Transcript Mechanisms of Heart Failure

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
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
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
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
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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
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
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.
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.
Pulmonary oedema:
Braunwald: Heart disease –p463
Braunwald: Heart disease –p463
Symptoms of heart failure
Reduced Exercise Capacity
• Dyspnoea - Pulmonary vascular congestion
• Insufficient blood flow to exercising muscles
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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.
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
Symptoms of heart failure
Congestive Symptoms
“Forward vs. Backward 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
Symptoms of heart failure
Congestive Symptoms
“Forward vs. Backward failure
– Left ventricle: Pulmonary congestion / oedema
– Right ventricle:
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Raised Jugular Venous Pressure
Hepatic congestion
Splancnic ooedema and ascites
Pleural effusion
Ankle oedema
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
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 <40%)
Generally accompanied by an increase in left ventricular end-diastolic
and end systolic volumes
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
Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion: HF
The Frank Starling mechanism -Increased preload helps to sustain cadiac
performance
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
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) Starling’s 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
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. Intraventricular pressure or reduction in wall thickness: see Laplace –
conditions that cause volume overload – I.e Aortic and mitral
regurgitation, dilated cardiomyopathies etc
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.
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
Pathophysiological mechanisms that causes raised
filling pressures and/ poor tissue perfusion: HF
The High Output States
• 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.
High output versus low output states
Systolic Failure:The 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
Narrows
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
•Paget’s disease
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.
Pathophysiological mechanisms that causes raised filling
pressures and/ poor tissue perfusion: HF
Diastolic dysfunction
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
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
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.
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
Diastolic dysfunction
Diastolic dysfunction
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.
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