Case 5

Is it possible to full empty the blood out of the heart?

no

How do you work out stroke volume?

edv - esv, volume of blood ejected is the difference

What is edv?

end dyastolic volume

What is esv?

end systolic volume

What is heart failure?

stroke volume comprimised, the difference isn’t as big as it should be

What are the two time based types of heart failure?

acute or chronic

What are the anatomical types of heart failure?

left sided failure, right sided failure, biventricular failure

What are the classes of heart failure?

class 1 - no symptoms during normal physical activity
class 2 - confortable at rest, normal physical activity triggers symptoms
class 3 - confortable at rest, minor physical activity triggers symptoms
class 4 - unable to carry out any physical activity without disconfort, may have symptoms even when resting

What are the clinical features of heart failure?

reduced ejection fraction (<40% on echocardiogram), stroke volume is reduced, this causes reduced extersize tolerance as not as much oxygen is being delivered round the body, hypotention as not enough blood is going round which causes tiredness and dizziness, reduced urine flow as less blood to kidneys, cold peripheries for the same reason, breathlessness due to pulmonary congestion, oedema due to fluid leaving the capillaries into the tissues, atrial fibrilation due to back pressure on the atrium stretching the muscle and causing random contractions/electrical disterbances

What does an echocardiogram do?

messures the amount of blood in the ventricle and is used to work out stoke volume

What are the causes of left-sided heart failure?

left ventricular systolic dysfunction - caused by impaited contracillity or a pressure overload
left ventricular diastolic dysfuntion - reduced complicence of ventricular wall
obstruction of left ventricular filling

What causes impaired contractillity of the heart?

myocardial aschemia - reduced blood flow to muscle as doesn’t generate enough pressure, myocardial infarction - less muscle to contract so can’t pump blood with as much pressure
over streached heart - leaky valves
falty left bundle branch - doesn’t normally need treatment unless there is something else going on

What can cause a pressure overload in the heart?

hypertention, and blood loss

What happens in systolic left-sided heart failure?

increase in volume of blood left in the left ventricle at the end of contraction so end systolic volume increases, as more venous return refills the left ventricle during diastole the reduced systolic emptying leads to end diastolic volume increasing, stroke volume reduces

What causes left ventticular diastolic dysfunction?

left ventricular hypertrophy - where the left ventricle wall gets thicker due to hypertention, this is stiff so doesn’t refill very well, increases chance of diastolic heart failure
myocardial infarction - muscles stiffer when starved of oxygen
angina - muscle are stiffer when starved of oxygen

What causes obstruction of left ventricular filling?

valves not opening at the right time - AV disease, valves are narrowed so more difficult for blood to flow through it
blood loss
veins are obstructed
pericarditis - fluid leaks out and builds up, squeezes down on heart, cardiac efusion and cardiac tamponade physically compress the heart

What is the pericardial membrane?

serious membrane secreations, membranes slide over each other to reduce friction

What happens in diastolic left-sided heart failure?

reduced ventricular complience may lead to diastolic dysfunction causing left sided heart failure, pressure in ventricle in diastole s increased due to stiffness of venticular wall, end diastolic volume reduces due to reduced fillling of the ventricle, stroke volume reduces

What are the compensatory mechanisms in heart failure?

when stoke volume decreases more blood is left behind, end dyostolic volume can increase, this backs up into the atria and the pressure increases, backs up into the veins and venous pressure increases, normally little bit of stretch and blood left over is a good thing but eventually too much, stroke output has gone down, cardiac output has gone down, blood pressure gone down, ventricular wall becomes thicker to compensate for this, blood pressure goes up for a little bit, pressure is going to back up and it goes round in a cycle.

What is the Frank-Starling law of the heart?

little bit of stretch in the ventricles of the heart that improves their function

What is the compensatory process of heart failure?

compramised cardiac function, decreased arterial blood pressure, baroreceptor reflex, increased sympathetic outflow, adrenic receptors leads to vasoconstiction, beta receptors leads to increased renin, then increased AtII, this causes vasoconstriction and increased aldosterone, increased aldosterone causes Na⁺ retention so water retention, intravascular volume expansion, increased preload (more strain on heart as more blood returning to the heart), this increases myocardial O₂ demand, vasoconstriction also leads to increased afterload and as the heart has to overcome more pressure it increases myocardial O₂ demand, this leads to worsening heart failure

Explain left ventricular performance curves

cardiac performance increases as a function of pre-load - normal, with decreased ventricular contacillity there is less ventricular emptying which increases end-diastolic volume so the fall in stroke volume is less than it would otherwise have been, futher increased left venticular filling leads to pulmonary congestion, as you are pumping out less then you are getting in, you want to get back to the first one

What are left ventricular performance curves called?

Frank-Starling curves

How do you get fluid out the lungs when someone is in repiratory failure?

use a diuretic to relive symptoms of pulmonary congestion as if you loose a large volume of water quickly it moves between departments and redistrubuted

How can stoke volume be increased?

give a drug to cause left ventricular muscle to make a more forcefull contraction, positive inotope, this alleviates symptoms, but because it is making the heart work harder it has no long term positive effect
reduce preload - heart doesn’t have to work so hard, dilate veins, reduce amount of venous blood returning to the heart, arterial vasodilate - afterload drops, but don’t want to drop blood pressure too much as something caused by heart failure
ACE inhibitors - takes workload off the heart

What are the different drug classes used to treat heart failure?

beta-antagonists, ACE inhibitors, spironolactone diuretics/loop diuretics, vasodilators, venodilators

How do you treat acute heart failure?

IV diuretic therapy - start with either bolus or infusion stratergy, start straight away to get fluid out the lungs
Closely monitor renal function, weight and urine output
once stabilised: start or restart beta-blocker treatment
acute heart failure due to left ventricular systolic dysfunction - ACE inhibitor, treat as chronic heart failure

What are the loop diuretics drugs?

furosemide, bumetanide, and torasemide

What are loop diuretics?

reduce electrolyte reabsorbtion in the thick ascending limb of the loop of henle, blocks sodium-potassium-chloride, promote urinary excretion of Na⁺, Cl⁻, K⁺, trap sodium in the filtrate, and H₂O, highly potent, ‘high ceiling’ diuretics, produces high volume of urine in minutes

What are loop diuretics used for?

pulmonary oedema due to acute ledt ventricular failure, chronic heart failure, used alongside antihypertensive treatment in resistant hypertention, intravenous administration - relief of breathlessness and reduction in pre-load sooner than onset of diuresis

What is the ADME stuff for loop diuretics?

oral administration with GI absorbtion - 50% bioavilibility, peak effect 30 mins, half life of 2 hours, action lasts 4-6 hrs
rapid onset if IV - about 10 mins
undergoes liver cytochrome P450 metabolism

What is the treatment for chronic heart failure?

relief of congestive symptoms and fluid retention - loop, if risk of thrombosis - anticoagulation should be considered as stationary blood, HF with reduced cardiac function (ejection fraction <40%) - first-line treatment ACE inhibitor plus beta-blocker, if symptoms continue - mineralocorticoid receptor antagonists spironolactone
specialist treatment using: Ivabradine, digoxin, SGLT2 inhibitors - dapagliflozin, sacubitril valsartan, hydralazine with nitrate

What are the ACE inhibitors?

ramipril, captopril, enalapril, lisinopril, and perindopril

What are the ARBs?

candesartan, losartan, telmisartan and valsartan

When would you give an ARB for heart failure?

as an alternative to an ACE inhibitor as it may not be as effective

Why do you give ACE inhibitors for heart failure with reduced ejection fraction?

1st line treatment, blocks renin angeotensin aldosterone system - blocks whole pathway that makes heart failure worse

What are the heart failure beta blockers?

bisoprolol, carvedilol, and nebivolol

Why are beta blockers used to treat heart failure with reduced ejection fraction?

mechanism of action - inhibits adrenergic beta1 receptors, blocks effects of adrenaline and noradrenaline, inhibits the release of renin
slows rate of firing of SAN/AV node, negative chronotropic effect, negative inotropic effect
slower heart rate means less work for heart, improves myocardial coronary blood flow, diastole time increases so more blood fills the ventricles

What are the side effects with beta blockers?

dizziness, tiredness and blurred vision, most people have either no or very mild side effects that become less troublesome with time

What are the things to consider when treating heart failure with reduced ejection fraction using beta blockers?

don’t withold treatment due to age, peripheral vascular disease, erectile dysfunction, diabetes and respiratory disease
start treatment as start low, go slow
if already taking a beta blocker for a co-morbility switch to a heart failure beta blocker

When do you give spironolactone for heart failure with reduced ejection fraction?

if patient doesn’t respond to first line treatment - it is an add-on therapy as not as effective as other diuretics, improves survival in chronic heart failure, contraindercated if hyperkalaemia (as potassium sparing) or renal impairment

What is spironolactone?

aldosterone antagonist, potassium sparing, steroid pro-drug - effects via active metabolite canrenone, spironolactone half life 10 mins, canrenone half life 9-16 hrs, blocks aldosterone-induced production of sodium transport proteins in the distal collecting ducts - causes both Na⁺ and H₂O loss and K⁺ retention

What is Ivabradine?

treatment for angina and mild to severe chronic heart failure, inhibits I_f current reducing cardiac pacemaker activity to slow heart rate (beta blocker alternative that can also be used alongside)
contraindications - MI, cardiogenic shock, heart block, slow heart rates
cautions - ineffective if AF is there, elderly and angina
common or very common side effects - arrhythmias; AV block; dizziness; headache

What is sacubitril valsartan?

if first line treatment doesn’t work, Sacubitril is a prodrug that inhibits the breakdown of natriuretic peptides causes increased diuresis, natriuresis and in combination with valsartan (ARB) causes vasodilation, for heart failure with reduced ejection fraction, may be used in patients not currently taking an ACEi or ARB, contra-indicated with systolic blood pressure <100 nnHg as could cause severe hypotention, common or very common side effects are: anaemia, cough, diarrhoea, dizziness, electrolyte imbalance, headache, hypoglycaemia, hypotention, nausea, renal impairment, syncope and vertigo

What is natriuresis?

more sodium passes out through urine

What is hydralazine with nitrate?

hydralazine is a aterlolar dilator - arterial vasodilator
nitrates do effects aterial muscle but has more effect on veins - venodilator
for heart failure with rejeduced ejection fraction
contra-indications - acute porphyrias, cor pulmonale, dissecting aortic aneurysm, poor cardiac function due to mechanical obstuction, tachycardia
common or very common side-effects - angina, headaches, tachycardia, diarrhoea, dizziness, flushing, gastrointestinal disorders, headache, hypertention, joint disorders, lupus-like syndrom
cautions - cerebrovascular or coronary artery disease

What do venodilators do?

reduce pre-load, reduce risk of pulmonary congestion, blood in veins not squeezed as much and less blood returns to the heart, risk - could blood back up into the lungs

What do arterial vasodilators do?

reduce after-load and increase stroke volume

Why give digoxin for heart failure?

antiarrhythmic drug - increases vagal tone to heart
postive inotrope - increases intracellular Ca²⁺
increases effect of the vagus nerve on the heart which slows down the heart rate
not first line as improves symptoms but not mortality rates as adds to cardiac workload as more forceful contraction
also used in AF which has an increased chance of occuring

How does digoxin produce a more forceful contraction?

digoxin targets the Na⁺ K⁺ ATPase pump - sodium outside the cell, potassium inside the cell, when blocked, more sodium trapped inside the cell, more calcium in the cytosol, increased tention between actin and myosin fillaments, causes stroke volume to go up, sodium calcium pump - puts calcium outside the cell, sodium moves in and this drives the mechanism, reduced driving force of this pump so it is switched off, calcium is trapped inside, so more calcium availbile for a forceful contraction

What are the ADME things for digoxin?

oral bioavailibility around 75%, onset of action - 30mins, peak effect IV - 1-5 h, half life 36hs, elimination around 70% renal, GFR?, Volume of Distribution 640L/70Kg (high) - binds to skeletal muscle - hard to monitor how much is in the blood, narrow therapautic index - risk of toxicity

What are the contra-indications of digoxin?

heart block

What are the cautions with digoxin?

risk of digatalis toxicity with electrolyte imbalances - early contraction of the heart - eptopic beat - more stretch, more blood, more powerful contraction, recent MI

What are the common or very common side effects of digoxin?

arrhythmias, cardiac conduction problems, cerebral impairment, diarrhoea, dizziness, nausea, skin reactions, vision disorders, and vomitting

What is a heart block?

block the electrical signal that goes down into the ventricles

What are the SGLT2 inhibitors?

treatment for type 2 diabetes and heart failure
blocks SGLT2 glucose transporter in renal PCT glycosuria and fluid loss - high volume with glucose in it - rebalance in fluid in different compartments
haemodynamic changes - reduces pre-load and after-load, cardiac funtion improves
adverse effects - rare severe ketoacidosis, contra-indications - diabetic ketoacidosis, cautions - elderly, hypotention, risk of volume depletion

What is the SGLT2 inhibitor drug?

dapagliflozin

What are the two types of heart failure?

HFrEF - heart failure with reduced ejection fraction
HFpEF - heart failure with preserved ejection fraction

What is end-diastolic volume?

volume of blood in the ventricles at the end of systole

What is end-systolic volume?

volume of blood left in ventricles at the end of systole

What is stroke volume?

amount of blood ejected from ventricles during systole/beat, end diastolic and systolic volumes determine this, normally 70-80mL/beat

What is ejection fraction?

fraction of end-diastolic volume ejected during a heart beat, stroke volume/end diastolic volume, normally 50-70%

What is cardiac output?

volume of blood ejected by each ventricle each minute, around 5L in adult at rest, stroke volume x heart rate

What is preload?

the amount of blood presented to the ventricles

What is afterload?

the resistance against which the ventricles contract

What is the ejection fraction in heart failure with reduced ejection fraction?

<40%, the volume of blood is not enough to perfuse the body and provide all the nutrients

How is the condition characterised?

patients fluctuate between two states and can change rapidly:
stable patient - mild to no symptoms - can rapidly deterioate and become short of breath at rest and onset of an arrhythmia
acutely decompensated patient - pulmonary oedema and/or severe symptoms, can improve rapidly with diuretic therapy, urgent treatment needed
deterioration in symptoms indicated heightened risk of hospitalisation and death, high risk of complications
very often have co-morbilities

What are the aims of treating heart failure?

reduce mortalitiy and reduce the number of hospitilisations

What is the difference between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction?

dilated cardiomyopathy, the ventricle muscles are thin and weak and there is an increased filling space, weaker muscles find it harder to pump blood out so there is a reduced ejection fraction, failure of myocardium to contract normally and dilation of myocardium
hypotrophic cardiac muscle - thickening and growing of the muscle, grows into the space of the ventricle, small filling space so the blood that is ejected isn’t suffcient to perfuse the body, ejection fraction is preserved, also known as right sided heart failure, there are not many treatments available - symptom management

Which type of heart failure has more problems with the lungs?

heart failure with preserved ejection fraction

How does heart failure occur?

body is trying to compensate for a failing heart causing futher cardiac remodelling, if kidney’s detect less cardiac output, they stimulate RAAS system, causes increased circulating volume, increases afterload, increases resistance, heart is working harder with every pump, trying to increase stroke volume, cardiac remodelling occurs to help deal with the stress

How does heart failure effect the heart?

heart failure comes from damage to heart, damaged hearts have reduced cardiac output which causes a drop in blood pressure, RAAS and SNS are stimulated - increasing contractility, tachycardia - improves CO but causes reduced filling time for heart’s chambers, and vascoconstriction, in the short term these help the heart but cardiac remodelling can occur if severe and sustained damage occurs, the heart has to work harder and harder to perform its function, causing more damage and repeating the cycle

How does heart failure effect the kidneys?

kidneys are sensitive to a drop in cardiac output, macular densa cells detect low sodium and chloride ions which stimulate juxtaglomerular cells to release renin, this causes the RAAS system to begin, renin converts angiotensinogen to angiotensin 1 and then to angiotensin 2, angiotensin 2 has two effects: vasoconstriction and aldosterone release which increases sodium and water retention with the hope to increase kidney perfusion, there are problems

How does heart failure effect the lungs?

fluid retention (due to kidneys), heart still not working as a good pump so all ends up backed up in the venous system, rise in pressure due to too much volume, fluid starts to leak out to deal with the pressure, can progress to fluid overload
in reduced ejection fraction (left-sided failure) - blood and therefore fluid accumulates in the lungs causing pulmonary oedema, leading to shortness of breath as it effects gas exchange, kerley B lines on X-ray, more blood flow to top of lungs as the bottom isn’t as effecient
Plural effusion
Cardiomegaly - size of the heart - no more than 1/3 of the cavity

What are the general body problems associated with heart failure?

fluid retention (due to kidneys), heart still not working as a good pump so all ends up backed up in the venous system, rise in pressure due to too much volume, fluid starts to leak out to deal with the pressure, can progress to fluid overload
in preserved ejection fraction (right-sided failure) - blood and therefore fluid accumulates in peripheral circulation so they have a raised JVP, and peripheral oedema, pools in legs to form pitting oedema, this is due to gravity and being futherest away from the heart, work up the leg to work out how much fluid they are holding on to - they are genrally immobile at this point so it forms a sacral oedema - fluid at the base of the back

How does heart failure present?

typical (specific) - breathlessness - worse on exertion, ankle swelling, reduced exersize tolerance, fatigue, orthopnoea, paroxysmal nocturnal dyspnoea
less typical (non-specific) - palpitations, bloating, nocturnal cough (white/pink frothy) (fluid), loss of appetite, syncope, weight gain (fluid), confusion, and wheezing

What is plural effusion?

plural is genrally well lumbricated and has good perfusion, fluid can leak out of blood vessel and sit in the plural space, this can cause pain on inspiration and shortness of breath, sits at the bottom of the lung, on X-ray blutting of the bottom corners of the lungs

Why do you get fatigue with heart failure?

heart unable to meet demands of body, not getting nutrients they need

What is orthopnea?

shortness of breath when you lie down as fluid lies down the bottom of your lungs, one pillow, progress eventually to sleeping in a chair

What is paroxysmal nocturnal dyspnoea?

patients wake up suddenly in fright as they are very short of breath, they feel like they are drowning, have to sit upright to fix

What are the classifications of heart failure?

class 1 - no limitations, ordinary physical activity does not cause undue fatigue, dyspnoea or palapitations - asymptomatic LV dysfunction
class 2 - slight limitation of physical activity, ordinary physical activity results in fatigue, palpitation, dyspnoea or angina pectoris - mild chronic heart failure
class 3 - marked limitation of physical activity, less than ordinary physical activity leads to symptoms - moderate chronic heart failure
class 4 - unable to carry on any physical activity without disconfort, symptoms of chronic heart failure present at rest - severe chronic heart failure

What do you do to diagnose heart failure once you have suspected it?

test for enzyme that is released when the cardiac wall is alterted called NT-proBNP - pro B type naturinic peptide, it is sensitive not specific, can have raised NT-proBNP without heart failure, but not heart failure without it, confirm with echocardiogram - get all the messages - if it is over 100bpm struggle to do it

What is a genralised treatment pathway for heart failure?

start with a couple, assess tolerability, add a couple, assess tolerability, if symptoms remain optimise them

What are the pillars of HFrEF treatment?

four (tablets) or five (pharmacological mechanisms)
ACEi/ARB, beta-blocker, MRA, SGLT2i, NI (sometimes considered part of the 1st one)

Why give an ACEi/ARB for heart failure?

first line treatment - ARBs used as second line for those that don’t tolerate ACEi
improve symptoms, improve exersize tolerance and improve quality of life while reducing mortality

What is the mechanism for ACEi in heart failure?

ACEi inhibits action of angiotensin converting enzyme, reducing conversion of angiotensin 1 to angiotensin 2, reducing vasoconstriction and stimulation of aldosterone secretion, decreased aldosterone concentration, increased sodium and water excretion, helps decrease preload

What are the clinical considerations of ACEi/ARBs in heart failure?

baseline - bloods and observations - around Us and Es and monitor to see if these change - electrolyte and kidney function changes can occur
initiation - start at lowest dose and titrate up to prevent first dose hypotention
titration - normally double dose at 2-4 weekly intervals (hospital is faster), repeat baseline checks within 1-2 weeks of initiation and before/after any dose changes, aim for highest licenced dose or maximum tolerated dose - causes problems: if blood pressure too low they can’t tolerate a higher dose, if we knock out the kidneys too much
Patient information - hypotention and dizziness are most common side effect, montior for increasing K+, avoid any OTC NSAIDs
acutely ACEi can be nephrotoxic, can reduce perfusion of the kidney and can cause an AKI, protective of kidney in long term as it maintains pressure

What is high potassium classed as?

a medical emergancy, ambulance

Why can’t you give OTC NSAIDs alongside an ACEi?

causes segnificant kidney damage, as ACEi open the afferent arterole and NSAIDs open the efferent arteriole so there is a net decrease in pressure and kidney isn’t perfused enough

What do you if someone has face, lips or tounge swelling when on an ACEi?

stop taking the medicine and go to A and E now

Why are ARBs second line for heart failure?

less evidence and more expensive, only if can’t tolerate an ACEi

What is the problem around the cough with ACEi?

sometimes could be because it could be due to fluid on the lungs, introduce it when stable and may find no problem

Why are beta blockers given for heart failure?

segnificant reduction in all cause mortality and in morbidity, block β₁-adrenergic receptor, reduce force of cardiac contraction, reduce speed of conduction, block the damaging effects of overactive sympathetic activity, negative chronotrope and negative inotrope, reduces workload on the heart

What are the clinical considerations of beta blockers in heart failure?

offered to all patients with left ventricular
don’t start if there are signs of fluid overload as can cause fluid retention, use cardioselective - especially in respiratory disease
need baseline HR, BP, fluid status, and possibly ECG?
start at lowest dose and titrate, increase every 2-4 weeks to get target or max tolerated dose, repeat baseline checks before each dose change, if it has been stopped for more the 2 weeks re-introduce cautiously and consider re-starting from the initiation dose
HR 50-60 is aim, don’t let BP get too low

What is the patient information for beta blockers in heart failure?

may take weeks/months to notice benifit, expect temporary increased fatigue/shortness of breath, do not stop suddenly without speaking to a healthcare proffessional

What are the 3 beta blockers you can give for heart failure?

bisoprolol, carvediol, and nebivolol

What are the side effects you should tell the patient about with beta blockers in heart failure?

low BP, weird dreams, cold peripheries, masks hypoglycemia in diabetes, fatigued

What are the drugs with intrinisid sympathomimetic activity?

pindolol, acebutol, celiprolol, oxprenolol - less bradycardia, less coldness of extremities

What are the water-soluble beta blockers?

celiprolol, atenolol, nadolol, sotalol - less likely to cross BBB, less nightmares and sleep disterbances, renally cleared

What are the cardio-selective beta blockers?

well-controlled asthma under a specialist if no other choice, bisoprolol, atenolol, metoprolol, acebutol, nebivolol