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Cardiac Failure

Presented by K.Harshitha

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ContentsDefinitionEtiologyClinical classification of cardiac failurePathophysiologyStages of cardiac failureCauses of cardiac failureMulti system effects of cardiac failureClassification of cardiac drugsMechanism of action of cardiac drugsDrug therapy and TreatmentReferences

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Definition of Cardiac failure Cardiac failure is a physiological state in which the heart cannot pump enough blood to meet the metobolic needs of the body.

• Cardiac failure occurs when the cardiac out put is inadequate to provide the oxygen needed by the body.

•The most common cause of cardiac failure is in Ejection fraction.

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Ejection fraction:

Etiology Cardiac performance is

depends on four essential components:

PreloadAfter loadContractility of the muscleHeart rate

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Preload: Volume of blood in ventricles at the end of

diastole

Due to CO Blood volume remains after systole

Stretch of myocardial fibers.But in failed heart Did not response

As heart failure worsens Preload contributes to symptoms

Dyspnoea Hepatic enlargement

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Afterload: The pressure against which the left ventricle ejects.

Systemic resistance CO

• Afterload is the tension or stress developed in the wall of the left Ventricle during ejection.

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Contractility of the muscle: It is the force of contraction generated by

the myocardium under loading conditions.

Heart Rate: it is the major determinant of the cardiac

failureAs the function of the heart in failure, an

in heart rate is the first compensatory mechanism.

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Clinical classification of Cardiac Failure:

According to the position • Backward failure • Forward failure

According to the location of heart failure• Left ventricular failure • right ventricular failure• Biventricular failure(Total Heart failure)

According to the cardiac out put• High output failure • low output failure

According to the function impaired• Systolic failure • Diastolic failure

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Backward failure : It is the condition of venous congestion arising from the damming of blood behind the failing chamber.

Forward Failure : it is the condition of inadequate perfusion. It results when reduced contractility produces stroke volume and cardiac output.

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Left ventricular failure(Left sided Heart failure) The failure of the left ventricle to maintain adequate

cardiac output.

In LVF basic fault lies in the heart muscles itself . Practically always result from damage to the ventricular myocardium.

Precipitating factors:

• MI• Hypertension• Dysrhythmias

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Right ventricular failure(Right sided Heart failure)

• Occurs when the right pump fails.• It develop as a result of the stress placed upon the right

ventricle it attempts to pumps blood against resistance into the patient’s congested lungs.

• Causes of right ventricular failurePulmonary diseasesConstrictive pericarditisTricuspid and pulmonic valve disordersInfarction of the right ventricle(rare)

Biventricular failure: LV Failure + RV failure

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High out put failure: It occurs when the body need excess oxygen. The heart increases out put but is still unable to meet body’s needs.

Low out put failure: It is the condition when the heart

is unable to pump an adequate supply of blood to the body.

• Low output failure results in Hypoperfused tissue cells.

• It occurs when the myocardium is so damaged that it cannot maintain adequate cardiac output.

• Right and left sided cardiac failure are sometimes referred to as low output failure.

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Systolic failure:Systolic dysfunction or ejection failure is the

inability of the ventricles to pump and empty adequately.

The ventricles are dilated and therefore need to develop higher tension in its walls to eject the blood efficiently.

Diastolic failure:Stiffening and loss of adequate relaxation of the myocardium during diastole.Cardiac out put is reduced but ejection fraction may benormal.

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Systolic Ventricles cannot pump

Dysfunction effectivelyDiastolic ventricles

cannot relaxDysfunction and fill during

diastole

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Systolic and diastolic heart compare with normal heart

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Pathophysiology of cardiac failure:

• Neurohumoral or extrinsic compensation involves two major mechanisms:

The sympathetic nervous systemRenin-angiotensin aldosterone

The most important intrinsic compensatory mechanism is Myocardial Hypertrophy or Ventricular Remodeling.

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Cardiac failure

Reduced CO Ses cardiac

filling Renin Sympathetic pressure NS activation Angiotension I vasoconstriction Na &

Water Angiotension II

retention

Aldosterone Cardiac remodeling

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Salt and water retentionDue to CO & RBF RAA

activation(renin angiotensin aldosterone activation)

Angiotensin Sympathetic activationAldosterone Causes salt and water

retention via renal tubulesBoth tries to compensate the low CO & low BPBut it can worsen the venous pressure(preload)More fluid accumulation in the interstitiumWorsens the signs of heart failure

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Ventricular remodeling:It is the most important intrinsic compensatory

mechanism referred as cardiac remodelingIt is the process of progressive of ventricular

size, shape and function owing to the influence of Mechanical, Neurohumoral and possibly genetic factors in clinical conditions including

• Myocardial infraction• Cardiomyopathy• Hypertension• Valvular heart disease

Hall marks are: Hypertrophy, loss of myocytes and interstitial fibrosis.

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Ventricular remodeling in diastole &systole

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Stages of Cardiac Failure: Stage A: A symptomatic with no heart damage but

have risk factors for heart failure.These could include persons with hypertension

diabetes, alcohol abuse, family history of cardiomayopathy.

Stage B: Asymptomatic but have signs of structural heart damage

Patients in this category may have left ventricular hypertrophy, valvular heart disease.

Stage C: Have symptoms and heart damage.Patients exhibit fatigue and dyspnoea as a result

of ventricular dysfunction Stage D: End stage cardiac failure

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New York Heart Association (NYHA) Classification of cardiac failure

Class-1 No limitation. Normal physical exercise does not cause fatigue,dyspnoea or palpitations

Class-2 Mild limitation. Comfortable at rest but normal physical activity produces fatigue,dyspnoea or palpitations

Class-3 Marked limitation. comfortable at rest but gentle physical activity produces marked symptoms of cardiac failure

Class-4 Symptoms of heart failure occur at rest and are exacerbated by any physical activity.

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Causes of Cardiac Failure® Dysfunction of myocardium

Myocardial damage Myocardial infraction Cardiomyopthay Myocarditis

Metabolic disturbanceIschemia and HypoxiaBeriberi

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Causes of cardiac failure cont’d…………….

• Overload of myocardium• Infection like lung infection• Arrhythmia• Tachycardia• Bradycardia• Excessive physical activity• Pregnancy and delivery• Anemia• Alcohol consumption, obesity• Dyslipidemia / Hypercholesterolemia

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Multisystem effects of cardiac failure:Respiratory system

Dyspnea on exertionShortness of breathTachypneaOrthopneaDry cough

Gastro intestinal Anorexia , nauseaAbdominal distentionLiver enlargementRight upper quadrant pain

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Multisystem effects of cardiac failure cont’d…….

Musculoskeletal FatigueWeakness

NeurologicConfusionImpaired memoryAnxiety , restlessnessInsomnia

Cardiovascular systemTachycardiaPalpitationsHepatojugular reflux

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Classification of the drugs:Cardiac Glycosides DigoxinOther positive inotropic drugs

Bipyridines Milrinone Beta adrenergic agonists Dobutamine , Dopamine

Drugs without positive inotropic effects Angiotension converting enzyme inhibitor(ACEI) Captopril ,

Enalapril , Lisinopril Diuretics Furosemide,Thiazide Angiotension II receptor blockers (ARB)

Losartan , Valsartan Vasodilators Hydralazine Beta Blockers Carvedilol , Bisoprolol , Metoprolol

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Drug Therapy:To increase force of contraction

Digoxin β agonists (dobutamine , dopamine)Bipyridines ( Milrinone)

To reduce cardiac workloadTo decrease preload(Diuretics , nitrates)To decrease afterload (arterial vasodilators)To decrease preload and afterload

(ACEI,ARB) (Nitrates , sodium, nitroprusside)To prolong the survival

β adrenoreceptor blockers

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Cardiac glycosidesDigoxin is the derivative of digitalis in

current useAll of the cardiac glycosides of which digoxin

is the prototype combine asteroid nucleus Cardiac glycosides are the extract of many

common plants Digitalis purpurea(red foxglove) Digitalis lutea

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Mechanism of action: Cardiac glycosides

Inhibit Na+ pump in cardiac cells Accumulation of intracellular Na+

Prevents extrusion of Ca+ entry of Ca++ into the cell

Intracellular Ca+ + Stored in sarcoplasmic reticulum

Ca++ released during each contraction force and velocity of contraction

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Mechanism of action of digoxinIt is the result of 2 step process

SERCA-sarcoplasmic endoplasmic reticulum calcium ATPaseRyR- Ryanodine receptor calcium channel, TnC- Troponin C

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Pharmacological action of digoxinCardiac effect• At therapeutic dose

Direct FOC of heartIndirect HR may leads to AV block

• At higher concentrationDirect Increase automaticity of heart

Indirect Sympathetic activation Both may lead to ventricular arrhythmias

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Therapeutic uses of digoxin

Heart failure with atrial fibrillation (use only when diuretics and ACEI have failed to control the symptoms

Mild symptoms Slow loading dose Acute heart failure Rapid

Digitalization

Treatment of atrial arrhythmia( atrial fibrillation & flutter)

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How digoxin corrects Cardiac FailureDue to FOC CO RBF (relieve

oliguria)Due to better tissue perfusion relieve

CyanosisDue to blockage of AV node , conducting

tissues Slow ventricular rate relieve tachycardia

Due to Co Better emptying of the ventricles increase venous return better drainage from the tissues with relief of congestion in the lungs and liver and reduction of oedema ,relief of dyspnea

Better results are obtained in patients with atrial fibrillation than with normal rhythm

Narrow therapeutic index (safety margin)

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Why digoxin is used in atrial fibrillation, flutter

In atrial flutter and fibrillation

Digitalis controls the excessive ventricular rate

Improvement is due to direct effect of digitalis as well as the effect of vagus on the SA node and conducting tissue

In atrial fibrillation , Reduction of ventricular rate is the best measure of glycoside effect.

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Adverse effects of digoxinCNS : Digitalis has little apparent CNS effect in

therapeutic doseHigher doses cause CTZ activation

nausea and vomitingHigher doses produces

Hyperpnoea Visual disturbancesDisorientationMental confusion

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Adverse effects of digoxin Cont’d…………..

CVS Ventricular arrhythmia Interaction with electrolytes

HypokalaemiaHypercalcaemia

d/t steroid structure gynaecomastia(rare)GIT : Gastrointestinal tract is most

common site of digitalis toxicity outside the heartANVD Anorexia , nausea , vomiting , diarrhea

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Digitalis ToxicityToxic effects may occur before the

therapeutic end point is detectedSerum digitalis , k+ levels and ECG should

be monitored during therapy of digitalis toxicity

In severe intoxication , serum k+ is already elevated , automaticity is depressed and antiarrhythmic agents may lead to cardiac arrest.

Digitalis antibodies(digoxin immune Fab)

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Positive inotropic drugs They increase the heart’s ability to pump more

effectively by improving the contractile force of the muscle.

It include selective beta agonists and BipyridinesDobutamine Mechanism of action: selective agonist on cardiac

activity Pharmacological action: Increase Cardiac output(CO)

Most commonly used inotropic agent other than digitalis

Mainly inotropic rather than chronotropic action Route of administration : Given by I.V infusion Adverse effects : cardiac arrhythmia Therapeutic use : used in acute decomposed heart

failure

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DopamineMechanism of action : Dose related action

D1,β1,α1Pharmacological action: Low dose activate D1

in RBFIntermediate dose activate β1

FOC,HR,CORoute of administration: Given by IV infusionAdverse effects: cardiac arrhythmiaTherapeutic use : used in acute decompensated

cardiac failure

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Bipyridines(Milrinone)Mechanism of action

• Inhibits phosphodiesterase type 3 enzyme• Decrease cAMP breakdown cAMP FOC of

heartPharmacological action : cause increase FOCRoute of administration ParentralAdverse effects Cardiac arrhythmiaTherapeutic use Acute heart failure or severe exacerbation of chronic heart failure

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Angiotension converting enzyme inhibitors (ACEI)

Plays a vital role in the management of cardiac failure due to systolic dysfunction . ACEI given in combine with diuretics.

ACE inhibitors promotes vasodilation and diuresis by decreasing afterload and preload

Decrease the secretion of aldosterone a hormone that causes the kidneys to retain sodium and water

Stimulate the kidneys to excrete sodium and fluid thereby reducing left ventricular filling pressure & decreasing pulmonary congestion

Patients receiving ACE inhibitors should be monitored for Hypotension , Hyperkalemia , alteration in renal function

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ACE Inhibitors : Captoprill,Enalapril,LisinoprilMechanism of action:• Inhibits angiotensin converting enzyme (which converts

angiotensin I to angiotensin II)• Reduce formation of angiotensin II • Angiotension II is the potent vasoconstrictor in body & it

causes production to aldosterone , which causes salt and water retention from kidney.

Pharmacological Action:• ACEI decrease the formation of Ang II and aldosterone• Atrial fibrillation Afterload• Venous dilation preload• Aldosterone action Salt & water retention Vascular volume• Sympathetic activation

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Diuretics• Eliminate excess body water and decrease

ventricular pressure.• A low sodium diet and fluid restriction

complement this therapy.• Some diuretics may have slight venodilator

properties.• Diuretics are used in chronic heart failure

usually in combination with others.

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Diuretics (Thiazide)Mechanism of action • Hydrochlorothiazide , chlorthalidone(milder

diuretics) inhibits Na +- Cl _ symport in PCT

(primary convoluted tubule) of nephronsPharmacological action• Mild diuresis action + venodilation action Can

cause salt and water excretion & reduction of preload

Route of administration : given orally Adverse effects : electrolyte imbalance

( especially Hypokalaemia which can worsen digitalis toxicity)

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Diuretics (Furosemide)Mechanism of action: • Highly potent loop diuretics inhibits Na+-k+-Cl- symport

in loop of Henley of nephrons.Pharmacological action: • Diuresis action + venodilation action + decreases in L.V

filling pressure• Can cause salt and water excretion & reduction of

preloadRoute of administration: available as oral as well as IVTherapeutic use: first choice in acute CHF to relieve

morbidityQuick onset , short durationAdverse effects: Hypotension,dehydration,temporary

deafness (with large doses),Hypokalaemia(offset by k sparing diuretics

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Angiotension II receptor blockers(ARB)Blocks the effects of Angiotension II at the Ang II

receptorACE inhibitors and ARBs have similar Hemodynamic effects: BP , systemic vascular

resistance, improved cardiac output ARBs are Used in patients who cannot tolerate ACEIdue to cough.

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Beta blockers:Epinephrine & nor epinephrine exert their

effects by binding to beta adrenergic in the heart and walls of the blood vessels.

β blockers bind to beta receptors thus obstructing the binding of catecholamines.

Hence β blockers reduce sympathetic of the heart and

blood vessels.Therefore ,beta blockers heart rate,

contractility and reduce blood pressure.

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Mechanism of Action of Beta blockers

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Vasodilators Ses the workload of the heart by dilating

peripheral vessels. By relaxing capacitance vessels(veins ,venules) ,

vasodilators decrease preload and volumes.Hydralazine predominantly affects arterioles ;

reduces arteriolar tone.Prazosin Balanced effect on both arterial

and venous circulation.Morphine venous return pain & anxiety.Sodium nitroprusside predominantly affects

arterioles.

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NitratesNitrates such as NTG , Isosorbate , NTG

ointment predominantly dilate systemic veins.Nitrates are useful for patients with pulmonary

congestion ,dyspnoea symptoms

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References:

Review articles from published journals.Principles of pharmacology by Sharma & Sharma.

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