chf dr.ramesh sir
TRANSCRIPT
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Heart Failure is the inability of the heart to pump an
adequate amount of blood to the bodys needs.
CONGESTIVEHEARTFAILURE
refers to the state in whichabnormal circulatory congestion
exists a result of heart failure.
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Congestive heart failure (CHF): pathophysiological
state in which the heart is unable to pump blood at a rate
commensurate with the requirements of the metabolizing
tissues or can do so only from an elevated filling pressure
Heart (or cardiac) failure: is an impairment of the
heart's ability to fill or empty the left ventricle leading to
a complex clinical syndrome characterized by fatigue,
shortness of breath, and congestion that are related to the
inadequate perfusion of tissue during exertion and often
to the retention of fluid.
Definitions:
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The Heart has the capacity to adapt to short-term changes
in preload or after load.
Progressivefailureofmyocardialfunctionisdue to :
Sudden or sustained changes in thepreload
(acute mitral regurgitation, excessive Left ventricular
hydration) .
Sudden or sustained changes in after load(aortic stenosis, severe uncontrolled hypertension).
Sudden or sustained change in demand
(from severe anemia, or hyperthyroidism).
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Pathophysiology of cardiac failure
Persistent compensatory mechanism
Leads to
Heart Failure.
Ventricular dilatation to increase Cardiac output
(compensatory mechanism)
Decrease in Cardiac output
Increase in Pre-load
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Persistent dilatation leads to
Congestive heart failure
Resistanceto outflow of blood
Ventricular dilatation
Increase In After-load(Hypertension)
Pathophysiology of cardiac failure
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Normal
Heart
PressureOverload
Volume overload
Increase systolic
pressure
Increase diastolic
pressure
Myocardial thickening Enlargement of Chambers of Heart
Eccentric Hypertrophy
Decrease Myocardial contractility
Pooling Of Venous Blood
Decreased Cardiac Output
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Left heart failure
IHD, Myocarditis,
Valvular heart diseases
Forward failureBackward failure
cardiac output
Tissue anoxia
renal perfusion
Activation of RAAS
PULMONARY
CONGESTION and
OEDEMA
Na+, H2O retention
Residual blood in left ventricle
Left atrial pressure and volume
Pressure in pulmonary venous circulation
Pulmonary arterial hypertension
Right ventricular pressure
SYSTEMIC VENOUS
CONGESTION and
PERIPHERAL OEDEMA
Right heart failure
Right side valvular disease
Rt side myocardial disease
Pulmonary hypertension
Congestive
Heart Failure
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Activation of NA, ANP
Tachycardia
CONGESTIVE
HEART FAILURE
Further stress on myocardium
Myocardial contractility
cardiac workload
Cell stretching
COMPENSATORY
HYPERTROPHY and
DILATATION
COMPENSATORY MECHANISMS
Lt. VENTRICULAR FAILURE
IHD, Myocardits, Valvular heartdisease
Rt. VENTRICULAR FAILURE
Pulmonary HT, Valvular heartdisease
Activation of RAAS
mechanism
Na+ and water
retention
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Neurohormonal
changes
Favorable effect Unfavorable effect
Sympathetic
activity
HR , contractility,
vasoconst. Vreturn,
filling
Arteriolar
constriction
After load workload
O2 consumption
Renin-
Angiotensin
Aldosterone
Salt & water
retention VRVasoconstriction
after load
Vasopressin Same effect Same effect
interleukins
&TNF-
May have roles in
myocyte hypertrophy
Apoptosis
Endothelin VasoconstrictionVR
After load
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PATHOGENESIS of HEART FAILURE
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Preload is the diastolic muscle sarcomere length leading to
increased tension in muscle before its contraction.
Pre load depends upon Starlings law.
Preload is directly proportional to End diastolic volume (EDV).
Preload
Starlings law :
Stretching the myocardial fibers during diastole by increasing
end-diastolic volume leads to increase in force of contraction during
systole.End diastolic volume(EDV) is the amount of blood
remaining in the ventricles at the end of the diastole.
When venous return (volume of blood returning to heart
increases), EDV increases.
Increase in EDV increases preload.
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After loadAfter loadis expressed as tension which must be developed in
the wall of ventricles during systole to open the semilunar valves
and eject blood to aorta/pulmunary artery.
After load depends on Laplace law.
Laplace law:
intraventricular pressure x radius of ventricle
wall tension = --------------------------------------------------------
2 x ventricular wall thickness
afterload is due to - elevation of arterial resistance- ventricular size- myocardial hypotrophy
afterload: due to - arterial resistance- myocardial hypertrophy
- ventricular size
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CausesofCongestiveheartFailure
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Myocardial infarctionChronic ischemia
Cardiomyopathy
ArrhythmiasDiastolic dysfunction
Valvular diseases
Aortic StenosisMitral Stenosis
Mitral Regurgitation
Predisposing Factors
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Precipitating Causes
Common Coronary Artery
Disease (70%)
SystemicHypertension
Idiopathic
Less Common
Diabetes Mellitus
Valvular Disease
Rare Anemia Connective Tissue Disease
Viral Myocarditis
Hemochromatosis
HIV
Hyper/Hypothyroidism
Hypertrophic Cardiomyopathy
Infiltrative Disease includingamyloidosis and sarcoidosis
Mediastinal radiation
Peripartum cardiomyopathy Restrictive pericardial disease
Tachyarrhythmias
Toxins
Trypanosomiasis (Chagasdisease)
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The signs and symptoms of heart failure (HF) are due
in part to compensatory mechanisms utilized by the
body in an attempt to adjust for a primary deficit in
cardiac output.
Signs and Symptoms
Shortness of breath
blood pooling in pulmonary veins fluid in lungs occurs during activity, rest, or
sleeping Persistent coughing/wheezing
produces white/blood mucus Edema (or excess fluid buildup in
body tissues) venous pooling swelling in extremities necrosis
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Tiredness/fatigue
decreased O2 supply
diversion of blood supply from limbs
Lack of appetite/nausea
decreased blood supply to digestive tract
Confusion / impaired thinking
Orthopnoea, paroxysmal nocturnal dyspnoea
Increased heart rate
baroreceptor reflex
SNS output
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Objectives of Treatment:
Increase cardiac contractilityDecrease preload ( left ventricular pressure)
Decrease afterload (systemic vascular
resistance)Normalize heart rate and rhythm.
Goals of treatment :
Alleviate Symptoms.Improve quality of life.
Arrest cardiac modeling.
Prevent sudden death.
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Pathophysiologic mechanisms of heartfailure and major sites of drug action
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Factor Mechanism Therapeutic Strategy
1. Preload (work or stress the
heart faces at the end ofdiastole)
increased blood volume and
increased venous tone--->atrialfilling pressure
-salt restriction
-diuretic therapy-venodilator drugs
2. Afterload (resistance against
which the heart must pump)
increased sympathetic
stimulation & activation of
renin-angiotensin system --->vascular resistance --->
increased BP
- arteriolar vasodilators
-decreased angiotensin II
(ACE inhibitors)
3. Contractility decreased myocardial
contractility ---> decreased CO
-inotropic drugs (cardiac
glycosides)
4. Heart Rate decreased contractility and
decreased stroke volume --->
increased HR (via activation of
b adrenoceptors)
Cl ifi ti f D d i C ti H t F il
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Classification of Drugs used in Congestive Heart FailurePositive Ionotropes :
Cardiac Glycosides : Digoxin
Phospho di esterase Inhibitors : Inamrinone, Milrinone
Sympathomimetics drugs : Dopamine, Dobutamine
Reduction in Preload :
Organic Nitrates : Glyceraltrinitrate.
Diuretics : Furosemide,
HydrochlorthiazideReduction in afterload :
Arteriolar Dilators : Hydralazine.
Reduction in Preload and afterload :
ACE Inhibitors : Enalapril, Ramipril, Lisinopril.Beta Blockers : Metaprolol, Carvedilol.
Aldosterone antagonists : Spirinolactone.
Novel Approaches :
Natriuretic Peptides : ANP, BNP, CNP
NEP Inhibitors : Candoxatril, Ecadotril,Sampatrilat
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derived from plants
Strophanthus - Ouabain
Digitalis lanata - Digoxin, Digitoxin
increase force of myocardial
contraction.alters electrophysiological properties.
Cardiac Glycosides
Fox Glove
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Digitalis purpurea Digitalis lanata
Strophanthus gratus
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Structure of Digoxin
Sugar moiety
Mechanism of action
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Mechanism of actionMechanism Of Action Of Positive Ionotropicity:Direct Effect: Inhibition of cardiac Na+ K+ ATPase.
Decrease Na+/Ca2+ exchange.Increases increase in intracellular Na+.
Increase in Intracellular Ca2+.
Increased release of Calcium from Sarcoplasmic reticulum.
Increases actin myosin interaction.
Increases force of contraction of myocardium.
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Mechanism Of Action for Negative Chronotropicity
Inhibits Neuronal Na+ K+ ATPase.
Increases Vagal activity.
Prolongs the effective refractory Period of Atrio
ventricular Node.
Decreases conduction Velocity.
Directly acts on Vagus nerve leading to M2
receptor stimulation decreases Acetylcholine and
decreases heart rate.
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T1/2 = 36 48 Hrs
Therapeutic plasma concentration: 0.5- 1.5 ng/ml
Toxic plasma concentration: >2 ng/ml
*digitalis must be present in the body in certain"saturating" amount before any effect on congestive
failure is notedthis is achieved by giving a large initial dose in aprocess called"digitalization.Principle tissue reservoir is Skeletal muscle.
Pharmacokinetics:
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Bioavailability : 70% - 80%
Route of Administration : Oral (common)
Intravenous (in acute emergency)
Metabolized in Liver.
Excretion is through Urine (unchanged).
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Properties DIGOXIN DIGITOXIN
Lipid solubility(oil/water coefficient) Medium High
Oral availability (%absorbed)
75 > 90
Half-life in the body(hrs)
40 168
Plasma protein binding
(% bound)
80
Volume of distribution 6.3 0.6
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ADVERSE EFFECTS
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Cardiac Manifestations :
Cardiac dysarrhythmias
Delayed AV conduction
Heart block ventricular tachycardia
Ventricular fibrillation
GI Manifestations:Nausea
Vomiting
Anorexia
CNS manifestations:Headache
Blurring of vision
Mental confusion
Yellow Tinted Vision.
ADVERSE EFFECTS
Interactions
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POTASSIUM
Hyperkalemia: reduces enzyme inhibiting actions ofdigitalis, abnormal cardiac automaticity is inhibited
Hypokalemia: facilitates enzyme inhibiting actions
CALCIUMFacilitates the toxic actions digitalis by accelerating the
overloading of intracellular calcium stores thatappears to be responsible for abnormal automaticity
Hypercalcemia: increases the risk of digitalis inducedarrhythmias
MAGNESIUM
Opposite to those of calcium.
Interactions
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Hypokalemia: Toxicity
WPW syndrome: VF may occur
Elderly, renal or severe hepatic disease: moresensitive to digitalis
Diastolic dysfunction of heart
Partial AV block: Complete block
Contraindications
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PHOSPHODIESTRASE INHIBITORS
InamrinoneMilrinone
positive inotropic effect.
increase rate of myocardial
relaxation.
decrease total peripheral
resistance and afterload.
Mechanism of Action
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Mechanism of Action
inhibition of type III phosphodiesterase intracellular cAMP
activation of protein kinase ACa2+ entry through L type Ca channels
cardiac output peripheral vascular resistance.
Site of Action Of
Phosphodiesterase Inhibitors
Pharmacokinetics
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Adverse Effects:Nausea
Vomiting
ThrombocytopeniaLiver enzyme changes (Hepatotoxicity)
Cardiac arrhythmias
Sudden death
Half-life : 2-3 hrs
Excretion : In urine (10-40% )
Route of administration : Parenteral
Pharmacokinetics
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Milrinone is ~1o fold more potent.
Milrinone has more selectivity for PDE III.
T 1/2 = 2.5 h for amrinone and 30-60 min for milrinone.
Effective in patients taking Beta-blockers.
Does not stop disease progression or prolong life in CHF
patients.
Prescribed to patients when they are non-responsive to
other therapies.
Sympathomimetics
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Sympathomimetics
Dopamine
Dobutamine
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Mechanism of Action:
Stimulation of cardiac b1-adrenoceptors:
inotropy leads to chronotropy leading to increase in
stroke volume and cardiac output.
Stimulation ofb2-adrenoceptors:
peripheral vasodilatation
Increase Myocardial Oxygen demand.
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Myocardial Contraction
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Route Of Administration:Parenteral
Contraindications:Pheochromocytoma
Tachyarrhythmia's
Adverse Effects:Precipitation or exacerbation of arrhythmias
Pharmacokinetics
Angiotenisin Converting
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Angiotenisin Converting
Enzyme inhibitors
Captopril
Enalapril
M h i Of A ti
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Inhibits angiotensin converting enzyme (ACE)
Prevents conversion of ATI to ATII
Decreases preload
Decreases afterload
Decreases cardiac remodeling
Mechanism Of Action
ACE Inhibitors
Acting Site
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ACE Inhibitors
Acting Site
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Adverse Effects
Cough
Angioneurotic edema
Hypotension
Hyperkalemia
Teratogenic
Organic Nitrates
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Organic Nitrates
Glyceryl trinitrate
Moderately volatile
Decreases oxygen demand of Myocardium.
Reduces Preload.
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Mechanism Of Action Of
Organic Nitrates
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Nitrates
Increase nitrites
Myocardial
relaxation
Ph ki ti
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Adverse effectsHeadache
Postural hypotension
Facial Flushing
Tachycardia
Pharmacokineticst1/2 of 1-3 minutes
Route of Administration : Sublingual tablet
or sublingual spray
Diuretics
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Diuretics
Drugs that increase the rate of urine flow.
Increase the rate of Na & Cl excretion.
Decrease reabsorption of K, Ca & Mg .
Loop DiureticsFurosemide
Thiazide diureticsHydrochlorothiazide
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Loop Diuretics :
Furosemide
Bumetanide
Torsemide
Mechanism Of Action
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Inhibits the coupled Na+/K+/2Cl symporter system in theluminal membrane of the thick ascending limb of the loop ofhenlereduce NaCl reabsorption.
Enchances K+ secretion.
Increases Mg & Ca+ excretion.
Induces synthesis of renal prostaglandins.
Increases renal blood flow.
Reduces pulmonary congestion & left ventricular fillingpressures.
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Pharmacokinetics
Bioavailability = 40-70 %
Route of administration : Oral / IV
Plasma Half Life: 1.5 hrs (Short acting)
Adverse Effects
Ototoxicity: tinnitus, hearing impairment, deafness,
vertigo, sense of fullness in ears.
Hypokalemic metabolic alkalosis
Hyperuricemia
Hypovolemia & cardiovascular complications
Thiazide diuretics:
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Thiazide diuretics:
Chlorthiazide
Hydrochlorothiazide
Inhibitors of Na+-Cl symport
Predominantly increase NaCl excretion
Primary site of action : Distal convoluted tubule
Mechanism Of Action
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Bind to Chlorine Binding
site of Na-Cl symport.
Inhibits the reabsorption
of Sodium (Na2+).
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Use of multiple drugs in the treatment of heart
failure. ACE = angiotensin-converting enzyme.
Treatment options for various stages of heart failure. ACE =
A i i i
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Angiotensin-converting enzyme;
ARB = angiotensinreceptor blockers. Stage D (refractory
symptoms requiring special interventions) is not
shown.
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