Clinical Management of Heart Failure

Question 1

Describe the major presenting signs of a dog or cat with heart failure

Answer 1

Signs depend on whether the heart disease is causing forward failure, left sided or right sided congestive failure

• Exercise intolerance / lethargy
• Depression
• Pallor
• Syncope
• Respiratory difficult
  
  • Dyspnoea
  • Tachypnoea
  • Cyanosis
• Cold extremities
• Abdominal effusion / ascites
• Subcutaneous oedema

Question 2

Describe the examination and testing findings to confirm a diagnosis of heart failure.

Answer 2

1. Historical findings consistent with cardiac insufficiency
   
   • appropriate clinical signs
   • Previously identified cardiac disease
2. Clinical examination confirming the presence of cardiac disease - note specific cardiac abnormalities may not always be evident on routine examination
   
   • Heart murmur or gallop rhythm
   • Arrhythmia
   • Tachycardia
   • Pulse deficits
3. Thoracic radiographs
   
   • Cardiomegaly and pulmonary oedema
   • Pleural effusion
4. Echocardiography - gold standard
5. ECG - to identify arrhythma and likely origin
6. NT-ProBNP

Question 3

List the circulatory abnormalites that may be present in heart failure

Answer 3

• Abnormalities of Preload (changes to wall stress)
• Abnormalities of afterload
• Abnormalities of myocardial contractility
• Abnormalities of cardiac filling (diastolic function)
• Abnormalities of heart rate +/or rhythm

Question 4

Note the changes to cardiac function with an increased preload.

Which medications can be used to reduce preload?

Answer 4

• Increased preload is essentially caused by an increased volume of fluid within the venous circulation
  
  • The increased volume can be pulmonary in the case of left sided heart failure or:
  • Systemic in the case of right sided failure
• leads to an increase in wall stress at end diastole

Increased preload can be managed with:

1. diuretics - eg. frusemide, spironolactone
2. venodilators - eg. nitro-glycerine

Question 5

Note the cardiac function changes that occur with an increased afterload (not caused by outflow tract obstruction)

Which medications can be used to reduce afterload?

Answer 5

• An increased afterload occurs with increased systemic or pulomonary arterial resistance.
  
  • Systemic vascular resistance for the left ventricle
  • Pulmonary vascular resistance for the right ventricle
• Increased afterload can be caused by activcation of compensatory mechanisms such as the RAAS and SNS
• Increased afterload inhibits ventriclar ejection and increased myocardial work

1. Vasodilators: ACEI inhibitors, nitroprusside, pimobendan, calcium channel blockers (amlodipine and diltiazem)
2. Pulmonary vasodilators: Sildenafil (+ other PDV inhibitors)

Question 6

Note the changes to cardiac function with reduced myocardial contractility

Which medications can help improve myocardial function

Answer 6

• Decreased contractility leads to a reduced ejection volume.
• There is therefore an increased end systolic volume and increased preload as a result
• Eccentric hypertrophy occurs to normalise wall stress caused by the increased end systolic volume
• Signs of forward failure and congestion can occur once there is decompensation

Positive inotropic drugs can improve myocardial contractility: digoxin, pimobendan, dobutamine

Question 7

Describe changes to cardiac function with impaired diastolic filling

Which medications can help improve diastolic dysfunction

Answer 7

• Impaired filling due to an increase in wall stiffness will lead to a decreased systolic ejection fraction.
• Diastolic dysfunction wil ultimately cause increased venous pressures (preload) to ensure adequate filling.
• Diastolic function is also decreased with markedly elevated heart rates

Lusiotropic drugs can assist with diastolic dysfunction: calcium channel blockers (diltiazem), sympathomimetic drugs (dobutamine)

Note: only weak evidence exists of the benefit of diltiazem therapy in cats with diastolic dysfunction. No evidence of superiority when compared with ACEIs

Question 8

Discuss the circulatory consequences of an abnormal heart rate or rhythm

Note medications that can be utilised to managed arrhythmias

Answer 8

• High grade second degree and third degree AV block will cause a significant bradycardia. This decreases systolic output and forward failure can occur
• Rapid rhythms due to atrial or ventricular tachycardia have a reduced diastolic filling time and thus above a critical rate, the cardiac output will decrease significantly
• Reduced diastolic filling during tachycardia is worsened if there is AV dyssynchrony as with atrial fibrillation

High grade AV block is typically managed with pace maker implantation.

Reciprocating tachycardia can be managed with radiofrequency ablation

Atril fibrillation can be managed with the negative chronotropes, diltiazem and digoxin.

Question 9

Mechanism of action, indications and contraindications for:

Frusemide

Answer 9

Mechanism of Action:

• Loop diuretic that acts on the ascending loop of Henle within the kidney, distal renal tubule and proximal tubule
• Blocks the Na⁺/K⁺/2Cl^- cotransporter
• Net effect is to block the reabsorption of sodium and chloride, while increasing excretion of potassium
• calcium, ammonium, magnesium, hydrogen, bicarbonate and water excretion is increased
• Bronchodilative effects in humans, horses, guinea pigs

Indications:

1. Diuretic activity as in CHF and with pulmonary oedema
2. hypercalcaemic nephropathy
3. adjunctive therapy in hyperkalaemia
4. uraemia?

Contraindications:

1. Anuria / oliguria
2. Renal insufficiency
3. Care if there are pre-existing electolyte abnormalities
4. Impaired hepatic function
5. Diabetes mellitus

Question 10

Mechanism of action, indications and contraindications for:

Spironolactone

Answer 10

• Spironolactone is an aldosterone receptor antagonist
• Works in the distal renal tubules to block sodium and chloride resoprtion (blocked expression of the NaCl symporter
• Blocks aldosterone mediated increased expression of the NaK pump in the collecting duct (K⁺ not excreted, Na⁺ not reabsorbed)
• Decreased excretion of potassium, ammonium, phosphate and acid.

Indications for use:

1. Hyperaldosteronism - Conns Syndrome
2. Potassium sparing diuretic effect
   
   • Typically used in combination with frusemide as the single agent diuretic effect is negligible
3. May be useful with ascites
4. May be reno-protective in cases of amyloidosis and glomerulosclerosis.
5. Anti-fibrotic effect in human cardiac disease

Contraindications:

• Hyperkalaemia
• Hypoadrenocorticism
• Anuria / renal failure / renal impairment
• Care with hepatic disease

Adverse effects:

Facial pruritis in cats

Question 11

Mechanism of action, indications and contraindications for:

Thiazide diuretics (hydrochlorothiazide)

Answer 11

• Primarily act by inhibiting sodium reuptake in the distal convoluted tubule
• Most likely competes for the chloride site on the Na⁺/Cl^- cotransported in the distal convoluted tubule.
• May in crease calcium resorption in the distal convoluted tubule
• Encourages natriuresis and loss of free water (diuresis)
• Increased excretion of potassium, magnesium, phosphate, iodide and bromide
• Overall decrease in GFR

Indications for use:

1. ​systemic hypertension
2. ascites
3. hypermagnesemia
4. Nephrogenic diabetes insipidus
5. CHF refractory to frusemide
6. Recurrent calcium oxalate urolithiasis

Contraindications:

• Hypersensitivity (may cross react with sulphonamide sensitivity)
• Anuria
• Renal disease / electolyte abnormalities
• Hypercalcaemia
• Hyperuricaemia (reduced uric acid excretion)

Question 12

Mechanism of action, indications and contraindications for:

Nitroglycerin

Answer 12

• Relaxes smooth muscle primarily in the venous circulation
• Does have a dose related effect on arteriolar smooth muscle also
• Reduced preload +/- afterload depending on dose
• Reduced myocardial work and oxygen demand
• Improved coronary artery flow (which occurs during diastole)

Clinical indications:

• Cardiogenic oedema - geneally life-threatening pulmonary oedema
• Typically for in-patient care only

Contraindications;

• Severe anaemia
• hypersensitivity
• Head trauma / cerebral haemorrhage
• Hypovolaemia or hypotension

Question 13

Mechanism of action, indications and contraindications for:

Nitroprusside

Answer 13

• Causes peripheral vasoldilation, independent of autonomic innervation
• Causes both venodilation and arteriolar dilatation
• Rapid acting and must be administered via a carefully monitored CRI
• Metabolised to the cyanide radical, cyanogen, which is slowly excreted after hepatic metabolism (half life 2.7-7 d)

Clinical indications:

1. Acute onset hypertension during CHF crisis
   
   • Ideally utilise dobutamine first to offset the hypotensive effects
2. Only indicated when constant blood pressure monitoring is available

Contraindications:

• Compensatory hypertension
• Inadequate cerebral circulation
• Hypotension / during emergency surgery
• Severe hepatic or renal impairment
• Hyponatraemia
• Hypothyroidism

Question 14

Mechanism of action, indications and contraindications for:

Angiotensin Converting Enzyme Inhibitors

Answer 14

• Block the conversion of angiotensin I to angiotensin II (primarily in the lung)
• Blocks vasoconstriction, therefore lowering blood pressure and lowering vascular resistance
• Reduce systemic arterial pressure in cats with renal insufficiency together with reduced glomerular filtration pressure
  
  • Dilation of efferent arterioles in the kidney
• Increases renal plasma flow and glomerular filtration rates
• Particularly useful to block RAAS stimulation when diuretics are utilised

Clinical Indications:

1. Vasodilator and RAAS inhibitor in dogs with CHF
2. Hypertension - both cats and dogs
3. Protein losing glomerulopathy / chronic renal disease

Contraindications:

• Hyponatraemia
• Coronary or cerebrovascular insufficiency
• Potentially worsens pre-existing renal insufficiency
• Haematological abnormalities or collagen vascular disease (eg. SLE)

Question 15

Mechanism of action, indications and contraindications for:

Pimobendan

Answer 15

• Phosphodiesterase III inhibitor / Calcium channel sensitiser (inodilator)
• Reduced systemic vascular resistance via combined arterial and venous vasodilation
• Increased myocardial contractility via increased calcium sensitivity
  
  • By combined effects, there is minimal increase in myocardial work

Clinical Indications:

1. CHF secondary to MMVD or DCM
2. Pulmonary hypertension secondary to MMVD
3. Preclinical DCM and MMVD once there is progression to stage B2
4. DCM and end stage HCM in cats

Contraindications:

1. Aortic Stenosis or other outflow tract obstructions
   
   • HOCM may not be a contraindication and new information in cats suggests it may be useful for treatment of HCM

Question 16

Mechanism of action, indications and contraindications for:

Amlodipine

Answer 16

• Calcium channel blocker - inhibis calcium influx across cell membrane
• Acts on the cardiac and cvascular smooth muscle
• Primary effect on vascular smooth muscle resulting in arterial dilatation and reduction of afterload
• Depresses automaticity / impulse formation and conduction velocity in cardiac muscle

Clinical Indications:

1. Primary indication as an arterial dilator in cats with hypertension
2. For renal disease induced hypertension in dogs. Will activate the RAAS, so use with an ACEI / ARB would be advised

Contraindications:

• Care in heart failure due to negative inotropic effects
• Care with hepatic disease due to increased risk of hypotension (the drug is slowly metabolised in the liver)
• May cause increased glomerular pressures due to efferent arteriolar constriction mediated RAAS activation.

Question 17

Mechanism of action, indications and contraindications for:

Diltiazem

Answer 17

• Calcium channel blocker.
• Exact mecahnism unknown but blocks transmembrane influx of calcium into myocardial and vascular smooth muscle cells
  
  • Inhibits cardiac and smooth muscle contractility
• Net effect to dilate systemic and coronary arteries
  
  • Reduced peripheral resistance, blood pressure and afterload
• Slows AV nodal conduction (rarely an effect on SA node)
• Prolongs refractory times

Clinical Indications:

1. Primarily used as an anti-arrhythmic in dogs. Slows AV nodal transport in supraventricular tachycardia
2. May be useful for hypertension

Contraindications:

• sick sinus syndrome
• second or third degree AV block
• Myocardial infarct
• During congestive heart failure

Question 18

Mechanism of action, indications and contraindications for:

Digoxin

Answer 18

• Digoxin is a cardiac glycoside
• Increased myocardial contractility (positive inotrope)
  
  • Increased cardiac output
• Decreases sympathetic tone - diuresis and oedema reduction (may cause increased vagal tone)
• Decrease conduction through the AV node and prolonged effective refractory period
• Increase PR interval, Decrease the QT interval
• Increase availability of Ca⁺⁺ to myocaridal fibres
• Inhibit Na⁺ K⁺ ATPase - increase intracellular sodium, reduced potassium

Clinical indications:

1. Primarily used for treatment of supraventricular tachycardia and atrial fibrillation with concurrent congestive heart failure
2. No longer first line therapy for CHF, including with DCM

Contraindications:

• Ventricular arrhythmias
• Extreme caution with glomerulonephritis
• Caution with pulmonary disease, acute myocarditis or infarct, constrictive pericarditis
• Eliminated by the kidneys - care with renal insufficiency

Question 19

Mechanism of action, indications and contraindications for:

Dobutamine

Answer 19

• Sympathomimetic that acts primarily through beta-1 receptors
• Mild beta-2 and alpha-1 effects
• Rapid acting drug used via CRI only - half life of ~ 2 minutes
• Does not cause norepinephrine relase (as dobamine does)
• Increases myocardial contractility (inotropic) and relaxation (lusitropic)
• Mildc chronitropic, vasodilative and arrhythmogenic effects

Clinical indications:

1. Short term treatment of heart failure, including as a rescue agent for chronic heart failure during an acute crisis
2. Primarily for dogs with acute myocaridal dysfunction or CHF with hypotension

Contraindications:

• Idiopathic hypertropic subaortic stenosis
• Hypovolaemic states - correct hypovolaemia first
• Care following myocardial infarct as there is an increased oxygen demand
• Can enhance atrioventricular conduction - digitalise prior to use with supraventricular tachycardia.
• Arrhythmogenic - do not use with ventricular tachycardia

Question 20

Mechanism of action, indications and contraindications for:

Dopamine

Answer 20

• Adrenergic and dopaminergic inotrope
• Precursor to noradrenaline and also stimulates norepinephrine release
• Acts on alpha and beta-1 receptors together with dopamine receptors
• Low doses act on domaine receptor preferentially
  
  • vasodilation of the renal, mesenteric, cerebral and coronary vascular beds
• mid range doses effect beta-1 and alpha receptors
  
  • net effect - positive inotropy
• Higher doses - dopaminergic effect is over-ridden by alpha response
  
  • Peripheral vascular resistance is increased, improving hypotension.
  • Renal and peripheral vascular flow is decreased

Clinical Indications:

1. To address the haemodynamic consequences of shock after adequate fluid volume replacement
2. Adjunctive treatment in the setting of acute heart failure

Contraindications:

• Phaeochromocytoma
• Ventricular fibrillation or uncorrected tacchyarrhythmia
• Care with hypovolaemia - not a replacement for appropriate fluid rescuscitation
• Ischaemic cardiac disease and occlusive vascular disease

Question 21

Mechanism of action, indications and contraindications for:

Atenolol

Answer 21

• Beta₁ adrenergic blocker
  
  • Beta₂ may be blocked at higher doses
• No sympathomimetic activity
• Negative inotropic and chronotropic effects predominate
  
  • Decreased sinus rate
  • Slowed AV conduction
  • Decreased cardiac output
• Also decreases myocardial oxygen demand and reduces systemic blood pressure

Clinical Indications:

1. Supraventricular tachyarrhythmia such as atrial tachycardia
2. May be useful in cats with HOCM
   
   • Evidence is considered weak
3. Systemic hypertension

Contraindications:

• Overt congestive heart failure
• Bradycardia including due to second or greater degree heart block
• Sinus node dysfunction
• Bronchospasm (eg. feline asthma)
• Care with use in diabetes mellitus - can cause hypo- or hyper-glycaemia and can mask clinical signs associated with hypoglycaemia.

Question 22

Mechanism of action, indications and contraindications for:

Sotolol

Answer 22

• Non-specific beta-blocker
• Class III anti-arrhythmic
  
  • Prolongs repolarisation and refractoriness without affecting condution
  • This effect is likely due to selective inhibition of potassium channels
• Beta blocking effect is ~30% of propranalol

Clinical Indications:

1. Boxers - arrhythmogenic right ventricular cardiomyopathy
   
   • Primarily help reduce the risk of ventricular tachycardia/fibrillation
2. Possibly useful for supraventricular tachycardia

Contraindications:

• Sinus bradycardia, 2nd or 3rd degree heart block
• Uncontrolled CHF or cardiogenic shock
• Long Q-T syndromes
• Renal insufficiency may prolong activity - increased dosage interval may be required
• May mask hypoglycaemia

Question 23

Mechanism of action, indications and contraindications for:

Sildenafil

Answer 23

• Phosphodiesterase type V Inhbitor
  
  • PDE5 degrades cyclic GMP
  • Effective increase in cGMP leads to increased NO
  • NO mediated vasodilation primarily in the pulmonary vascular smooth muscle

Clinical Indications:

1. Pulmonary hypertension

Contraindications:

• Hypotension or fluid depletion
• Pulmonary veno-occlusive disease
• Do not use concurrently with nitrates due to potentially life threatening hypotension.

Question 24

Mechanism of action, indications and contraindications for:

Mexiletine

Answer 24

• Class IB anti-arrhythmic with similar mechanism of action to lignocaine
  
  • Inhibits the inward sodium current (fast sodium channel)
  • Reduces the rate of rise of the action potential
• Automaticity is decreased within the Purkinje fibres
  
  • action potential is also shortened
  • effective refractory period is decreased
• Conduction is typically unaffected

Clinical Indications:

1. Primarily used to treat ventricular arrhythmia including ventricular tachycardia
   
   • Most of the arrhythmias that respond to lignocaine will also respond to mexiletine
2. Useful for arrhythmogenic right ventricular cardiomyopathy

Contraindications:

• Not to be used with second ro third degree AV block
• Not to be used in the face of cardiogenic shock or overt CHF
• care with hepatic function impairment
• Hypotension
• Intraventricular conduction abnormalities

Question 25

Mechanism of action, indications and contraindications for:

Lignocaine

In the management of arrhythmia

Answer 25

• Class IB anti-arrhythmic
• Rapid rates of attachment and dissociation to sodium channels
• Causes phase 4 diastolic depolarisation attenuation
• Decreased automaticity
• At therapeutic levels, SA node automaticity and AV node conduction is maintained

Clinical Indications:

1. Ventricular tachycardia/arrhythmia

Contraindications:

• High second degree or third degree AV block
• Intraventricular block (eg. bundle branch block)
• Caution with liver dysfunction
• CHF, hypovolaemia, shock
• respiratory depression or hypoxia