Heart failure Flashcards
What are the top 2 causes of death globally?
Ischaemic heart disease and stroke are top 2
How is cardiovascular disease geographically distributed?
Countries of lower income have a higher death rate
Risk factors of CVD – Modifiable
- Hypertension – /
- Hypercholesterolaemia – /
- Diabetes mellitus - U
- Obesity – U
- Exercise
- Smoking
- Diet
Risk factors of CVD – Non-modifiable
- Age
- Ethnicity
- Gender
- Family history
What does CVD risk factors increase?
- CVD
- Ischaemic heart disease – heart attack
- Heart failure
- Cerebrovascular accidents (Strokes)
- Renal failure
- Aortic disease
- Peripheral arterial disease (reduced blood to legs)
What is left heart failure?
• Fluid build-up in lungs – leading to pulmonary oedema
Symptoms:
• Breathlessness and cough + tiredness
What is right heart failure?
• Fluid build-up in body – leading to peripheral oedema
Symptoms:
• Heavy painful legs + difficulty walking + tiredness
current heart failure treatments - lighten the load
Use diuretics
• Helps us lose salt and water through kidneys so less volume
current heart failure treatments Make the task easier
ACE inhibitors/angiotensin II blockers or aldosterone antagonists
• ACE inhibitors prevent an enzyme in the body from producing angiotensin II, a substance that narrows blood vessels
current heart failure treatments Slow down the heart
Beta-blockers
• Slow down the heart by blocking the action of adrenaline
current heart failure treatments Make the heart pump harder
Digoxin
• Increases the force of myocardial contraction
What are the limitations of current therapy?
Despite improvements in life expectancy with the use of ACEi/ARB and beta blockers the overall prognosis is still POOR
Side effects risk:
• Hypotension
• Impact on kidneys/electrolytes
What are the main therapies for heart problems?
- Beta blockers – target sympathetic nervous system
- The Renin-Angiotensin-Aldosterone System (RAAS)
- A hormone system within the body that is essential for the regulation of blood pressure and fluid balance
- The system is mainly comprised of the three hormones renin, angiotensin II and aldosterone.
- Natriuretic peptides target the NP receptors
What are natriuretic peptides
- When there is a strain on the heart – the heart tries to reduce this
- It uses natriuretic peptides
- It tries to reduce salt in the blood (natriuresis) by excreting salt in the urine through the action of the kidneys
NP also reduces things like:
• Blood pressure
• Aldosterone – can cause high BP
• Vasopressin – regulated body fluid (stimulated water reabsorption)
What is neprilysin?
It inactivates natriuretic peptides
What is ARNI?
- Angiotensin receptor neprilysin inhibitor
* Blocks the effects of angiotensin 2 and neprilysin
What is Entresto?
A NEW OPTION
- In 2010
- Combined angiotensin receptor blockade (valsartan)
- And neprilysin inhibition (sacubitril)
- Still aimed to reduce the effect of excess RAAS system
- Potentiate beneficial effects of natriuretic peptides
Difference between entresto and omapatrilat?
- Omapatrilat has ACE inhibitor – lowers blood pressure by preventing production of angiotensin 2
- Entresto has angiotensin receptor blockers which reduce the action of angiotensin 2
Why is entresto better?
• Because ACE inhibitors from omapatrilat also work on bradykinin which can cause angioedema
Clinical trials for entresto
• Showed a reduction in death and hospitalisation
What is OMAPATRILAT – 1990s
- In the 1990s a Combined ACE inhibitor and neprilysin inhibitor was made
- Aimed to reduce the effect of excess RAAS system
- Potentiate beneficial effects of natriuretic peptides
Omapatrilat clinical trial data
- Clinical trials showed no significant decrease in death rate
- It did show a big reduction in blood pressure however
What is Ivabradine
A NEW OPTION •
Slows the heart down
• Inhibition of the I channel (funny current) in the sinus node (where the electrical current starts)
Clinical trial data on ivabradine
- Clinical trials have been studied
- Ivabradine tested on patients with severe heart failure already taking a ACEi, ARB or beta blocker
- Ivabradine is useful in reducing death if heart rate >70 despite full dose of beta-blockers
What are SGLT2 inhibitors
A NEW OPTION
Canagliflozin, dapagliflozin, empagliflozin
• Lighten the load
• Inhibit glucose reabsorption
• Has diuretic effect – decrease volume
What is Omecamtiv mecarbil
A NEW OPTION
- Proposed to increase myocardial systolic function
- Selective cardiac myosin activator
- Activates myocardial ATPase and improves energy utilisation (activates cardiac myosin and augments the speed of ATP hydrolysis)
- Enhances myosin cross-bridge formation and duration
- Improves cardiac muscle contraction
Omecamtiv clinical trials
- Small phase 3 studies
- Small reduction in CV death or admission
- No effect on CV deaths alone
