Institute of Pathological Physiology

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Institute of Pathological Physiology Martin
Vokurka mvoku_at_lf1.cuni.cz WS 2006/07
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HEART FAILURE
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normal situation
heart failure
congestion
backward
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normal situation
heart failure
decreased cardiac output
congestion
forward
backward
Insufficient organ perfusion muscles, kidneys,
skin, GIT
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heart insufficientlyfilled
decreased venous returne.g. shock bad filling
of the ventricles(e.g. constrictive
pericarditis)
decreased cardiac output
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heart changes
heart failure
decreased cardiac output
congestion
compensatory events
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HEART FAILURE
pathophysiologic 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
and/or can do so only from an abnormally
elevated diastolic volume
decrease of cardiac output
increase of the ventricular filling pressure
(enddiastolic pressure, EDP)
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Heart failure is not only failing of the heart as
a pump, but it is systemic disorder with
activation of hormonal processes, with changed
metabolism, changed regulation of water-mineral
balance, with cytokines involved, heart changes,
changesof gene expression etc. HEMODYNAMIC
ASPECTS NEUROHUMORAL ASPECTS CELLULAR AND GENE
EXPECT
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Frequency of heart failure
In the Czech Rep. the prevalence is about 1-2
(i.e. 100 000 of patients) The number of
patients is increasing among others due to
successful treatment of other heart diseases
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TYPES OF HEART FAILURE - LEFT-SIDED -
RIGHT-SIDED - BOTH-SIDED according to the
failing ventricle
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MAIN SYMPTOMES 1. CONGESTION - left-sided -
DYSPNEA, LUNG EDEMA - right-sided - LOWER
EXTREMITY EDEMAS, HEPATOMEGALY 2. DECREASED
CARDIAC OUTPUT WEAKNESS, FATIGUE, DECREASED
ORGAN PERFUSION
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Causes of heart failure
Myocardial failure - defect in myocardial
contraction (ischemia, cardiomyopathy) - loss of
myocardium (myocardial infarction) Excessive,
long-term hemodynamic burden - increased pressure
burden (systemic or lung hypertension) -
increased volume burden (valvular
abnormalities) - hyperkinetic cirkulation
(increased CO) Most commonly it is the
combination of CHD and arterial hypertension
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In heart failure CO decreases Activation of
compensatory mechanisms trying to increase CO
backto normal values
How are the distinct mechanism influencing the
COregulated ?
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Cardiac output (CO) heart rate (HR) stroke
volume (SV) 70 /min 70 ml 4 900 ml/min
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• Heart rate
• vegetative nerves
• (disturbances in) heart rhythm
• has impact of heart cycle duration, mainly
  shortens diastole when the heart is filling
  with blood
• Increases CO but high rates decrease the
  ventricle filling and heart is easier exhausted

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Cardiac output (CO) heart rate (HR) stroke
volume (SV) 70 /min 70 ml 4 900 ml/min
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• Stroke volume
• preload
• contractility
• - afterload
• How is the heart filled before the systole
• What is its force of contraction
• What is resistance against the pumping

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Preload filling of the heart at the end of the
diastole enddiastolic volume
EDV Frank-Starling mechanisms Volume in the
ventricle corresponds to the pressure
enddiastolic pressure, EDP, filling pressure
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• Factors influencing preload
• Venous return
• total blood volume
• blood distribution (position of the body,
  intrathoracic pressure, venous tonus)
• atrial systole
• size of ventricle cavity
• - intrapericardial pressure
• Low preload is the cause of the decreased CO in
  case of syncope and shock
• In heart failure the preload is not decreased but
  it is increased as one of the the compensatory
  mechanisms

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The relation between the filling of the
ventricleand the intraventricular
pressure diastolic filling curve volume EDV -
enddiastolic volume pressure EDP - enddiastolic
pressure, filling pressure - amount of the blood
in the ventricle - properties of the ventricle
wall
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J.Kofránek
intraventricular pressure
ventricle volume
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enddiastolicpressure (EDP)
enddiastolicvolume (EDV)
preload
changes in the ventricle geometry
pressure transfer to the regions precceding
the heart
dilatationincreased wall tensionincreased
oxygen consumptionfailure of Frank-Starling mech.
ventricle wall properties(compliance)ischemia -
impaired relaxationfibrosishypertrophy/dilatatio
n
P
L - lung edemaP - e.g. hepatomegaly
V
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Sympathetic nerves catecholamins
Izovolumic maxims
Intraventricular
pressure
Failing heart
Diastolic filling
Ventricle volume
J.Kofránek
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Izotonic maxims
Intraventricular
pressure
Isotonic maxims
Diastolic filling
Ventricle volume
J.Kofránek
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Denoting the condition in which a contracting
muscle shortens against an increasing
load.Relating to a muscle contracting to
accommodate an increasing load.
Isovolumic maxmis
Intraventricular pressure
Isovolumic contraction
Isotonic maxims
Auxotonic contraction
Diastolic filling
Isotonic contraction
Ventricle volume
J.Kofránek
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Intraventricular pressure
Isovolumic maxmis
Isotonic maxims
Diastolic filling
Ventricle volume
J.Kofránek
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J.Kofránek
Intraventricular pressure
Isovolumic maxims
Izotonic maxims
Diastolic filling
Increased preload...
Ventricle volume
increases cardiac output.
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J.Kofránek
Intraventricular pressure
Decreased preload...
Ventricle volume
decreases cardiac output.
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• Stroke volume
• preload
• contractility
• - afterload
• How is the heart filled before the systole
• What is its force of contraction
• What is resistance against the pumping

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Contractility Increasesympatic nerves,
catecholamines Decreasedischemia, hypoxia,
acidosis, proinflammatory cytokines, some drugs
etc. Decreased contractility is often the
causative mechanism of heart failure.
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Intraventricular pressure
Isovolumic maxims
Shifted isovolumic maxims
Catecholamines increase systolic volume
without increasing preload
Ventricle volume
J.Kofránek
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• Stroke volume
• preload
• contractility
• - afterload
• How is the heart filled before the systole
• What is its force of contraction
• What is resistance against the pumping

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• Afterload
• the force against which it contracts, the tension
  or stress developed in the ventricular wall
  during ejection
• - arterial pressure- systemic vascular
  resistence- blood viskosity
• geometry of the ventricle (Laplace law)
• T P r / d
• Increased volume of the ventricle and thiner wall
  (i.e. dilatation) increase afterloadcontribute
  to the decrease of COincrease requirements for
  oxygen

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Intraventricularpressure
Izovolumic maximx
Increase of afterload does not chane SV
Isotonic maxims
Diastolic filling
... but preload is increased
Ventricular volume
J.Kofránek
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Cardiac output
insufficiency
increased preload
Enddiastolic pressure
J.Kofránek
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Cardiac output
insufficiency
increased preload
Enddiastolic pressure
J.Kofránek
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Types of heart failure
According to the ventricle
Acc. to the intensity

• left-sided
• right-sided (cor pulmonale due to lung diseases,
  lung embolism etc.)
• both-sided

According to the course
According to the CO

• acute
• chronic (development of the compensatory
  mechanisms)
• compensated
• decompensated

• low-output (most)
• high-output (hyperkineticcirkulation)

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whether the principal abnormality is - the
inability to contract normally and expel
sufficient blood (systolic failure) - or to
relax and fill normally (diastolic failure)
Systolic failure
Blood ejection from the ventricle is
disturbed Stroke volume might be maintaind at
the costs of increased EDV (and EDP)
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Ejection fraction EF SV / EDV the ratio of
stroke volume to end-diastolic volume normal
value 67 8 percent SV 70 ml, EDV 120
ml EF 70 / 120 58
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Normal heart stimulated by the sympatic nerves -
EF increases, SV increases (contractility
increased) Heart with noncompensated systolic
failure - EF low, SV low Heart with compensated
systolic failure and increased preload - EF low,
SV might be normal (EDV is increased)
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EDV1
End of diastole 1
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SV1
ESV1
EF1 SV1/EDV1
End of systole 1
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SV2
ESV2
EF2 SV2/EDV2
EF2 gt EF1
End of systole 2
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EDV2
End of diastole 2
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SV3
ESV3
EF3 SV3/EDV3
End of systole 3
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SV1
ESV1
EF1 SV1/EDV1
EF1 gt EF3
SV1 SV3
End of systole 1
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Diastolic failure

• usually the decrease in compliance of heart wall
• EDP increases
• CHD
• Hypertension with hypertrophy
• Some cardiomyopathies etc.

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J.Kofránek
intraentricular
pressure
ventricular volume
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EDP measurement heart catheterization as a
pulmonary wedge pressure
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Evaluation / monitoring of hemodynamic heart
function

• - EF (ultrasound)
• - cardiac output (ultrasound or catheterization)
• EDP (catheterization)
• - Heart rate (HR)
• - Blood pressure (BP)

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Symptoms of heart failurefrom the hemodynamic
point of view
Low CO
Weakness, fatigue, decreased organ perfusion
incl. kidneys, muscles - redistribution of
CO FORWARD
Blood congestion in organs from which blood is
collected to the failing ventricle
Edemas etc. BACKWARD
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Apart from hemodynamic changes heart failure is
characterized by important involvement of
compensatory mechanisms, mainly neurohumoral,
which can, however, if persisting, lead to
further progression of failure. Another changes
involve the heart itself. Compensatory
mechanisms can in short-term have a positive
role, in long-term persistence contribute to
theworsening of the failure.
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• Main compensatory mechanisms in heart failure
• They lead to incrase (maintain) CO
• Sympatic activity
• Increase of preload
• Salt and water retention
• Myocardium changes
• Short-term effective, long-term have deletirious
  effectsthemselves and contribute to the symptoms
  and progressionof HF
• Vitious circle

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Sympatic activity inheart failure

• Heart rate
• Contractility
• Venous return

• CO

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Negative consequences
Tachycardia Increase in oxygen
consumption shortening of the diastole
(impairment of diastolic filling and myocardial
blood flow)
Increased risk for arrhytmias
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Norepinephrine cardiotoxicity (increase of
calcium in myocardium)
Periphery vasoconstriction increase of
afterload CO/blood flow redistribution
Metabolic action hyperlipidemia, hyperglycemia
During the heart failure the ? receptors in
myocardium are down-regulated
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Low doses of betablockers are nowadays used to
treat and improve the moderately severe heart
failure.
Extremely activated sympatic activity is in SHOCK
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Heart changes Reaction to biomechanical stress
(tension in the wall)and to neurohumoral
stimuli REMODELATION important for further
outcome of heart failure
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Dilatationprimary du to volume burdenthin
wall increased tension in the wall (higher r,
lower h)secondary from previous hypertrophy
(excentric hypertrophy) Hypertrophyconcentric
in hypertensionexcentric secund. in increased
volume burden and increased preload
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Molecular and cellular changes Angiotensin
IIendotelinIGF-Igrowth factorscytokinsIL-6ca
rdiotropin 1 etc. Distension leads to gene
expression, e.g. of the genes for natriuretic
peptides and fetal genes
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Heart changes cellular level - dysregulated
myogenesis (abnormal, embryonal growth) -
apoptosis Further worsening of heart function
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Consequences of heart changes - increased wall
tension in dilatation - increase in afterload and
oxygen consumption - impaired oxygen delivery in
hypertrophy - decrease of compliance - diastolic
failure - overstretched dilatation impairs
contraction and leads to relative valvular
insuficiency - arrhytmias - prognostic factor
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Water and salt retention increase in
preload Negative consequences - heart
dilatation - congestion, edemas - changes in
water/mineral equilibrium, sodium retention and
potassium depletion contributes to electrical
nestability of the myocardium
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cardiac output - decrease in effective plasmatic
volume
tissue perfusion
ADH
sympaticus
glomerular filtration
renin
angiotensin II
aldosterone sec. hyperaldosteronisms
periphery vasoconstriction
BP
ECT expansion
afterload
preload
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• Neurohumoral adjustments
• influence vasoconstriction, fluid retention,
  myocardium
• angiotensin II
• aldosterone
• natriuretic peptids
• norepinephrin
• ADH
• endotelin
• prostaglandins keeping the renal perfusion

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Cytokines in heart function / heart
failure Actionnegative inotropicproapoptoticfi
broplasticarrhytmogenic etc. Mainly
proinflammatory cytokines TNF?, IL-1,
IL-6 Originate in systemic inflammatory reaction
(inflammation, tumor)locally in heart failure as
a response to hemodynamic changes
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Right-sided failure
BACKWARD
FORWARD
decreased ejection from RV
decreased flow from RV to the lungs
EDV, EDP in RV
decreased flow to the left atrium
pressure in R atrium
cardiac output
volume and pressure in large veins
fluid retention
symptomes of decreased CO
volume in distensible organs (hepatosplenomegaly)
capillary pressure
edemas, transsudation (ascites, hydrothorax)
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Left-sided failure
BACKWARD
FORWARD
decreased ejection from LV
cardiac output
EDV, EDP in LV
tissue perfusion
kidney perfusion
pressure in L atrium
symptomes of decreased CO
volume and pressure in pulmonary veins
fluid retention
capillary pressure
fatigue, weakness pale skin impairment of organ
functions
fluid volume in the lung fluid transsudation to
the alveoli
pulmonary edema, dyspnea
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Left-sided failure
Right-sided failure
BACKWARD
decreased ejection from LV
EDV, EDP in LV
pressure in L atrium
volume and pressure in pulmonary veins
postcapillarypulmonary hypertension
capillary pressure
fluid volume in the lung fluid transsudation to
the alveoli
pulmonary edema, dyspnea
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left-sided failure
increase of filling pressure fluid retention
pulmonary edema
hypoxemia
dyspnea
-
increase burden forrespiratory muscles
myocardial hypoxia
impairment of myocardial contractility
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• Heart failure classification
• NYHA -New York Heart Associationaccording to
  the dyspnea
• Class I patients with no limitation of
  activities they suffer no symptoms from
  ordinary activities.
• Class II patients with slight, mild limitation
  of activity they are comfortable with rest or
  with mild exertion.
• Class III patients with marked limitation of
  activity they are comfortable only at rest.
• Class IV patients who should be at complete
  rest, confined to bed or chair any physical
  activity brings on discomfort and symptoms occur
  at rest.

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Principles of the treatment (acc. to Harrisons
Principles of Internal Medicine) - reduction of
cardiac work load - control of excessive fluid
retention - diuretics - vasodilator therapy -
improves (decreases) afterload - enhancement of
myocardial contractility - digitalis -
sympathomimetic amines - dopamine -
betablockers
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The End