heart failure

Question 1

heart failure trajectory

Answer 1

• progressive decline in cardiac function
  chronic- progressive ventricular remodelling leads to gradual decline, episodes of acute decompensation
  -

Question 2

symptoms

Answer 2

Breathlessness
Ankle swelling
Fatigue

Question 3

decline in left ventricular systolic function

Answer 3

• leads to activation of three major compensatory neurohormonal systems in an attempt to increase cardiac output (CO):1
  Sympathetic nervous system (SNS)
  Renin-angiotensin-aldosterone system (RAAS)
  Natriuretic peptide (NP) system

Question 4

SNS

Answer 4

Stimulation of the SNS releases epinephrine and norepinephrine, which have direct effects on the heart (increased heart rate and contractility) and peripheral vasculature (vasoconstriction) and indirect effects on vasopressin release.

The effects on the SNS are mediated through α1, β1 and β2 receptors. In the peripheral vasculature, activation of α1 and β1 receptors leads to activation of the RAAS.

Question 5

RAAS (angiotensiN II)

Answer 5

Although activation of the RAAS is initially beneficial in patients with heart failure, long-term activation of this system leads to increased levels of the primary mediator angiotensin (Ang) II.

Ang II acts via the Ang II type 1 receptor (AT1R), leading to vasoconstriction and increased blood pressure, increased aldosterone secretion, and promotion of hypertrophic and fibrotic processes.1,2

Question 6

natriuretic peptide system

Answer 6

Activation of natriuretic peptide system leads to the release of several natriuretic peptides (NPs).

NPs act via natriuretic peptide receptors (NPRs) to cause decreased blood pressure through vasodilation, diuresis and natriuresis.

NPs have also been shown to reduce aldosterone concentration and inhibit RAAS-mediated aldosterone secretion.

Furthermore, atrial natriuretic peptide (ANP) reduces sympathetic tone in the peripheral vasculature and inhibits the secretion of vasopressin, and inhibits hypertrophic and fibrotic processes.4

Question 7

SNS and RAAS suppression

Answer 7

long term over action thought to be harmful and blockade of these pathways has been the focus of current HF therapies.

Question 8

natriuretic peptide system enhancement

Answer 8

potentially beneficial counter-regulatory system in HF.2

Augmentation of this system is a new therapeutic strategy being considered for HF.
This can be achieved by blocking the enzyme neprilysin which is responsible for the breakdown of NPs.

Neprilysin inhibition may enhance the effects of natriuretic and other vasoactive peptides, which include vasodilation, diuresis and natriuresis, reduced sympathetic tone, reduced aldosterone, and antifibrotic and hypertrophic effects.

Question 9

SGLT2 inhibitors

Answer 9

Inhibit proximal tubular glucose reabsorption, cause diuresis and natriuresis, lower BP and reduce weight.
Also renoprotective

Question 10

why do patients with heart failure die

Answer 10

Cardiovascular
Progressive HF (“pump failure”)
Myocardial infarction
Arrhythmia (“sudden death”)
Stroke
PE

Non-cardiovascular
Cancer
Infection

Question 11

heart transplant

Answer 11

A last resort!
Mortality of 19% at 1yr
Mean survival of ~10 years
Increased risk of:
Opportunistic infection
Malignancy
Renal failure
Hypertension
Coronary artery disease