Treatment of Heart Failure

Question 1

What is heart failure?

Answer 1

When the heart is incapable of generating sufficient cardiac output to meet the demands of the body.

When CO can only be maintained at sufficient levels by an elevated end diastolic pressure.

Question 2

Aim of drug treatment

Answer 2

To reduce symptoms

• pulmonary and systemic oedema through use of diuretics
• increase myocardial contractility through digoxin

Improve quality of life
- increase exercise tolerance

To lengthen survial

Decrease disease progression

• reduction in stimuli leading to hypertrophy and remodelling
• neurohormonal modulators: ACE-I, Beta blockers, ARB, aldosterone antagonist, ivabradine

Must also treat underlying and precipitating factors/ comorbidities e.g. AF, HTN and angina

Question 3

ACE-I

Answer 3

Ramipril 1.25mg OD increased up to 10mg OD
Slows progression of cardiac remodelling of hypertrophy and fibrosis
Vasodilates, reduces preload and afterload which reduces cardiac work and increases CO
Diuretic effect as it blocks ACE- inhibiting formation of angiotensin II which increases Na+ reabsorption

Reduces symptoms, lengthens survival, reduces hospitilisation, slows progression

Adverse effects: chronic cough, hypotension, renal failure, hyperkalaemia

Question 4

ARB

Answer 4

angiotensin II receptor blockers
e.g. losartan
Blocks angiotensin II receptors, more specifically AT1 receptors
Same effects on survival and symptoms as ACE-I without causing the cough
Similar side effects and contraindications
ARB + ACE-I if symptoms persist

Question 5

Beta blockers

Answer 5

Carvedilol (alpha 1 blocker + non selective beta blocker)
3.125mg BD increase to 6.25mg BD, max 25mg

Bisoprolol (beta 1- cardioselective)
1.25mg OD, max 10mg

Prolong survival
Reduce symptoms of HF
Reduce sudden death by VF
Reduce cardiac modelling
Reduce renin release
Negatively ionotropic so start with low dose and slowly increase
Contraindicated in asthamtics 

inc in ejection fraction, reduce systolic and diastolic volume, cause regression of left ventricular hypertrophy
reduced ischaemia, reduced HR, improve myocardial perfusion, inhibition of deleterious effects of excess catecholamines on myocardial structure/ metabolism, reduction of cytokine release

Question 6

Aldosterone antagonists

Answer 6

Antagonists cause increase in Na+ reabsorption, reduce NO release, induce cardiac fibrosis and remodelling, promote arrythmias by lowering plasma K+ and low NA release

• Spironolactone
• Reduce in mortality in severe HF when added to standard therapy
• Due to reduction in fibrosis/ remodelling of heart
• Aldosterone ‘escape’- levels initially fall during ACE-I treatment but often rise again
• But: can cause gynaecomastia, hyperkalaemia, and renal dysfunction
• Less gynaecomastia with eplerenone

Question 7

Sacubatril/ valsatran

Answer 7

• Is a combination of an ARB and a neprolysin inhibitor
• Neprolysin is a neutral endopeptidase which is highly expressed in the kidneys, and breaks down several peptides which cause vasodilatation and natriuresis and suppress cardiac remodelling
• Sacubitril also increases levels of Ang II, but the deleterious effects of this are prevented by the ARB (valsartan)
• Can be used instead of an ARB or ACE-I in mild-to moderate CHF with a reduced ejection fraction (heart is pumping less blood)
• However, neprolysin also breaks down beta-amyloid peptide in the brain, so inhibiting it might increase the risk of Alzheimer’s

Question 8

Ivabradine

Answer 8

• Ivabradine lowers the HR by blocking If in the SA node
. Acts on the funny current that regulates pacemaker activity.
• CHF- ejection fraction <35%
• The effect was greater in patients with a faster HR

• Possible mechanisms
o Reduction in HR allows more time for blood to perfuse the myocardium, reducing ischaemia
o Unlike in the healthy heart, increased rate tends to decrease cardiac contractility in CHF
o Reduction in HR improves contractility In CHF
o Reduction in HR reduces afterload
o Reduces cardiac work

• Adverse effects: luminous phenomena- a sensation of enhanced brightness; bradycardia

Question 9

Diuretics

Answer 9

• Furosemide
• Loop diuretics used for CHF but thiazide can be added in if required
• Increase salt and water excretion by the kidneys therefore lowers CVP (central , oedema, dyspnoea
• Exercise capacity is improved when oedema is reduced
• Side effects: loop diuretics and thiazides can cause K+ loss leading to arrhythmias
• Hypokalaemia is reduced with spironolactone, ACE-I, ARBs, ENaC blockers (e.g. amiloride) or K+ supplements

Question 10

Cardiac glycosides

Answer 10

• increase contractility
• Reduce symptoms but survival is not prolonged
• Also reduces AV node conduction via vagus
• -mainly used for atrial fibrillation in CHF
• BUT INCREASES WORK
• Narrow therapeutic band, toxicity causes arrhythmias, possible AV node block
• Toxicity occurs at lower plasma concentrations in hypokalaemia