Week 2 Valve Disease

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Week 2 – Valve Disease

1. Valve Disease

● Describe the epidemiology of the different types of Valve Disease. Classify valvular heart disease.

● Outline the risk factors for coronary artery disease. Describe the praecordium, how valvular diseases are graded. Describe BNP and relevance.

● Compare and contrast the symptoms and signs produced by the different types of valve disease

● Describe the management of common Valvular Heart Diseases. Include types of value replacement and surgery. Include treatment of heart failure

2. Cardiac Rehabilitation

● Describe the phases involved in cardiac rehabilitation and effect on physiology. 3. Endocarditis

● Describe the predisposing factors, symptoms and signs, treatment and complications of Endocarditis.

4. Pharmacology

● Discuss the drugs involved in management of coronary artery disease, their mechanisms of action, and side effects. Include clopidogrel, aspirin, ACE inhibitors, digoxin,

Fondaparinox (difference vs enoxaparin – why better). 1. Investigations in Cardiology

● Describe the radiological investigations used to assess the heart echocardiograms,  angiography and nuclear medicine. Pros and cons of different tests.

2. Heart murmurs

● Describe murmurs

M4, W2 Valve Disease Notes

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Valve Disease

Epidemiology

● In the developed world degenerative valve disease is more common than other types e.g. valve disease caused by infections such as rheumatic fever and syphilis, due to the larger proportion of elderly people. In developing countries, valve disease is much more commonly caused by previous infections. I’ll go through each type of valve pathology and talk about the epidemiology for it.

Pulmonary stenosis

● Highly associated with congenital heart disease – 30% of those with congenital heart disease have this.

● Slightly more common in people of black ethnic origin Pulmonary regurgitation

● Very rare, asymptomatic (can be asymptomatic even in severe cases) so incidence/prevalence is difficult to measure.

Tricuspid stenosis

● Similarly to mitral stenosis this is nearly always caused by rheumatic heart disease

● Overall incidence of tricuspid stenosis in patients with rheumatic heart disease is between 9 and 15%.

● Tricuspid stenosis can be congenital but this is very rare. It affects <1% of the population Tricuspid regurgitation

● This is often asymptomatic – 50% of young adults have mild regurgitation of their tricuspid valve.

● Usually secondary to other pathology

o In the developed world this is normally degenerative or ischaemic disorders o In the developing world this is normally rheumatic fever

Pathophysiology

● Valve stenosis is when the valve opening does not open wide enough increasing the force required to pump blood through the valve thus inhibiting the hearts’ ability to pump blood through the body.

● Valve regurgitation (also referred to as valve insufficiency) is when the valve does not close completely, causing backflow of blood. ● Valve prolapse is when the valve bulges

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when it closes, thus allowing small amounts of blood to flow back into the previous chamber.

MITRAL STENOSIS (MS)

● The most common cause of mitral stenosis is rheumatic fever due to an acute streptococcal throat infection. This leads to cardiac inflammation (myocarditis) 7-10 days later which causes chronic inflammation of valves, causing narrowing (stenosis).

● Other causes are rarer: congenital (isolated lesion or associated with an atrial septal defect), malignant and SLE

● Rheumatic fever affects men and women equally but women are 3 times more likely to get stenosis as a consequence.

Pathology:

● Normally, the valve orifice has an area of 4-6cm2_{. In severe stenosis, this reduces to under 1cm}2_. This obstructs flow out of the left atrium to the left ventricle, which causes increase in left atrial pressure leading to left atrial hypertrophy and dilatation. Pulmonary artery and vein pressure also increases (pulmonary hypertension) which leads to right ventricular hypertrophy and dilatation. Eventually, there is a loss of coordinated atrial contraction

Symptoms

● Asymptomatic for years – becomes symptomatic when significantly stenosed (<2cm2₎

● Fatigue due to right-sided heart failure from the pulmonary hypertension, as well as weakness and peripheral oedema

● Cough:with frothy sputum and haemoptysis due to increased incidence of pulmonary vein and alveolar capillary rupture from the increased pulmonary pressure

● Dyspneoa: due to pulmonary hypertension, pulmonary oedema or atrial fibrillation (due to loss of atrial conduction which causes reduction in cardiac output)

● Atrial fibrillation: this is very common due to the hypertrophic left atrium caused by constant pressure on it – presenting with palpitations, dyspnea and systemic emboli

● Other symptoms due to left atrial enlargement: hoarseness (due to stretching of recurrent laryngeal nerve), dysphagia (due to oesophageal compression), leftlungcollapse (due to compression of the left main bronchus)

● Differential diagnoses of mitral stenosis are hypertrophy cardiomyopathy, left atrial thrombus M4, W2 Valve Disease

Notes 3

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and left atrial myxoma – which all obstruct the flow of blood into the left ventricle.

MITRAL VALVE REGURGITATION

Pathology:

● A leaky mitral valve is due to abnormalities of the papillary muscles, the chordae tendinae and/or the left ventricle. It is usually caused by general degeneration, ischaemia heart disease, rheumatic disease and/or infective endocarditis. This causes increased left atrial pressure which the heart accommodates for over time by left atrial dilatation and hypertrophy, which leads to left ventricular hypertrophy.

● Overall prevalence of 2% worldwide Symptoms

● Often asymptomatic for many years

● Heart failure symptoms: dyspnea, excessive tiredness, fluid build up ● Infective endocarditis may develop (see Matt’s PBL for more on IE) ● Palpitations due to atrial fibrillation

● Other presentations include anorexia, weight loss, fever, night sweats, vasculitis rashes Signs

● Hyperdynamic and laterally displaced apex: from left ventricular hypertrophy (+/- systolic thrill – hopefully future weeks will go into thrills)

● Pan-systolic murmur (a murmur that occurs throughout systole) (+/- systolic clicks)

AORTIC STENOSIS (AS)

● This is the narrowing of the aortic valve orifice causing obstruction of blood flow out of the left ventricle. It is most commonly caused by calcification which leads to valve stiffness and opening. Risk factors include old age, being male, hypertension and diabetes. Can also be due a bi-leaflet aortic valve rather than a tri-leaflet valve that most people have

● Comes after aortic sclerosis – thickening of the valve

● Most common valve disease in Europe and most common reason for valve replacement surgery ● Increased risk with age – symptoms tend to present between 70-90 years

● Prevalence of 2.6% in patients aged >75 years Pathology:

● The obstruction of blood flow out of the left ventricle causes increased peripheral resistance leading to an augmented cardiac output by a compensatory left ventricular hypertrophy. Diastolic function becomes impaired which increases myocardial oxygen consumption,

shortening the period of coronary artery filling, reducing perfusion pressure causing ischemia. M4, W2 Valve Disease

Notes 4

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Symptoms

● Asymptomatic until stenosis is moderate (1-1.5cm2₎

● There is a classic triad of symptoms that if they develop, the prognosis is poor: 1. Angina - due to the ischemia

2. Exertional syncope– due to insufficient oxygen demand due to narrowed valve 3. Breathlessness

● Other complications: infective endocarditis, transient ischaemic attacks and stroke ● Sudden deathmost frequently occurs in patients who are symptomatic

Signs

● Pulsus tardus et parvus: a late and weak pulse (also referred to as slow upstroke) ● Apex beat sustained and more obvious – due to the hypertrophic left ventricle ● Systolic thrill – in cardiac apex

● Ventricular hypertrophy

● Murmur in ejection systolic phase (longer in more advanced disease)

AORTIC REGURGITATION/INSUFFICIENCY

● This leads to left ventricular hypertrophy and cardiac ischemia can develop. Symptoms

● Often asymptomatic –symptoms only develop until left ventricular failure has occurred ● Dyspnoea

● Orthopnoea and pulmonary oedema – due to pulmonary venous hypertension that occurs due to backflow of blood from the left side of the heart

● Fatigue ● Angina Signs

● Hyperdynamic and laterally + inferiorly displaced apex beat –hypertrophic left ventricle ● Auscultation: early diastolic murmur +/- mid-diastolic murmur

● Rarer signs specific to AR

o Quincke’s sign: capillary pulsation in nail beds o De Musset’s sign: head nodding with each heart beat

o Pistole shot femorals: sharp bang heart over auscultation over femoral arteries

TRICUSPID VALVE LESIONS

● These are uncommon, are more often seen in women than men and are usually due to rheumatic heart disease. They often develop secondary to mitral or aortic valve disease.

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Tricuspid Valve Stenosis

● This leads to reduced cardiac output which the heart accommodates for by developing right atrium hypertrophy. The systemic venous system becomes congested as blood flow is inefficient leading to fluid accumulation.

Tricuspid Valve Regurgitation

● This occurs with rheumatic heart disease and infective endocarditis. Symptoms and signs include:

● Right ventricular hypertrophy ● Right heart failure symptoms

● Auscultation: right ventricular impulse and murmur on inspiration at left sternal edge ● Atrial fibrillation

PULMONARY STENOSIS

● Pulmonary stenosis usually occurs due to congenital causes. However, it can rarely be secondary to rheumatic fever. It is also associated with rubella during pregnancy.

Signs and Symptoms

● If mild stenosis, asymptomatic

● Right ventricular hypertrophy - due to increased demand on the right ventricle

● Atrial hypertrophy ● Fatigue

● Syncope

● Right heart failure symptoms ● Severe stenosis can be fatal

PULMONARY REGURGITATION

● Most commonly due to acquired heart valve disease ● Rarely requires treatment as usually asymptomatic ● Diastolic murmur present

Management

Rheumatic Fever

● Rheumatic fever is an inflammatory disease notably affecting the heart that is caused as a complication of a group A streptococci throat infection occurring mainly in children and young adults. ● Diagnosis is made clinically and one can use the ‘Jones Criteria’

which is included below.

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● To diagnose Rheumatic Fever using the Jones criteria patients must have at least either 2 major features or 1 major and 2 minor features. Concerns have been raised about its adequacy and the in addition column are other helpful ways to assist in diagnosis

TREATMENT

● We need to reduce the inflammation and can do this via aspirin and steroids.

1- Symptoms- Rest and analgesia. Paracetamol, Aspirin (very, very effective at reducing arthritis but can cause Reye’s syndrome in children which affects the brain and can quickly become fatal. Other NSAIDS are also an option. In extreme cases of carditis steroids are useful but usually NSAIDS are preferable. Diazepam is an anti-convulsant that can treat Syndeham’s Chorea. 2- Control heart failure. This can be treated using diuretics such as bendroflumethiazide or

furosemide. ACE inhibitors can also be used to treat the heart failure. Heart valve replacement may be assessed if there is chordae rupture or other valve issue

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Major Minor In addition Carditis (inflammation of the heart and

surrounding tissues)

General Fever Recent Strep Infection Arthritis (migrating polyarthritis, quickly moving

between joints, usually the larger ones. N.B rheumatic fever doesn’t normally result in

chronic arthritis.)

Previous Rheumatic Fever History of Scarlett Fever

(collection of symptoms also caused by strep A infection, notably a bright red tongue.)

Syndeham’s Chorea (also known as St Vitus’ Dance, occurring potentially a few months after

the disease. This is a condition where a patient may make involuntary jerking movements also associated with facial grimacing. This is due to toxins from the Strep affecting the nervous

system)

Raised CRP/ESR Throat swab positive to strep

Erythema marginatum (fairly rare, this is a non- itchy, red rash occurring on the trunk with slightly raised edges and maybe a clear centre.

Honestly looks a little bit like erythema multiforme as you can tell from the picture

below)

Arthralgia (N.B if arthritis is used as a major criteria arthralgia cannot act as a minor one)

Raised ASO titre (Anti Streptolysin O is an antibody

made by streptococcal bacteria. It can be detected in

blood plasma

Subcutaneous nodules (Fairly small, pea shaped nodules which are mobile and don’t cause any pain may appear on the elbows, wrists, ankles and some areas of the spine. One of the rarest manifestations of rheumatic fever occurring in

<5% of cases).

Long PR interval – indicates heart block as there is a delay to the impulse from the atria

to the ventricles

Raised Anti-DNase Antibody

(antis deoxyribosenucleic acid antibody is produced by the body in defense against group

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3- Treat the infection. Penicillin will treat the streptococcal infection but prophylactic penicillin is necessary to prevent reoccurrence. BMJ best practice recommends an IM injection every 3 to 4 weeks. The World Health Organization recommends that for patients without proven carditis, they should continue anti biotic prophylaxis for 5 years or up until age 18 whichever is the longer should be chosen. Patients with definite carditis should continue up until 25 or for 10 years, once again whichever is longer.

Mitral Stenosis Investigations

● Include ECG showing AF, and an abnormally long P wave in lead 2, maybe having an M shape. ● CXR may show enlarged left atrium and a wider angle of carina splitting. Calcification of the

mitral valve itself will show up on an x-ray.

● An echo will give a good view of the valve itself and allow it to be measured.

● Cardiac catheterization can be used to look for any coexisting cardiac diseases as well. Management

● Medical treatment - Digoxinor a low dose of a beta blocker to treat AF and prolong diastole, allowing the left ventricle to fill more. Anti-coagulation should be maintained, warfarin being an old favourite however the DOACs such as apixaban can now be used. Diuretics such as those previously named will treat pulmonary oedema.

● Mitral Valvuloplasty- a wire is passed up a peripheral vein using only local anaesthetic and a catheter and guide wire are passed into the right atrium, then through the

atrial wall into the left atrium and into the mitral valve. Then the balloon is inflated repeatedly to split any fused leaflets. If successful this may

completely avoid the need for a replacement, but is not recommended for all patients. It is especially useful in asymptomatic patients with severe disease.

● A mitral valvuloplasty may be off the cards if a patient has either marked mitral regurgitation, a history of systemic emboli or calcified/ thickened, rigid, mitral valve leaflets.

● Surgery- options include an open mitral valvotomy or full replacement. I will cover these options at the end.

Mitral Regurgitation Investigations

● ECG showing left ventricular hypertrophy and AF.

● CXR will show an enlarged ventricle and maybe a calcified mitral valve. ● Echo will show the regurgitation in action.

● Cardiac catheterization can measure mitral regurgitation and can also assess coronary artery disease whilst you’re still investigating.

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Management

● In acute MR, where there is extreme dyspnoea due to pulmonary oedema, this can be suddenly fatal and it is of paramount importance that this is dealt with swiftly. Annuloplasty, where a ring is used to reshape the valve can be used, as can mitral valve repair surgery/ replacement. Diuretics will follow surgery to treat oedema

● Non-acute MR where the left ventricular ejection fraction > 60% (the left ventricle is offloading at least 60% of the blood into the aorta) - ACE inhibitors are first linesuch as captopril or lisinopril. Used in combination with a beta blocker such as atenolol.

● Non-acute MR where left ventricular ejection fraction <60%. Surgery is recommended with either a repair or a valve replacement being preferable.

Tricuspid Stenosis Management

● In severe congenital cases surgery is recommended and since this in neonatal infancy it is incredibly demanding, complicated surgery.

● In mild to moderate disease diuretics are the mainstay treatment, mainly furosemide. In severe cases a replacement is the best option.

Tricuspid Regurgitation Investigations

● ECG will usually show cor pulmonale with a peaked P wave in lead 2, CXR may note some respiratory disease.

● Echo will show regurgitation. Treatment

● Treat the underlying cause, mainly diuretics are used as are ACE inhibitors to treat any fluid overload and RVF. Tricuspid valves have a high rate of thrombosis due to their large size and so are only considered in extreme circumstances.

Aortic Stenosis Investigations

● ECG will show signs of left ventricular hypertrophy ● CXR may show signs of calcification on the aortic valve. ● Echo will show great detail regarding the aortic valve.

● Cardiac Catheterization will give you a value in terms of left ventricular failure and can also assess cardiac arteries.

Management

● Apart from using diuretics to treat the left ventricular failure, anti-angina drugs and ACE inhibitorsare avoided as there is a risk that they will cause pulmonary oedema (due to a

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negative inotropic effect), or cause vasodilation resulting in an even worse pressure gradient across the aortic valve.

● Surgery is an option in all symptomatic patients with marked stenosis (an aortic valve gradient greater than 50 mmHg). Without surgery outcomes are very poor for aortic stenosis and an aortic valve replacement is preferable.

Aortic Regurgitation Investigations

● ECG, CXR, Echo and a cardiac catheterization, same as literally everything else to do with valves.

Management

● In a patient with mild to moderate AR, where their left ventricle is ejecting >50% of its blood into the aorta, often no treatment is needed, just reassurance

● Patients start to require a valve replacement when their left ventricle is failing to eject blood, and often they will not need reoperation.

Mitral Valvuloplasty

● Insert catheter and guideline into a peripheral vein.

● Feed up all the way to right atrium and pass through septum

● Place in between mitral valve and inflate balloon to separate out any fused bits of valve.

Mitral valvotomy

● Nearly completely replaced by balloon valvuloplasty

● Effectively involves placing a finger or dilator into the mitral valve in order to open it.

Mitral Valve Repair

● Also known as an annuloplasty, a prosthetic ring is inserted into the base of a valve and then sewn to it in order to keep structural integrity and prevent regurgitation.

● Keeping the original valve reduces the risk of emboli. Valve replacements

Mechanical

● Three broad types, ‘ball and cage’ ‘tilting disc’ and ‘bileaflet valve' 1. Ball and cage is currently the oldest type of mechanical valve

prosthesis and comprises a metal cage encasing a silicon ball. These are bulky however and have a higher risk of embolus forming.

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2. Tilting disc- nearly completely replaced by bileaflet discs, which is very similar.

3. Bifleaflet disc- the least thrombogenic of the 3 aforementioned valves, from my reading it seems to be the best choice

● All of these are very durable but do increase the risk of an embolus forming and require anticoagulation.

Bio Prostheses

● Normally made from cow or human cadavers, these valves avoid the need for long term anticoagulation but are prone to failing after about 10 years, therefore needing to be replaced. Apparently the rate of deterioration is inverse to age so bio prostheses should be avoided in the young as they will wear out fairly quickly.

● To replace a valve we need to do a median sternotomy to access the heart under general anaesthetic. It would be a bit tricky to perform the surgery with the heart beating so we stop it using medication and use a technique called cardiopulmonary bypass. The lungs are replaced with a respirator and the heart with a pump. The valves are accessed via the atria or aorta and the native valves are cut out and replaced.

Cardiac Rehabilitation

● “Cardiac rehabilitation is a complex intervention offered to patients diagnosed with heart disease, which includes components of health education, advice on cardiovascular risk reduction, physical activity and stress management”

● Evidence is mounting that cardiac rehabilitation reduces mortality, morbidity, hospital admissions and quality of life and is now recommended in international guidelines. It is important as it is estimated every 3 minutes someone in the UK

has a myocardial infarction and the number of people living with coronary heart disease in the UK has increased to an estimated 2.3 million.

● It is important to offer cardiac rehabilitation to combat

modifiable risk factors. So not only are health professionals using medication to treat diabetes, high blood cholesterol and

hypertension but lifestyle changes too. It has been proven, for example, that weight loss, changes in diet, reduced salt intake,

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physical activity and only consuming moderate amounts of alcohol (less than 14 units a week) has a greater effect on lowering blood pressure than drugs.

● Programmes include:

o Medical evaluation

o Prescribed exercise

o Cardiac risk factor modification (physical activity and exercise, diet, smoking cessation)

o Education

o Counselling; focussing on psychosocial health ● The aims are:

o To limit the physiological and psychological effects of cardiac illness

o Reduce the risk of sudden death or re-infarction

o Control cardiac symptoms

o To stabilise or reverse the atherosclerotic process

o Help patients back to work.

● There are certain groups of patients that have been shown to benefit the most from cardiac rehabilitation:

o Patients with Acute Coronary Syndromes.

o Patients undergoing reperfusion such as PPCI or CABG.

o Patients with newly diagnosed chronic heart failure or those whose heart failure has got worse

o Patients with a heart transplant.

o Patients who have undergone surgery for implantation of intra-cardiac defibrillator or cardiac resynchronisation therapy.

o Those with heart valve replacements.

o Those with a confirmed diagnosis of exertional angina. ● There is a specific 7 stage pathway shown in the picture below.

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● Formal rehabilitation programmes vary in intensity and duration. In the UK it’s provided in supervised groups by specialised nurses or physiotherapists supported by exercise therapists. Other health professionals may include a dietician, psychologist and an occupational therapist. Attendance is usually required for an average of 56 days. Prior to discharge, clinicians should ensure that patients are prescribed drugs for secondary prevention. Good communication between secondary and primary care also optimises results.

● However, despite encouraging results the participation rate ranges from 20-50%. This is thought to be due to poor referral rates, poor adherence rates and high drop-out rates.

Endocarditis

● Definition - Inflammation of one of the four valves of the heart, the walls of the endocardium, or the chordae tendinae

Predisposing Factors

● Underlying/pre-existing valve disease e.g. mitral stenosis, aortic stenosis, mitral regurgitation etc.

● Patients who have previously had a valve replacement

● Over 50% of patients who present with endocarditis are over the age of 60 ● Males are 2.5 times more likely to develop the condition than females ● IV drug users are at a higher risk than non-drug-users of a comparable age

Aetiology & Pathophysiology

● Caused by the growth of bacteria on one of the heart valves. A build-up of nodules known as 'vegetations'. The infection may be introduced into the valves during brief periods of having an infection in the blood stream. This could occur after dental work, colonoscopies, or similar procedures.

● The infection occurs in areas damaged by turbulent blood flow. As a result, platelets and fibrin adhere to the underlying collagen surface and create a prothrombotic environment.

Bacteraemia leads to colonisation and finally produces a mature, infected vegetation. ● Most common organisms responsible include:

o Viridans group streptococci

o Staphylococcus aureus

o Enterococci

o Haemophilus parainfluenzae

Prophylaxis

● Patients who have predisposing conditions are sometimes given prophylactic antibiotics prior to surgery such as dental work (any

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procedure similar) in which body tissue may be damaged. Examples of courses of antibiotics would include:

o Amoxicillin and erythromycin OR

o Intravenous vancomycin and gentamicin

● However, the evidence for the efficacy of this prophylaxis is weak and so NICE have now recommended that this practice cease.

Symptoms

● Fever

● Fatigue/weakness ● Chills

● Aching joints and muscles ● Night sweats

● Peripheral oedema (impaired valve) ● Shortness of breath (impaired valve)

Signs

● Patients can sometimes develop anaemia ● Blood in the urine

● Elevated white cell count ● New heart murmur

Diagnosis

● The nodules present from the build-up of bacteria can be detected

by echocardiography, which is essentially an ultrasound examination of the heart. ● The most accurate method of detecting these vegetations is through a procedure called

transoesophageal echocardiography (TEE). This procedure involves passing an endoscope through the oesophagus, with an echo-transducer attached to the flexible tip. The echo-transducer can then take sound-wave 'pictures' of the valves adjacent to the lower oesophagus.

● Vegetations are sometimes not present in endocarditis, and so cannot be detected through imaging. In these cases, an appropriate blood culture associated with a relevant clinical picture is sufficient to make the diagnosis.

● ECGs can also be useful as they sometimes show a lengthened PR interval, and non-specific ST/T wave abnormalities.

Complications

● Congestive heart failure - high likelihood ● Emboli - high likelihood

● Valvular rupture - medium likelihood

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Treatment

● The typical treatment is with aggressive intravenous antibiotics for 4-6 weeks. Duration and intensity of the therapy depends on the severity of the infection, as well as the organism involved.

● In some cases, the valves can become damaged as a result of a severe infection. It may be necessary to perform valve replacement surgery to supply adequate valve function. ● During treatment, look out for fever reduction, negative findings on blood cultures, and

improved findings on electrocardiography. These are all signs that the treatment is effective.

Pharmacology

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Antiplatelets - Indications: following ischaemic stroke or MI, peripheral vascular disease, ACS, post coronary artery stent insertion.

Mechanism -Clopidogrel: irreversibly modifies the adenosine diphosphate (ADP) receptors on platelets, meaning ADP cannot bind to platelets to activate aggregation and cannot form a thrombus. Often used alongside aspirin or instead of (if aspirin is contraindicated or poorly tolerated. –Aspirin: platelets contain a high concentration of COX-1 for the production of thromboxane A₂. By inhibiting this process, aspirin inhibits platelet aggregation, and consequently

thrombus formation.

Side effects Common: GI disturbance, rash

Rare: GI or intracranial haemorrhage, neutropenia, thrombotic thrombocytopenic purpura, hepatic impairment

Contraindications Active bleeding, breastfeeding, intracranial haemorrhage

Interactions Increased risk of bleeding in combination with anticoagulants, other antiplatelet drugs and NSAIDs

Examples Clopidogrel, aspirin

Statins (HMG CoA reductase inhibitors)

- Indications: hypercholesterolemia, hyperlipidaemia, patients with high risk of cardiovascular disease

Mechanism Act on hepatocytes and reversibly inhibit HMG CoA reductase. The liver expresses an increased concentration of LDL receptors = more LDL removed from blood plasma. Lowering the amount of plasma LDLs means a lower total cholesterol.

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additional benefits include anti-inflammatory effects, improved endothelial function, and atheromatous plaque stabilisation.

Side effects Common: headache, muscle cramps, flatulence

Rare: reversible myositis, GI disturbance, rash, alopecia, altered liver function tests (LFTs), hepatitis, acute pancreatitis

Contraindications Acute liver disease or persistent and unexplained abnormal LFTs, pregnancy and breastfeeding, acute porphyria

Interactions Increased risk of myositis with: ciclosporin, clarithromycin, erythromycin, fibrates. Increased risk of myopathy with itraconazole, ketoconazole. Enhanced anticoagulation effect when given with warfarin.

Examples (suffix: –statin ) Simvastatin, atorvastatin

Beta-blockers -main indications: hypertension, IHD, cardiac dysrhythmias, secondary prophylaxis of MI, heart failure

Mechanism There are 2 types of beta-blocker: selective (beta₁ receptor blocking) and is used in patients for whom beta₂ blockage would be harmful (asthmatics), and non selective (beta₁ and beta2 receptor blocking.

Blockade of beta₁ results in reduction to myocardial contractile force and heart rate.

Contraindications Asthma, uncontrolled heart failure, cardiac conduction defects, bradycardia, COPD, severe peripheral vascular disease, hypotension

Interactions Increased risk of bradycardia and atrioventricular block with diltiazem. Increased risk of heart failure, severe hypotension and asystole with verapamil.

Examples (suffix: –olol normally) Bisoprolol, atenolol, propanolol

ACE inhibitors - Indicaitons: hypertension, heart failure, post MI (high risk patients or if left ventricular dysfunction), diabetic nephropathy

Mechanism inhibition of Angiotensin-converting enzyme results in reduced synthesis of the

vasoconstrictor angiotensin II, and accumulation of the vasodilator bradykinin - a double antihypertensive effect. ACE inhibitors protect against glomerular injury in the kidneys, and reduce myocardial damage subsequent to an MI.

ACE inhibitors prevent post MI coronary events through prevention of atherogenesis and thrombosis in vessels, and prevention of left ventricular hypertrophy.

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Rare: hyperkalaemia, worsening renal function (in patients with underlying renal ischaemia or severe heart failure), angio-oedema, haematological toxicity (e.g. neutropenia,

agranulocytosis)

Contraindications Renal vascular disease, pregnancy

Interactions Increased risk renal impairment with NSAIDs, increased risk hyperkalaemia with potassium-sparing diuretics

Examples (suffix: -pril) Ramipril, lisinopril, captopril

Angiotensin II receptor

antagonists (ARBs)

- Indicaitons: hypertension, diabetic nephropathy (in type 2), heart failure (in combination with ACE inhibitors or instead of if ACE inhibitors are not tolerated)

Mechanism ARBs are reversible competitive antagonists that act upon angiotensin II receptors (though oddly these are referred to as AT1 receptors) which are found within the adrenal glands and smooth muscle tissue. The adrenal cortex secretion of aldosterone is then reduced. Angiotensin II in smooth muscle produces a vasoconstrictive effect, and so ARBs effectively block this to have an antihypertensive result.

Unlike ACE inhibitors, ARBs do not inhibit kinin breakdown, and as such are not associated with the dry cough and angio-oedema which can make ACE inhibitors poorly tolerated.

Side effects Common: headaches, dizziness, diarrhoea

Rare: myalgia, vasculitis, hepatitis, taste disturbance, hyperkalaemia, rash, pruritis (severe itching of the skin)

Contraindications Breastfeeding and pregnancy

Interactions Increased risk of hyperkalaemia in combination with any of the following: ACE inhibitors, ciclosporin, potassium-sparing diuretics

Examples (suffix: -sartan) Candesartan, eprosartan, irbesartan

Calcium-channel blockers

- indications: hypertension, angina, supraventricular dysrhythmias

Mechanism Calcium-channel blockers act calcium channels in the myocardium, the conducting system of the heart, and vascular smooth muscle.

-Dihydropyridines (most CCBs) act mainly on coronary and peripheral vessels and so used in the treatment of angina.

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-Verapamil and diltiazem, unlike other CCBs, act on both the heart itself and peripheral vessels, featuring anti-arrhythmic properties, and reducing heart rate and contractile force. They cause dilation in peripheral vessels and coronary arteries.

Side effects Common: headache, flushing, ankle swelling, dizziness, hypotension, bradycardia, constipation

Rare: urinary frequency, GI disturbance, mood changes, palpitations, impotence, lethargy, atrioventricular block

Contraindications Pregnancy and breastfeeding, cardiogenic shock, advanced aortic stenosis, unstable angina, acute porphyria, severe bradycardia, heart failure

Interactions Diltiazem: increased risk of bradycardia and atrioventricular block with beta-blockers. Verapamil: increased risk of heart failure, severe hypotension and asystole with beta-blockers.

Examples (suffix: -pine) Amlodipine, Felodipine, verapamil, diltiazem

Diuretics (thiazides, loop)

- indicated in hypertension (thiazides), chronic heart failure and fluid overload in kidney or liver disease (loop, thiazides or both)

Mechanism -Thiazides act on the proximal distal tubule of the kidney and inhibits sodium and chloride reabsorption. The result is an increase in sodium, chloride, and water excretion. Leads to hypokalaemia, hyponatraemia and a reduction in intravascular volume. The reduction in intravascular volume produces decrease in cardiac output, and a reduction in peripheral resistance, giving an initial and longer term antihypertensive effect.

- Loop diuretics inhibit sodium, chloride, potassium, hydrogen and water reabsorption in the ascending limb of the loop of Henle. leads to such side effects as hypokalaemia,

hyponatraemia and hypochloraemia.

Side effects Common: hypokalaemia, hyponatraemia, dehydration, postural hypotension

Rare: impotence, hyperuricaemia, hyperglycaemia, hyperlipidaemia, hypercalcaemia, thrombocytopenia, photosensitivity, acute pancreatitis

Contraindications Thiazides - Hypokalaemia, hyponatraemia, hypercalcaemia, gout, Addison's disease Loop - Renal failure

Interactions Thiazides - Digoxin. Increases plasma concentration of lithium when taken in combination. Loop - High risk of toxicity with certain antibiotics. Digoxin, lithium.

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Anticoagulants (see mod 3 for more detail)

Heparin indications: prophylaxis and treatment of DVT and PE, acute coronary syndrome,

acute occlusion of peripheral arteries

Warfarin indications: prophylaxis and treatment of DVT, PE, thromboembolism (e.g. in AF or prosthetic heart valves), prevention of TIAs and ischaemic stroke.

Mechanism -Heparin inactivates thrombin and other clotting factors, inhibiting thrombus formation. It also has an antiplatelet effect through binding to and inhibiting von Willebrand factor. -Warfarin inhibits the reduction of vitamin K by inhibiting vitamin K epoxide reductase. As vitamin K is an essential cofactor for the synthesis of clotting factors, it limits clotting factor production.

Side effects Heparin - Common: haemorrhage

Rare: osteoporosis or alopecia with long-term use, skin necrosis, rash, anaphylaxis, thrombocytopenia, hyperkalaemia

Warfarin - Common: haemorrhage

Rare: osteoporosis or alopecia with long-term use, skin necrosis, rash, anaphylaxis, thrombocytopenia, hyperkalaemia, liver impairment

Contraindications Heparin - Haemorrhage, haemophilia/thrombocytopenia, active peptic ulcer, post major trauma, recent haemorrhagic stroke or surgery, severe hypertension, severe liver disease, renal impairment

Warfarin - Pregnancy, severe hypertension, active peptic ulcer

Interactions Heparin - Aspirin, Clopidogrel. GTN infusion increases heparin excretion Warfarin- wide range of medications that can interact.

Examples Heparin, dalteparin (LMWH), warfarin

Cardiac glycosides (Digoxin)

- Indicaitons: atrial fibrillation, atrial flutter, heart failure (that is not controlled by other medication)

Mechanism inhibition of the Na+/K+ ATPase, mainly in the myocardium. causes an increase in intracellular sodium levels, resulting in a reversal of the action of the sodium-calcium exchanger, which normally imports three extracellular sodium ions into the cell and transports one intracellular calcium ion out of the cell. The reversal of this exchange causes an increase in the intracellular calcium concentration. Increased intracellular calcium lengthens the cardiac action potential, which leads to a decrease in heart rate. Also INCREASES blood pressure

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Investigations in Cardiology

Echocardiograms

Introduction

● Use ultrasound waves to create an image of the heart. Ultrasound waves are created by a piezoelectric transducer, reflected back from heart structures and then detected by the same transducer. The time taken from emission to detection is used to estimate the distance travelled by the wave, and from several waves you can build up an image of the structures of the heart. ● There are three main types of echocardiograms that are important

o Two dimensional

o M mode

o Doppler.

● The others are used less frequently or for more specific indications.

Two-Dimensional Echocardiography

● The ultrasound wand moves from side to side in an arc, so that a cross-section of the heart can be visualized.

● Most commonly used form of echo, and can be used to assess heart movement in real time. Usually this echo takes parasternal long axis (a), parasternal short axis (b), and apical (c) cross-sectional views. The image below shows each view.

● It is used to observe:

o Valve structure and function

o Left ventricle contractility

o Size of chambers

o Congenital cardiac malformations

o Pericardial disease

● There are a few limitations to this method though:

o Presence of lung between the heart and chest wall precludes ultrasound travel

o The posterior part of the heart is furthest from the transducer and may not be viewed adequately, particularly when searching for thrombi and vegetation

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Rare: Black, tarry stools, bleeding gums, bloody vomit, rash, severe stomach pain

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M Mode Echocardiography (M for motion)

● Here the transducer is stationary and only observes structures in one plane of the heart, so creates a one dimensional image.

● Although heart anatomy cannot be visualized using this method, it can be used to make precise measurements. It is mostly used for:

o Looking at mitral and aortic valve leaflets

o Left ventricular dimensions and functions

o Aortic root size

o Right atrial size

● Below is an M Mode Echo, (a) shows a healthy aorta and left atrium (b) shows a healthy mitral valve. The x axis represents time, and the y axis represents movement, so you can see that the atria and valve movement.

Doppler Echocardiography

● When the ultrasound wave is reflected off of a moving object, the wave frequency changes. This is the Doppler effect. The change in wave frequency can be used to assess blood flow in terms of speed and volume. Doppler echocardiography can be used to assess:

o Valve stenosis and regurgitation

o Atrial and ventricular septal defects, patent ductus arteriosus and other congenital abnormalities

o Pulmonary hypertension ● There are three subtypes of Doppler.

● Continuous wave Dopplermeasures velocity along the entire length of the ultrasound beam, but not at a specific depth.

Therefore it does not localize velocity measurements of blood flow, and is only used to estimate the severity of valve stenosis or regurgitation through assessing the shape or density of the output

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● Pulsed wave Doppler is used to make localized velocity measurements of turbulent flow (it measures the blood-flow velocity within a small area at a specified tissue depth). It is used to assess ventricular in-flow patterns, intracardiac shunts, and to make precise measurements of blood flow at valve orifices.

● Colour mapping converts the change in ultrasound wave frequency caused by blood flowing towards or away from the ultrasound wand into colour. Traditionally, flow towards the transducer is red, flow away from the transducer is blue, and higher velocities are shown in lighter shades. To aid observation of turbulent flow there is a threshold velocity, above which the colour changes (in some systems to green). This leads to a "mosaic" pattern at the site of turbulent flow and enables sensitive screening for regurgitant flow.

Three Dimensional Echocardiography

● As the name suggests the image taken is the same as any other echocardiogram, but in three dimensions. This enables you to look at structure in more detail, and function using real-time imaging.

Transoesophageal Echocardiography (TOE)

● Another version of a two dimensional echo. Here the probe is inserted into the distal portion of the oesophagus. Because it is closer to the heart, you can create a much clearer image. It is used to assess:

o Intracardiac thrombus

o Prosthetic valve function

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o Valve vegetation in endocarditis

o Congenital heart lesions

Stress Echocardiography

● Another version of a two dimensional echo. This is used to assess areas of ischaemia when the heart is “stressed”. Drugs such as dubotamine act to increase the rate and strength of

contraction, and a clinician can observe blood flow before, during and after the drug admission. Ischaemia is seen as abnormal heart wall movement.

Myocardial Perfusion Imaging

● Uses radiolabelled agents, which are taken up by the myocardium proportional to local myocardial blood flow

● A number of radiolabelled agents are used

o Technetium-99m-labelled agents (eg. 99m_{T-sestamibi – MIBI scan) – has a half-life of 6h –} taken up by perfused myocardium. Remains in the myocardium for several hours and imaging provides an accurate picture of regional myocardial perfusion. Because of this, resting and exercise images are obtained on two different days with an injection of 99m_{T-sestamibi for each day}

o Thallium-201 is also taken up by the myocardium only in perfused areas. Unlike

99m_{T-sestamibi, thallium is continually being passed across the cell membrane. However,} it has a higher radiation dose. This redistribution allows for early and late images to be

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taken after exercise using only a single injection. The image early after exercise shows any areas of reduced uptake and the second image a few hours later will show whether these areas have normal uptake, suggesting the presence of reversible ischaemia.

Methods of Stressing the Heart

● Wherever possible, physical exercise should be used

● For those unable to do this, pharmacological stress can be used (patients who have severe aortic stenosis or cardiac failure shouldn’t have stress testing)

● The following agents are commonly used:

o Dipyridamole – blocks reabsorption of adenosine into the cells, so increasing

intravascular adenosine concentrations – adenosine is a powerful vasodilator and dilates normal coronary arteries, but not diseased ones. It therefore redistributes blood flow away from diseased vessels. This relative hypoperfusion of diseased areas is picked up by radionucleotide myocardial imaging

o Adenosine – a direct infusion of adenosine may be used

o Dobutamine – this drug mimics exercise by increasing myocardial rate and contractility

o Both the bottom two are contraindicated in patients with bronchospasm#

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Multigated Acquisition Scanning

● MUGA

● Radionucleotide technique for evaluating cardiac function

● Technetium-99m label is used to label the patient’s red blood cells

● The amount of radioactivity detected within the left ventricle is proportional to its volume and its degree of contractility during systole will affect this

● The imaging od the cardiac blood pool is synchronized to the ECG trace and each image is identified by its position within the cardiac cycle

● Hundreds of cycles are recorded and an overall assessment of the left-ventricular ejection fraction can be made using the averaged values for end-systolic and end-diastolic volume. This method is used less often than in the past but it remains superior to echocardiography for the accurate assessment of ejection fraction

Heart Murmurs

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● Turbulence as blood flows across diseased heart valves creates murmurs. This occurs when the velocity of blood is disproportionate to the size of the orifice it is moving through. These can be readily detected with a stethoscope.

● It is generally accepted that normal blood flow across valves is silent, although murmurs can occur with increased blood flow (e.g., exercise) and are not infrequently heard in young, thin individuals with dynamic circulations. There are 6 grades of murmur listed below.

● Many conditions can give rise to a murmur such as:

o Valve lesions- either stenosis (the abnormal narrowing of a passage in the body) or regurgitation (leaking of blood in the wrong direction).

o Left-ventricular outflow obstruction- such as hypertrophic cardiomyopathy.

o Ventricular septal defect

o Vascular disorders for example a patent ductus arteriosus or arteriovenous malformations

o Increased blood flow. This could be due to anaemia or pregnancy.

● There are three different categories of murmur, depending on where they occur in the cardiac cycle: systolic, diastolic or continuous.

Systolic Murmurs

● SYSTOLIC murmurs can be split up. The first group is an ‘ejection systolic’ murmur. This can be due to:

o Aortic stenosis: from congenital valve abnormalities, rheumatic fever, senile calcification

o Aortic sclerosis: the roughening of the aortic valve

o Hypertrophic cardiomyopathy (HCM): there is left ventricular outflow tract stenosis

o Increased flow across a normal valve: due to high-output states such as anaemia and pregnancy.

● The other group of systolic murmurs are pansystolic. This means that the murmur occurs throughout systole. These can be caused by:

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Grade 1 Barely audible Grade 2 Slightly easier to hear Grade 3 Audible

Grade 4 Easily audible

Grade 5 The loudest murmur requiring a stethoscope

Grade 6 Can be heard with the stethoscope off the chest and is often accompanied by thrills (palpable murmur).

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o Mitral regurgitation (MR): functional due to dilation of mitral valve annulus. Valvular due to rheumatic fever, infective endocarditis, chordal rupture

o Tricuspid regurgitation (TR): functional due to dilation of tricuspid valve annulus or valvular due to rheumatic fever or infective endocarditis.

Diastolic Murmurs

● DIASTOLIC murmurs either occur in early diastole due to:

o Aortic regurgitation

o Pulmonary regurgitation

● Or in mid-diastole due to mitral stenosis or tricuspid stenosis (and rarely left and right atrial myxomas which are tumours obstructing the valve orifice in diastole).

● Continuous murmurs occur for more congenital reasons such as:

o Patent ductus arteriosus (PDA)

o Arteriovenous fistula (an abnormal connection between an artery and vein)

o Cervical venous hum (a continuous murmur heard over the internal jugular vein, due to partial compression by transverse process of atlas. It is common in children with anaemia.)

● The diagram below shows where you need to listen to hear each valve. It is important to note that valves on the left side of the heart (mitral and aortic) are heard best in expiration.Those from the right side of the heart (pulmonary and tricuspid) are heard best in inspiration.

● There are also different characteristics for each murmur, some radiate to different places and they can be heard differently at different angles (for example the patient at 45 degrees). I have included a table including this for reference as well as an algorithm which shows you what diagnosis to expect from different heart murmurs.

● One thing to note is that a diagnosis cannot be made by observing a murmur alone. Further investigations such as ECGs must be performed to get a clearer clinical picture. Also many murmurs are simply a variation of what is normal and are referred to as “innocent murmurs”.