Mechanisms of heart failure

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Mechanisms of heart failure

• Definition of heart failure

Heart failure is a complex clinical syndrome that
can result from any cardiac disorder that
impairs the ability of the ventricle to eject
blood. The cardinal manifestations of heart
failure are dyspnoea and fatigue (which may limit
exercise tolerance) and fluid retention (Which
may lead to pulmonary and peripheral oedema).
Both abnormalities impair the functional capacity
and quality of life of affected individuals.
Consensus recommendations for the management of
chronic heart failure ACTION HF - AJC Jan 21,1999
vol 83(2A) - Packer M et al
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Definition of heart failure
"Heart failure occurs when an abnormality of
cardiac function causes the heart to fail to pump
blood at a rate required by the
metabolizing tissues or when the heart can do so
only with an elevated filling pressure. The
heart's inability to pump a sufficient amount of
blood to meet the needs of the body tissues may
be due to insufficient or defective
cardiac filling and/or impaired contraction and
emptying. Compensatory mechanisms increase blood
volume and raise cardiac filling pressures,
heart rate, and cardiac muscle mass to maintain
the heart's pumping function and cause
redistribution of blood flow. National Heart,
Lung and Blood Institute
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Mechanisms of heart failure

• Reduced volume of blood delivered to the systemic
  arterial bed.
• One or both ventricles has elevated filling
  pressures.
• Result Retention of sodium and water in the
  intravascular and intersititial compartments.
• Dyspnoea and oedema

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Symptoms of heart failure

• Dyspnoea - breathlessness - Increased awareness
  of respiration or difficulty in breathing .
• If due to cardiac causes it is usually due to
  left ventricular failure and pulmonary
  congestion.
• Pulm. capillary Hypertension
• Restrictive ventilatory defect -VC and TV reduced
• Lungs are stiffer -increased work of breathing
• Air trapping - earlier closure of dependent
  airways
• Airways resistance increased - congestion of
  peripheral airways.
• V/Q mismatch - hypoxaemia
• Increased ventilatory drive
• Stretch receptors pulm. vessels interstitium
• hypoxia acidosis
• Incr. Work of breathing impaired perfusion of
  resp. musc (low CO) - fatigue - dyspnoea

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Symptoms of heart failure

• Orthopnoea Dyspnoea present when recumbent and
  relieved by elevation. No. of pillows.
• Mech Reduced pooling of fluid in lower
  extremities and abd. Increased venous return
  Failing L Ventricle (flat portion of depressed
  F-S curve) - cannot accept extra volume -
  Increased pulmonary venous pressure - Pulmonary
  oedema

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Symptoms of heart failure

• Paroxysmal nocturnal dyspnoea
• Patient awakes suddenly with feeling of anxiety
  and suffocation - sits upright and gasps for
  breath.
• Bronchspasm (Wheezing - cardiac asthma)
• Congestion bronchial mucosa
• Compression of small bronchi by interstitial
  pulmonary. oedema.
• Increased work of breathing.

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Symptoms of heart failure

• Pulmonary oedema
• Increased pulmonary venous pressure - (failing
  LV)
• Increased pulmonary capillary pressures.
• Interstitial pulmonary oedema
• Reduced pulmonary compliance
• Increased airway resistance
• Dyspnoea.

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Pulmonary oedema
Braunwald Heart disease p463
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Braunwald Heart disease p463
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Reduced Exercise Capacity
Symptoms of heart failure

• Dyspnoea - Pulmonary vascular congestion
• Insufficient blood flow to exercising muscles
• Inadequate augmentation of CO with exercise.
• Impaired vasodilatation
• Abnormal skeletal muscle. Metabolism
• Deconditioning skeletal respiratory muscles
• Anxiety
• Grade cardiac status NYHA 1-4 - Degree of
  exertion - Determine if a change has occurred.

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Symptoms of heart failure

• Fatique and weakness -Poor perfusion of skeletal
  muscles.
• Impaired vasodilatation
• Abnormal skeletal musc. Metabolism
• sodium depletion / hypovolaemia / beta blockers.
• Urinary symptoms
• Nocturia - redistribution blood flow to kidneys
  at night.
• Cerebral symptoms
• Confusion, memory impairment, insomnia,
  disorientation, etc

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Congestive SymptomsForward vs. Backward failure
Symptoms of heart failure

• Fluid localizes behind the chamber initially
  affected.
• Pressure in the venous and capillary bed behind
  the failing ventricle rises - Transudation of
  fluid into the interstitial bed
• Fluid retention
• Reduced GFR
• Activation of RAAS

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Congestive SymptomsForward vs. Backward failure
Symptoms of heart failure

• Left ventricle Pulmonary congestion / oedema
• Right ventricle
• Raised Jugular Venous Pressure
• Hepatic congestion
• Splancnic ooedema and ascites
• Pleural effusion
• Ankle oedema

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Reduced cardiac contraction
• An increased cardiac load
• Valvular dysfunction
• Diastolic dysfunction
• High output states

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Reduced cardiac contraction myocardial failure

• Primary abnormality of the heart muscle -
  Cardiomyopathies/myocarditis
• Coronary atherosclerosis - Ishaemia and
  infarction of the muscle
• Longstanding excessive haemodynamic burden i.e
  valvular abnormality
• causing myocardial damage

Systolic dysfunction with a depressed LV ejection
fraction (usually lt40) Generally accompanied by
an increase in left ventricular end-diastolic
and end systolic volumes
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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Reduced cardiac contraction myocardial failure

• Adaptive mechanisms
• The Frank Starling mechanism -Increased preload
  helps to
• sustain cadiac performance
• Myocardial hyperthophy
• Neuro-hormonal actvation - to maintain arterial
  pressure and
• perfusion vital organs. Vasoconstriction and
• fluid and water retention

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• The Frank Starling mechanism -Increased preload
  helps to sustain cadiac performance

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• An increased cardiac load
• Cardiac output Stroke vol x heart rate
• Pre-load Contractility Afterload
• Preload Tension of the myocardial fibers at the
  end of diastole (degree of stretch) Venous
  filling pressure.
• Afterload Myocardial wall tension developed
  during systolic ejection LV resistance of
  aortic valve, peripheral vascular resistance and
  elasticity of major blood vessels. Laplace T
  PR/2xwall thickness. Ventricular wall tension is
  increased by ventricular dilatation, incr.
  intra-ventricular pressure or reduction in wall
  thickness

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• An increased cardiac load
• Preload
• HF Ejection fraction reduced increase in
  volume blood remaining after systole increase
  in diastolic volume and venous pressure.
• Depression of the ventricular function curve
• Slight myocardial depression CO maintained by
  increase in venous pressure (diastolic volume)
  Starlings law and HR.
• More severe myocardial dysfunction large incr.
  in venous pressure systemic and pulm. oedema.
  CO at rest may still be normal but fails to incr.
  with exercise
• Severe HF Decr. CO at rest CO redistributed to
  vital organs

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Afterload
• Systemic and pulmonary resistance
• Physical characteristics of the vessel walls
• The volume of blood that is ejected.
• Increase in after load decreases CO with an
  increase in end-diastolic volume which in turn
  increases afterload (Laplace)
• Examples (LV)
• Aortic stenosis
• Hypertension
• Elderly (Compliance vessels)
• Conditions which causes ventricular dilatation,
  incr. Intra-ventricular pressure or reduction in
  wall thickness see Laplace conditions that
  cause volume overload I.e Aortic and mitral
  regurgitation, dilated cardiomyopathies etc

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Mechanisms of load induced effects on cardiac
performance

• Myocardial remodelling in heart failure
• Geometric remodelling
• Change in myocardial gene expression
• Contractile proteiens (Myosin heavy chains),
  Na-K-ATPase,
• Ca-ATPase,Beta 1 adrenoreceptors
• Abnormal calcium homeostasis
• Prolongation of the calcium current in
  association with
• prolongation of contraction and relaxation
• (Decr. Sarcolemmm Ca-ATPase activty etc.)
• Apoptosis.
• Programmed cell death initiated cytokines, free
  radicals etc.

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Mechanisms of load induced effects on cardiac
performance

• Myocardial remodelling in heart failure
• Geometric remodelling
• Ventricular hypertrophy - compensatory mechanism
  of increased load
• Increase in size of cells, mitochondria,
  myofibrils,interstitial collagen
• Stimulus for hypertrophy
• Pressure overload
• Systolic wall stress increases
• Parallel replication of myofibrils
• Thickening of myocytes
• Concentric hypertrophy
• Volume overload
• Diastolic wall stress increases
• Sarcomeres replicates in series
• Elongation of myocytes
• Ventricular dilatation / eccentric hypertrophy

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The High Output States
Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Low out-put failure (commonest)
• Impaired peripheral circulation with systemic
  vasoconstriction and shunting of blood to the
  vital organs
• Cold, pale / cyanotic extremities.
• Pulse pressure may narrow
• High output failure Heart is required to pump
  abnormally large quantities of blood to deliver
  the required quota of oxygen to metabolizing
  tissues
• Reduced vascular resistance, increased vascular
  capacitance and blood volume
• Extremities are warm and flushed, pulse pressure
  may be wide
• Arterial-mixed venous oxygen difference normal or
  reduced due to delivery of large amounts of
  arterial blood to non-metabolizing tissues.

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High output versus low output states
Systolic FailureThe heart does not deliver the
quantity of oxygen required by the
metabolizing tissues. High output Low
output Cardiac output Rest N -high Low -
N Exercise Fail to rise normally Fail to rise
normally Arterial-mixed venous oxygen
difference Low (? N rest) High (? N
rest) (Admixture of blood diverted
from metabolizing tissue) Peripheral
circulation Blood volume Increased Vascular
resistance Reduced Increased Vascular
capacitance Increased Extremities Warm/flushed
Cold/pale/cyanotic Pulse pressure Widens Narr
ows
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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• The high output states

• Causes
• Hyperthyroidism
• Thyroid hormone Direct effect on cardiac
  contractility and
• Metabolism. Increased metabolic demands and decr.
  SVR
• Aneamia (O2 delivery blood flow x Hb x A V
  sat)
• Tissue hypoxia, decr. Blood viscosity, decr. SVR,
  incr. CO
• Beriberi
• Thiamine deficiency impairs pyruvate dehydrog.
• Accumulation lactate and pyruvate, periheral
  vasodilatation,
• decr. SVR, Incr CO. (also impairs myocardial
  metabolism)
• Pregnancy
• Arteriovenous fistulas Decreased SVR
• Pagets disease

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Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Valvular Dysfunction
• Mitral stenosis LA pressure incr., pulm. venous
  congestion, pulm. arterial hypertension, R heart
  failure.
• Mitral regurgitation LA dilates and pressure
  rises (compliance), LV dilates (vol. overload -
  proportion of CO regurgitated) CO increases. LV
  dysfunction Pulm. venous congestion due to
  mitral regurgitation and LV failure.
• Aortic stenosis Obstruction to LV outflow, LV
  hypertrophy (concentric pressure overload),
  relative LV ischaemia, LV dysfunction LV
  end-diastolic pressures and LA pressures rise,
  pulm. congestion.
• Aortic regurgitation Proportion of LV EF
  regurgitated,
• LV Dilates (volume overload) and CO
  increases. Diastolic pressure declines and
  coronary flow decreases. Dilated LV incr.
  myocardial O2 demand. LV dysfunction - LV
  end-diastolic pressures and LA pressures rise,
  pulm. congestion.

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Diastolic dysfunction
Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion HF

• Altered ventricular relaxation(isovolumetric
  relax. early vent filling phases)
• Dynamic process
• Uptake Ca sarcoplasmic reticulum Ca efflux from
  myocyte
• Sarcoplasmic retic Ca ATPase and sarcolemmal Ca
  pumps.
• Energy consuming

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Diastolic dysfunction

• Altered Ventricular Filling
• Early ventricular filling Myocardium lenghtens
  rapidly and in-homogeneously
• diastolic asynergy Regional variation in onset
  rate and extent of lengthening
• diastolic asynchrony temporal dispersion.
• End-diastolic filling
• Myocardial elasticity Change muscle length for
  change in force
• Ventricular compliance Change in volume for
  change in pressure
• Ventricular stiffness Inverse of compliance

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Diastolic dysfunction

• Increased chamber stiffness
• Rise in filling pressure. (steeper portion of
  pressure volume curve)
• Volume overload Acute valvular regurgitation /
  Acute LV failure - myocarditis.
• Steeper ventricular pressure volume curve
  Increase ventricular mass / wall thickness
  (hypertrophy) or intrinsic stiffness
  (infiltration, fibrosis, ischaemia)
• Pressure volume curve displaced parallel upwards
  (Decreased ventricular distensibility Extrinsic
  compression of ventricle. - constrictive
  pericarditis.

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Diastolic dysfunction

• Effects of ventricular interaction
• Ventricles anatomically interlinked
• Systolic ventricular interaction
• Septum part of load against which each ventricle
  must work
• LV hypertrophy includes septum R ventricle must
  work harder and becomes hypertrophied
• Diastolic ventricular interaction
• Bernheim effect/reverse
• Volume overloading of one ventricle impairs the
  filling/function of the other ventricle

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Diastolic dysfunction
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Diastolic dysfunction
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Left Heart Failure Leads to Right heart failure

• Left Ventricular Failure Causes Elevation of
• Left Ventricular diastolic
• Left Atrial
• Pulmonary venous pressures
• Backwards transmission of pressure
• Protective mechanism against Pulmonary Oedema
• Increased lymphatic drainage
• Capillary/alveolar barrier thickened and less
  permeable
• Constriction of pulm. resistance vessels
• Pulmonary vasoconstriction / Increased pulmonary
  vasc. resistance
• Pulmonary hypertension
• Ultimately Right Ventricular failure.

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Right Heart Failure due to Pulmonary Disease (Cor
Pulmonale)

• Chronic Bronchitis and Emphysema
• Hypoxia induced pulmonary vasoconstriction.
• Vasoconstrictive effect of hydrogen ions
• Pulmonary artery pressure correlates
• inversely with O2 sat
• directly with PCO2
• Muscular hypertrophy of pulmonary arterioles
• Increased blood viscosity - Increased hematocrit.
• Interstitial Pulm. Fibrosis / Vasculitides
• Reduction in cross sectional area of pulm. vasc.
  bed