PATHOPHYSIOLOGY OF HEART FAILURE

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PATHOPHYSIOLOGY OF HEART FAILURE

• Prof. J. Hanacek

Technical co-operation L. Šurinová
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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 comming 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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Adaptive mechanisms of the heart
to increased load Frank - 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 4 phases - 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/pulmunary artery
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 failure abnormalities 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 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
les then 45) in failing hearts, the LV
end-diastolic volume (or pressure) may increse
as the stroke volume (or CO) decreases
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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) ?
end-diastolic ventricular pressure is increased
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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 (e.g. alcohol)
d) metabolic abnormalities (e.g. hyperthyreoidism)
2. Secondary
a) oxygen deprivation (e.g. coronary heart
disease)
b) inflammation (e.g. 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 ? ? 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 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
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 filling of ventricles

Diastolic failure is a widely recognized clinical
entity
But, 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
a) Intramyocardial causes myocardial fibrosis,
hypertrophy of
ventricular wall,restrictive
cardiomyopathy
b. Extramyocardial causes constrictive
pericarditis
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 of non-myocytic cells in
myocardium and their influence on structure
and function 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 comming 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....