Heart FailureHeart Failure

Heart failure, also Heart failure, also called congestive called congestive heart failure, is a heart failure, is a disorder in which the disorder in which the heart loses its ability heart loses its ability to pump blood to pump blood efficiently.efficiently.

Causes of Heart FailureCauses of Heart Failure Coronary Artery Disease and Heart AttackCoronary Artery Disease and Heart Attack High Blood PressureHigh Blood Pressure Valvular DiseaseValvular Disease Other ConcernsOther Concerns a-a-DiabetesDiabetes. Diabetes is linked to obesity, high blood pressure, and coronary . Diabetes is linked to obesity, high blood pressure, and coronary

artery disease. These conditions also can contribute to heart failure. artery disease. These conditions also can contribute to heart failure. b-b-Alcohol abuseAlcohol abuse. Too much alcohol can damage the heart muscle and lead to . Too much alcohol can damage the heart muscle and lead to

high blood pressure, which is also a risk factor for heart failure. high blood pressure, which is also a risk factor for heart failure.

symptomssymptoms1-Edema leading to:1-Edema leading to: IN Tissues: IN Tissues: Swelling of Swelling of feetfeet and ankleand ankle Swelling of the abdomenSwelling of the abdomen In lungs: In lungs: Shortness of breathShortness of breath FatigueFatigue, , weaknessweakness 2-Decreased urine production2-Decreased urine production 3-Tachycardia3-Tachycardia

Compensatory mechanisms in Compensatory mechanisms in heart failureheart failure

Inadequate CO = decreased O2 delivery to tissues { So kidney and the brain get mad}

CO stimulate VMC & CAC in brain NE: from sympathoadrenal system reflex tachycardia + increases the after load (due to VC. of blood vessels) which requires the heart to do more work

CO decreased renal filtration pressure + increase in the sympathetic

supply to kidney release renin angiotensin II aldosterone (increase in preload & after load )

Enlarged heart and stretching in its muscle fibersEnlarged heart and stretching in its muscle fibers: (mainly due to in : (mainly due to in angiotensen II & aldosteron) angiotensen II & aldosteron) the heart enlarge, this eventually cause the heart enlarge, this eventually cause more weaking in heart.more weaking in heart.

All these effects make the heart muscle itself become more and more All these effects make the heart muscle itself become more and more

weekend. weekend.

Heart Failure DiagnosisHeart Failure Diagnosis

medical history medical history Any symptoms you may Any symptoms you may

have have

Also,to confirm a heart Also,to confirm a heart failure diagnosis:failure diagnosis:

Laboratory blood tests.Laboratory blood tests. Chest X-RaysChest X-Rays Electrocardiogram Electrocardiogram

(ECG)(ECG)

Medications for Treating Heart FailureMedications for Treating Heart Failure

1- 1- DiureticsDiuretics Most patients with heart failure require treatment with diuretics to Most patients with heart failure require treatment with diuretics to

relieve symptoms of fluid retention (edema and congestion), but relieve symptoms of fluid retention (edema and congestion), but their is no evidence that diuretics slow the progression of the their is no evidence that diuretics slow the progression of the disease or decrease mortality.disease or decrease mortality.

Loop diureticsLoop diuretics ( (furosemidefurosemide, , bumetanidebumetanide, , torsemidetorsemide) are the ) are the most effective diuretics most effective diuretics

Thiazide diureticsThiazide diuretics (e.g. (e.g. Hydrochlorothiazide ) Hydrochlorothiazide ) act on the distal act on the distal loop and are less effective than loop diuretics loop and are less effective than loop diuretics

-The most -The most serious adverse effect of diuretic therapy is potassiumserious adverse effect of diuretic therapy is potassium depletion (hypokalemia)depletion (hypokalemia) as it can lead to arrhythmia which can as it can lead to arrhythmia which can be prevented by use of supplemental potassium or a potassium-be prevented by use of supplemental potassium or a potassium-sparing diuretic (sparing diuretic (spiranolactone which also heart remodeling)spiranolactone which also heart remodeling)

2- 2- VasodilatorsVasodilators aa-Angiotensin-converting enzyme (ACE) inhibitors-Angiotensin-converting enzyme (ACE) inhibitors. . Examples include enalapril , lisinopril and captopril .Examples include enalapril , lisinopril and captopril . Mechanism of action :Mechanism of action :

-ACEI inhibits Ag II formation (most pressor agent) VD. of BV. In -ACEI inhibits Ag II formation (most pressor agent) VD. of BV. In pre- & after loadpre- & after load

-ACE inhibitors also inhibits the increase in aldosteron( Na &H2O retention -ACE inhibitors also inhibits the increase in aldosteron( Na &H2O retention as well as heart remodeling) as well as heart remodeling)

- ACE is also responsible for the inactivation of bradykinin, so that - ACE is also responsible for the inactivation of bradykinin, so that inhibition of this enzyme also leads to increased bradykinin level which can inhibition of this enzyme also leads to increased bradykinin level which can act as a local vasodilator agent.act as a local vasodilator agent.

Adverse effectsAdverse effects:: · Dry cough (due to bradykinin)………not used in asthmatic pat.· Dry cough (due to bradykinin)………not used in asthmatic pat. · Loss of taste· Loss of taste · Severe hypotension· Severe hypotension · Rash· Rash · Angioedema (due to bradykinin)· Angioedema (due to bradykinin)

b-Angiotensin II (Ag-II) receptor blockers These drugs, which include These drugs, which include losartanlosartan and and valsartanvalsartan have many of the have many of the

beneficial effects of ACE inhibitors, beneficial effects of ACE inhibitors, but they don't cause abut they don't cause a persistent persistent cough (they do not affect bradykinin metabolism)cough (they do not affect bradykinin metabolism). They may be an . They may be an alternative for people who can't tolerate ACE inhibitors. alternative for people who can't tolerate ACE inhibitors.

c-c-Nitrates:Nitrates:Ex. Glycerol trinitrate & Isosorbide dintrateEx. Glycerol trinitrate & Isosorbide dintrate 1-These drugs are prodrugs which ultimately form NO, a powerful 1-These drugs are prodrugs which ultimately form NO, a powerful

vasodilator· NO is capable of dilating all blood vessels ( pre- & after vasodilator· NO is capable of dilating all blood vessels ( pre- & after load). load).

2-They can improve symptoms and reduce mortality, but the less 2-They can improve symptoms and reduce mortality, but the less effective than ACE inhibitors.effective than ACE inhibitors.

Adverse effects of Nitrates:Adverse effects of Nitrates:· Postural hypotension · Postural hypotension · Tachycardia (mild and brief, resolves quickly) · Tachycardia (mild and brief, resolves quickly) · headache (central VD)· headache (central VD)· Flushing of the face· Flushing of the face

ββ-Blockers-Blockers

Beta-blockers were widely considered to be contraindicated for Beta-blockers were widely considered to be contraindicated for patients with heart failure (due to its –ve inotropic effect) ,only a patients with heart failure (due to its –ve inotropic effect) ,only a decade ago, they are now considered first-line therapy for decade ago, they are now considered first-line therapy for patients with patients with mild to moderatemild to moderate heart failure heart failure

Beta-blockers are contraindicated in patients with asthma or Beta-blockers are contraindicated in patients with asthma or

severe bradycardia , severe bradycardia , AV heart block and sinus bradycardia, diabetes.

Ex. Ex. Carvedilol:Carvedilol: A nonselective beta-blocker with alpha1-adrenergic A nonselective beta-blocker with alpha1-adrenergic

antagonist activity (vasodilator) ; this agent also possesses antagonist activity (vasodilator) ; this agent also possesses significant antioxidant properties which may be beneficial significant antioxidant properties which may be beneficial

• - - ββ blocking sympathetic effect on heart & blocking sympathetic effect on heart & kidney ( tachycardia & rennin angiotensin system)kidney ( tachycardia & rennin angiotensin system)

• - - αα1 blocking effect VD in blood vessels( pre -& 1 blocking effect VD in blood vessels( pre -& after load )after load )

3-Inotropic Drugs3-Inotropic Drugs

all of these drugs work by increasing the contractility of the heart.

Bottom Line: ALL INCREASE Ca2+i.

Digitalis (cardiac glycosides)Digitalis (cardiac glycosides) Digoxin is the most widely used preparation of Digoxin is the most widely used preparation of

digitalis, although digitoxin is also used digitalis, although digitoxin is also used Mechanism of Action The cardiac glycosidesThe cardiac glycosides partially partially inhibit the Na+/K+ - inhibit the Na+/K+ -

ATPase pump, which causes an increase in ATPase pump, which causes an increase in intracellular Na+, slowing the rate of the Na+,Ca++-intracellular Na+, slowing the rate of the Na+,Ca++-exchanger, and thereby causing an increase in exchanger, and thereby causing an increase in intracellular Ca++ ,thus increasing intracellular Ca++ ,thus increasing contractile force and CO

This increases in the force of contraction (This increases in the force of contraction (positive positive inotropic effectinotropic effect), increases renal perfusion ( this ), increases renal perfusion ( this why digoxin has diuretic effect in patients with why digoxin has diuretic effect in patients with CHF).CHF).

It decreases heart rate (It decreases heart rate (negative chronotropic negative chronotropic effecteffect), and decreases ), and decreases AV nodeAV node conduction velocity conduction velocity (indirectly by stimulating vagus nerve + its (indirectly by stimulating vagus nerve + its antiaderenergic effect) .antiaderenergic effect) .

Summary:Summary:– It inhibits Na-K ATPase, leading to increase

in: intracellular Ca, contractile force and CO

– It increases Conduction rate through heart specially ventricles Toxicity……arrhythmia)

– But it decreases AV nodal conduction (via vagus & antiadrenergic effect) which can leads to bradycardia & heart block.

-The increase in CO will cause decrease in sympathetic activity, Rennin Ang. System activity, cardiac load & cardiac remodeling & produce a diuretic effect.

Therapeutic effectiveness and toxicity of Digoxin depend on potassium levels

» Low potassium – leads to toxicity (arrhythmia) » High potassium – leads to decreased effectiveness –Adverse EffectsAdverse Effects & toxicity& toxicity CNS: CNS: Headache, weakness, drowsiness, visual disturbancesHeadache, weakness, drowsiness, visual disturbances

GI: GI upset, anorexia (as it stimulates CTZ in brain)GI: GI upset, anorexia (as it stimulates CTZ in brain) CV:- Arrhythmias (due to hypokalemia treated with CV:- Arrhythmias (due to hypokalemia treated with

lidocaine and KCl solution)lidocaine and KCl solution) -Partial or complete heart block (due to its indirect vagal and -Partial or complete heart block (due to its indirect vagal and

antiaderenergic effects on AV node which is treated with atropine)antiaderenergic effects on AV node which is treated with atropine)

--Fab fragment :Antibodies to digoxin to remove the excess free drug.

Other Inotropic drugs:Other Inotropic drugs:b-Beta1-agonistsb-Beta1-agonists Ex. Dopamine, dobutamine Ex. Dopamine, dobutamine have been used to treat acute and chronic heart failure (arrhythmogenic)have been used to treat acute and chronic heart failure (arrhythmogenic)

Dopamine (i.v.) is used in acute heart failure (cardiogenic shock) to Dopamine (i.v.) is used in acute heart failure (cardiogenic shock) to increase blood pressure and increase cardiac outputincrease blood pressure and increase cardiac output

Dobutamine is a somewhat selective beta1-adrenergic agonist that lacks Dobutamine is a somewhat selective beta1-adrenergic agonist that lacks vasoconstrictor activity and causes minimal changes in heart ratevasoconstrictor activity and causes minimal changes in heart rate

c-c-Phosphodiasterase inhibitorsPhosphodiasterase inhibitorsEx. Amirnone & milrinoneEx. Amirnone & milrinone They increase They increase myocardial and vascularmyocardial and vascular smooth muscle cAMP & c.GMP smooth muscle cAMP & c.GMP

concentrations through inhibition of phosphodiesterase activity concentrations through inhibition of phosphodiesterase activity

These agents therefore increase cardiac contractility and cause VD of BV These agents therefore increase cardiac contractility and cause VD of BV (reduce afterload and preload)(reduce afterload and preload)

Their main side effect ………arrhythmogenic.Their main side effect ………arrhythmogenic.