HEART FAILURE

Prepared by:•Sohail khan•Rana Rabnawaz•Momina zaib•Sufia yasmeen

INTRODUCTION• Inability of the heart to pump an

adequate amount of blood to the body’s needs

• CO is inadequate to provide oxygen needed by peripheral tissues

AFTERLOAD AND PRELAOD

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

• Preload is the stretch exerted on the muscle in the resting state. (diastolic phase.)

PATHOPHYSIOLOGICAL CAUSES OF FAILURE

Increased work load Increased work load

Improper Contraction of Improper Contraction of musclesmuscles

Compensatory mechanismsCompensatory mechanisms

PATHOPHYSIOLOGY OF CHF

CAUSES OF HEART FAILURE• Hypertension• Prolonged Alcohol or Drug Addiction• Previous Heart Attack• Chronic Rapid Heart Beats

SYMPTOMS OF HEART FAILURE

• Edema of the bronchial mucosa

• Pulmonary edema• Cardiomegaly• Edema in other body

parts• Tachycardia• Coughing• Dyspnea• Fatigue

Types of heart failure• SYSTOLIC DYSFUNCTION• DIASTOLIC DYSFUNCTION• HIGH OUTPUT FAILURE• ACUTE HEART FAILURE• CHRONIC HEART FAILURE

SYSTOLIC DYSFUNCTION (FORWARD FAILURE)

• Inadequate force is generated to eject blood normally

• Reduce cardiac output, ejection fraction (< 45%)Typical of acute heart failure

• Responsive to inotropics

DIASTOLIC DYSFUNCTION (BACKWARD FAILURE)

• Inadequate relaxation to permit normal filling • Hypertrophy and stiffening of myocardium• Cardiac output may be reduced • Ejection fraction is normal• Do not respond optimally to inotropic agents

HIGH OUTPUT FAILURE

• Increase demand of the body with insufficient cardiac output

• Hyperthyroidism, beri-beri, anemia, AV shunts• Treatment is correction of underlying cause

ACUTE HEART FAILURE

• Sudden development of a large myocardial infarction or rupture of a cardiac valve in a patient who previously was entirely well, usually predominant systolic dysfunction

CHRONIC HEART FAILURE

• Typically observed in patients with dilated cardiomyopathy or multivalvular heart diseases that develops or progresses slowly

COMPENSATORY MECHANISMS OF BODY DURING HEART FAILURE

• Three types of compensatory mechanisms

1. Neuronal Responses

2. Neuro-endocrinal system

3. Autoregulatory systems

Neuronal Responses

• Baroreceptors in the vascular system detect decrease in BP

• Enhanced sympathetic outflow to the heart and to peripheral vasculature

• Individual feeling status will also increase sympathetic system

• Results in release of nor adrenaline and catecholamines which increase heart rate and redistribution of blood to vital organs

• Kidney will also help by retention of water and electrolytes

•

Neuro-endocrinal system

• Reduced blood pressure will Stimulate the renin angiotensin system

• Reduced blood supply to kidney lead to secretion of renin

• Production of angiotensin II• Retention of water and electrolyte• Less oxygen supply to kidney enhances production of

erythropoetin which increases RBC’s production

FLOW CHART OF COMPENSATORY MECHANISMS

CARDIAC OUTPUT

BLOOD PRESSURE

SYMPATHETIC ACTIVITY

RENAL BLOOD FLOW

RENIN ANGIOTENSIN II

ALDOSTERONE

SODIUM RETENTION

Heart rate

Redistribution towards vital organs

Autoregulatory systems

• Neuronal structures of heart capable of secreting catecholamines due to anoximia

• Self stimulation of heart muscle called as catecholamine heart drive

• Do not work during congestive heart failure

ATRIAL NATRIURETIC FACTOR

• Atrio-peptide• Natriuretic and vasodilatory effect• Atrial muscle detects tachycardia• Releases atrio-peptide• Suppress aldosterone and vasopressin secretion• Suppress compensatory mechanisms

AUTOREGULATORY MECHANISMS

Oxygen supply

Self Stimulation of heart muscle

Release of catecholamine

Heart rate

Atrial pressure

Tachycardia

Atrio-peptide releases

Relaxation of blood vessels

Compensatory mechanism

STRATEGIES FOR CHF

• Increase cardiac contractility• Decrease preload ( left ventricular pressure)• Decrease after load (systemic vascular resistance)• Normalize heart rate and rhythm

REDUCE WORK LOAD OF HEART

1.Adjustment of heart rate(AV and SA nodal blocking agents)

2. Restrict sodium (low salt diet)

3. Give diuretics (removal of retained salt and water)

4. Give angiotensin-converting enzyme inhibitors(decreases afterload and retained salt and water)

5. Give digitalis (positive inotropic effect on depressed heart)

6. Give vasodilators (decreases preload & afterload)

STRATEGIES TO TREAT CHF

Factor Mechanism Therapeutic Strategy

1. Preload (work or stress the heart faces at the end of diastole)

increased blood volume and increased venous tone--->atrial filling pressure

-salt restriction-diuretic therapy-venodilator drugs

2. After load (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)

CLASSIFICATION OF DRUGS USE TO TRAET CONGESTIVE HEART FAILURE

• Drugs improving force of cardiac contractility(postive ionotropic)

• Drugs improving compensatory stresses upon the cardiac performance

Drugs improving force of cardiac contractility(positive ionotropic)

• Cardiac glycosides (digoxin,digitoxin)• Phospho-di-estrase inhibitors (Inamrinone)• Beta I agonists(dobutamine)

Drugs improving compensatory stresses upon the cardiac performance

• Diuretics(Thaizides)• Vasodilators(diazoxide,minoxidil)• ACE Inhibitors(captopril,inapril)• Angiotensin II receptor inhibitor(losartan,candisartan)• Beta-blockers (atinolol,propranol)

CARDIAC GLYCOSIDES

• Stimulates myocardial contractility(+ inotropic)• Improves ventricular emptying• Increase cardiac output• Augments ejection fraction• Promotes diuresis so lowers blood volume.• Reduce cardiac size• Used in acute congestive HF• Not used with diuretics • Reduces pace maker conduction by stimulating vegal

nerve

PHOSPHO-DI-ESTRASE ENZYME INHIBITORS(INAMRINONE,MILRENONE)

• Increase CAMP and CGMP levels that activates IP3• These enzymes inhibitors increase cytosolic ca level• Alter intracellular SR calcium • Increase cardiac contractility(positive ionotropic effect)• Cause vasodilatation• Reduce preload• Used in acute or refractory HF

Beta I agonists

• Stimulate cardiac muscles for rapid contractility• Increase cardiac output with decrease ventricular filling

pressure• Used in last stages when patients is in ICU in proper

monitoring• Used to keep alive the patients at last stages

DIURETICS(THIZIDES)

• Increase water secretion from kidney• Decrease blood volume• Redude oedema• Decrease venous return(reduce oxygen demand)• Reduce cardiac size • Decrease ventricular pre load• Improve cardiac efficiency• E.g Spironolactone• Aldosterone receptors inhibitors• Aldosterone cause myocardial and vascular fibrosis and baro-

receptors dysfunctioning• Beneficial in patients receiving ACE inhibitors

VESODILATORS

• Reduce TPR by dilating vessels• Reduce preload and after load• Beneficial in CHF

ACE INHIBITORS• Inhibits ACE • Reduce TPR• Reduce blood volume• Reduce sodium water retention by inhibiting aldosterone• Reduce after load and some how preload• Reduction in sympathetic outflow• Excellent drug for long term remodeling of heart and

blood vessels

Angiotensin II receptor inhibitor(losartan,candisartan)

• Block AT1 receptors on blood vessels• Reduce vasoconstriction • Reduce preload and after load • Used in patient with angioedema and cough

BETA-BLOCKER(atinolol,propranalol)

• Blocks beta I receptors on heart• Relax cardiac muscle by reducing cardiac work• Save from extra heart muscle exercise• Used in long term therapy

CARDIAC GLYCOSIDES

• Also called as cardinolides.• In 1875 William Withering wrote a treatise on Digitalis.• It was considered essential in the treatment of CHF.• It is used in chronic CHF. with chronic atrial fabriliation.• It is still extremely favoured drug.

Images of Cardiac GlycosidesImages of Cardiac Glycosides

Digitalis purpurea Digitalis lanata

Strophanthus gratus

ADVANTAGES:

• It has two main advantages

1. It is an inotropic agent ( increases myocardial contractility)

2. It can be administered orally.

DISADVANTAGES:

• Its therapeutic index is low.• Its correct dose, correct therapeutic blood level ranges

are uncertain.• It has many interactions.

CHEMISTRY:

• Molecule consisting of

1. A CPP ring

2. Sugar

3. Lactone• CCP ring + Lactone together is called Aglycon

CHEMICAL STRUCTURES OF CARDIAC GLYCOSIDES

BIOLOGICAL ORIGIN:

• Digitalis purpurea• Digitalis lanata• Stropenthus gratus• Stropenthus kombe• Most popular Cardiac glycoside is Digoxin and

Digitoxin

PHARMACOKINETICS OF CARDIAC GLYCOSIDES:

• Administration• Absorption• Metabolism• Excretion

ADMINISTRATION

• It is administered orally

ABSORPTION

• Digoxin is less lipid soluble than Digitoxin• Digitoxin completely absorbed after oral administration• Digoxin can be converted to ineffective agent by bacteria

of gut flora• Half life of digoxin is 1.5 days• Half life if digitoxin is 5 days

METABOLISM

• Therapeutic window of digoxin is narrow• Metabolized by liver microsomal enzymes• Digitoxin is converted to inactive products• Digitoxin is converted into digoxin after hydroxylation of

digitoxin• Digoxin level should be measured in patients receiving

this drug

THERAPEUTIC INDICATIONS OF DIGITALIS

• In chronic CHF with chronic atrial fibrillation• In chronic CHF with sinus rhythm

CONTRAINDICATIONS

• Obstructive cardiac myopathy• Diastolic dysfunction of heart• AV nodal block

ADVERSE EFFECTS

• Cardiac dysrhythmias• Delayed AV conduction• Heart block ventricular tachycardia• Ventricular fibrillation• Nausea• Vomiting• Anorexia• Headache• Blurring of vision• Mental confusion

FACTORS FACILLATING TOXICITY

• Depletion of serum potassium level• Concomitant use of drugs• Presence of renal failure• Hypothyroidism• Old age

PHARMACODYNAMICS OF DRUGS DEALING WITH CHF

• Cardiac glycosides (digoxin,digitoxin)• Phospho-di-estrase inhibitors (Inamrinone)• Beta 1 agonists(dobutamine)• Diuretics(Thaizides)• Vasodilators(diazoxide,minoxidil)• ACE Inhibitors(captopril,inapril)• Angiotensin receptor inhibitor(losartan,candisartan)• Beta-blockers (atinolol,propranol)

DRUG INTERACTIONS

• Cholestyramine, cholestipol• Quinidine • Beta blocker, verapamil,edrophonium• Erythromycin,omeprazole• Sypathomimetics• Thiazides

CARDIAC GLYCOSIDES• MODE OF ACTION:MODE OF ACTION:• Direct Effect on Myocardial contractility, and Direct Effect on Myocardial contractility, and

electrophysiological properties and also has vagomimetic electrophysiological properties and also has vagomimetic effecteffect

• Force of contraction:Force of contraction:• Dose dependent increase in force of contraction in failing Dose dependent increase in force of contraction in failing

heart – positive ionotropic effectheart – positive ionotropic effect• Systole is shortened and prolonged diastoleSystole is shortened and prolonged diastole• Contracts more forcefully when subjected to increased Contracts more forcefully when subjected to increased

resistanceresistance• Increase in cardiac output – complete emptying of failed Increase in cardiac output – complete emptying of failed

and dilated heartand dilated heart• Tone:Tone:

• Decrease end diastolic size of failing ventricleDecrease end diastolic size of failing ventricle• Reduction in oxygen consumptionReduction in oxygen consumption

Contd. ---Contd. ---

• Rate and Conduction: Rate and Conduction: 1.1. BradycardiaBradycardia2.2. Slowing of impulse generation (SAN)Slowing of impulse generation (SAN)3.3. Delay of conductivity of AVNDelay of conductivity of AVN

• Direct depressant action on SA and AV nodes Direct depressant action on SA and AV nodes (extravagal)(extravagal)

• Increase in vagal tone:Increase in vagal tone:• Is due to improvement in circulationIs due to improvement in circulation• Also due to direct stimulation in vagal center, Also due to direct stimulation in vagal center,

sensitization of baroreceptors and sensitization of SA sensitization of baroreceptors and sensitization of SA node to Achnode to Ach

Digitalis – mechanism of actionDigitalis – mechanism of action

EFFECTS ON HEART

• Increases force of myocardial contraction• Heart size

• Ejection fraction

• Refractory period in AV node and bundle of hiss

• Number and irregularity of ventricular contraction

VAGAL EFFECTS

• Vagal effects at early stages when there is minimum therapeutic value

• Slowed down the activity of pace maker• Relaxation phase• Ejection fraction

PHOSPHODIESTRASE INHIBITORS

• Mechanism of Action• inhibition of type III phosphodiesterase

intracellular cAMP activation of protein kinase A

o Ca2+ entry through L type Ca channels

• cardiac output

• peripheral vascular resistance

BETA I AGONIST

Mechanism of Action:Mechanism of Action:Stimulation of cardiac adrenoceptors: inotropy > chromotropy

peripheral vasodilatation

ACE INHIBITORS

• Mechanism of Action:• Afterload reduction

• Preload reduction

• Reduction of facilitation of sympathetic nervous system

• Reduction of cardiac hypertrophy

BETA BLOCKERS

• Mechanism of Action:

• influences in the heart (tachycardia, arrhythmias, remodeling)

• Reduction in damaging sympathetic inhibition of renin release

DIURETICS

• Mechanism of Action:• Preload reduction: reduction of excess plasma volume

and edema fluid • After load reduction: lowered blood pressure• Reduction of facilitation of sympathetic nervous system

VASODILATORS

• MODE OF ACTION:• Reduction in preload through venodilatation or

reduction in afterload through arteriolar dilation or both

ANY QUESTION