Wk 5 HF

Question 1

Discuss the differences between systolic heart failure and diastolic heart failure

Answer 1

Systolic heart failure:

• most common, with S/S of left ventricular pumping weakness
• impaired pumping ability causes ↓CO

Diastolic heart failure:
- impaired relaxation and ventricular filling ability

Question 2

Illustrate how activation of systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system may be detrimental in patients with systolic heart failure

Answer 2

When heart begins to fail, many systems are brought into play in attempts to maintain CO:

• RAAS
• Sympathetic nervous system/SNS

Activation of RAAS & SNS is beneficial in the short-term in restoring cardiovascular function, BUT NOT IN THE LONG-TERM - ASSOCIATED WITH DISEASE PROGRESSION:

• Long term activation of RAAS: makes the heart work harder and harder → results in ↑ in preload/afterload
• Long term activation of SNS: myocardial stress → ↑O2 use → myocardial hypertrophy → ↑risk for dysrhythmias

Question 3

Explain the terms preload and afterload

Answer 3

Preload: venous return (as the blood comes back to the heart = the load that the heart has to pump)
Afterload: the pressure/resistance under which the heart has to pump

Question 4

Discuss the mechanism of action and major adverse drug reactions (side effects) of the following drug groups in the treatment of systolic heart failure

Answer 4

ACEI: ramipril, perindopril, captopril

• ↓ vasoconstriction, aldosterone release, sodium reabsorption
• AEs: cough, hypotension, hyperkalemia, renal failure
• CON: renal impairment, elderly, pregnancy

> preferred initial therapy
slow progression of HF
monitor renal function, potassium level

A2RA: candasartan, irbesartan

• ↓ vasoconstriction, aldosterone release, sodium reabsorption
• AEs: hypotension, hyperkalemia, renal failure
• CON: renal impairment, elderly, pregnancy

> less effective than ACE
substitute if ACEI is not tolerated (cough)
monitor renal function + potassium

Neprilysin inhibitors
- Sacubitril
- NI inhibits the breakdown of natriuretic peptides [hormone that synthesized by the heart] and prolongs their action
- Natriuretic peptides:
> vasodilator, diuresis, inhibition of renin & angiotensin release, ↓in SNS, ↓preload & afterload
- Sacubitril is combined with Valsartan
- Sacubitril NEVER administer with ACEI → risk of angioedema

Diuretics (loop & thiazide diuretics)

• shouldn’t be used as monotherapy in the treatment of SHF
• can add-on to ACEI/A2RA to control S/S, ie pulmonary congestion
• ↑ Na+, H2O, K+ excretion - monitor electrolytes

Potassium-sparing diuretics (spironolactone)

• competitive antagonist of aldosterone
• ↑ Na+, H2O, ↓ K+ excretion
• low dose = beneficial in severe SHF = improve survival rate
• Extreme caution when combined use with ACEI/A2RA → hyperkalemia

BB

• ↓ sympathetic activity on heart
• ↓ cardiac ischaemia/arrhythmias

Ivabradine
- used in SHF → reduce HR [selectively inhibiting the current in the SA node]

Digoxin (particularly if atrial fibrillation)

• last resort - stimulate the heart (NONE of the other drugs stimulates the heart)
• MOA: Inhibits the Na+/K+ in the heart (Cardiac cells). Increase of Na+ in the cardiac cells (intracellular Na+) reduces the amount of calcium pumped out of the cell = increases the force of contraction of the heart
• AEs: N/V, diarrhoea, bradycardia, arrhythmias
• Increases parasympathetic tone on the heart (hence why it causes bradycardia)
• NP: always check pts HR prior to administration – never give if HR <60 (causes bradycardia)
• Reduces hospitalisations for pts with heart failure, but doesn’t improve mortality rate. Limited role in heart failure
• Useful for pts with HF and AF (slows conduction through the AV node and increases the refractory period of the AV node)
• low therapeutic index
• long half-life