Cardiac Failure and the

Therapeutics of Failure

Rebecca E. Gompf

Normal Heart Function Maintain blood pressure Perfuse lung and tissues Maintain normal venous pressure Maintain systemic and pulmonary

capillary pressures

Abnormal Heart Function

Low blood pressure Decreased tissue perfusion Increased venous pressures Increased capillary pressures

Factors of Cardiac Performance

Cardiac output = heart rate X stroke volume

Stroke volume = end diastolic volume-end systolic volume

Stroke VolumeSV = contractility X preload afterloadSince CO = HR X SV

ThenCO = heart rate X contractility X PL afterload

Preload Force that stretches ventricular

fibers Increases contractility at first Increases stroke volume Estimated as end diastolic

volume

Afterload Impedes ventricular contraction

and ejection of blood Due to vascular resistance Increases ventricular wall stress Increases work load of heart Decreases stroke volume

Contractility Sarcomere contraction Many factors affect it—cardiac

and systemic factors Increased contractility increases

stroke volume and vice versa

Compliance Pliability of the ventricles so that

they can fill. Influenced by wall thickness Also influenced by pericardial

diseases

Heart Rate Influenced by many factors Increased heart rate will increase

cardiac output up to a point Decreased heart rates can

decrease cardiac output

Synergy

Coordinated function of the atria and ventricles to optimize heart function

Arrhythmias disrupt synergy and decrease cardiac output

Heart Disease Abnormal heart Heart may or may not be in

failure Congenital Acquired 10% of dogs have heart disease

Circulatory Failure Insufficient cardiac output of any

cause One cause is heart failure

Heart Failure Heart cannot pump blood

presented to it-congestive Or heart cannot meet body’s

needs- output failure

Heart Failure Venous overload results in

congestion Inadequate perfusion

Heart Failure Normal heart=low diastolic size

and low venous pressure Failing heart=high diastolic size

and high venous pressure Failing heart=cardiac reserve is

used at rest

Heart Failure Congestive failure--edema,

effusions Low output failure

Heart failure Clinical syndrome Not a specific disease!

Left sided Congestive Heart Failure

Left sided congestive heart failure (CHF)

Cascade of events that starts with increased left ventricular diastolic pressure

Left sided congestive heart failure

Increased LV diastolic pressure Increased LA diastolic pressure Increased pulmonary venous

pressure

Left sided congestive heart failure

Increased pulmonary capillary hydrostatic pressure

Fluid into interstitial and alveolar areas

Pulmonary edema

Causes of increased LV diastolic pressure

Increased preload Decreased compliance Increased afterload Combinations of the above

Right sided congestive heart failure

Increased right ventricular diastolic pressures

Increased right atrial diastolic pressure

Increased central venous pressure

Right sided Congestive Heart Failure

Increased systemic capillary bed pressure

Edema (pleural effusion, ascites)

Causes of Right Sided CHF

Increased preload Decreased compliance Increased afterload Combination of above

Biventricular Heart Failure

Both sides of the heart fail

Low output failure Either right or left side cannot

pump enough blood to perfuse tissues

Dilated cardiomyopathy (end stage)

Causes of Heart Failure Pressure overload Volume overload Pump failure

Causes of Heart Failure Arrhythmias Myocardial restriction High output states

Pressure Overload Excessive afterload diastolic dysfunction Contractility ok Examples: subaortic stenosis,

pulmonic stenosis, hypertension

Volume Overload Excessive preload Systolic dysfunction Contractility ok at first Examples: Mitral regurgitation,

patent ductus arteriosus

Pump Failure Insufficient contractility Systolic dysfunction Low output failure Also, congestive failure

Pump Failure Dilated cardiomyopathy Ischemia/infarcts Chronic heart disease Dysenergy Drugs

Arrhythmias Changes in rate, rhythm, or

conduction Affects heart rate, synergy, and

ventricular filling Examples: tachycardias,

bradycardias, heart blocks

Myocardial Restriction Interferes with ventricular filling Diastolic dysfunction Contractility ok Examples: hypertrophic

cardiomyopathy, pericardial effusion

High output states Increased need for tissue blood

flow Heart is normal until later Examples: hyperthyroidism,

chronic anemia, chronic fever

Classes of Heart Failure

Mild Moderate Severe Modified NYHA Classes

Compensatory Mechanisms

Sympathetic Nervous System RAAS system activation Myocardial remodeling

Sympathetic Nervous System

Heart rate increased due to stimulation of Beta1 receptors on SA and AV nodes

Increases cardiac output at up to 2 ½ times normal rate

Sympathetic Nervous System

Increased contractility by stimulation of Beta1 receptors and epinephrine and norepinephrine

Effects blunted in chronic disease and can make things worse

Sympathetic Nervous System

Causes peripheral arteriolar vasoconstriction by stimulation of Alpha1 receptors

Prevents hypotension Creates increased afterload and

increased workload on the heart

RAAS System Increases preload to try to

increase cardiac output Activated by decreased renal

perfusion Renin released, converted to

angiotension I converted to angiotension II by ACE

RAAS System Angiotension II is potent

vasoconstrictor which increases afterload and preload

Angiotension II has adrenals release aldosterone so that sodium and water retained which also increases preload

RAAS System In early heart disease, can return

CO to normal In later heart disease, increases

preload which increases cardiac work load and increases failure

RAAS System Antidiuretic hormone (ADH)

released by increased angiotension II

ADH causes renal retention of fluid which increases preload

Myocardial Remodeling Chronic volume overload

increases diastolic stress Heart lays down more sarcomers

end to end Result is dilation of the heart and

eventually some hypertrophy (eccentric hypertrophy)

Myocardial Remodeling Chronic pressure overloads Heart lays down more sarcomers

in parallel so that wall becomes thicker

Concentric hypertrophy

Side Effects of Remodeling Dilated ventricle eventually has

decreased contractility Excessively hypertrophied

ventricle results in decreased lumen size, stiff ventricle, and decreased coronary artery filling

Clinical Signs of Heart Failure

Decreased cardiac output (exercise intolerance)

Pulmonary congestion (coughing, dyspnea)

See notes on hormones and cardiac failure p.96

Physical Exam Findings with Left Heart Failure

Possible murmur or gallop Tachycardias or bradycardias Coughing and/or dyspnea are the

main 2 signs

Physical Exam Findings with Left Heart Failure

Pulmonary crackles (rales), not always

Prolonged capillary refill time => decrease CO

Weak femoral pulses (not always)

Physical Exam Findings with Right Heart Failure

Systemic congestion (ascites in dogs, pleural effusion in cats, peripheral edema in horses, cows)

Hepatomegaly, splenomegaly Distended jugular veins Cardiac cachexia

Cats with Left or Right Heart Failure

Dyspnea is primary sign** Cats may or may not cough with

left heart failure (usually not detected)

Therapy Goals Reduce congestion Increase cardiac output Decrease cardiac work load Control arrhythmias, heart rate Treat cause of heart failure

Therapy Goals Modify the neurohormonal

compensation Modify cardiac remodeling Improve the patient’s quality of

life Increase patient’s longevity

RAAS Beta blockers decrease renin

release ACE inhibitors interupt

conversion of AGI to AGII ARBs (angiotension receptor

blockers) Aldosterone antagonists

Sympathetic Stimulation Beta blockers prevent stimulation

of heart by sympathetic system Alpha antagonists block alpha

one receptors in arterioles (over 50% dogs will get hypotensive). ACE I don’t cause hypotension.

Water retention

Diuretics counteract it ACE inhibitors also counteract it

Cardiac Remodeling ACE inhibitors and aldosterone

antagonists Beta blockers Arteriolar dilators to reduce

afterload Reduce preload with ACE

inhibitors and diuretics

Reduce Preload Diuretics ACE inhibitors Venodilators Low salt diet Do not reduce preload too much!

b/c these rely on preload for CO

Afterload Reduction ACE inhibitors - dilate Arteriolar dilators Must treat other diseases causing

the increased afterload. Hyperthyroid in cats

Don’t overdo it as get hypotension.

Increase Contractility Digoxin (wk. positive inotrope) Pimobendan (st. pos. inotrope) Catetcholamines IV Increases myocardial oxygen

demand and ATP consumption (down side)

Find and treat underlying disease

Increasing Compliance Calcium channel blockers may

relax heart Decrease heart rate so heart can

fill Remove pericardial effusion. This

is easy to do and rewarding. Find cause and treat

Heart Rate Must treat tachycardias or

bradycardias Antiarrhythmic therapy if needed. Find and treat any underlying

systemic problem contributing to the change in heart rate.

Restore Synergy

Treat significant arrhythmias with appropriate drugs

Treat heart blocks

Stabilize Patient Diuretics Cage rest Oxygen Venodilators Find and treat underlying problem

Positive Inotropes

Digitalis Pimobendan (newest ones) Catecholamines (emergency) Others

Positive Inotropes Affect calcium in some manner Used only with systolic function

with decreased contractility Increases oxygen and energy

used by heart, so heart works harder

Arrhythmogenic

Positive Inotropes Do not cure disease!!*** Efficacy varies b/t patients Give symptomatic improvement

is the goal of Tx

Digitalis Increases contractility in normal

and failing hearts Only increases cardiac output in

failing hearts Weak positive inotrope

Digitalis Negative chronotrope Increases myocardial excitability Better for volume overloads and

myocardial disease. Not good for pressure overloads.

Digoxin ECG Changes Seen mainly with toxicity Slower heart rate First degree heart block Mild ST changes (depression) Arrhythmias

Digitalis Digoxin Digitoxin Oral drugs Well absorbed but, absorption

decreased by food, drugs, and malabsorption states

Digitalis Digoxin eliminated by kidneys Slow oral method of dosing Cats (sick) are more intolerant of

digoxin. Don’t use it.

Digitoxicity Vomiting, diarrhea, anorexia Arrhythmias Negative inotrope Enhanced by hypokalemia, low

magnesium, hypercalcemia, and alkalosis

Digoxin Drug Interactions

Quinidine Aspirin (high levels) Amiodarone (same class w/

Sotalol) Spironolactone Cimetidine (decreases absorp of

Dig) Verapamil Chronic phenobarbital (increases

Dig levels)

Digoxin Crosses placenta Older dogs less tolerant of

digoxin Giants breeds need less Hypothyroid dogs have problems

unless being treated

Digoxin Levels

Run in human hospitals Low therapeutic index

Indications for Digoxin

SVT (Supraventricular tachycardia) or

Hearts with decreased contractility

Does not prevent progression of the disease process

Contraindications for Digoxin

Ventricular arrhythmias (severe) Animals with just a murmur Pericardial disease Restrictive cardiomyopathy Sinus node disease

Contraindications for Digoxin

AV blocks Hypertrophic cardiomyopathy Aortic stenosis Pulmonic stenosis Pulmonary hypertension

Pimobendan Inodilator = positive inotrope and

peripheral vasodilator Increases cardiac output Decreases preload and afterload Increases efficiency of cardiac

cells

Pimobendan Oral drug Well absorbed Out via feces Used in addition to other

medications (instead of digoxin)

Pimobendan No drug interactions But, it is a vasodilator so when

using other vasodilators, be careful of hypotension.

Negative inotropes may attenuate its positive inotropic effects

Pimobendan Side Effects Uncommon – yea! Vomiting/diarrhea-uncommon Polyuria/polydipsia-uncomon Anorexia-uncommon Sinus tachycardia at high doses Usually doesn’t worsen VPCs,

but can cause them at high doses

Pimobendan Efficacy in cats being studied Does not stop the progression of

the disease process Can accelerate the progression

of mitral regurgitation (murmurs) if used too soon in the disease. Don’t start p on this drug if just has murmurs.

Catecholamines Stimulates beta receptors and

cyclic AMP Synergistic with digoxin Metabolized in the liver (IV drugs)

Catecholamines Contraindications

Hypotension or hypertension Sinus tachycardia Arrhythmias Cardiac disease with mechanical

obstruction (aortic stenosis) With beta blockers

Epinephrine Increases heart rate (thru beta

receptors) Increases blood pressure Increases cardiac output

(contractility thru beat receptors) Increases arrhythmias Used mostly in CPR

Isoproterenol Increases contractility Increases heart rate Increases cardiac output Causes hypotension Used for heart block

Dopamine Increases contractility Increases heart rate (sinus

tachycardia) Increases blood pressure

(vasoconstricts) (dose dependent)

Dopamine Side Effects Tachycardias--high doses Arrhythmias--high doses Hypotension--low doses Hypertension--high doses

(vasoconstriction) Increases pulmonary capillary

pressure--high doses. Right heart to work against increased pressure

Dobutamine Hydrochloride

Increases contractility No vasodilatation or

vasoconstriction Cats can seizure or vomit Dogs can vomit

Dopamine versus Dobutamine

Same price now Dobutamine does not induce

tachycardias or affect peripheral vasculature

Both cannot be used more than 72 hours b.c they up regulate beta receptors and the receptors then become ineffective

Amrinone

Increases contractility Vasodilates Expensive

Diuretics

To relieve excessive fluid accumulation

Decrease preload Relieve signs of failure only

Types of Diuretics Xanthine derivative Thiazides Aldosterone inhibitors Ethacrynic acid Loop diuretics—furosemide –

used the most - Lasix

Xanthines Bronchodilators

Weak diuretics Weak positive inotropes Dilates coronary, pulmonary ,

renal, and systemic arterioles and veins (v little effect)

Bronchodilator

Bronchodilators

Aminophylline Theophylline

Bronchodilators

Metabolized in the liver Side effects: vomiting, sinus

tachycardia, hyperexcitability (MAY happen and could last for 8 hrs.)

Thiazide Diuretics

Effects are not dose dependent Not as potent as furosemide but

have a more sustained diuretic effect

New lipid soluable ones Not effective with compromised

renal function

Thiazides

Side effects uncommon Cheap No drug tolerance develops Can be used with other diuretics Well tolerated Effects aren’t dose related

Thiazides

Only disadvantage--only oral form

Drug interactions--penicillins

Aldosterone InhibitorsSpironolactone

Takes 2-3 days to be effective Weak diuretic Used in combination with other

diuretics Other benefits being explored Drug interactions—ACE inhibitors

Furosemide

Loop diuretic Effect is dose dependent Will dehydrate animal Comes in IV and oral forms Inexpensive

Furosemide

Side effects--hypokalemia, hyponatremia, dehydration, prerenal azotemia

Tolerance develops Drug interactions--cephaloridine,

polymixins, aminoglycosides

Vasodilators

Arterial dilators Venodilators Mixed vasodilators

Arterial dilators Counteract reflex

vasoconstriction of heart failure Decreases work load of left

ventricle Improves tissue perfusion Decreases mitral regurgitation

(indirectly) Side effect is hypotension

Venodilators Increase vascular capacity Decrease venous pressure (less

bld goes back to the heart) Decrease preload Decreases pulmonary edema

indirectly Side effect is decreased CO (be

careful with this)

Vasodilator Uses Chronic, congestive heart failure Valvular heart disease (leaky

valves) Congenital heart problems (PDA,

VSD) Pulmonary hypertension (some) Cardiac arrhythmias due to

hypoxia Hypertension

Vasodilator Contraindications

Hypotension Coronary artery disease (some) Poor cardiac contractility Tachycardias

Vasodilator Net Effects Decreased preload Decreased afterload Increases cardiac output Decreased workload of heart Antiarrhythmic

Hydralazine

Pure Arterial dilator Uses--dogs with mitral

regurgitation, hypertension Side effects in 50%--hypotension,

GI side effects, increased pulmonary artery pressures

Nitrates

Nitroglycerine ointment--venodilator, no side effects, topical

Sodium nitroprusside--IV, mixed vasodilator, metabolized to cyanide

Prazosin Arterial and venous dilator Metabolized in the liver Does not cause a reflex

tachycardia Unknown if animals develop a

tolerance to it or not.

Angiotension Converting Enzyme

Inhibitors (ACE)

Captopril (not used much b/c had many problems)

Enalapril Benazapril Lisinopril Other “Pril” drugs

ACE Inhibitors Stop conversion of angiotensin I

to angiotensin II in lungs Decreases plasma aldosterone

levels Increases blood flow to kidneys Effects are progressive

ACE Inhibitors Increases effects of thiazide

diuretics Causes retention of potassium Does not cross blood brain

barrier

ACE Inhibitors Used in: Dilated cardiomyopathy Mitral regurgitation Volume overloaded hearts

(shunts such as PDA, VSD) Advanced heart disease in

people

Enalapril Side effects uncommon--

hypotension Improves heart failure and

increases survival Takes 7-10 days to reach

maximum benefits Only one clinically tested in

animals

Enalapril Hard to use in renal patients so

use benazepril Improves dog’s quality of life and

increases longevity Use in cat needs more study Not effective in horses, not

absoped well in their GI tract

Beta Blockers’ Actions Decrease contractility (negative

inotrope) Decrease heart rate Decreases myocardial oxygen

consumption Blocks sympathetic stimulation of

heart

Beta Blockers

Used to slow AV conduction and slow heart rate with SVT

Also used in hypertrophic cardiomyopathy

Beta Blockers

Propranolol Atenolol Metroprol Carvedilol Other “–ol” drugs

Beta Blockers Side Effects Blocking beta 1 receptors in heart

will decrease contractility and heart rate

Blocking beta 2 receptors cause bronchoconstriction

Heart blocks Heart failure

Carvedilol Blocks beta 1 and beta 2

receptors Extends life span in people May help in dogs—studies

ongoing

All Beta Blockers Start at low dose and increase

gradually Do not stop abruptly Don’t start until heart failure

under control

Additional Therapy

Cage rest Low sodium diet Narcotics Removing accumulated fluids

Acute Pulmonary Edema Diuretics Cage rest with oxygen Nitrol ointment ACE inhibitors Hydralazine or nitroprusside Catecholamines

Pleural Effusion

Thoracentesis—but do NOT stress

Cage rest and diuretics

Chronic CHF Therapy Diuretics Venodilators—ACE inhibitors Treat the underlying heart

disease with appropriate drugs Beta blockers

Pressure Overload

Excessive afterload Systolic dysfunction Subaortic stenosis or pulmonic

stenosis Pulmonary hypertension Systemic hypertension

Volume Overload

Excessive preload Systolic dysfunction Mitral or tricuspid regurgitation Shunts--PDA, VSD

Pump Failure Systolic dysfunction Cardiomyopathies--dilated,

myocarditis Chronic heart disease Dysynergy Drugs

Arrhythmias Changes in rate, rhythm, or

conduction Affects heart rate, synergy and

filling of the ventricles Effect depends on ventricular

heart rate Bradyarrhythmias,

tachyarrhythmias

Myocardial Restriction

Diastolic dysfunction Restrictive cardiomyopathy Pericardial disease Tumors infiltrating myocardium Hypertrophic cardiomyopathy

High Output States

Excessive tissue demands Shunts Anemia Fever Hyperthyroidism

Cardiac Preformance

Preload Afterload Contractility

Cardiac Performance

Distensibility Heart rate Synergy