Heart Failure

Question 1

Define heart failure.

Answer 1

The inability of the heart to supply adequate blood flow, and therefore oxygen, to peripheral tissues and organs.

Question 2

How many people in the UK have heart failure?

Answer 2

1,000,000.

Question 3

What proportion of patients diagnosed with heart failure die within a year of diagnosis?

Answer 3

40%.

Question 4

What is the most common cause of heart failure?

Answer 4

Post-MI.

Question 5

Define myocardial infarction.

Answer 5

Death of cardiac tissue due to a loss of blood flow (ischaemia) to an area of the myocardium.

Question 6

List 4 changes that occur to tissue when ischaemia occurs.

Answer 6

1 - The tissue becomes hypoxic.

2 - The tissue becomes hypercapnic.

3 - The tissue becomes glycolytic.

4 - The tissue becomes acidotic.

Question 7

What is a percutaneous coronary intervention (PCI)?

Give an example of when it might be used.

Answer 7

• A non-surgical procedure that uses a catheter to place a stent to open up blood vessels in the heart that have been narrowed.
• It is often used following an MI.

Question 8

List 3 causes of heart failure (other than the most common cause).

Answer 8

1 - Pressure overload (due to baroreceptor reflex).

2 - Volume overload (due to baroreceptor reflex).

3 - Contractile dysfunction.

Question 9

List 4 causes of contractile dysfunction.

Answer 9

1 - Coronary artery disease.

2 - Myocardial disease.

3 - Pregnancy.

4 - Congenital cardiomyopathies.

Question 10

How does heart failure affect the starling ventricular function curve?

Answer 10

1 - The graph becomes increasingly shallow with more severe heart failure.

2 - The graph is translated downwards with more severe heart failure.

Question 11

What is the risk of increasing cardiac work over long periods of time?

Answer 11

Pathological hypertrophy.

Question 12

List 3 mechanisms by which persistent adrenergic stimulation of the heart can cause disease.

Answer 12

1 - Hyperphosphorylation of Ca2+ handling proteins, which can lead to dysfunctional Ca2+ homeostasis, contractile dysfunction and arrhythmia.

2 - Pathological hypertrophy by increasing cardiac work.

3 - Beta adrenoceptor internalisation, leading to a loss of adrenergic sensitivity.

Question 13

What are delayed afterdepolarisations?

Answer 13

Depolarisations that occur after repolarisation is completed but before another action potential would normally occur.

Question 14

Describe the process by which delayed afterdepolarisations (DADs) occur.

Answer 14

1 - An increase in beta adrenoceptor stimulation increases PKA activity.

2 - PKA causes elevated phosphorylation of L-type calcium channels, increasing their permeability to Ca2+.

3 - PKA causes elevated phosphorylation of RyR2 channels (channels responsible for Ca2+ release from the SR).

4 - PKA causes elevated phosphorylation of PLB (an inhibitor of SERCA), inhibiting its function.

5 - This acts to increase the SR Ca2+ load, and therefore raises the probability of spontaneous Ca2+ leak.

Question 15

List 2 treatments that reduce the risk of DADs.

Answer 15

1 - Beta blockers.

2 - Calcium channel blockers.

Question 16

Why are DADs dangerous?

Answer 16

They can cause arrhythmias and ectopic activity.

Question 17

Define lusitropy.

Answer 17

The rate of myocardial relaxation.

Question 18

How is Ca2+ removed from the cytosol of a myocyte?

Answer 18

Via the Na+/Ca2+ exchanger (NCX), which removes 1 Ca2+ for 3 Na+.

Question 19

Why do patients with heart failure have chronically high plasma angiotensin ii?

Answer 19

• Patients with heart failure have a low arterial blood pressure.
• This reduces baroreceptor afferent activity.
• This increases sympathetic activity to the kidney, causing an increase in renin release.
• Renin results in an increase in angiotensin ii through the renin-angiotensin system.

Question 20

How does the kidney contribute to pressure and volume overload in patients with heart failure?

Answer 20

• Patients with heart failure experience a decrease in arterial blood pressure. This causes:

1 - Low Na+ delivery to the macula densa.

2 - Decreased tubule wall tension in renal afferent arterioles.

3 - Increased sympathetic activity to the kidney via decreased baroreceptor activity.

• These factors increase renin release, increasing angiotensin ii.
• Angiotensin ii increases secretion of aldosterone from the adrenal cortex and ADH from the posterior pituitary, as well as increasing thirst.

Question 21

Why might volume loading cause (and exacerbate) heart failure?

Answer 21

• An increase in blood volume results in an increase in central venous pressure.
• This increases cardiac filling, and therefore EDV.
• Initially, this results in an increase in SV, but as EDV increases further, the plateau of the Starling curve is exceeded and SV starts to decrease.

Question 22

How does oedema occur with heart failure?

Answer 22

• If there is a mismatch in LV and RV cardiac output due to poor cardiac function, then blood can start to accumulate in the systemic or pulmonary system.
• This leads to an increase in capillary hydrostatic pressure and therefore increased capillary filtration.
• This is worsened by increases in blood volume.

Question 23

How does oedema impair diffusion across alveoli?

Answer 23

By increasing diffusion distance.

Question 24

List 3 treatments of oedema.

Answer 24

1 - Loop diuretics.

2 - ACE inhibitors.

3 - Angiotensin ii receptor type 1 (AT1R) antagonists.

Question 25

What effect can volume loading have on valves?

Answer 25

Volume loading can cause aortic / mitral valve regurgitation (leaky valves).

Question 26

List 3 treatments that reduce risk of development of hypertrophy in patients with heart failure.

Answer 26

1 - Reducing afterload with vasodilators.

2 - Surgical valve replacement.

3 - Beta blocker therapy to reduce cardiac work.

Question 27

Why is cardiac hypertrophy dangerous?

Answer 27

1 - Increases susceptibility to ischaemia.

2 - Increases incidence of arrhythmias.