23Heart Failure JH

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PATHOPHYSIOLOGY OF

HEART FAILUREProf. J. Hanacek

Technical co-operation: L. urinov


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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 tissueto the heart

Essential conditions for fulfilling these functions

normal structure and functions of the heartadequate filling of the heart by blood


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Essential functions of the heart are securedby integration of electrical and mechanical

functions of the heartCardiac 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-diastolicvolume is influenced

-stretching of the sarcomere maximises the numberof 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 forceby contraction that occur independently on thechanges in myocardial fibre length

Mechanisms involved in changes of contractility

amount of created cross-bridges in the sarcomereby ofCa ++i concentration

- catecholamines Ca++i contractility- inotropic drugs Ca++i contractility

contractilityshifting the entire ventricular functioncurve upward and to the left

contractilityshiffting the entire ventricular functioncurve (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 understandingthe 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 differentconditions


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It is expressed as tension which must be developed in the wall

of ventricles during systole to open the semilunar valves andeject blood to aorta/pulmunary arteryLaplace law:

intraventricular pressure x radius of ventriclewall 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

Afterload


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Heart failure

Definition

It is the pathophysiological process in whichthe 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 leadto inability of myocardium to fulfilling its function

Circulatory failure= any abnormality of the circulationresponsible for the inadequacy in body tissueperfusion, e.g. decreased blood volume, changesof vascular tone, heart functiones disorders

Congestive heart failure= clinical syndrome which is developeddue to accumulation of the blood in front

of the left or right parts of the heart


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General pathomechanisms involved in heartfailure development

Cardiac mechanical dysfunction can develop asa consequence in preload, contractility and afterload

disorders

Disorders of preload

preloadlength of sarcomere is more than optimal strength of contraction preloadlength of sarcomere is well below the optimal strength of contraction


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Important:failing ventricle requires higher end-diastolic volumeto 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 resistancevalvular 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 (>50%) or supranormal

ventricle is usually hypertrophied

ventricle is filling slowly in early diastole (during the periodof 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 fillingvalvular 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

1. Damage of cardiomyocytescontractility, complianceConsequences:

defect in ATP production and utilisationchanges 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 of1-adrenergic receptors on the surface of cardiomycytes


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2. Changes of neurohumoral control of the heartfunction

Physiology:SNS contractility HR activity of physiologic pacemakersMechanism: sympathetic activity cAMP Ca ++icontractility

sympathetic activity influenceof parasympathetic system on the heart

Pathophysiology: normal neurohumoral control ischanged and creation of pathologic

neurohumoral mechanisms are present


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Chronic heart failure (CHF) is characterized by an imbalance ofneurohumoral 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 moreduring equal load in patients suffering from CHF thanin 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 arterialBP

The role of angiotensin II in development of heartfailure

vasoconstriction ( in resistant vesels) retention of Na blood volume releasing of arginin vasopresin peptide (AVP )

from neurohypophysis


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sensitivity of vessel wall to norepinephrinemitogenic effect on smooth muscles in vessels and

on cardiomyocytes hypertrophy constriction of vas efferens ( in glomerulus ) sensation of thirst secretion of aldosteron from adrenal glandmesangial conctraction glomerular filtration rate

facilitation of norepinephrine releasing fromsympathetic nerve endings


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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

But, which of the cardiac cycle is real diastole ?

Diastolic failure is a widely recognized clinical entity


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Definition of diastolic heart failure

It is pathophysiological process characterized by symptoms andsigns 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 primarysystolic dysfunction


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Main causes and pathomechanisms of diastolicheart failure

1. structural disorderspassive 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. myocardialischemia, advanced hypertrophy of ventricles,

failing myocardium, asynchrony in heart

functions


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Causes and mechanism participating on impairedventricular relaxation

a)physiological changesin chamber relaxation due to: prolonged ventricular contraction

Relaxation of ventricles is not impaired!

b) pathological changesin 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 ismore dependent on diastasisand onthesystole 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 ventricleSource of compliance: cardiomyocytes and other heart

tissue to stretching


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Ventricular compliance is caused by structural abnormalitieslocalized 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 ofheart failure

adaptive remodelling of the heart pathologic remodelling of the heart


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Main causes and mechanisms involved inpathological remodelation of the heart

1.Increased amount and size of myocytes=hypertrophyDue to:- volume and/or pressure load

(excentric, concentric hypertrophy)

- hormonal stimulation of cardiomyocytes by

norepinephrine, angiotenzine II

2. Increased % ofnon-myocytic cellsin myocardium

and their influence on structure and function of heart

a.endothelial cellsendothelins : 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

1. 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 hypoperfusionb) forward failure of right heart:- hypoperfusion of thelungs disorders of gas

exchange

-decreased blood supplyto 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

a. 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....

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23Heart Failure JH

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