PATHOPHYSIOLOGY OF HEART FAILURE

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PATHOPHYSIOLOGY OF HEART FAILURE

• Prof. J. Hanacek

Technical co-operation L. urinová
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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 by blood

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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
vol.(SV)
- changes of the heart rate
- changes of stroke volume

• Control of HR

- autonomic nervous system
- hormonal(humoral) control

• Control of SV

- preload
- contractility
- afterload
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Relationship among preload, afterload,
contractility and heart performance
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Adaptive mechanisms of the heart
to increased load Starling
mechanism Ventricular hypertrophy
increased mass of contractile elements ?
?strength of contraction Increased
sympathetic adrenergic activity increased
HR, increased contractility Incresed activity
of RAA system
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Causes leading to changes of number and size of
cardiomyocytes
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Preload
Stretching the myocardial fibers during diastole
by increasing end-diastolic volume? ?force of
contraction during systole Starlings law
preload diastolic muscle sarcomere length
leading to increased tension
in muscle before its
contraction (Fig.2,3)

• venous return to the heart is important ?
  end-diastolic
• volume is influenced

• stretching of the sarcomere maximises the number
• of actin-myosin bridges responsible for
  development
• of force

- optimal sarcomere length ? 2.2 ?m
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Myocardial contractility
Contractility of myocardium Changes in
ability of myocardium to develop the force by
contraction that occur independently on the
changes in myocardial fibre length
Mechanisms involved in changes of contractility

• ? amount of created cross-bridges in the
  sarcomere
• by ? 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
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The pressure volume loop
It is the relation between ventricular volume
and pressure This loop provides a
convenient framework for understanding the
response of individual left ventricular
contractions to alterations in preload,
afterload, and contractility
It is composed of - filling of the
ventricle - isovolumic contraction of
ventricle - isotonic contraction of
ventricle(ejection of blood) - isovolumic
relaxation of ventricle
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Pressure volume loops recorded under different
conditions
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Afterload
It is expressed as tension which must be
developed in the wall of ventricles during
systole to open the semilunar valves and eject
blood to aorta/pulm. art.
Laplace law
intraventricular pressure x
radius of ventricle wall tension
--------------------------------------------------
------ 2 x
ventricular wall thickness
? afterload due to - elevation of arterial
resistance - ? ventricular
size - myocardial
hypotrophy
? afterload due to - ? arterial resistance
- myocardial
hypertrophy - ?
ventricular size
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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
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Explanation of the terms

• Myocardial failureabnormalities reside in the
  myocardium
• and lead to
  inability of myocardium to
• fulfilling
  its function

• Circulatory failure any abnormality of the
  circulation
• responsible
  for the inadequacy in body
• tissue
  perfusion, e.g. decreased blood
• volume,
  changes of vascular tone,
• heart
  functiones disorders.

• Congestive heart failure
• clinical syndrome which
  is developed
• due to accumulation of
  the blood in front
• of the left or right
  parts of the heart

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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
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Important failing ventricle requires higher
end-diastolic volume to
achieve the same improvement
of CO that the normal ventricle achieves
with lower ventricular volumes

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

• fluid retention in the body

• ? arterial resistance

• valvular heart diseases ( stenosis )

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Characteristic features of systolic
dysfunction (systolic failure) ventricular
dilatation reducing ventricular contractility
(either generalized or localized) diminished
ejection fraction (i.e., that fraction of
end-diastolic blood volume ejected from the
ventricle during each systolic contraction) in
failing hearts, the LV end-diastolic volume
(or pressure) may increse as the stroke volume
(or CO) decrease
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Characteristic features of diastolic
dysfunctions (diastolic failure) ventricular
cavity size is normal or small myocardial
contractility is normal or hyperdynamic
ejection fraction is normal (gt50) or
supranormal ventricle is usually hypertrophied
ventricle is filling slowly in early diastole
(during the period of passive filling)
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Causes of heart pump failure
A. MECHANICAL ABNORMALITIES
1. Increased pressure load
central (aortic stenosis, aortic coarctation...)
peripheral (systemic hypertension)
2. Increased volume load

• valvular regurgitation
• hypervolemia

3. Obstruction to ventricular filling
- valvular stenosis
- pericardial restriction
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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
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C. ALTERED CARDIAC RHYTHM
1. ventricular flutter and fibrilation
2. extreme tachycardias
3. extreme bradycardias
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Pathomechanisms involved in heart failure
A. Pathomechanisms involved in myocardial failure

• Damage of cardiomyocytes ? ? contractility,
• 
  ?? compliance

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 ?1-adrenergic receptors on the
  surface
• of cardiomycytes

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2. Changes of neurohumoral control of the heart
function

• Physiology SNS ? ? contractili
• ? 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 are
present
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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 at the rest than in
• healthy subjects

- 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 of cardiomyocytes to
  catecholamines ?
• ? ? contractility

System rennin angiotensin aldosteron
heart failure ?? CO ?? kidney perfusion ? stim.
of RAA system
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Important
Catecholamines and system RAA compensatory

mechanisms
? heart function and arterial BP
The role of angiotensin II in development of
heart failure
? vasoconstriction ( in resistant vesels)
? retention of Na ?? blood volume

• ? releasing of arginin vasopresin peptide (AVP
  )
• from neurohypophysis

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• 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
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Pathophysiology of diastolic heart failure

• systolic heart failure failure of ejecting
  function of
• the
  heart

• diastolic heart failure failure of filling the
  ventricles,
• ?
  resistance to feeling of
• 
  ventricles

Diastolic failure is a widely recognized clinical
entity
? Which of the cardiac cycle is real diastole ?
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Definition of diastolic heart failure
It is pathophysiological process characterized by
symptoms and signs of congestive heart failure,
which is caused by increased filling resistance
of ventricles and increased intraventricular
diastolic pressure
Primary diastolic heart failure

• no signs and symptoms of systolic dysfunction is
  
• present
• - ! up to 40 of patients suffering from heart
  failure!

Secondary diastolic heart failure
- diastolic dysfunction is the consequence of
primary systolic dysfunction
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? Main causes and pathomechanisms of diastolic
heart failure
1.structural disorders ?? passive chamber
stiffness

• 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 in heart
functions
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• Causes and mechanism participating on impaired
• ventricular relaxation

a) physiological changes in chamber relaxation
due to prolonged ventricular contraction
Relaxation of ventricles is not impaired
b) pathological changes in chamber relaxation due
to Impaired relaxation process
? delayed relaxation ( retarded )
? incomplete ( slowed ) relaxation
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? Consequences of impaired ventricular relaxation

• filling of ventricles is more dependent on
  diastasis
• and on the systole of atrias than in healthy
  subjects

Symptoms and signs
? exercise intolerance early sign of diastolic
failure
? ? coronary blood flow during diastole
? Causes and mechanisms involved in development
of ventricular stiffness
? ventricular compliance passive property of
ventricle
Source of compliance cardiomyocytes and other
heart
tissue to stretching
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? 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
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Main causes and mechanisms involved in
pathological remodelation of the heart
1.Increased amount and size of myocytes
hypertrophy
Due to - ? volume and/or pressure load
(excentric, concentric hypertrophy)
- hormonal stimulation of cardiomyocytes by
norepinephrine, angiotenzine II
2. Increased percentage of non-myocytic cells on
structure of myocardium and their influence
on structure of heart
a. endothelial cells endothelins mitogenic
ability ? stimulation growth of smooth
muscle cells of vessels, fibroblasts
b. fibroblasts - ? production of kolagens
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Symptoms and signs of heart failure

• forward failure symptoms result from inability
  of the
• heart 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....
? general mechanism tissue hypoperfusion
b) forward failure of right heart -
hypoperfusion of the
lungs ? disorders
of gas
exchange

• decreased blood supply
• to the left heart

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

• backward failure of left heart
• increased pulmonary capillary pressure ?
  dyspnoea
• and tachypnoea, pulmonary edema (cardiac
  asthma) ?
• ? arterial hypoxemia and hypercapnia....

b. backward failure of right heart
increased pressure in systemic venous system ?
? peripheral edemas, hepatomegaly , ascites
- ?nocturnal diuresis....