Inherited cardiac conditions Flashcards
What are the 3 types of inherited cardiac condition?
Cardiomyopathies
Channelopathies
Aortopathies
What are some examples of inherited cardiomyopathies?
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy
What is meant by a cardiomyopathy?
A disorder of the heart muscle
What is meant by a channelopathy?
A condition that affects the ion channels of the heart
What is meant by an aortopathy?
A condition affecting the aorta
What are some examples of channelopathies?
Congenital long QT syndrome
Brugada syndrome
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
What are some examples of aortopathies?
Marfan’s syndrome
Ehlos Danlos syndrome
Luiz Dietz syndrome
What are the 5 main types of cardiomyopathies (Not all inherited)
Dilated cardiomyopathy
Restrictive cardiomyopathy
Hypertrophic obstructive cardiomyopathy
Arrhythmogenic right ventricular dysplasia
Amyloidosis
What is hypertrophic obstructive cardiomyopathy (HOCM)?
A condition in which there is hypertrophy (Bigger cells) of the ventricular wall, which decreases the volume of the heart chambers
Describe the pathology of hypertrophic obstructive cardiomyopathy
This results in a large, solid heart with a disarray of muscle fibres, which can lead to stronger contractions but decreased filling
What are the most common mutations present in inherited hypertrophic obstructive cardiomyopathy?
Mutations for sarcomeric genes:
- ß-Myosin heavy chain
- Myosin bindin protein C
- Alpha tropomyosin
What are some common presentations of hypertrophic obstructive cardiomyopathy?
Sudden death (Especially in athletes)
Heart failure
Angina
Atrial fibrillation
Describe the pathology of dilated cardiomyopathy
This is a condition resulting in an increase in heart size by 2-3 times, with some hypertrophic changes, but mostly a floppy heart wall
What are some common mutations in dilated cardiomyopathy?
Heart muscle protein genes:
- Desmin
- Dystrophin
- Titin
- Lamin C
What are some other, non genetic causes of dilated cardiomyopathy?
Toxins
Alcoholism
Doxorubicin (Chemotherapy agent)
Myocarditis
Childbirth
What are some clinical features associated with dilated cardiomyopathy?
Shortness of breath
Low ejection fraction
What is the main treatment for dilated cardiomyopathy?
The same as heart failure:
A - ACE inhibitor/ ARB
B - ß-Blocker
A - Aldosterone antagonist
L - Loop diuretic
Describe the pathology of arrhythmogenic right ventricular cardiomyopathy
This is a condition characterised by the fibro-fatty replacement of cardiomyocytes in the right ventricle (Left ventricular involvement in <50% of cases)
What type of mutation affects desmosomal proteins in arrhythmogenic right ventricular cardiomyopathy?
Autosomal dominant
What type of mutation affects non-desmosomal proteins in arrhythmogenic right ventricular cardiomyopathy?
Autosomal recessive
What are the possible consequences of arrhythmogenic right ventricular cardiomyopathy?
This can cause syncope and arrhythmia, which can occasionally lead to sudden death
What is the most common ion channel mutation in long QT syndrome?
Potassium channel
What is the most common ion channel mutation in Brugada syndrome?
Sodium channel
What is the most common ion channel mutation in catecholaminergic polymorphic ventricular tachycardia?
Ryanodine receptors
What is meant by long QT syndrome?
A cardiac condition in which the QT interval of some cardiac myocytes is prolonged, caused by mutations in ion channels
What is the definition of a prolonged QT interval in males?
> 440ms
What is the definition of a prolonged QT interval in females?
> 460ms
What proportion of people carry the genes for long QT syndrome?
1 in 2000
How many subtypes of long QT syndrome are there?
13
Give an example of an autosomal dominant sub-type of long QT syndrome
Romano-Ward syndrome
Give an example of an autosomal recessive sub-type of long QT syndrome
Jervell and Lange-Nielssen syndrome which is associated with deafness
What are some general symptoms of long QT syndrome?
Polymorphic ventricular tachycardia
Lone atrial fibrillation
Heart block
Syncope
What are some possible arrhythmogenic symptom triggers in long QT syndrome?
Exercise
Sudden auditory stimuli
Sleep
Hypokalaemia
Some QT prolonging medication
Describe the pathogenesis of arrhythmia in long QT syndrome
Abnormally long depolarisation of some of their heart cells, but not all
A potassium ion channel mutation can cause malfunction and cause early after-depolarization
If the EAD is large enough it might propagate out and depolarize the ventricles, causing an unexpected ventricular contraction
If at this point, some neighboring cells are ready for another depolarization and some aren’t, and when those not ready cells come around, the wave of depolarization can double back, potentially creating a reentrant circuit, which leads to reentrant tachycardia, and then polymorphic ventricular tachycardia, Torsades du Pointes (Twisting of points)
What are some management option in long QT syndrome?
Trigger avoidance
ß-Blockers
K+ infusions
How will long QT syndrome present on ECG?
What is Brugada syndrome?
A form of inherited idiopathic ventricular fibrillation, with no evidence of structural cardiac disease, caused mostly by mutations to sodium channels
Is Brugada syndrome autosomal dominant or recessive?
Autosomal dominent
Describe the arrhythmogenic pathophysiology of Brugada syndrome
Mutations in sodium ion channels affect the ability of some of the cardiac myocyte’s ability to conduct an action potential
This results in abnormal depolarisation in some regions of the heart
Triggers can cause this and thus leads to polymorphic ventricular tachycardia and atrial fibrillation
What are some arrhythmias that can occur as a result of Brugada syndrome?
Polymorphic ventricular tachycardia
Atrial fibrillation
What are some common triggers of Brugada syndrome?
Rest
Sleep
Fever
Excessive alcohol
Excessive food
Certain medications
What are some medications to avoid in Brugada syndrome?
Anti-arrhythmic drugs
Psychotropics
Analgesics
Anaesthetics
What are some management options in Brugada syndrome?
Avoidance of contraindicated drugs
Avoidance of excessive alcohol
Treatment of fevers with antipyretics
What are some diagnostic ECG changes in a person with Brugada syndrome?
ST elevation in V1-3
RBBB in V1-3
What are some drugs that can induce ECG changes in Brugada syndrome?
Flecainide
Ajmaline
How is family testing carried out in inherited cardiac conditions?
Direct relatives are tested first and only if they are positive are further family members are tested
What is an S-ICD?
Subcutaneous Implantable Cardioverter Defibrillator
This is a device that sits under the skin and cardioverts the heart in cases of arrhythmia
