chf dr.ramesh sir

7/30/2019 Chf Dr.ramesh Sir

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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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chf dr.ramesh sir

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