Heart Failure

Patophysiologic &
Clinical Aspect
Arie Bachtiar Dwitaryo
Cardiology Division
Dr Kariadi Hospital
Semarang

Definition
CHF is a complex clinical syndrome
caharacterized by dysfunction of the left-right or
both ventricles and changes in neurohumoral
regulation
This syndrome consist of :
Exercise intolerance
Disrythmia
LV-RV Dysfunction
Fluid Retention : Pretibial Edema, Ascites,
Pulmonary Edema

Definition of Heart Failure

Heart failure is the pathophysiological
state in which the heart is unable to pump
blood at a rate commensurate with the
requirements of the metabolizing tissues
or can do so only from an elevated filling
pressure.
Heart failure is a complex clinical
syndrome that can result from any
structural or functional cardiac disorder
that impairs the ability of ventricle to fill
with or eject blood.

Patients surviving %

100

Progression
Mechanism of death
Sudden death 40%
Worsening CHF 40%
Other 20%

Further damage
Excessive wall stress
Neurohormonal activation
Myocardial ischemia

Annual mortality
0

<5%
Asymptomatic

10%

20 to 30%

30 to 80%

Mild

Moderate

Severe

Left ventricular dysfunction and symptoms

(Massie & Shah, 1997)

Activation of Neurohormonal Pathways in HF

Coronary Disease

Cardiac Overload

Cardiomyopathy

Left Ventricular Dysfunction

Vasoconstriction

Neurohormonal Activation
Cathecholamines
RAS
AVP
Endothelin

Peripheral Organ
Blood Flow
skeletal
muscle flow
Exercise Intolerance

Cardiac Remodelling

RBF
Na retention

LV dilatation

LV hypertrophy

Arrhythmias

Edema, Congestion

Sudden Death

Pump Failure

Ruffolo, J Cardiovasc, Pharmachol, 1998

EPIDEMIOLOGY
Morbidity and Mortality rates remain high.
USA : estimated more than 2 million
patient.
400.000 new patient each year.
900.000 required hospitalization.
200.000 patient die/year.
Annual mortality rate : 40-50% in NYHA
Class IV

HAEMODINAMIC ASPECT in
HEART FAILURE
Increased

in : Ventricular and diastolic

volume and pressure
Atrial volume & pressure
Atrial & Ventricular Contractility
Volume & Pressure in Venous System
Capillary Pressure-Transudation of Fluid
Lymphatic Flow

Myocyte Death
Decreased CO

Neutrophil
infiltration

Activation
of MMPs
in ECM

Degradation of
inter-myocyte
collagen
struts

Enhanced NE release
from adrenal medulla
and sympathetic nerve
terminals

Elevated
plasma NE

Juxtaglomerular
Apparatus
Activation of
RAAS

Increased
ANP
BNP

Macrophage & fibroblast chemotaxis

Fibroblast proliferation
Macrophage transformation

Elevated
Plasma
AII

Increased
Na+
Water
excretion

ACE
expression

Decreased
Volume
SVR

Local AII &

Aldosterone
production

ET-1
release

Myocyte
slippage

Myocyte Hypertrophy
Wall thinning
Ventricular
Dilatation

Increased
wall stress

Mechanical
stretch

Early Remodeling (<72 hours)

TGF-1
release

Transient
Improvement
LV function

Local AII release

Activation of fetal gene program
Increased contractile proteins

TGF-1
release from
macrophages

Fibroblast
transformation into
myofibroblast

TGF-1 expression
Activation of TIMPs
Type I & III collagen
synthesis

Fibrosis
Late Remodeling

Diagrammatic representation of the many factors involved in

the pathophysiology of ventricular remodeling. (Sutton & Sharpe, 2000)

Pathophysiology of CHF
Injury to myocytes
and EC matrix
Neurohumoral activation
Increased cytokines
Immune and
inflammatory changes
altered fibrinolysis

Ventricular
remodelling

Oxidative stress
Apoptosis
Altered gene
Expression
Energy starvation

Electrical, vascular, renal,

pulmonary, muscle effects
CHF

McMurray J, Pfeffer M. Circulation. 2002 (in press)

Progression of Cardiovascular Disease

Coronary
artery Hypertension
disease

Left ventricular
remodeling

Arrhythmia

Remodeling

Low ejection
fraction

Pump
failure

Cardiomyopathy Valvular
disease

Death

Neurohormonal stimulation
Endothelial dysfunction
Vasoconstriction
Renal sodium retention

Noncardiac
factors

Symptoms:
Dyspnea
Fatigue
Edema

Chronic
heart
failure
(Abraham, 2000)

Risk
Factors
Heart disease

HEART FAILURE SPECTRUM

Asymptomatic
LV Dysfunction

Symptoms
NYHA II-III

Symptoms
NYHA - IV

Symptoms
?

ECHO / LV dysfunction
BNP

Stages of Heart Failure

Stages

Examples

Stage A: At high risk for HF but

without structural heart disease
or symptoms of HF

HTN, CAD, DM, cardiotoxins,

FHx of CM

Stage B: Structural heart disease

but without symptoms of HF

Previous MI, LV systolic dysfunction,

asymptomatic
valvular disease

Stage C: Structural heart disease

with prior or current symptoms
of HF

Known structural heart disease,

SOB and fatigue, reduced exercise
tolerance

Stage D: Refractory HF requiring

specialized interventions

Marked symptoms at rest

despite maximal medical therapy
ACC/AHA Heart Failure Practice Guidelines 2001

Aims of treatment
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

Morbidity
Maintenance or improvement in quality of life

Mortality
Increased duration of life
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560

PATHOPHYSIOLOGY &
ETIOLOGY
Increase preload : MR, AR, TR
Decrease preload : Cardiac tamponade
Decrease contractility : AMI, Cardiomyopathy
Decrease compliance : LVH Hypertrophic
Cardiomyopathy
Increase afterload : Hypertention, AS, PS,
HOCM
Impaired Atrial Contraction : AF

Contractility
Preload

Cardiac Output

Frequence & Rhytm

Afterload

SYMPTOMPS & SIGN

Shortness

of Breath / Dyspnea on Exertion

Paroxysmal Nocturnal Dyspnea
Orthopnea
Non Productive Cough
Fatigue & Weakness
Nocturia & Oligouria
Cerebral Symptoms
Abdominal Symptoms

Types of Heart Failure

Chronic vs Acute HF
Left vs Right sided HF
High Output vs Low Output HF
Backward vs Forward HF
Diastolic vs Sistolic HF

Physycal Examination

Cardiomegaly (RVH, LVH, or Both)

Gallop Rhytm
Tachycardia
Increased P2 Sound
Basal Rales (Pulmonic)
Increased JVP
Ascites
Edema Pretibial

LABORATORIUM ECG
- Chest X-Ray

Lab :
Leucocytosis, Urine : Oligouria
ECG :
Dysrythmia, LVH, RVH, IHD, Tachicardia,
Chest X-Ray :
Cardiomegaly
Inceased Bronchovascular Marking
Alveolar Edema
Pleural Efusion
Bat-Wing App / Kerley B-Lines

ESSENTIAL Of DIAGNOSIS

Orthopnea,PND,Dyspnea D
Effort.
JVP :R+2 Or More,
Tachycardia,Peripheral pitting
edema,Basal rales throughout
both lung fields,Cardiomegaly
&Hepatomegaly.
LV Systolic DysfunctionDiastolic Dysfunction(S3-S4
Gallop)

ECHOCARDIOGRAPHY
The Most usefull Examination to detect:
LV Systolic & Diastolic Dysfunction
Anatomical examination: LVH-RVHLAH,Valvular stenosis / Incompetence,
Segmental Wall motion Abnormality(IHD)
Intra Cardiac shunts : ASD,VSD
Trombus formation in LV(IMA),LA (MS)

Other Diagnostic Studies

Radionuclide Ventriculography
Cardiac Catheterization
Tissue Imaging Echo-Doppler
Exercise Stress Test : Evaluate
Treatment

Differential Diagnosis
Chronic

Obstructive Pulmonary

Disease
Asthma Bronchiale
Bronchiectasis
Pulmonary Embolism, Pneumonia,
Pneumothorax
Neurotic-Anxiety

MANAGEMENT
GENERAL MEASURES
Preventive Strategy : Improving LV function
Unloading LV
Reducing Wall Stress
Lowering MVO2
Lessening the degree of Neurohumoral
Activation (Renin-Angiotensin-Aldosteron
system & Simpatetic System)

Correction of precipitating factors :

Dysrhytmia
Infection : most frequent
Pregnancy
Anemia
Volume Excess
Psychosocial stress
Cardiotoxic drug

Change in Activity & Diet :

Bed Rest/Restriction of physical activity
Sodium & Fluid `restriction
Reducing Emotional stress
Calory restriction in overweight patient

PHARMACOLOGIC

Diuretics : Loop Diuretics(Furosemide)

Digitalis
ACE-Inhibitor Angiotensin Receptor
Blocker
Beta Blockers (Cardioselective, Low Dose)
Spironolactone
Inotropic Drugs : Dopamine / Dobutamine /
Noradrenaline
Antiarrhytmic drugs : Amiodarone.
Nitrate : IV (Nitrocine)
Electrolyte`Suplementation:If necessary.

Stages in the evolution of HF and recommended therapy

by stage
Stage A

Stage B

Pts with:
Pts with:
Previous MI
Hypertension
Struct. LV systolic
CAD
Heart
DM
dysfunction
Disease
Asymptomatic
Cardiotoxins
FHx CM
Valvular disease

Stage C
Pts with:
Struct. HD
Develop. Shortness of
Symp. of
breath and fatigue,
HF
reduce exercise
tolerance

Stage D
Pts who have
Refract. marked symptoms
Symp. of at rest despite
HF at rest maximal medical
therapy

THERAPY

THERAPY

THERAPY

THERAPY

Treat Hypertension
Stop smoking
cessation
Treat lipid disorders
Encourage regular
exercise
Stop alcohol &
drug use
ACE inhibition

All measures under

stage A
ACE inhibitor
Beta-blockers

All measures under

stage A
Drugs for routine use:
diuretic
ACE inhibitor
Beta-blockers
digitalis

All measures under

stage A, B and C
Mechanical assist
device
Heart transplantation
Continuous IV
inotrophic infusions
for palliation

ACC/AHA Guidelines for the

Evaluation and Management of Chronic Heart Failure in the Adult 2001

ACE
ACE inhibitors
inhibitors for
for congestive
congestive heart
heart failure
failure
NEUROHUMORAL EFFECTS OF HEART FAILURE
Poor organ
perfusion

BACKWARD FAILURE
INTO LUNGS & RV

kidney

JVP

FORWARD FAILURE
LOW BLOOD PRESSURE

Low BP

Baroreflexes
Adrenergic stimulation

RV failure

RV

ANP

LA

big liver
edema
Left
ventricle

RENIN
Angiotensin

back
ward
pressure

Aldosterone

heart

Increasing
preload

Na+ loss
INCREASING
BACKWARD
FAILURE

Na+ retension
Edema

EXCESS
AFTERLOAD

Increasing
forward
failure

EXCESS
BLOOD VOLUME

low renal
blood flow
(Opie, 1994)

Chronic Congestive Heart Failure

DIURETICS
Cortex

Thiazides
Inhibit active exchange of Cl-Na
in the cortical diluting segment of
ascending loop of Henle
K-sparing
Inhibit reabsorption of Na in the
distal convoluted and collecting tub

Loop diuretics
Inhibit exchange of Cl-Na-K in
Medulla
the thick segment of the ascendi
loop of Henle
Loop of Henle
Collecting tubule

Trial or
Number Odds Ratio
Redn (%)
group of trials
of patients & 95% CL
Vasodilator
beta-blocker
trials
SD
Carvedilol trials
ANZ
415 2527
US Dose ranging
345 8024
US Moderate
278 4139
US Severe
105 5475
US Mild
366 7841
Three smaller trials
149
-392
Subtotal vasodilator beta-blocker trials (1658)
4915
Other vasodilator beta-blocker trials
Six small trials
250
486
Subtotal all vasodilator (1908) 4715
beta-blocker trials
Non-vasodilator beta-blocker trials
CIBIS
641 2518
MDC
383
-833
Eight smaller trials
209 3240
Subtotal non-vasodilator (1233)
beta-blocker trials
TOTAL

3141

1815

3111

OR=0.69, 95% Cl 0.54 to 0.89

0 0.5 1.0 1.5

An overview
of all
available
randomized
trials of betablocking
therapy in
heart failure
involving a
total
of 3141
patients.

Probability of Survival

1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.00

Spironolactone

Placebo
p<0.001

9 12 15 18 21 24 27 30 33 36
Months

No. At Risk
Placebo
841 775 723 678 628 592 565 483 379 280 179 92
Spironolactone 822 766 739 698 669 639 608 526 419 316 193 122

36
43

Kaplan-Meier Analysis of the Probability of Survival among Patients

in the Placebo Group and Patients in the Spironolactone Group
(Pitt et al, 1999)

HF: Mortality Remains

High
ACEI

-blockers

Risk reduction 38% (mortality amd

hospitalization)2

Spironolactone

Risk reduction 35% (mortality and

hospitalization)1

Mortality reduction 23%

Oral nitrates and hydralazine

Benefit vs placebo; inferior enalapril

However: 4-year mortality remains ~40%
(mortality)

1 Davies MK et al. BMJ. 2000. 320: 428-431. (meta-analysis: 32 trials. N=7105)

2 Gibbs CR et al. BMJ. 2000. 320: 495-498. (meta-analysis: 18 trials. N=3023)

-Receptor
Sympathetic
Na+/H2O retention signaling pathway
ACE/AII
Vasoconstriction
Aldosterone
Vascular
remodelling
Sympathetic
Sympathetic
activation
RAAS
Neurohormonal
activation
Wound healing
fibrosis
Neurohormonal
hypertrophy
activation
Remodelling

Ca2+
homeostasis
Metabolism
SR/Mitochondrial
abnormalities

LV dysfunction

Remodelling
Vasoconstrictio
n

Stunning

Endothelin

Ischaemia
Injury

O
radic
als

Cytokines
TNF
Contractile

depression iNOS/NO-O
radicals
Neurohormon
al
Apoptosis
AII?

Ischaemia
Reperfusio
n

Remme, 1998

HEMODYNAMICS OF VASODILATORS IN CHF

Decreased fatigue
Increased cardiac output

+ Inotropic
Normal
HF
C
d
l
Mi
Sev
ere
CHF
PRELOAD REDUCTION

AFTERLOA
D
REDUCTIO
N

Decreased pulmonary wedge pressure

Decreased dyspnea

Theoretical Frank-Starling curves in CHF.

2001)

(Opie,

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