PATHOPHYSIOLOGY OF HEART FAILURE

Prof. J. Hanacek Hanacek

Technical co-operation: L. urinov co-

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

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 SV:

- contractility - afterload

Adaptive mechanisms of the heart to increased load

Frank - Starling mechanism Ventricular hypertrophy
increased mass of contractile elements p ostrength of contraction

Increased sympathetic adrenergic activity

increased HR, increased contractility

Incresed activity of R A A system

Causes leading to changes of number and size of cardiomyocytes

Preload
Stretching the myocardial fibers during diastole by increasing endenddiastolic volume p oforce of contraction during systole = Starling 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 p end-diastolic endvolume is influenced

- stretching of the sarcomere maximises the number

of actin-myosin bridges responsible for development of force actin-

- optimal sarcomere length b 2.2 Qm

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 fibr

Mechanisms involved in changes of contractility

o amount of created cross-bridges in the sarcomere crossby o of ?Ca ++Ai concentration - catecholamines p o?Ca++Aip o contractility o?Ca

- inotropic drugs p o?Ca++Aip o contractility o?Ca

o contractility p shifting the entire ventricular function curve upward and to the left q contractility p shiffting the entire ventricular function curve (hypoxia, acidosis) downward and to the right right

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

Pressure

volume loops recorded under different conditions

Afterload
It is expressed as tension which must be developed in the wall of ventricles during systole to open the semilunar valves and valves eject blood to aorta/pulmunary artery Laplace law: intraventricular pressure x radius of ventricle wall tension = -------------------------------------------------------2 x ventricular wall thickness o afterload: due to - elevation of arterial resistance afterload: - o ventricular size - myocardial hypotrophy q afterload: due to - q arterial resistance afterload: - myocardial hypertrophy - q ventricular size

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

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

General pathomechanisms involved in heart failure development

Cardiac mechanical dysfunction can develop as a consequence in preload, contractility and afterload disorders Disorders of preload
oo preload p length of sarcomere is more than optimal p p q strength of contraction optimal qq preload p length of sarcomere is well below the optimal p p q strength of contraction

Important: failing ventricle requires higher end-diastolic volume endto 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, hypoxia, metabolic disorders... ) disorders...

Disorders of afterload due to:

fluid retention in the body o arterial resistance valvular heart diseases ( stenosis )

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

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 period of passive filling)

y end-diastolic ventricular pressure is increased

Causes of heart pump failure

A. MECHANICAL ABNORMALITIES 1. Increased pressure load
central (aortic stenosis, aortic coarctation...) stenosis, coarctation...) 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 (e.g. alcohol) (e.g. d) metabolic abnormalities (e.g. hyperthyreoidism) (e.g. hyperthyreoidism)

2. Secondary
a) oxygen deprivation (e.g. coronary heart disease) (e.g. b) inflammation (e.g. increased metabolic demands) (e.g. c) chronic obstructive lung disease

C. ALTERED CARDIAC RHYTHM

1. ventricular flutter and fibrilation 2. extreme tachycardias

3. extreme bradycardias

Pathomechanisms involved in heart failure

A. Pathomechanisms involved in myocardial failure 1. Damage of cardiomyocytes p q contractility,
oq compliance

Consequences:
y defect in ATP production and utilisation y changes in contractile proteins y uncoupling of excitation contraction process

y q number of cardiomyocytes y impairment of relaxation of cardiomyocytes with decrease compliance of myocardium

y impaired of sympato-adrenal system (SAS) p q number of sympatoF1-adrenergic receptors on the surface of cardiomycytes

2. Changes of neurohumoral control of the heart function

Physiology: SNS p o contractility contractility o HR o activity of physiologic pacemakers activity

Mechanism: y o sympathetic activity po cAMP p po?Ca po?Ca ++Ai p ocontractility y o sympathetic activity p qinfluence of parasympathetic system on the heart Pathophysiology: normal neurohumoral control is changed and creation of pathologic neurohumoral mechanisms are present

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

- q number of beta 1

adrenergic receptors p pq sensitivity of cardiomyocytes to catecholamines p p q contractility

System rennin

angiotensin

aldosteron

heart failure pq CO pq kidney perfusion p stim. Of RAA system stim.

Important:
Catecholamines and system RAA = compensatory mechanisms

o heart function and arterial BP

The role of angiotensin II in development of heart failure

y vasoconstriction ( in resistant vesels) y retention of Na po blood volume

y o releasing of arginin vasopresin peptide (AVP )

from neurohypophysis

y facilitation of norepinephrine releasing from

sympathetic nerve endings y o sensitivity of vessel wall to norepinephrine

y mitogenic effect on smooth muscles in vessels and

on cardiomyocytes p hypertrophy y constriction of vas efferens ( in glomerulus )

y o sensation of thirst
y o secretion of aldosteron from adrenal gland

y mesangial conctraction p qglomerular filtration rate

Pathophysiology of diastolic heart failure

y systolic heart failure = failure of ejecting function of the heart y diastolic heart failure = failure of filling the ventricles,
o resistance to filling of ventricles

Diastolic failure is a widely recognized clinical entity

But, which of the cardiac cycle is real diastole ?

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

Main causes and pathomechanisms of diastolic heart failure 1. structural disorders popassive chamber stiffness popassive
a) intramyocardial e.g. myocardial fibrosis, amyloidosis, hypertrophy, myocardial ischemia... ischemia... b) extramyocardial e.g. constrictive pericarditis

2. functional disorders p q relaxation of chambers e. g. myocardial ischemia, advanced hypertrophy of ventricles, failing myocardium, asynchrony in heart functions

Causes and mechanism participating on impaired ventricular relaxation

a) physiological changes in chamber relaxation due to: to: prolonged ventricular contraction Relaxation of ventricles is not impaired !

b) pathological changes in chamber relaxation due to: to: Impaired relaxation process y delayed relaxation (retarded) y incomplete (slowed) relaxation

y 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: y exercise intolerance = early sign of diastolic failure y q coronary blood flow during diastole

y Causes and mechanisms involved in development of ventricular stiffness

y ventricular compliance = passive property of ventricle Source of compliance: cardiomyocytes and other heart tissue to stretching

q 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

y adaptive remodelling of the heart y pathologic remodelling of the heart

Main causes and mechanisms involved in pathological remodelation of the heart

1.Increased amount and size of myocytes = hypertrophy Due to: - o volume and/or pressure load (excentric, concentric hypertrophy) hypertrophy) - hormonal stimulation of cardiomyocytes by norepinephrine, angiotenzine II 2. Increased % of non-myocytic cells in myocardium non-myocytic and their influence on structure and function of heart a. endothelial cells endothelins : mitogenic ability p p stimulation growth of smooth muscle cells of vessels, fibroblasts b. fibroblasts - o production of kolagens

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, heart:dyspepsia, oliguria.... oliguria.... y general mechanism: tissue hypoperfusion mechanism: b) forward failure of right heart: - hypoperfusion of the heart: lungs p disorders of gas exchange

- decreased blood supply

to the left heart

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

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

b. backward failure of right heart: increased pressure in systemic venous system p p peripheral edemas, hepatomegaly, ascites ponocturnal diuresis.... ponocturnal diuresis....