L6 - LV Dysfunction and Heart Failure II Flashcards
Why is heart failure a modern disease?
Our body’s mechanism for reacting to a shock to the circulation was mainly due to blood loss
Sympathetic nervous and renin-angiotensin-aldosterone system responds to this
How does renin get to aldosterone?
Renin –> angiotensin –> aldosterone
Which two systems work together in heart failure?
Renin-angiotensin-aldosterone
Sympathetic nervous system - releases noradrenaline
Renin-angiotensin-aldosterone and the sympathetic nervous system impact which two factors?
Peripheral resistance – vasoconstriction/dilation to maintain blood pressure
Cardiac out – heart rate and force of contraction
Does the sympathetic nervous system lead to vasodilation or vasoconstriction?
Vasoconstriction –> increases peripheral resistance –> maintain blood pressure
Does the best with what blood volume you have
Does the sympathetic nervous system lead to increased or decrease cardiac output?
Increases heart rate and force of contraction –> increased cardiac output
When is renin released from the kidney?
Perfusion pressure to the kidney has decreased - assumes blood loss has occured
Low levels of Na going out to the distal tubules kidneys - assumes water/Na loss
What converts angiotensinogen to angiotensin I?
Renin
What converts angiotensin I to angiotensin II?
ACE
What does angiotensin II lead to?
Vasoconstriction –> increases peripheral resistance
Aldosterone release
Tubular Na reabsorption
Na and water retention
What leads to aldosterone release?
Angiotensin II
How do the sympathetic nervous system and angiotensin II interact?
Sympathetic nervous system - activates renin release
Angiotensin II - helps the sympathetic nervous system release noradrenaline
Overall what does the renin-angiotensin-aldosterone system and the sympathetic nervous system do?
Increase peripheral resistance
Increase cardiac output
Retain Na and water
What can the body not distinguish between?
Blood loss and heart failure
How does the body compensate for acute blood loss?
Tachycardia –> increased cardiac output
Positive ionotropic effect –> increased cardiac output
Vasoconstriction –> increased blood pressure
Sodium and water retention –> increased circulatory volume
During acute blood loss why does vasoconstriction occur?
Try to preserve vital organs such as the brain and kidney, blood diverted from skin etc
How does the body compensate for LV systolic dysfunction?
Kidneys sense a loss of perfusion pressure –> think the person is losing blood
Tachycardia –> increased workload and oxygen demand of heart
Positive ionotropic effect –> increased workload and oxygen demand
Vasoconstriction –> increased afterload
Sodium and water retention –> increased preload and oedema
Chronic adrenergic stimulation –> myocyte toxicity and arrythmia
During LV systolic dysfunction why the faster the heart rate the less efficient the heart?
The faster the heart rate the less efficient the heart is in term of metabolic needs and the amount of blood it can deliver
During LV systolic dysfunction why is vasoconstriction bad?
Leads to increased after load which makes it harder for the heart to eject blood?
Why is the same compensation for both acute blood loss and LV systolic dysfunction bad and good?
Good if losing blood
Bad for heart failure
What are the 6 different treatments for heart failure?
Diuretics Aldosterone antagonist Vasodilators Angiotensin II receptor blockers ACE inhibitors Beta blockers
How do diuretics treat heart failure?
Release congestion
Block Na and water retention
How do aldosterone antagonists treat heart failure?
Block renin-aldosterone-angiotensin
Weak diuretics – not powerful enough to remove congestion
How do vasodilators treat heart failure?
Overcome peripheral resistance
Anything that blocks the sympathetic nervous system will act as vasodilators themselves as they block the vasoconstriction triggered by this pathway
How do ACE inhibitors treat heart failure?
Block ACE enzyme therefore angiotensin II
How do beta blockers treat heart failure?
Block sympathetic nervous system
What is the best treatment approach for heart failure?
Blocking at several different levels
What is an example of an ACE inhibitor used to treat severe heart failure?
Enalapril
What % decrease in mortality did Enalapril cause compared to placebo in severe heart failure?
31%
What is an example of an ACE inhibitor used to treat mild-moderate heart failure?
Ramipril
What % decrease in mortality did Ramipril cause compared to placebo in mild-moderate heart failure?
25%
Benefit is less as the absolute risk is less in the first place as only mild to moderate heart failure
What is LV dysfunction without heart failure?
Definite impairment in contractility of the heart
No-mild heart failure symptoms
What change in death or hospitalisation did Enalapril cause compared to placebo in LV dysfunction without heart failure?
Reduced all the combined end points
What are the main clinical indicators of ACE inhibitors?
Hypertension
Heart failure - severe and moderate
Diabetic nephropathy
LV dysfunction with no heart failure
What are some examples of ACE inhibitors?
Ramipril
Perindopril
Enalapril
What are all the adverse effects of ACE inhibitors related to?
Reduced angiotensin II production
Increased kinins
What are the adverse effects of ACE inhibitors related to reduced angiotensin II?
Hypotension
- Angiotensin II supports the blood pressure
Acute renal failure
- Angiotensin II restricts the efferent arteriole increases filtration pressure in glomerulus
Hyperkalaemia
- Angiotensin II causes aldosterone release which preserves Na and loses K
- Block to get excess K in blood
Teratogenic effects in pregnancy
- ACE enzyme is important in fetal development
What are the adverse effects of ACE inhibitors related to increased kinins?
Cough
- Occurs in 10% of ACE inhibitor patients
Rash
Anaphylactoid reaction
What does ACE do?
Breaks down angiotensin I to angiotensin II
- Not specific
- Also breaks down bradykinin
- If you block ACE you also block the breakdown of bradykinin
What are some examples of beta blockers?
Carvedilol
Bisoprolol
Metoprolol
What were the results when beta blockers were used on top of other heart failure drugs?
Looking for an additional benefit – either given carvedilol or placebo
12 month mortality
- Placebo - 10%
- Carvedilol – 4%
If they had a beta blocker on top of standard therapy they had better survival/event free survival
What are the main clinical indications of beta adrenoceptor blockers?
Ischaemic heart disease – prevents angina
Heart failure
Arrhythmia
Hypertension
What are some examples of beta adrenoceptor blockers?
Bisoprolol Metoprolol Carvedilol - All important for heart failure – these have had successful trials - Atenolol
What is the selectivity of different beta adrenoceptor blockers?
Beta 1 selective - Metoprolol - Bisoprolol Beta 1/2 nonselective - Carvedilol - Propranolol In the middle – atenolol
As you increase the dose of beta adrenoceptor blockers the become more and more?
Unselective
What does the term cardioselective imply?
β-1 selectivity
Inaccurate - up to 40% of cardiac β-adrenoceptors are β-2
What are the adverse effects of beta adrenoceptor blockers?
Fatigue - Due to blocking of adrenaline Headache - Can cross blood brain barrier Sleep disturbance/nightmares Bradycardia Hypotension Cold peripheries - Body response to bradycardia/reduced cardiac output by preserving central blood temperature/pressure by shutting down pathways to the skin Erectile dysfunction
What diseases do beta adrenoceptor blockers cause worsening of?
Asthma or COPD
- Due to bronchoconstriction
PVD – Claudication or Raynaud’s
- If peripheral system already compromised it can make it worse
Heart failure – if given in standard dose or acutely
- Need low starting dose and slow uptitrate over weeks
How does digoxin help in heart failure?
Can slow heart rate in atrial fibrillation - positive ionotopic activity
Go to hospital less due to heart failure
Develop new heart failure less frequency
Why might digoxin not improve death rates in heart failure patients?
Potentially due to side effects such as
- Positive ionotropic effects
- Pre-arrythmic effects
- Off set any benefits in the longer term
What is Ivabrine used to treat?
Angina – slows the heart down
Heart failure – if after adequate treatment with other drugs you still have heart rate >70bpm
- Implies you haven’t overcome the sympathetic drive
What current does Ivabradine block to help treat heart failure?
Blocks the If current in the sinus node
Slows sinus node rate
What % did Ivabradine reduce hospitalisation for heart failure?
26% compared to placebo
What % did Ivabradine reduce death due to heart failure?
0
What is Sacubitril?
Neprilysin inhibitor - potentiates AMP
- Fluid and Na loss from kidney
- Increases levels of natriuretic peptides
What is Valsartan?
Angiotensin II blocker - vasodilator
How well did the combined therapy of sacubitril and valsartan (Entresto) treat heart failure? - hospitalisation and death
Hospitalisation
- Small reduction over and above other therapies
Death from any cause
- Small reduction
Only small reductions as already been significantly reduced by other drugs previously
What are the symptoms of acute heart failure?
Pressures go up –> pulmonary oedema
What are the treatments for acute heart failure?
Oxygen - can’t oxygenate properly
Diamorphine/heroine - treats pain and vasodilates
Nitrates - venal and arterial dilators –> reduce preload and afterload
LOOP diuretics - helps with excess congestion and vasodilates
Inotropes
PDE III inhibitors - PDE III break down cAMP –> inhibit to allow more cAMP
In what situations would you use inotropes to treat acute heart failure?
When patients can’t maintain their cardiac output
Might have to stimulate the heart over a short period of time
What are inotropes?
Adrenergic agonists - mimic the sympathetic nervous system
Either
- Inoconstrictors
- Inodilators
What do inoconstrictors do?
Ionotropic effects and vasoconstriction
Noradrenaline, adrenaline and dopamine
What do inoconstrictors act on?
Alpha 1 – in vasculature – vasoconstriction
Beta 1 – in the heart – ionotropic
What do inodilators do?
Ionotropic effects and vasodilation
Dobutamine
What do inodilators act on?
Beta 2 – in vasculature – vasodilation
Beta 1 – in the heart – ionotropic
What is an example of a PDE II inhibitor?
Milirinone
If used chronically - 60% mortality
40% mortality in placebo
