmonary or
Systemic Thromboembolic Events)
SYMPTOMS AND SIGN
Breathlessness, Ankle Swelling, Fatique

Characteristic Symptoms
Peripheral Oedema, JVP , Hepatomegaly

Signs of Congestion of Systemic Veins
S3 , Pulmonary Rales , Cardiac Murmur
ECG
A low Predictive Value

LAH and LVH May Be Associated wit LV Dysfunction
Anterior QQ-wave and LBBB a good predictors of EF
Detecting Arrhytmias as Causative of HF
CHEST XX-RAY
A Part of Initial Diagnosis of HF
Cardiomegaly, Pulmonary Congestion
Relationship Between Radiological Signs and
Haemodynamic Findings may Depend on the Duration
and Severity HF
HAEMATOLOGY & BIOCHEMISTRY
A Part of Routine Diagnostic

Hb, Leucocyte, Platelets
Electrolytes, Creatinine, Glucose, Hepatic Enzyme,
Urinalysis
TSH, CC-RP, Uric Acid
ECHOCARDIOGRAPHY
The Preferred Methods
Helpful in Determining the Aetiology
Follow Up of Patients Heart Failure
PULMONARY FUNCTIONS
A Little Value in Diagnosis Heart Failure

Usefull in Excluding Respiratory Diseases
EXERCISE TESTING
Focused on Functional, Treatment Assessment and
Prognostic
STRESS ECHOCARDIOGRAPHY
For Detecting Ischaemia

Viability Study
NUCLEAR CARDIOLOGY
Not Recommended as a Routine Use
CMR
( CARDIAC MAGNETIC RESONANCE IMAGING)

Recommenmded if Other Imaging Techniques not
Provided Diagnostic Answer
INVASIVE INVESTIGATION
Elucidating the Cause and Prognostic Informations
Coronary Angiography :
in CADs Patients
Haemodynamic Monitoring :
To Assess Diagnostic and Treatment of HF
Endomyocardial Biopsy :
in Patients with Unexplained HF
NATRIURETIC PEPTIDES
Cardiac Function (LV Function

))
Plasma Natriuretic Peptide Concentration
(Diagnostic Blood Use for HF)
Natriuretic Peptide :
Greatest Risk of CV Events
Natriuretic Peptide :
Improve Outcome in Patients with
Treatment
Identify Pts. With Asymptomatic LV

Dysfunction (MI, CAD)
ALGORITHM FOR THE DIAGNOSIS OF THE HF

(ESC, 2001)
Suspected Heart Failure Because
of symptoms and signs
Assess Presence of Cardiac Disease by ECG, XX-Ray

or NatriureticPeptides (Where Available)
If Normal
Heart Failure
Unlikely
Tests Abnormal
Imaging by Echocardiography (Nuclear

Angiography or MRI Where Available)
If Normal
Heart Failure
Unlikely
Tests Abnormal
Assess Etiology, Degree, Precipitating

Factors and Type of Cardiac Dysfunction
Choose Therapy
Additional Diagnosis Tests

Where Appropriate (e.g.
Coronary Angiography)
Treatment of C H F
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
ACC/AHA & EUROPE (ESC) 2001

GUIDELINES FOR THE MANAGEMENT
OF HEART FAILURE
ACE-inhibitor
Use as first line therapy
Should be up titrated to the dosages shown in the large

clinical trial, and not titrated based on symptomatic
improvement
DIURETIC to control fluid overload

-BLOCKER
For all patients with stable mild-severe HF on
standard treatment
ACC/AHA & EUROPE (ESC) 2001

GUIDELINES FOR THE MANAGEMENT
OF HEART FAILURE
Aldosteron Receptor Antagonis
in advance HF ( NYHA III-IV )
DIGOXIN
in AF
May be added for symptom relief
ARB
Considered in patients not tolerate ACE
inhibitors and not on - blocker
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
TREATMENT
Correction of aggravating factors
Pregnancy
Endocarditis
Arrhythmias (AF)
Obesity
Infections
Hyperthyroidism
Thromboembolism
Hypertension
Physical activity
Dietary excess
MEDICATIONS
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
DRUGS
HEMODYNAMIC EFFECTS
Normal
I
Stroke
Volume
A+V
V
D
CHF
Ventricular Filling Pressure
PHARMACOLOGIC THERAPY
Improved Decreased Prevention Neurohumoral
Control
symptoms mortality
of CHF
DIURETICS
yes
NO
DIGOXIN
yes
minimal
yes
INOTROPES
yes
no
Vasodil.(Nitrates)
yes
yes
no
yes
YES
yes
YES
yes
+/-
YES
ACEI
Other neurohormonal
control drugs
mort.
TREATMENT
Normal
Asymptomatic
LV dysfunction
EF <40%
Symptomatic CHF
ACEI
NYHA II Symptomatic CHF
NYHA - III
Diuretics mild
Neurohormonal
Symptomatic CHF
Loop
inhibitors
NYHA - IV
Diuretics
Digoxin?
Inotropes
Specialized therapy
Transplant
Secondary prevention
Modification of physical activity
Pharmacological therapy
Stages in the evolution of HF and recommended therapy by stage
Stage A
Stage B
Pts with :
Hypertension
CAD
DM
Cardiotoxins
FHx CM
Pts with :
Previous MI
LV systolic
dysfunction
Asymptomatic
Valvular disease
Struct.
Heart
Disease
THERAPY
Treat Hypertension
Stop smoking
Treat lipid disorders
Encourage regular
exercise
Stop alcohol
& drug use
ACE inhibition
THERAPY
All measures under
stage A
ACE inhibitor
Beta-blockers
Stage C
Stage D
Pts with :
Develop
Symp.of
HF
Struct. HD
Refract.
Shortness of
Symp.of
breath and fatigue,
HF at rest
reduce exercise
tolerance
THERAPY
All measures under
stage A
Drugs for routine use:
diuretic
ACE inhibitor
Beta-blockers
digitalis
Pts who have

marked symptoms
at rest despite
maximal medical
therapy.
THERAPY
All measures under
stage A,B and C
Mechanical assist
device
Heart transplantation
Continuous IV
inotrphic infusions for
palliation

1. ACE INHIBITOR
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.
VASODILATOR DRUGS
PRINCIPLES
Normal Contractility
CO
VV
Diminished
Contractility
PRELOAD
Normal Contractility
AV
Diminished
Contractility
AFTERLOAD
VASODILATORS
CLASSIFICATION
VENOUS
Nitrates
Molsidomine
MIXED
Venous
Vasodilatation
Calcium antagonists
a-adrenergic Blockers
ACEI
Angiotensin II inhibitors
K+ channel activators
Nitroprusside
Arterial
Vasodilatation
ARTERIAL
Minoxidil
Hydralazine
ACEI
MECHANISM OF ACTION
VASOCONSTRICTION
ALDOSTERONE
VASOPRESSIN
SYMPATHETIC
VASODILATATION
PROSTAGLANDINS
Kininogen
tPA
Angiotensinogen
RENIN
Angiotensin I
A.C.E.
ANGIOTENSIN II
Inhibitor
Kallikrein
BRADYKININ
Kininase II
Inactive Fragments
ACEI
HEMODYNAMIC EFFECTS
Arteriovenous Vasodilatation
-
PAD, PCWP and LVEDP

SVR and BP
CO and exercise tolerance
No change in HR / contractility
MVO2
Renal, coronary and cerebral flow
Diuresis and natriuresis
ACEI
FUNCTIONAL CAPACITY
100
No
Additional
Treatment
Necessary
(%)
95
Quinapril
continued
n=114
90
p<0.001
85
Quinapril
stopped
Placebo
n=110
80
75
Class II-III
2
Quinapril Heart Failure Trial
JACC 1993;22:1557
10
12
Weeks
14
16
18
20
ACEI
ADVANTAGES
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
ACEI
UNDESIRABLE EFFECTS
Inherent in their mechanism of action
- Hypotension
- Hyperkalemia
- Angioneurotic edema
- Dry cough
- Renal Insuff.
Due to their chemical structure

- Cutaneous eruptions
- Neutropenia,
thrombocytopenia
- Digestive upset
- Dysgeusia
- Proteinuria
ACEI
CONTRAINDICATIONS
Renal artery stenosis
Renal insufficiency
Hyperkalemia
Arterial hypotension
Intolerance (due to side effects)
ACE-Inhibitors in Asymptomatic Heart Failure
Development of symptomatic HF
Hospitalization of HF
SAVE & TRACE Study

ACE-Inhibitors in Symptomatic Heart Failure

All patients symptomatic Heart Failure should receive ACE-I.
A) No fluid retention, ACE-I should be given first.
B) With fluid retention, ACE-I + Diuretic
ACE-I : A) improves survival and symptoms.

B) reduces hospitalization.
ACE INHIBITORS USED TO TREAT HEART FAILURE
DRUG
DOSE RANGE
(mg)FREQUENCY
TARGET DOSE FOR

SURVIVAL BENEFIT*
Captopril
Enalapril
Lisinopril
Ramipril2.5 10
Quinapril
Zofenopril
Trandolapril
Imidapril HCl
6.25 150
Three times daily 50 mg three times daily
2.5 20 Twice daily
10 mg twice daily
2.5 40 Daily
Once or twice daily 5 mg twice daily
5 20
Twice daily
30 mg twice daily
4 mg daily
5 10
Once daily
10 mg daily
* Target doses are those associated with increased survival in clinical trials
This drug is not approved in the United States
ACEI SURVIVAL
0.8
0.7
Placebo
0.6
PROBABILITY 0.5
OF
0.4
DEATH
p< 0.001
p< 0.002
0.3
Enalapril
0.2
0.1
CONSENSUS
N Engl J Med 1987;316:1429
MONTHS
10 11 12
ACEI SURVIVAL
50
p = 0.30
Placebo
n=2117
40
%
MORTALITY
n = 4228
No CHF symptoms
EF < 35
30
20
10
0
SOLVD (Prevention) 0
N Engl J Med 1992;327:685
Enalapril
n=2111
12
18 24 30
Months
36 42
48
ACEI SURVIVAL
50
p = 0.0036
Placebo
n=1284
40
%
MORTALITY
30
Enalapril
20
n = 2589
CHF
- NYHA II-III
- EF < 35
10
0
SOLVD (Treatment) 0
N Engl J M 1991;325:293
n=1285
12
18 24 30
Months
36 42
48
ACEI SURVIVAL
30
Asymptomatic
ventricular
dysfunction post MI
Placebo
n=1116
20
Mortality,
%
n = 2231
3 - 16 days post AMI
EF < 40
12.5 --- 150 mg / day
SAVE
Captopril
n=1115
10
0
N Engl J Med 1992;327:669 0
-19%
p=0.019
Years
ACEI
SURVIVAL POST MI
ACEI
Benefit
Pt Selection
ISIS-4
Captopril
0.5 / 5 wk
All with AMI
GISSI-3
Lisinopril
0.8 / 6 wk
All with AMI
SAVE
Captopril
4.2 / 3.5 yr
EF < 40
asymptomatic
SMILE
Zofenopril
4.1 / 1 yr
Ant. AMI, No TRL
TRACE
Trandolapril
7.6 / 3 yr
Vent Dysfx / Clinical CHF
Ramipril
6 / 1 yr
Clinical CHF
AIRE
EF < 35
2. DIURETICS
Diuretics
Essential for symptomatic treatment when

fluid overload is present and manifest.
Always be administered in combination
with ACE inhibitors if possible.
DIURETICS
Thiazides
Cortex
Inhibit active exchange of Cl-Na

in the cortical diluting segment of the
ascending loop of Henle
K-sparing
Inhibit reabsorption of Na in the
distal convoluted and collecting tubule
Medulla
Loop of Henle
Loop diuretics
Inhibit exchange of Cl-Na-K in
the thick segment of the ascending
loop of Henle
Collecting tubule
THIAZIDES
MECHANISM OF ACTION
Excrete 5 - 10% of filtered Na+
Elimination of K
Inhibit carbonic anhydrase:
increase elimination of HCO3
Excretion of uric acid, Ca and Mg
No dose - effect relationship
LOOP DIURETICS
MECHANISM OF ACTION
Excrete 15 - 20% of filtered Na+
Elimination of K+, Ca+ and Mg++

Resistance of afferent arterioles
-
Cortical flow and GFR
Release renal PGs
NSAIDs may antagonize diuresis
K-SPARING DIURETICS
MECHANISM OF ACTION
Eliminate < 5% of filtered Na+
Inhibit exchange of Na+ for K+ or H+
Spironolactone = competitive
antagonist for the aldosterone receptor
Amiloride and triamterene block

Na+ channels controlled by aldosterone
DIURETIC EFFECTS
Volume and preload
Improve symptoms of congestion
No direct effect on CO, but

excessive preload reduction may
Improves arterial distensibility
Neurohormonal activation
Levels of NA, Ang II and ARP
Exception: with spironolactone
DIURETICS
ADVERSE REACTIONS
Thiazide and Loop Diuretics
Changes in electrolytes:
Volume
Na+, K+, Ca++, Mg++
metabolic alkalosis
Metabolic changes:
glycemia, uremia, gout
LDL-C and TG
Cutaneous allergic reactions
DIURETICS
ADVERSE REACTIONS
Thiazide and Loop Diuretics
Idiosyncratic effects:
Blood dyscrasia, cholestatic jaundice and

acute pancreatitis
Gastrointestinal effects
Genitourinary effects:
Impotence and menstrual cramps
Deafness, nephrotoxicity
(Loop diuretics)
DIURETICS
ADVERSE REACTIONS
K-SPARING DIURETICS
Changes in electrolytes:
Na+,
K+, acidosis
Musculoskeletal:
Cramps, weakness
Cutaneous allergic reactions :

Rash, pruritis
3. ALDOSTERONE INHIBITORS
ALDOSTERONE INHIBITORS
Spironolactone
ALDOSTERONE
Competitive antagonist of the

aldosterone receptor
(myocardium, arterial walls, kidney)
Retention Na+
Retention H2O
Excretion K+
Excretion Mg2+
Edema
Collagen
deposition
Fibrosis
Arrhythmias
- myocardium
- vessels
ALDOSTERONE INHIBITORS
INDICATIONS
FOR DIURETIC EFFECT

Pulmonary congestion (dyspnea)
Systemic congestion (edema)
FOR ELECTROLYTE EFFECTS
Hypo K+, Hypo Mg+
Arrhythmias
Better than K+ supplements
FOR NEUROHORMONAL EFFECTS
Please see RALES results,
N Engl J Med 1999:341:709-717
Aldosterone receptor antagonists - spironolactone
Recommended in advanced HF (NYHA III-IV),

in addition to ACE inhibition and diuretics to
improve survival and morbidity
Aldosterone receptor antagonists - spironolactone
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).
4. -Blockers
Start Low Go Slow
Activation and Blockade of Neurohumoral

System in CHF
RAA System
SNS System
Angiotensin II
Noradrenalin
ACE-I
-Blocker
Hypertrophy, apoptosis, ischaemia,

arrhytmia, remodeling, fibrosis
ADRENERGIC ACTIVATION
CNS Sympathetic
Outflow
Sympathetic
activity to kidneys
& blood vessels
Cardiac
Sympathetic activity
1-receptors
2-receptors
a1-receptors
Mycocyte hypertrophy & death,

dilatation, ischaemia & arrhytmias
Vasoconstriction
Sodium Retention
Packer, AHA 2000
Why addadd-on -blocker

blocker,,
if HF patient is already stable
on standard therapy with
ACE--I, diuretics digoxin
ACE
Survival
1.0
-Blockers in CHF All--cause Mortality

All
US Carvedilol Study
Carvedilol
(n=696)
0.9
Placebo
(n=398)
0.8
Risk reduction = 65%
0.7
P<0.001
0.6
0.5
0 50 100 150 200 250 300 350 400

Days
Mortality %
20
Survival
1.0
CIBIS--II
CIBIS
Packer et al (1996)
MERIT--HF
MERIT
Placebo
Bisoprolol
15
0.8
Metoprolol CR/XL
10
Placebo
0.6
P=0.0062
P<0.0001
200
400
Time after inclusion (days)
600
800
Lancet (1999)
3
6
9
12 15
Months of follow-up
18
21
The MERIT-HF Study Group (1999)
Benefits of Add-on -Blocker

Short-term :
1. Improvement of symptoms (LVEF )
2. Improvement of NYHA class
3. Improvement of daily activities

4. Reduction of hospitalization rate & length of
hospital stay (financial & psychological burden)
Long-term :
1. Slowing the progression of CHF

2. Increase of survival rate
A Clear DoseDose-Effect Relationship

(MOCHA Study)
LVEF (EF Units)
P < 0.001
8
7
6
5
4
3
2
1
0
% improved
90
**
6.25
12.5
60
30
6.25
12.5
25
mg bid
% worse
Plc
- 30
Plc
*
25
mg bid
Mortality (%)
Hospitalization/Pts
16
0.4
P = 0.01
0.2
**
*
**
0.1
P < 0.001
12
0.3
Bristow et al (1996)
Patient Global Assessment
**
**
0
Plc
6.25
12.5
25
mg bid
0
Plc
6.25
12.5
25
mg bid
COPERNICUS
All--cause mortality
All
100
% Survival
90
80
Carvedilol
70
Placebo
P=0.00013
60
0
12
Months
15
18
21
COPERNICUS
Effect of carvedilol on mortality
Annual placebo mortality rate
(per patientpatient-year)
19.7%
All
patients
28.5%
Recent or
recurrent
decompensation
0.25
0.5
Favors treatment
0.75
1.0
1.25
Favors placebo
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.
CIBIS II, MERIT HF, US CARVEDILOL AND
COPERNICUS study
Reduction in total mortality, cardiovascular
mortality, sudden death and death due to
progression of heart failure in patients in func.
class II-IV.
reduces hospitalizations
improves the functional class and leads to
less worsening of heart failure.
PHARMACOLOGICAL PROPERTIES OF
-BLOCKING AGENT FOR HF
a-
1BLOKADE
2BLOKADE
BLOKADE
ISA
ANCILLARY
EFFECTS
Carvedilol
+++
+++
+++
+++
Metoprolol
+++
Bisoprolol
+++
AGENT
THE RECOMMENDED PROCEDURE FOR

STARTING -BLOCKER
1. Patient should be on standard therapy
(ACE inhibitor +/- diuretic)
2. Patient in stable conditions

No iv inotropic therapy
Without signs of marked fluid retention
3. Start initial low doses and titrate to maintenance dose

(the dose may be doubled every 1 2 weeks)
(ESC.Guidelines for HF, 2001)
DOSES OF -BLOCKER
BLOCKER
FIRST DOSE
TARGET DOSE
TITRATION
PERIOD
Bisoprolol
1.25 mg
10 mg
Weeks Month
Metoprolol
Tartrate
5 mg
150 mg
Weeks Month
Metoprolol
Succinate
12.5 mg
200 mg
Weeks Month
Carvedilol
2 x 3.125 mg
2 x 25 mg
Weeks Month
(European Heart Journal, vol. 22, Sept. 2001)
CONTRAINDICATIONS OF
-BLOCKER IN PATIENT H F
Asthma Bronchial
Severe Bronchial Desease
Symptomatic Bradycardia and
Hypotension
INTOLERANCE OF -BLOCKER
Symptomatic
Bradycardia
Worsening HF
Hypotension
How to Handle Intolerance

SYMPTOMATIC BRADYCARDIA
Check Blood Digoxin and/or reduce
other AV nodus inhibiting drugs
Reduces -Blocker dose
or if necessary stop it
Consider implantation of
peacemaker

WORSENING HF
Increase dose of Diuretics
Reduces -Blocker dose

or if necessary stop it
If indicated, give inotropic drugs or
nitroprusside or nitroglycerin

HYPOTENSION
Reduces ACE-I or
vasodilator
Take -Blocker :
After meal
At different time than ACE-I
Reduces dose or if necessary stop it
-BLOCKER IN HIGH RISK GROUPS PTS
WITH CHF
(Post-Hoc Analysis of the CIBIS II)

Elderly Patient
Type 2 Diabetes Mellitus
Renal Failure
Digitalis / Aldosteron Antagonist /

Amiodaron
5. Angiotensin II receptor
antagonists
ANGIOTENSIN II INHIBITORS
MECHANISM OF ACTION
RENIN
Angiotensinogen
Other paths
AT1
RECEPTOR
BLOCKERS
AT1
Vasoconstriction
Angiotensin I
ACE
ANGIOTENSIN II
RECEPTORS
Proliferative
Action
AT2
Vasodilatation
Antiproliferative
Action
AT1 RECEPTOR BLOCKERS

DRUGS
Losartan
Valsartan
Irbersartan
Candesartan
Competitive and selective
blocking of AT1 receptors
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.
Angiotensin II receptor antagonists
VAL-H
Patients were randomized to placebo or
valsartan on top of standard therapy.
The results showed no difference in overall

mortality, but a reduction in the combined endpoint all-cause mortality or morbidity
expressed as hospitalization because of
worsening heart failure.
6. Cardiac glycosides
DIGOXIN
Na-K ATPase
Na+
K+
K+ Na+
Na-Ca Exchange
Na+
Myofilaments
Ca++
Ca++
CONTRACTILITY
DIGOXIN
PHARMACOKINETIC PROPERTIES
Oral absorption (%)
Protein binding (%)
Volume of distribution (l/Kg)
Half life
Elimination
Onset (min)
i.v.
oral
Maximal effect (h)
i.v.
oral
Duration
Therapeutic level (ng/ml)
60 - 75
25
6 (3-9)
36 (26-46) h
Renal
5 - 30
30 - 90
2-4
3-6
2 - 6 days
0.5 - 2
DIGOXIN
DIGITALIZATION STRATEGIES
Loading dose (mg)
i.v
0.5 + 0.25 / 4 h
ILD: 0.75-1
oral 12-24 h
oral 2-5 d
0.75 + 0.25 / 6 h 0.25 / 6-12 h

1.25-1.5
1.5-1.75
Maintenance
Dose
(mg)
0.125-0.5 / d
0.25 / d
ILD = average INITIAL dose required for

digoxin loading
DIGOXIN
HEMODYNAMIC EFFECTS
Cardiac output
LV ejection fraction
LVEDP
Exercise tolerance
Natriuresis
Neurohormonal activation
DIGOXIN
NEUROHORMONAL EFFECTS
Plasma Noradrenaline
Peripheral nervous system activity
RAAS activity
Vagal tone
Normalizes arterial baroreceptors
DIGOXIN
EFFECT ON CHF PROGRESSION
30
Placebo n=93
WORSENING
OF CHF
DIGOXIN
Withdrawal
20
p = 0.001
DIGOXIN: 0.125 - 0.5 mg /d

(0.7 - 2.0 ng/ml)
10
EF < 35%
Class I-III (digoxin+diuretic+ACEI)
Also significantly decreased exercise
time and LVEF.
0
RADIANCE
N Engl J Med 1993;329:1
DIGOXIN n=85
20
40
60
Days
80 100
OVERALL MORTALITY
50
40
30
20
Placebo
n=3403
10
DIG
0
0
p = 0.8
DIGOXIN
n=3397
12
N Engl J Med 1997;336:525
24
Months
36
48
DIGOXIN
LONG TERM EFFECTS
Survival similar to placebo

Fewer hospital admissions
More serious arrhythmias

More myocardial infarctions
DIGOXIN
CLINICAL USES
AF with rapid ventricular response
CHF refractory to other drugs
Other indications?
Can be combined with other drugs
DIGOXIN
CONTRAINDICATIONS
ABSOLUTE:
- Digoxin toxicity
RELATIVE
- Advanced A-V block without pacemaker
- Bradycardia or sick sinus without PM
- PVCs and TV
- Marked hypokalemia
- W-P-W with atrial fibrillation
DIGOXIN TOXICITY
CARDIAC MANIFESTATIONS
ARRHYTHMIAS :
- Ventricular (PVCs, TV, VF)
- Supraventricular (PACs, SVT)
BLOCKS:
- S-A and A-V blocks
CHF EXACERBATION
DIGOXIN TOXICITY
EXTRACARDIAC MANIFESTATIONS
GASTROINTESTINAL:
- Nausea, vomiting, diarrhea
NERVOUS:
- Depression, disorientation, paresthesias
VISUAL:
- Blurred vision, scotomas and yellow-green
vision
HYPERESTROGENISM:
- Gynecomastia, galactorrhea
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.
7. Vasodilator agents
Vasodilator agents in chronic heart failure

No specific role for vasodilators in the treatment of HF
Used as adjunctive therapy for angina or concomitant
hypertension.
In case of intolerance to ACE inhibitors ARBs are
preferred to the combination hydralazinenitrates.
HYDRALAZINE-ISOSORBIDE DINITRATE
Hydralazine (up to 300 mg) in combination with ISDN (up to 160
mg) without ACE inhibition may have some beneficial effect on
mortality, but not on hospitalization for HF.
Nitrates may be used for the treatment of concomitant angina or
relief of acute dyspnoea.
8. Positive inotropic therapy
POSITIVE INOTROPES
CARDIAC GLYCOSIDES
SYMPATHOMIMETICS
Catecholamines
-adrenergic agonists
PHOSPHODIESTERASE INHIBITORS
Amrinone
Enoximone
Others
Milrinone
Piroximone
-ADRENERGIC STIMULANTS
CLASSIFICATION
B1 Stimulants
Increase contractility
Dobutamine Doxaminol Xamoterol
Butopamine Prenalterol Tazolol
B2 Stimulants
Produce arterial vasodilatation and reduce SVR

Pirbuterol Rimiterol Tretoquinol Terbutaline Soterenol
CarbuterolFenoterol Salbutamol SalmefamolQuinterenol
Mixed
Dopamine
DOPAMINE AND DOBUTAMINE

EFFECTS
DA (g / Kg / min)
Dobutamine
<2
DA1 / DA2
2-5
1
>5
1 + a
Contractility
++
++
++
Heart Rate
++
Arterial Press.
++
++
++
++
Receptors
Renal perfusion
Arrhythmia
POSITIVE INOTROPES
CONCLUSIONS
May increase mortality
Safer in lower doses
Use only in refractory CHF
NOT for use as chronic therapy
Positive inotropic therapy
Commonly used to limit severe episodes of

HF or as a bridge to heart transplantation
in end-stage HF.
Repeated or prolonged treatment with oral
inotropic agents increases mortality.
Currently, insuffcient data are available to
recommend dopaminergic agents for heart
failure treatment.
Positive inotropic therapy

POSITIVE INOTROPHIC AGENTS
Dobutamin
Milrinone
Levosimendan
DOPAMINERGIC AGENTS
Ibopamine is not recommended for the treatment of
chronic HF due to systolic LV dysfunction.
Intravenous dopamine is used for the sort-term
correction of haemodynamic disturbances of severe
episodes of worsening HF.
9. Antiarrhythmics
ANTIARRHYTHMICS
Sustained VT, with/without symptoms
- Blockers
- Amiodarone
Sudden death from VF
- Consider
implantable
defibrillator
ANTIARRHYTHMICS
MORTALITY
15
13.6
ns
13.7
MORTALITY
AT 2 YEARS
10
%
n=1486
5-21d post MI
Amiodarone
5
200 mg/d
Follow up 1 - 4 years
EMIAT
Am Coll Cardiol 1996
101 / 743
102 / 743
Placebo
Amiodarone
Antiarrhythmics
No indication for the use of antiarrhythmic agents in HF
Indications for antiarrhythmic drug therapy include AF
(rarely flutter), non-sustained or sustained VT.
CLASS I ANTIARRHYTHMICS
should be avoided
CLASS II ANTIARRHYTHMICS
Beta-blockers reduce sudden death in heart failure

CLASS III ANTIARRHYTHMICS
Amiodarone is the only antiarrhythmic drug without

clinically relevant negative inotropic effects.
10. Anticoagulation
11. Antiplatelet Drugs
ANTICOAGULANTS
PREVIOUS EMBOLIC EPISODE
ATRIAL FIBRILLATION
Identified thrombus
LV Aneurysm (3-6 mo post MI)
Class III-IV in the presence of:
- EF < 30
- Aneurysm or very dilated LV
Phlebitis
Prolonged bed rest
Anticoagulation
Recommendation
1. All pts with HF and AF should be treated with
warfarin unless contraindicated.
2. Patients with LVEF 35% or less.
HFSA Guidelines for Management of Patients With Heart Failure Caused by Left
Ventricular Systolic Dysfunction - Pharmacological Approaches 2000
Antiplatelet Drugs
Recommendation
There is insufficient evidence concerning the
potential negative therapeutic interaction
between ASA and ACE inhibitors.
Antiplatelet agent for pts with HF who have
underlying CAD.
HFSA Guidelines for Management of Patients With Heart Failure Caused by Left
Ventricular Systolic Dysfunction - Pharmacological Approaches 2000
Chronic heart failure choice of

pharmacological therapy
LV systolic dysfunction
ACE inhibitor
Diuretic
Beta-blocker
Aldosterone
Antagonist
Asymptomatic LV
dysfunction
Indicated
Not indicated
Post MI
Not indicated
Symptomatic HF (NYHA II)
Indicated
Indicated if
Fluid retention
Indicated
Not indicated
Worsening HF (NYHA III-IV)
Indicated
Indicated
comb. diuretic
Indicated
End-stage HF (NYHA IV)
Indicated
Indicated
comb. diuretic
Indicated
Indicated
Indicated

Chronic heart failure choice of

pharmacological therapy
LV systolic dysfunction
Angiotensin
II receptor
antagonists
Asymptomatic LV
dysfunction
Not indicated
Symptomatic HF (NYHA II)
Worsening HF (NYHA III-IV)
End-stage HF (NYHA IV)
Vasodilator
(hydralazine/ Potassium -sparing
Cardiac glycosides
isosorbide
diuretic
dinitrate)
With AF
Not indicated
(a) when AF
If ACE inhibitors
If ACE inhibitors
and angiotensin
are not tolerated (b) when improved
from more severe II antagonists
and not on betaare not
HF in sinus
blockade
tolerated
rhythm
If ACE inhibitors
If ACE inhibitors
and angiotensin
are not tolerated
indicated
II antagonists
blockade
tolerated
If ACE inhibitors
If ACE inhibitors
and angiotensin
are not tolerated
indicated
II antagonists
blockade
tolerated
Not indicated
If persisting
hypokalaemia
If persisting
hypokalaemia
If persisting
hypokalaemia

Intervention
Revascularization
Surgical
Non Surgical
Pts with heart failure of ischaemic origin revascularization

symtomatic improvement.
A strong negative correlation of operative mortality and LVEF,
a low LVEF (<25%) was associated with increased
operative mortality. Advance HF symptoms (NYHA IV)
resulted in a greater mortality rate.
Off pump coronary revascularization may lower the surgical
risk for HF.
Heart Transplantation is an accepted mode of treatment for

end-stage HF.
Care and Follow-up

Recommended components of programs
use a team approach

vigilant follow-up, first follow-up within 10 days of
discharge
discharge planning
increased access to health care
optimizing medical therapy with guidelines
intense education and counselling inpatient and
outpatient
strategies address barriers to compliance
early attention to signs and symptoms
flexible diuretic regimen
Future treatment
Neurohormonal modulation
1.
2.
3.
4.
5.
6.
7.
Sympathetic nervous system

The RAA system
Atrial and brain natriuretic peptides
Arginin vasopressin
Endothelin
Growth hormone
Calcitonin gene related peptide
Cardiac reparation: fixing the heart

with cells, new vessels and genes (1)
Cell based
interventions
Aims: to repopulate fibrous scars with new
contractile cells
1. Multiplication of residual myocytes
(forcing the cells to enter mytotic cycle)
2. Transforming fibrablasts in the scar
3. Implanting exogenous contractiles cells
(foetal cardiomyocites, skeletal
myoblasts, stem cells)
Eur Heart J 2002;4: D73D73-81
CONT (2)
Angiogenesis
Aims:: to provides new blood supply to
Aims
the diseased heart
1. Administration of angiogenic growth factors
VEGF, basic FGF
2. Problems: nature of compound , dose,
route, and adverse events (abnormal blood
vessels, proliferative retinopathy, etc)
Eur Heart J 2002;4: D73D73-81
CONT(3)
Gene therapy
Aims: to improve the function of the failing

heart
1. Gene manipulation of 3 majors areas: Ca
handling, betabeta-adenergic signalling and
apoptosis
2. Inducing expression of silent genes
Safety problems:
problems: control of targeted protein
expression, inflammation, autoimmunity
and oncogenesis (basically irreversible)
Eur Heart J 2002;4: D73D73-81
Dual--chamber pacemakers are

Dual
beneficial
Drug-resistant CHF
DrugIntact sinus rhythm
Absence of chronic atrial dysrhythmias
EF <20%
Viable myocardium
No or stable angina
DMC and PR >, MR and TR, QRS >, QRS
PR + QRS > 350 ms.
QRS >140 ms, MR > 450 ms, and LV filling
time <200 ms
HOCM
Cardiac resynchronization
therapy
Reason:
Patients with CHF frequently exhibited
QRS prolongation with disease
progression. The delayed ventricular
activation leads to asynchronous
ventricular contraction with negative
effects on LV performance
Aim:
To normalize AV activation sequence
and disturbed ventricular contraction
patterns
Cardiac resynchronization
therapy
Study
Path-CHF
Path(n=42)
In Sync
(n=81)
Alouco
(n=26)
MUSTIC
(n=67)
NYHA
QRS (ms)
EF (%)
0 mo 3 mo 0 mo 3 mo 0 mo 3 mo
3.0
2.0
3.4
2.2
179
143
21
24
3.3
2.0
179
159
176
23
J Inv Cardiol 2002; 14: 4848-53
Resume
Pharmacological Treatment :
I.
Asymptomatic Systolic LV dysfunction :
II.
ACE Inhibitor
-Blocker (in CAD)
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
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
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.
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.
Thank YoU
DIASTOLIC HEART
FAILURE
SCOPE OF THE PROBLEM

Epidemiological studies of HF have
suggested that 30-50% of cases of HF
have preserved LV systolic function.
DHF has mortality rate equal as
systolic heart failure
No guideline yet regarding the

treatment of DHF
Greenberg & Hermann 2004
Defining Diastolic Heart Failure

Diastolic dysfunction refers to a condition in which
abnormalities in mechanical function are presenting
during diastole.
Diastolic dysfunction is a condition in which higher
than normal LV filling pressure are needed to maintain
a normal cardiac output.
Diastolic heart failure is a clinical syndrome
characterized by the symptoms and signs of heart
failure, a preserved EF and abnormal diastolic
function.
(Vasan & Levy 2000)
Echo--Doppler and Diastolic Dysfunction

Echo
Normal diastolic
function
Mild diastolic
dysfunction
Pseudonormal
stage
Restrictivefilling stage
Left ventricular relaxation
Normal
Left ventricular stiffness
Normal
Left atrial contractility
Normal
Normal
Preload
Normal
Normal
QRS
Electrocardiogram
E wave
A wave
Mitral flow
Diastole
Systole
Pulmonary venous
flow
Atrial reversal
( Garcia, 2000 )
Diastolic Heart Failure : Effects of

Age on Prevalence and Prognosis
Age, y
<50
50-70
>70
Prevalence
15
33
50
Mortality
15
33
50
Morbidity
25
50
50
( Zile & Brutsaert, 2002 )
CHARACTERISTICS
Age
Sex
Left ventricle EF
Left ventricle cavity size
LVH on echo
Chest radiography
Gallop rhythm present
Coexisting conditions
Hypertension
Diabetes mellitus
Previous MCI
Obesity
Chronic lung disease
Sleep apnea
Long term dialysis
Atrial fibrillation
(NEJM 2003)
DIASTOLIC HEART
FAIURE
Frequently elderly
Frequently female
Preserved or normal (+ > 40%)
Usually normal,often LVH
concentric
Usually present
Congestion with/out cardiomegali
Fourth heart sound
SYSTOLIC HEART
FAILURE
All ages,typically 50-70 yr
More often male
Depressed,+ < 40%
Usually dilated
Sometimes present
Congestion & cardiomegali
Third heart sound
+++
+++
+
+++
++
++
++
+
Usually paroxismal
++
++
+++
+
0
++
0
+
Usually persistent
Conditions Associated with Diastolic

Dysfunction
Condition
Coronary artery disease
Hypertensive heart disease
Valvular heart disease
Normal aging
Hypertrophic cardiomyopathy
Infiltrative disease of the
myocardium
(amyloid,sarcoid,haemocromatosis,
lympoma)
Possible Contributory Mechanism :

Asynchronous myocardial relaxation
secondary,to ischemia or scar and
altered mechanical loading
LVH
AS leading to LVH , MS leading to reduced
filling
Impaired early filling due to reduced
compliance with associated increase in late
filling
Hypertrophy,fibrosis, and asynchronous
regional lengthening, hence impaired
relaxation.
Reduced LVED distensibility (increased
LVEDP)
(Vasan & Levy 1998)
(Mandinov,Eberli,Seiler,Hess.Cardiosvasc Res 2000)
Diagnostic Criteria for Diastolic Heart Failure

Signs or symptoms of congestive heart failure
Exertional dyspnoea [eventually objective evidence by reduced peak exercise oxygen consumption
(<25 ml.kg-1.min-1)], orthopnea, gallop sounds, lung crepitations, pulmonary oedema
and
Normal or mildly reduced left ventricular systolic function:
LVEF45% and LVEDIDI<3.2 cm.m-2 or LVEDVI<102 ml.m-2
and
Evidence of abnormal left ventricular relaxation, filling, diastolic distensibility and diastolic stiffness:
Slow isovolumic left ventricular relaxation:
LVdP/dtmin <1100 mmHg.s-1
and/or IVRT<30y>92 ms, IVRT30-50y>100 ms, IVRT>50y>105 ms
and/or >48 ms
and/or slow early left ventricular filling:
PFR<160 ml.s-1.m-2
and/or PFR<30y<2.0 EDV.s-1, PFR30-50y<1.8 EDV.s-1, PFR>50y<1.6 EDV.s-1
and/or E/A<50y<1.0 and DT<50y>220 ms, E/A>50y<0.5 and DT>50y>280 ms
and/or S/D<50y>1.5, S/D>50y>2.5
and/or reduced left ventricular diastolic distensibility:
LVEDP>16 mmHg or mean PCW>12 mmHg
and/or PV A Flow > 35 cm.s-1
and/or PV A t>MV A t+ 30 ms
and/or A/H>0.20
and/or increased left ventricular chamber or muscle stiffness:
b>0.27
and/or b>16
( European Study Group on DHF, 1998 )
Criteria for Definite DHF

Criterion
Definite evidence of CHF
AND
Objective evidence of normal LV
systolic function in proximity to
the CHF event
Objective Evidence
Includes clinical symptoms and signs, supporting
laboratory tests (such as chest X-ray), and a typical
clinical response to treatment with diuretics, with or
without documentation of elevated LV filling pressure
(at rest, on exercise, or in response to a volume load)
or a low cardiac index
LV EF > 0.50 within 72 h of event
AND
Objective evidence of LV diastolic
dysfunction
Abnormal LV relaxation /filling/distensibility indices on

cardiac catheterization
( Vasan & Levy, 2000 )
Criteria for Probable DHF

Criterion
Definitive evidence of CHF
AND
Objective evidence of normal LV systolic
function in proximity to the CHF event
Objective Evidence
Includes clinical symptoms and signs, supporting laboratory tests
(such as chest X-ray), and a typical clinical response to treatment
with diuretics, with or without documentation of elevated LV filling
pressure (at rest, on exercise, or in response to a volume load) or a
low cardiac index
LV EF > 0.50 within 72 h of CHF event
BUT
Objective evidence of LV diastolic
dysfunction is lacking
No conclusive information on LV diastolic function
Criteria for Possible DHF

Criterion
Definitive evidence of CHF
AND
Objective evidence of normal LV systolic

function, but not at the time of the CHF event
Objective Evidence
Includes clinical symptoms and signs, supporting laboratory test (such
as chest X-ray), and a typical clinical response to treatment with
diuretics, with or without documentation of elevated LV filling pressure
(at rest, on exercise, or in response to a volume load) or a low cardiac index
LV EF > 0.50
AND
Objective evidence of LV diastolic dysfunction

is lacking
No conclusive information on LV diastolic function
( Vasan & Levy, 2000 )
Other Methods in diagnosing DHF
Plasma Brain Natriuretic Peptide

Doppler tissue imaging
Magnetic resonance imaging
Radionuclide angiography
Cardiac catheterization
Greenberg & Hermann 2004
Treatment of Diastolic Heart Failure

The guidelines are based on :
Clinical investigations in relatively small
groups of patients
Clinical experience
Concepts based on pathophysiology
mechanisms
Treatment of Diastolic Heart failure

symptom targeted treatment
disease / pathological targeted treatment

the underlying mechanism targeted
treatment
Diastolic Heart Failure: Treatment

Symptom targeted treatment
Decrease pulmonary venous pressure
Reduce LV volume
Maintain atrial contraction
Prevent tachycardia
Improve exercise tolerance
Use positive inotropic agents with caution
Diastolic Heart Failure: Treatment

Symptom targeted treatment
Nonpharmacological treatment
Restrict sodium to prevent volume overload
Restrict fluid to prevent volume overload
Perform moderate aerobic exercise to improve cardiovascular
conditioning, decrease heart rate and maintain skeletal muscle
function
Pharmacological treatment
Diuretics including loop diuretics thiazides, spironolactone
Long-acting nitrates, -Adrenergic blockers
Calcium channel blockers
Renin angiotensin-aldosterone antagonists including ACE
inhibitors, angiotensin II receptor blockers and aldosterone
antagonists
Diastolic Heart Failure

Disease-targeted treatment
Prevent/treat myocardial ischemia

Prevent/regress ventricular hypertrophy
Mechanisms targeted treatment
Modify myocardial and extramyocardial mechanisms

Modify intracellular and extracellular mechanisms
An ideal therapeutic agent.
- Should target the underlying mechanisms

- Improve calcium homeostasis and energetics
- Blunt neurohumoral activation
- Prevent and regress fibrosis
Trials of Diastolic Heart Failure

Trial
PEP-CHF
Comparison
Follow-up (n)
Diagnostic Criteria
for DHF
Placebo
Perindopril
1.000
Minimum 18 months
3 of 9 clinical and
2 of 4 echocardiographic
criteria
Other Important
Inclusion/ Exclusion
Criteria
Age > 70 years
Diuretics
Death or HF-related
hospitalization
Placebo
Candesartan
Placebo
Irbesartan
Placebo
Nebivolol
2.500
Minimum 24 months
3.600
Approx 48 months
2.000
(% DHF uncertain)
EF > 40%
Hospital admission in last

3 months
None
EF > 45%
Clinical diagnosis of HF
EF > 35% and a cardiac

abnormality
Hong Kong
Placebo
Ramipril
Irbesartan
450
Minimum 12 months
Doppler criteria
Aged > 70 years

Hospital admission within
last 12 months
Diuretics
SWEDIC
Placebo
Carvedilol
140
9 months
Doppler criteria
AF excluded
CHARM-2
I-PRESERVE
SENIORS
(diastolic subset)
Main Outcomes
Death or hospitalization
for HF
Death and hospitalization
cardiovascular disease
Death or hospitalization
for HF
Quality of life 6-minute
walk test
Regression of diastolic
dysfunction
( Banerjee, et.al, 2002)

All About CHF

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All About CHF

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CHRONIC CONGESTIVE HEART

Dr. Cholid Tri Tjahjono,

Pathophysiological state in which an

DEFINITION OF HEART FAILURE.

1. Symptoms of heart failure

(in cases where the diagnosis is in doubt)

3. Response to treatment directed towards heart

The prevalence of symptomatic HF range from 0.4-2%.

DESCRIPTIVE TERMS in HEART FAILURE

Systolic vs Diastolic Heart Failure

New York Heart Association (NYHA)

No limitation : ordinary physical exercise does

ACC/AHA A New Approach To The Classification of HF

Patient who is at high risk for

Hypertension; CAD; DM;

Patient with a structural disorder

Patient with past or current

Dyspnea or fatigue ec LV systolic

Patient with end-stage disease

Frequently hospitalized pts ; pts

ACC/AHA Guidelines for the

Stages in the evolution of HF and recommended therapy by stage

Pts who have

ACC/AHA Guidelines for the

Symptoms not controlled

Evolution of the Concept of Heart Failure

Slowly progressive (remodelling)

Improve quality of life

The Wiggers cycle

Diastolic function Systolic function

Block diagram of left ventricular pump performance

PRESSURE VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILURE

Left Ventricular Volume

Left Ventricular Pressure

Left Ventricular Pressure

Left Ventricular Volume

(Zile & Brutsaert 2002)

Left ventricular pressure

Mechanisms that cause diastolic dysfunction.

Ventricular Function Curve:

Factors That Influence Ventricular

The Pathophysiology of Heart Failure

Inadequate Cardiac Output

Perfusion of Vital Organs

Sympathetic nervous system up-regulation

Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002

Causes of Heart Failure

Excess Load on Ventricle

Volume/ Pressure Overload

Resistance to Flow into Ventricle

Primary Changes in CHF

Right Heart () Systemic

MI-INDUCED HEART FAILURE

With a Syndrome of Decrease Exercise

With a Syndrome of Fluid Retention

With No Symptoms or Symptoms of

SYMPTOMS AND SIGN

Breathlessness, Ankle Swelling, Fatique

Peripheral Oedema, JVP , Hepatomegaly

S3 , Pulmonary Rales , Cardiac Murmur

A low Predictive Value

HAEMATOLOGY & BIOCHEMISTRY

A Part of Routine Diagnostic

A Little Value in Diagnosis Heart Failure