HEART FAILURE

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HEART FAILURE
BY Prof. Azza El-medany
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Heart failure

• Results from any structural or functional cardiac
  disorder that impairs the ability of the
  ventricle to fill with or eject blood to meet the
  body,s needs at rest or during exercise.

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Low out put failure
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Factors affecting cardiac output

• Intrinsic factors which regulate myocardial
  contractility .
• Extrinsic factors including contractile state of
  arterioles veins.

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Pathophysiology of cardiac performance in heart
failure

• - Intrinsic changes .
• Extrinsic changes.
• Intrinsic changes
• Myocardial hypertrophy to maintain cardiac
  performance in the face of adverse effects as
  decrease in myocardial contractility.

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• Extrinsic changes
• Decrease in cardiac output??renal blood flow??
  renin release ,? angiotensin 11?
• ?in after load, preload ,sympathetic
  discharge??cardiac output
• Remodeling Proliferation of connective tissue
  cells, abnormal myocardial cells.

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Clinical manifestations of heart failure

• Tachycardia, decreased exercise tolerance with
  rapid muscular fatigue, dyspnea ( pulmonary
  congestion) peripheral edema, cardiomegaly.

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Classification of Low out put Failure

• Left Heart Failure Most common due to L.V.S .
  Dysfunction
• Right Heart Failure In Pulmonary hypertension

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Classification of Heart Failure

• According to NYHA
• Class 1 No limitations on ordinary activities
  and symptoms occur only with greater than
  ordinary exercise.
• Class11 Slight limitation of ordinary activities
  , that result in fatigue palpitation

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• Class 111 No symptoms at rest, fatigue occur
  with less than ordinary physical activity
• Class 1V Is associated with symptoms even at
  rest

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High output failure

• Even though there is an increase in cardiac
  output still not enough to meet all the body
  needs as in hyperthyroidism, anemia.

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Drugs used in treatment of heart failure

• Drugs with positive inotropic effect as
• Cardiac glycosides
• Phosphodiesterase inhibitors
• ß- adrenoceptor agonist

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Drugs without positive inotropic effect

• Diuretics
• Aldosterone antagonist
• ACEI Angiotensin receptor blockers
• Vasodilators
• ß- adrenoceptor blockers

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Vasodilators

• The chose of vasodilators according to signs and
  symptoms and hemodynamic changes
• Selective venodilators as nitrate group is used
  when the main symptoms is dyspnea due to
  pulmonary congestion.
• Selective arteriodilators as hydralazine is used
  when the main complain is rapid fatigue due to
  low cardiac output.
• Non-selective vasodilators as ACEI

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Clinical uses of vasodilators

• Acute heart failure
• Chronic heart failure
• Long-term use of hydralazine isosorbide
  dinitrate can reduce remodeling of heart

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ACEI Angiotensin11 receptor blockers

• ? afterload
• ?preload
• ?sympathetic activity
• ?remodeling??mortality rate

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ß-adrenoceptor blockers

• Antagonism the enhancing action of sympathetic
  overactivity .
• Reduce mortality ( reduce the remodeling changes
  through inhibition the mitogenic activity of
  catecholamines.
• Inhibit renin release
• Some of them have antioxident activity
• E.g. carvedilol metoprolol

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Diuretics

• Reduce salt and water retention??ventricular
  preload .
• Reduction of edema and its symptoms
• Reduction of cardiac size ?improve cardiac
  performance
• Spironolactone has two benefitspotassium sparing
  effect inhibit the action of aldosterone .

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ß-agonist

• Dopamine acts on a ,ß1 and dopamine receptors.
• Dobutamine selective ß1- agonist.
• Both of them are given intravenously used in
  acute cardiac emergencies.
• Dopamine is effective in patients with impaired
  renal function.

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Adverse effects

• Tachycardia
• Angina
• Tachyphylaxis

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Phosphodiesterase inhibitors

• Bipyridines (Amrinone ,Milrinone )
• They are given only intravenously.
• Half-life 3-6hrs.
• 10-40 excreted in urine.

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Mechanism of action

• Inhibit phosphodiesterase enzyme (isozyme 3)
  in both cardiac smooth muscles resulting an ?
  in cAMP leading to
• - Positive inotropism .
• - Dilation in both resistance capacitance
  vessels (reduction in after load
  preload.)

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Therapeutic uses

• Used only for acute heart failure
• ( Short term use )

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Adverse effects

• Nausea ,vomiting
• Arrhythmias (less than digitalis )
• Thrombocytopenia
• Liver toxicity
• Milrinone less hepatotoxic and less bone marrow
  depression than amrinone.

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Digitalis (cardiac glycosides )

• Origin
• Chemistry
• Preparations

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Structure o of cardiac glycoside
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Pharmacokinetics

• Oral availability
• Ouabain Digoxin
  Digitoxin
• 0 75
  gt 90
• Half- life
• 21 40
  168
• Plasma protein binding
• 0 20-40 gt
  90
• Percentage metabolized
• 0 lt 40 gt
  80

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Pharmacodynamics

• At the molecular level cardiac glycosides inhibit
  Na / K ATP ase (sodium pump ).
• Cardiac effects
• A) Mechanical
• B) Electrical

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Mechanism of action
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(A) MECHANICAL EFFECT
Increase in myocardial contractility
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(B) ELECTRICAL EFFECTS
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At Therapeutic Doses

• A)
• Slow conduction through S.A.N. A.V.N.
• ? prolong conduction time between atrium and
  ventricles ( prolong P-R interval in ECG.) .
• B)
• Short duration of action potential refractory
  periods of both atrium ventricles (Short in QT
  interval ).

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At Toxic Doses

• ? in automaticity of ectopic focus ?All forms of
  arrhythmias can be detected - - Second-degree
  of A-V block.
• - In Purkinje conducting system leading
  bigeminy rhythm.

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Extra cardiac effects

• GIT Anorexia, nausea,vomiting, diarrhea.
• C.N.S. Disorientation,hallucination,visual
  disturbances, agitation, convulsions.
• Gynecomastia
• Kidney Diuretic effect
• Improve renal function .
• Inhibit Na reabsorption from P.C.T.

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Adverse effects

• Heart
• All forms of cardiac arrhythmias
• GIT
• C.N.S.
• Skin rash
• Gynecomastia

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Contraindications

• Toxic myocarditis
• Constrictive pericarditis
• Cardioversion
• Digitalis are effective in H.F. due to
  hypertension, atherosclerosis or ischemic heart
  diseases.

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Factors increase digitalis toxicity

• Small Lean body mass
• Renal disease
• Hypothyroidism
• Hypokalemia
• Hypomagnesemia
• Hypercalemia

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Treatment of digitalis toxicity

• Stop drug
• Potassium therapy
• Cholestyramine
• Atropine
• Lidocaine
• Fab antibodies in life-threating or severe cases.

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Clinical uses

• Heart failure ( LVSD)
• 2-Atrial flutter or fibrillation

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Drug interactions

• Diuretics? hypokalemia (arrhythmia)
• Quinidine ?plasma level of digitalis through
  (1) displaces from protein binding sites (2)
  ?renal clearance.
• Antibiotics that alter intestinal flora ?digoxin
  bioavailability
• Agents that release catecholamines sensitize
  myocardium to digitalis to induce arrhythmias.

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Management of chronic heart failure

• Reduce work load of the heart
• Limit activity
• Reduce weight
• Control hypertension
• Restrict sodium
• Diuretics
• ACEI or receptor blockers

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Cont.

• Digitalis
• ß- blockers ( class II-IV stable HF)
• Vasodilators

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Management of acute heart failure

• Volume replacement
• Diuretics
• Positive inotropic drugs
• Vasodilators