PATHOPHYSIOLOGY OF

HEART FAILURE
 Notes to heart physiology
• Essential functions of the heart

• to cover metabolic needs of body tissue

(oxygen, substrates) by adequate blood supply
• to receive all blood coming back from the tissue to
the heart

• Essential conditions for fulfilling these functions

• normal structure and functions of the heart

• adequate filling of the heart

 Essential functions of the heart are secured
by integration of electrical and mechanical
functions of the heart
Cardiac output (CO) = heart rate (HR) x stroke
volume(SV)
• Determinants of cardiac
output
- changes of heart rate
- changes of stroke volume
• Control of HR:

- autonomic nervous system

- hormonal(humoral) control
• Control of SV:- preload
- contractility
- afterload
 Preload

Stretching the myocardial fibers during diastole by increasin

end-diastolic volume will increase the force of contraction
during systole = Starling´s law

preload = diastolic muscle sarcomere length before

contraction (Fig.2,3)
- venous return to the heart is important!

- stretching of the sarcomere maximises the number of

actin-myosin bridges responsible for development of forc

- optimal sarcomere length ∼ 2.2 µm

 Myocardial contractility
Contractility of myocardium
Changes in developed force by contraction that occur
independently on changes in myocardial fiber length

Mechanisms involved in changes of contractility

• ↑ amount of created cross-bridges in the sarcomere
by changes of [Ca ++]i concentration

- catecholamines → ↑[Ca++]i→ ↑ contractility

- inotropic drugs → ↑[Ca++]i→ ↑ contractility
↑ contractility → shifting the entire ventricular function
curve upward and to the left
↓ contractility → shiffting the entire ventricular function
curve (hypoxia, acidosis) downward and to the right
 Afterload
It is expressed as tension which must be
developed
in the wall of ventricles during systole to open
the
Laplace law:
semilunar valve and eject blood to aorta/pulm.
art. intraventricular pressure x radius of ventricle
wall tension = --------------------------------------------------------
2 x ventricular wall thickness

↑ afterload: due to - elevation of arterial pressure

- ↑ ventricular size

↓ afterload: due to - ↓ arterial pressure

- myocardial hypertrophy
 Heart failure

Definition
It is the pathophysiological process in which
the heart as a pump is unable to meet
the metabolic requirements of the tissue for
oxygen and substrates despite the venous
return to heart is either normal or increased
 Terms explanation

Myocardial failure = abnormalities reside in the myocardi

and lead to decreased function of
myocardium

• Circulatory failure = any abnormality of the

circulation
responsible for the inadequacy in
body
tissue perfusion, e.g. decreased
blood
• Congestive heart failurevolume, changes of vascular tone,
heartsyndrome
= clinical disorders.which is developed
due to accumulation of the blood in fro
of the left or right parts of the heart
 General pathomechanisms involved in heart
failure development

Cardiac mechanical dysfunction can develop as a

consequence in preload, contractility and afterload
disorders

Disorders of preload

↑↑ preload → length of sarcomere is more than optimal →

→ ↓ strength of contraction

↓↓ preload → length of sarcomere is well below the optimal

→ ↓ strength of contraction
mportant : failing ventricle requires higher end-diastoli
volume to achieve the same improvement
of CO that the normal ventricle achieves
with lower ventricular volumes

Disorders of contractility
In most forms of heart failure the contractility of
myocardium is decreased (ischemia, hypoxia, acidosis
acidosi
inflammation, toxins, metabolic disorders )

Disorders of afterload
• fluid retention
∀↑ arterial resistance
• valvular heart diseases ( stenosis )
Causes of heart pump failure
A. MECHANICAL ABNORMALITIES
1. Increased pressure load
– central (aortic stenosis)

– peripheral (systemic hypertension)

2. Increased volume load
- valvular
regurgitation
– hypervolemia
3. Obstruction to ventricular filling
- valvular stenosis
- pericardial restriction
 B. MYOCARDIAL DAMAGE
1. Primary
a) cardiomyopathy
b) myocarditis
c) toxicity (alcohol)
d) metabolic abnormalities (hyperthyreoidism)

2. Secondary

a) oxygen deprivation (coronary heart disease)

b) inflammation (increased metabolic demands)

c) chronic obstructive lung disease

 C. ALTERED CARDIAC RHYTHM

1. ventricular fibrilation

2. extreme tachycardias

3. extreme bradycardias
 Pathomechanisms involved in heart failure
A. Pathomechanisms involved in myocardial failure

. Damage of cardiomyocytes → ↓ contractility, ↑↓ complian

Consequences:
• defect in ATP production and utilisation
• changes in contractile proteins
• uncoupling of excitation – contraction process
• ↓ number of cardiomyocytes

• impairment of relaxation of cardiomyocytes with

decrease compliance of myocardium
• impaired of sympato-adrenal system (SAS) → ↓
number
of β1-adrenergic receptors on the surface of
. Changes of neurohumoral control of the heart functio
functi

• Physiology: sympathetic systém → ↑ contractility

↑ HR
↑ activity of physiologic
pacemakers
Mechanism: • ↑ sympathetic activity →↑ cAMP
→↑[Ca ++]i→↑contractility
• ↑ sympathetic activity → ↓
influence
of parasympathetic system on
the heart
• Pathophysiology: normal neurohumoral control
is
changed and creation of
pathologic
neurohumoral mechanisms is
Chronic heart failure (CHF) is characterized by an
imbalance of neurohumoral adaptive mechanisms
with a net results of excessive vasoconstriction and
salt and water retention (Fig.6)
Catecholamines : - concentration in blood :
- norepinephrin – 2-3x higher than at rest
- circulating norepinephrin is increased much more
during equal load in patients suffering from CHF than in
healthy subject
-↓ number of beta 1 – adrenergic receptors →↓ sensitivity o
cardiomyocytes to catecholamines →↓ contractility
• System rennin – angiotensin – aldosteron
heart failure →↓ CO →↓ kidney perfusion →
stimulation of
RAA system
 Important:
atecholamines and system RAA = compensatory mechanism

↑ heart function and arterial BP

he role of angiotensin II in development of heart failu

• vasoconstriction ( in resistant vesels)

• retention of Na →↑ blood volume

• ↑ releasing of arginin – vasopresin peptide (AVP ) from

neurohypophysis
• facilitation of norepinephrine releasing from sympathetic
nerve endings

• ↑ sensitivity of vessel wall to norepinephrine

• mitogenic effect on smooth muscles in vessels and on

cardiomyocytes → hypertrophy
• constriction of vas efferens ( in glomerulus )

• ↑ sensation of thirst

• ↑ secretion of aldosteron from adrenal gland

• mesangial conctraction →↓glomerular filtration rate

 Pathophysiology of diastolic heart failure

systolic heart failure = failure of ejecting function of the hea

• diastolic heart failure = failure of filling the ventricles

↑ filling resistance of ventricles

• Which of the cardiac cycle is real diastole ?

• Definition of diastolic heart failure
is pathophysiological process characterized by symptom
nd signs of congestive heart failure, which is caused b
ncreased filling resistance of ventricles and increased
ntraventricular diastolic pressure

Primary diastolic heart failure

- no signs and symptoms of systolic dysfunction

! up to 40% of patients suffering from heart failure!
Secondary diastolic heart failure

- diastolic dysfunction is the consequence of primary

systolic dysfunction
 • Main causes and pathomechanisms of diastolic
heart failure

1.structural disorders →↑ passive chamber stiffness

a) intramyocardial – e.g. myocardial fibrosis, amyloidosis

hypertrophy, myocardial ischemia

b) extramyocardial – e.g. constrictive pericarditis

2. functional disorders →↓ relaxation of chambers

e. g. myocardial ischemia,
advanced hypertrophy of ventricles
failing myocardium, asynchrony
• Causes and mechanism participating on impaired
impaire
ventricular relaxation

a) physiological changes in chamber relaxation lead to:

– prolonged ventricular contraction
Relaxation of ventricles is not impaired

b) pathological changes in chamber relaxation lead to:

– impaired relaxation process

• delayed relaxation ( retarded )

• incomplete ( slowed ) relaxation

Consequences of impaired ventricular relaxation

- filling of ventricles is more dependent on diastasis and

systole of atrias
Symptoms and signs:
• exercise intolerance = early sign of diastolic failure

• ↓ coronary blood flow during diastole

• Causes and mechanisms involved in developmen
of ventricular stiffness

• ventricular compliance = passive property of ventricle

Norm : resistance of cardiomyocytes and other heart
tissue to stretching
• ↓ ventricular compliance is caused by structural
abnormalities localized in myocardium and in
extramyocardial tissue (Fig.11)

a. Intramyocardial causes : myocardial fibrosis,

hypertrophy of ventricular wall,
restrictive cardiomyopathy

b. Extramyocardial causes : constrictive pericarditis

(Fig.12)

The role of myocardial remodelling in genesis of

heart failure
• adaptive remodelling of the heart

• pathologic remodelling of the heart

Main causes and mechanisms involved in pathologica
remodelation of the heart

.Increased amount and size of cardiomyocytes = hypertroph

Due to: - ↑ volume and/or pressure load
(excentric, concentric hypertrophy)
- hormonal stimulation of cardiomyocytes by
norepinephrine, angiotenzine II

2. Increased percentage and influence of non-myocytar

cells on structure of myocardium
a., endothelial cells – endothelins :mitogenic ability →
stimulation growth of smooth muscle cells of vessels,
fibroblasts

b., fibroblasts - ↑ production of kolagens

 Symptoms and signs of heart failure

forward failure: symptoms result from inability of the hear

to pump enough blood to the periphery
(from left heart ), or to the lungs
(from the right heart)

a) forward failure of left heart: muscle weakness, fatigue,

dyspepsia, oliguria....

• generally: tissue hypoperfusion

b) forward failure of right heart: - hypoperfusion of the
lungs → disorders of gas
exchange

- decreased blood supply to the left heart

. backward failure: symptoms result from inability of
the heart to accept the blood coming
from periphery and from lungs

a., backward failure of left heart: increased pulmonary

capillary pressure → dyspnoea and tachypnoea, pulmonar
edema (cardiac asthma) → arterial hypoxemia and
hypercapnia

b., backward failure of right heart: increased pressure in

venous system → peripheral edemas, hepatomegaly ,
ascites - ↑nocturnal diuresis