Week 5/6 - H - Channelopathy (Long qt/brugada), Cardiomyopathy (dilated/hypertrophic/A.R.V.C/restrictive), myo/pericarditis, tumours

Question 1

What is the key investigation in understanding the cause of sudden unexplained death?

Answer 1

POST MORTEM

Question 2

Sudden death is a feature of inherited cardiac conditions - namely channelopathies and cardiomyopathies Name different types of channelopathy and cardiomyopathy?

Answer 2

Channelopathies - the two we shall discuss here * Congenital long QT syndrome * Brugada Syndrome Cardiomyopathy * Dilated cardiomyopathy * Hypertrophic cardiomyopathy * Arrhythmogenic RV cardiomyopathy (ARVC) * Restrictive

Question 3

What are channelopathies?

Answer 3

Channelopathies are mutations in the genes that encode the cardiac ion channels causing abnormal cardiac cellular electrophysiology

Question 4

There are different causes of inherited cardiac conditions Can you name the three categories?

Answer 4

Cardiomyopathy - where there is structural change to the heart muscle Channelopathies - where there is heart rhythm abnormality Aortopathy - where there is altered blood vessel abnormality as seen in Marfan’s syndrome and Ehler’s Danlos syndrome

Question 5

What happens to the cardiac structure and function in channelopathies? What is there a propensity to develop?

Answer 5

There is normal cardiac structure and function in channelopathies There is a propensity to develop arrhythmias both atrial and ventricular and these can be seen as abnormalities on ECG

Question 6

CONGENITAL LONG QT SYNDROME Congenital Long QT syndrome is a genetic disorder that so far, is known to be caused by up to 13 different genes There is both an autosomal dominant and autosomal recessive type of cLQTS * What are they known as? * Which is more common?

Answer 6

The most common form of Long QT syndrome is the autosomal dominant Romano-Ward syndrome A less commonly seen form is known as Jervell and Lange-Nielsen Syndrome - autosomal recessive

Question 7

The most common form of Long QT syndrome is the autosomal dominant Romano-Ward syndrome A less commonly seen form is known as Jervell and Lange-Nielsen Syndrome - autosomal recessive Are these conditions isolated with the long QT syndrome or are there other defects in the patient?

Answer 7

Romano-Ward syndrome is an isolated form of Long QT syndrome Jervell and Lange-Nielsen syndrome is also assoicated with severe congenital bilateral sensorineural deafness

Question 8

What is the hallmark arrhythmia in cLQTS? What are the main channels which are effected in cLQTS?

Answer 8

The hallmark arrythmia for cLQTS is polymorphic ventricular tachycardia (torsades de pointes) The main channels affected in cLQTS are the potassium channels due to mutations in the genes which code for these channels - causing prolongation of the repolarisation phase of the ventricular action potential (sodium channels are less commonly involved)

Question 9

What is the primary presenting complaint of cLQTS?

Answer 9

Patients usually present with syncope or sudden cardiac death - usually presenting as children or young adults

Question 10

What are the triggers of the polymorphic ventricular tachycardia in cLQTS?

Answer 10

Triggers include exercise Sudden auditory stimuli Sleep QT prolonging states * Medication * Hypokalaemia

Question 11

How long should the QT interval last in males and females and what does it span from?

Answer 11

The QT interval spans from the start of the QRS complex to the end of the T wave It should last <0.44seconds in males and <0.46seconds in females (around 2 big boxes)

Question 12

Which drugs are associated with prolonging the QT interval? There is a long list so just try name some

Answer 12

Drugs associated with this are macrolides -mainly erythromycin and clarithromycin
Ciprofloxacin
Also class III anti-arrhythmic drugs eg amiodorane which inhibit potassium channels many more

Question 13

What is the treatment of cLQTS?

Answer 13

Beta blockers Avoid QT prolonging druggers Avoidance of triggers - exercise, loud auditory stimuli Correction of electrolyte abnormalities where potassium is low Implantable cariac defibrillators or pacemakers can also be used

Question 14

BRUGADA SYNDROME Brugada syndrome (BrS) is a genetic disorder in which the electrical activity within the heart is abnormal. It increases the risk of abnormal heart rhythms and sudden cardiac death * What is the most commonly involved channel in Brugada syndrome? * What are the abnormal heart rhythms that may be seen in this disease?

Answer 14

Most commonly involved channel in Brugada syndrome is the sodium channels Abnormal heart rhythms that may be seen in this disease include VT and VF Atrial fibrillation is also common

Question 15

What is the inheritance of Brugada syndrome and how is it diagnosed? Which sex is it more common in?

Answer 15

Brugada syndrome is an autosomal dominant condition however is seen more commonly in males (typically presents with SCD or arrhythmia in a young male) Diagnostic ECG changes are usually seen

Question 16

If ECG fails to show the diagnostic changes, what can be given to cause this?

Answer 16

Patient may be injected with drugs that block the cardiac sodium channel eg type 1 anti arrhythmic such as flecainide

Question 17

What are the diagnostic ECG findings for Brugada syndrome?

Answer 17

Coved ST segment elevation >2mm in more than 1 lead of V1 to V3 followed by a negative T wave Occurring spontaneously or after provactive IV administration of sodium channel blocker simulate RBBB appearance

Question 18

What are the VT or VF triggers in patients with Brugada Syndrome?

Answer 18

Usually occurs in patients at rest or sleep Can be due to fever, excessive alcohol or large meals

Question 19

What is the management of Brugada Syndrome? (lifestyle and intervention)

Answer 19

Avoid drugs that may induce Brugada changes on ECG Avoid excessive alcohol and large meals Prompt treatment of fever with anti-pyretic medications ICD if ventricular arrhythmia

Question 20

INHERITED CARDIOMYOPATHY Now we discuss the different cardiomyopathies * Dilated * Hypertrophic * Arrhythmogenic RV cardiomyopathy * Restrictive What happens to the heart in dilated cardiomyopathy?

Answer 20

The heart itself becomes very dilated and is increasd in size This results in a flabby/floppy heart which is very thin walled and therefore it cannot contract properly to pump blood around the body

Question 21

What are the causes of dilated cardiomyopathy?

Answer 21

Genetic inheritance accounts for half of the cases Due to genes that encode the heart muscle proteins mutating Many different acquired causes

Question 22

What are the clinical features of DCM?

Answer 22

Symptoms are more typical of heart failure because if you have dilated cardiomyopathy, you’re at greater risk of heart failure, where the heart fails to pump enough blood around the body at the right pressure. Would cause HFrEF as cannot pump an effective stroke volume Dyspnoea, fatigue, poor exercise tolerance, pulmonary (orthopneoa, PND, pink frothy sputum) and peripheral oedema

Question 23

What is the leading cause of sudden cardiac death in the young?

Answer 23

Hypertrophic cardiomyopathy

Question 24

HYPERTROPHIC CARDIOMYOPATHY What happens to the heart in this disease?

Answer 24

In hypertrophic cardiomyopathy, the heart muscle cells enlarge and the walls of the heart chambers thicken. The heart chambers are reduced in size so they cannot hold much blood, and the walls cannot relax properly

Question 25

What can the hypertrophy in HCM lead to?

Answer 25

The main heart chambers can become stiff, leading to back pressure on the smaller collecting chambers. This can sometimes worsen the symptoms of heart failure and lead to abnormal heart rhythms (atrial fibrillation). Eventually there is outflow obstruction and is called obstructive hypertrophic cardiomyopathy

Question 26

What valvular problem can it lead to?

Answer 26

Can cause mitral regurgitation due to the back pressure of the blood into the left atrium causing the mitral valve to become leaky

Question 27

What genes do the mutations occur in in hypertrophic cardiomyopathy? What is seen on ECG?

Answer 27

Mutations occur in sarcomeric genes LVH seen on ECG

Question 28

Arrhythmogenic right ventricular cardiomyopathy What happens to the heart in arrhythmogenic right ventricular cardiomyopathy?

Answer 28

There is the replacement of normal heart tissue with fibrofatty cells In arrhythmogenic right ventricular cardiomyopathy (ARVC), the proteins that usually hold the heart muscle cells together are abnormal. Muscle cells can die and the dead muscle tissue is replaced with fatty and fibrous scar tissue.

Question 29

The walls of the main heart chambers become thin and stretched and cannot pump blood around the body properly. What can the symptoms of the disease be?

Answer 29

The symptoms can include arrhythmia, worsening heart failure, syncope during exercise and occassional sudden death

Question 30

Restrictive cardiomyopathy Restrictive cardiomyopathy is rare. It’s most often diagnosed in children, although it can develop at any age. What happens in restrictive cardiomyopathy?

Answer 30

Restrictive cardiomyopathy occurs when the walls of the ventricles become very stiff and rigid and cannot relax properly - grossly the heart may appear normal

Question 31

What are the features of restrictive cardiomyopathy?

Answer 31

The features are similar to those of right heart failure (similar to how constrictive pericarditis presents) - breathlessness, tiredness, ankle swelling, acites, increased JVP

Question 32

What causes restrictive cardiomyopathy?

Answer 32

Cause can be inherited But can also be caused due to deposition of something in th emyocardium eg ayloid

Question 33

What is the treatment of the different cardiomyopathies?

Answer 33

There’s usually no cure for cardiomyopathy, but the treatments can be effective at controlling symptoms and preventing complications.

Question 34

What is myocarditis? What are the most common cause of infectious myocarditis?

Answer 34

Myocarditis is inflammation of the myocardium and is often associated with pericardial inflammation (myopericarditis) Can be idiopathic but often secondary to viruses Enteroviruses are the most common viral cause, list is extensive

Question 35

What are the symptoms of myocarditis? How is it diagnosed?

Answer 35

Symptoms are usually typical off ACS - eg chest pain and heart failure symptoms - palpitations, tachycardia, gallop rhythm, breathlessness

Question 36

How is acute myocarditis diagnosed? What is the treatment?

Answer 36

Diagnosed via viral PCR (throat swab and stool for enteroviruses) - endomyocardial biopsy is gold standard but not uually necessary Supportive treatment is the management

Question 37

Pericarditis is the inflammation of the pericardial layers What is usually the infectious cause? What is it known as when it occurs post-MI? What are other causes?

Answer 37

Usually the infectious cause is due to ECHO viruses or Coxsackie viruses

Also uraemia, post MI (Dressler’s), rarer - EBV

Post MI - it is known as Dressler’s syndrome - usually about 2-10 weeks post MI Can also be caused by autoimmune conditions eg SLE

Question 38

What are the clinical features of pericarditis?

Answer 38

Central chest pain worse on inspiration or lying flat that is relieved by sitting forward Also can hear a pericardial rub often ECG classically shows widespread saddle shaped ST elevation >1 vascular territory Also there are PR depressions

Question 39

How is the diagnosis of pericarditis confirmed?

Answer 39

ECG changes

• the changes in pericarditis are often global/widespread, as opposed to the ‘territories’ seen in ischaemic events
• ‘saddle-shaped’ ST elevation
• PR depression: most specific ECG marker for pericarditis

All patients with suspected acute pericarditis should have transthoracic echocardiography

Question 40

How is an MI believed to cause Dressler’s syndrome?

Answer 40

It is thought that the myocardial injury released previously unencountered material that stimulates the formation of autoantibodies against the heart muscle

Question 41

What is the treatment of acute pericarditis?

Answer 41

Treatment of acute pericarditis usually involves high dose aspirin

Add Colchichine for 3 months to prevent recurrence (affects the way in which white cells work) Consider steroids if not improving or autoimmune cause

Question 42

What are the different complications of pericarditis?

Answer 42

• Pericardial effusion
• Cardiac tamponade - an effusion that raises intrapericardial pressure reducing ventricular filling and dropping CO
• Constrictive pericarditis
• Cardiac failure
• Death

Question 43

Why are primary tumours of the heart so very rare?

Answer 43

Because the cells in the heart do not divide, heart cancer is a rare condition. But tumors, both cancerous (malignant) and noncancerous (benign) can form

Question 44

Primary tumours of the heart are very rare What is the commonest primary tumour of the heart and where is it located?

Answer 44

Atrial myxoma - it is benign - 90% in atria and usually in the left

Question 45

What may atrial myxoma mimic and how is it diagnosed/treated?

Answer 45

Atrial myxoma often mimics mitral stenosis - breathlessness, fatigue, AF Can cause pulmonary oedema due to backpassage of pressure Diagnosed with echo and treated with excision