LV heart dysfunction Flashcards
What is chronic heart failure?
NICE- Complex clinical syndrome of symptoms and signs that suggest the efficacy of the heart as a pump is impaired
What is early HF
Filling start to increase so contraction increase and have the same Cardiac output
Fact about the epidemiology of HF
- 1 million cases
- expected 50% increase in next 25 years
- rise exponentially with age
Population age by 2032? and affects on NHS?
- 16 million in UK will be older than 65
- 3 million older than 85
- 5% of emergency budget will be on chronic heart failure
- 2% of NHS budget
- poor prognosis only 30% mortality rate within 1 year
5year survival curves with a first time diagnosis of HF compared to common cancers
For both men and women HF lies in the same survival rates as cancer prognosis
- breast cancer higher survival
- lung lower
Roughly 60% survival
What is LVHD and HFPEF?
Left ventricular heart dysfunction
Heart failure with a preserved ejected fraction (diastolic failure)= the % of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled - is normal
5 facts about heart failure
What is it? what causes it? effects? phgarmacology?
- HF is a clinical syndrome with signs and symptoms that suggests the efficacy of the pump is impaired
- It is caused by structural or functional abnormalities of the heart
- most common cause is coronary artery disease
- causes morbity, mortality, hospital admissions and substantial cost
- Evidence for pharmacology is in chronic heart failure due to LVSD
- Main benefit is with vasodilator therapy via neurohumoral blockade (RAAS-SNS) and not from direct LV stimulants
Western countries affect
Increase coronary artery disease- smoking, drinking, diet, hypertension etc block the arteries and
- common cause of heart attacks
- most trials done on chronic not acute
Where do drugs act?
On the periphery not the heart itself
LV dysfunction verses heart failure
1. reduced cardiac output
Forward flow
- output impaired and filling pressures are increased
- reduced flow to muscles and lungs
- exercise intolerance and fatigue
LV dysfunction verses heart failure
2. Increased filling pressures
Backward flow
- left arterial pressure up= pulmonary pressure up
- pulmonary edema= excess fluid in the lungs. This fluid collects in the numerous air sacs in the lungs, making it difficult to breathe.
- cause by a rise in the left arterial pressure, backward pressure
- Symptoms = wake up in the middle of the night breathless as fluid has flown back into the lungs after lying down, reverse this by sitting up
- right side= fixed conjunction on jugular vein
What happens if the pressure is increased in the venous system?
causes fluid to leak out, aggrevated by gravity ( ankle swelling when stood up)
Go to bed and redistributed in sleep
seen by pressing on leg and leaving a thumb print
Marked fluid edema= get fluid in abdominal cavity
Frank starling law
Graph of LVEDP v Cardiac output (stroke volume)
-Line to high then you have a higher cardiac output at lower LVEDP= pulmonary congestion
- Line below horizontal the
A law that states that the energy liberated with each cardiac contraction is a function of the length of the muscle fibers in the ventricular wall; as preload ↑, so does end-diastolic pressure, which ↑ force of ventricular contraction
Frank starling graph- horizontal and vertical line explanations
- Above vertical line=lower cardiac output at higher LVEDP= pulmonary congestion
- Line below horizontal= below volume so you have a problem= hypotension
What should you add if in pulmonary congestion?
- diuretics
- vasodilators
moves right to left on the graph lowering the LVEDP`
diuretics clinical indications and classes
Indications= HF and hypertension Classes 1. Thiazides and related drugs (distal tubule) 2. Loop diuretics (loop of henle) 3, potassium- sparing diuretics 4. aldosterone antagonists
Thiazide diuretics
Weak more in HF than hypertension - Bendroflumethiazide - hydrochlorothiazide - chlorthalidone
Loop diuretics
Could get hold of easily
pass lots of urine
- Furosemide
- Bumetanide
Potassium sparring diuretics
Not common
- Spironolactone
- Eplerenone
- Amiloride
- Triamterene
Aldosterone antagonists
Important as help block renal aldosterone
Main adverse effects of Diuretics
- Hypovolaemia- decrease bolume of circulating blood(LD)
- Hypotension (LD)
- Low serum potassium (hypokalemia)
- Low serum sodium (hypoantraemia)
- Low serum magnesium (hypomagnesaemia)
- Low serum calcium (hypocalcaemia)
- erectile dysfunction (thiazides)
- Raised uric acid (hyperuricaemia- gout)
- impaired glucose tolerance (mainly thiazides)
What is vasodilator therapy?
Reduce afterload (work of heart goes down and O2 demand decreases) and can store blood in venous system reducing preload
- Dinitrates- venous dilators
- Hydralazine- artery dilators
What is the effect of vasodilators on mortality in chronic congestive HF?
- trial= 642 men with HF symptoms
- placebo, prazosin and hydralazine + isosorbide dinitrate
- prazosin= no difference
- hydralazine= significantly reduce in mortality (36% reduction in 3 years) and improved LVEF
Haemorrhage
Bleeding out
2 pathways to control cardiac output and noradrenaline
- renin-angiotensin aldosterone system
2 sympathetic nervous system (noradrenaline)
reactions interact with each other
Renin-angiotensin aldosterone pathway
Poor renal blood flow triggers
- Angiotensinogen (liver) to Angiotensin- by RENIN (kidney)
- Angiotensin to angiotensin II - by ACE (surface of the pulmonary and renal endothelium)
- Angiotensin II to salt retention ( 1. aldosterone release and 2. tubular sodium reabsorption) which is a direct cause of sodium and water retention
- Angiotensin II to peripheral resistance
Sympathetic nervous system (noradrenaline pathway)
- Peripheral resistance
- cardiac output
What does angiontensin II do?
1- Increases sympathetic activity
2- tubular NA and CL reabsorbed and K excreted
3- adrenal gland secrete aldosterone which increases Na/cl reabsorption and CL secretion
4- Arteriolar vascontriction increases BP
5- Pituitary gland secretes ADH which goes to the collecting duct and causes water reabsorption
This all causes H20 and salt retention, effective circulation volume increase. perfusion of the jugularglomerular apparatus increase
recycled back to the kidney to stop RENIN
What is angiotensin?
Derived from the N terminal of the precursor angiotensinogen
Renin required to produce angiotensin I which is secreted into circulation from the kidney
Compensation to acute blood loss
All good things
- tachycardia- increases CO
- positive ionotropic effects (noradrenaline increases the work of the heart)- increased CO
- vasoconstriction- increased blood pressure
- sodium and water retention- increased circulating volume
Compensation- LV systolic dysfunction
- tachycardia- increased workload and O2 demand
- positive inotropic effect- increased workload and O2 demand
- vasoconstriction (pump into more restrictive circulation)- increased afterload
- sodium and water retention- increased preload and oedema
- Chronic adrenergic stimulation- myocyte toxicity and arrhythmia
- All bad things
Where are most treatments directed?
Response is the problem so most treatments are directed to this rather than the heart itself
Different types of drugs used?
ACE Inhibitor- inhibit ACE to stop angiotensin II production
ARB- stops angiotensin II to peripheral resistance
aldosterone antagonist- inhibits sodium and water retention
Beta blockers and vasodilators- noradrenaline pathway- reduces peripheral resistances
Ace inhibitors trial in HF
235 patients
severe HF
enalapril vs placebo
31% mortality reduction
Trial for ace inhibitors
Grade 4 HF- breathless at rest
given ACE inhibitors or placebo
mortality for placebo was 60% over 1 year
decreased to 30% with enalapril
What is mild HF? and the effect of ACE inhibitors on this
Bad heart but not in heart failure (ventricular dysfunction) so more than one end point is taken into account
- death= 10-12% reduced by ace inhibitor
- hospitalisation= reduced
Angiotension converting enzyme inhibitors (ACE)
clinical indications for needing this and what are the different types of drugs?
hypertension, heart failure and diabetic nephropathy
Drugs- Ramipril (*most common) perindopril, enalapril and trandolapril
What are the main adverse effects of ACE inhibitors?
- related to reduced angiotensin II formation
- hypotension
- acute renal failure
- hyperkalaemia
- teratogenic effects of pregnancy - related to increased Kinins (cause breakdown in bradykinin, block ace you potentiate bradykinin)
- cough
- rash
- anaphylactoid reactions
ACE recycling
Angiotensin I - ACE - angiotensin II decrease
increase bradykinin - ACE - inactive peptides
What are betablockers?
mortality benefits demonstrated for carvedilol, bisoprolol (most common) and metoprolol- these 3 are licensed
*Ace and BB can be used together- effects are additive
Beta blockers survival against time
mild heart failure
BB significantly improved outlook
event free survival (developed or ending in hospital) effect is more profound
Main clinical implications of Beta blockers
Ischaemic heart disease- angina (reduced HF- decrease pressure on heart)
heart failure
arrhythmia
hypertension
What is the selectivity of beta blockers
B1 selective- metoprolol and bisoprolol
both- atenolol
B2 selective- propranolol, nadolol, carvedilol
Selectivity is relative rather than absolute
increase the dose it becomes more selective = relative as dose dependent
cardioselective
imply B-1 selectivity
misnomer since up to 40% of cardiac B adrenoreceptors are B2
BB main adverse effects
- fatigue
- headache
- sleep disturbance and nightmares
- bradycardia- slow HR, light headed
- Hypotension as low BP
- cold peripheries- cold peripheries shut down systems - erectile dysfunction
Worsening of asthma, COPD, PVD (Reynard’s) or HF
Why can BB worsen HF?
If given in standard dose and acutely sympathetic ns doing what it can to stop drop of heart pressure - low doses - slowly titrate up *takes weeks to establish dose
How is Digoxin used in heart failure?
-avoid drugs that stimulate HR digoxin directly stimulates the heart: - makes no difference to mortality -hospitalisation for HF improves but decrease In life expectancy -relatively linked
Ivabradine in heart failure? and the results from using it
- blocks the funny current If in the sinus node slowing sinus node rate
- used in angina and HF
(used if someone cant use BB- slows HR)
Results= no benefit to death, hospitalisation reduced, overall benefit
Sacubitinal/ valsartan in HF?
sabcutitinal= neprillysin inhibitor
Valsartan= angiotensin II blocker
*benefit on top of ace inhibitor
- small benefits to death and hospitalisation
What is the difference between acute and chronic HF?
Acute= heart attack, failure in minutes- ruptured or leaky valves= dangerous Chronic= elderly, LVsystolic or diastolic dysfunction heart not coping well enough to cope with demands
Acute- What do you use?
- O2- drowning from inside
- dimorphine- opiates to get rid of the pain and act as vasodilator
- nitrates- venus dilation improve preload, arterial dilation improves afterload
- loop diuretics- work quickly- dilation and pass urine
- Ionotropes- acute HF with treatable cause
- adrenergic agonists- mimic CNS
- PDE II inhibitors- breakdown cAMP (block stimulation from inside)
PDE3 inhibitors experiment
Stimulate heart
same drugs that kill people used acutely
- 18month survival rate- placebo = 60%,, milrinone= 30%
