Inherited cardiac conditions Flashcards
What are the 3 main inherited heart muscle abnormalities ?
Cardiomyopathies:
- Hypertrophic cardiomyopathy
- Dilated cardiomyopathy
- Arrhythmogenic Right Ventricular cardiomyopathy (ARVC)
What are the 3 main inherited heart rhythm abnormalities ?
Channelopathies:
- Congenital Long QT syndrome
- Brugada Syndrome
- Catecholaminergic Polymorphic Ventricular tachycardia (CPVT)
What is long QT syndrome and why is it important to recognise ?
- It is an inherited condition associated with delayed repolarization of the ventricles.
- It is important to recognise as it may lead to ventricular tachycardia/torsade de pointes and can therefore cause collapse/sudden death.
On ECG what is defined as a prolonged QT interval ?
QTc interval prolongation:
- >440 ms in males
- >450 ms in females
What is the main mutation associated with long QT syndrome ?
KCNQ1
What are the 2 congenital causes of long QT syndrome and how do you differentiate between the two ?
- Autosomal dominant - Romano-Ward syndrome (no deafness)
- Autosomal recessive - Jervell-Lange-Nielsen syndrome (includes deafness and is due to an abnormal potassium channel)
What is the main presenting complaint of long QT sydrome ?
Syncope, SCD in children and young adults
What are the potential triggers of torsades de pointes & syncope in patients with long QT syndrome ?
- Exercise
- Sudden auditory stimuli
- Sleep
- QT prolonging states - Medication, hypokalaemia
What drugs can cause or worsen long QT syndrome ?
- Amiodarone, sotalol, class 1a antiarrhythmic drugs
- Tricyclic antidepressants, SSRI’s (especially citalopram)
- Methadone
- Chloroquine
- Terfenadine
- Erythromycin
- Haloperidol
- Ondanestron
List the other causes of long QT syndrome
- Electrolyte: hypocalcaemia, hypokalaemia, hypomagnesaemia
- Acute myocardial infarction
- Myocarditis
- Hypothermia
- Subarachnoid haemorrhage
What is the management of long QT syndrome ?
- 1st line = Beta blockers + Avoidance (of QT prolonging drugs triggers e.g. strenuous swimming, Breath holding, Loud sudden noises)
- Also correction of electrolyte abnormalities, maintenance of serum K at upper limit of normal range.
What is brugada syndrome ?
It is an autosomal dominant inherited cardiovascular disease with may present with sudden cardiac death
Who is burgada syndrome most common in ?
Asians
What is the main mutation associated with causing brugada syndrome ?
SCN5A mutation
What arrhythmias can burgada syndrome result in (& hence SCD)?
- Risk of polymorphic VT, VF
- AF common
How is brugada syndrome diagnosed ?
1st line for diagnosis = ECG (after administration of flecainide or ajmaline)
What are the characteristic ECG changes of brugada syndrome ?
- convex ST segment elevation > 2mm in > 1 of V1-V3 followed by a negative T wave
- partial RBBB
What are the triggers of arrhythmias in people with brugada syndrome ?
- Usually rest or sleep
- Fever
- Excessive alcohol, large meals
What is the treatment of brugada syndrome ?
- ICD if ventricular arrhythmia
- Avoidance of drugs that may induce Brugada changes, excessive alcohol and large meals & prompt treatment of fever with anti pyretic medications
What drugs should be avoided in patients with brugada syndrome ?
- Anti-arrhythmic drugs (beta blockers may aggravate ECG changes, therefore only under supervision).
- Psychotropics
- Analgesics
- Anaesthetics
Define what cardiomyopathy is
- Any disease of the cardiac muscle
- Often result in changes in the size of the heart chambers and thickness of the heart
Describe what hypertrophic obstructive cardiomyopathy (HOCM) is
It is an autosomal dominant disorder of muscle tissue caused by defects in the genes encoding contractile proteins.
What are the main mutations which cause HOCM?
Mutation in sarcomeric genes (2 main ones are MYBPC3 or MYH7)
Describe the pathophysiology of HOCM
Mutations result in diastolic dysfunction → left ventricle hypertrophy → decreased compliance → decreased CO
What are the clinical features suggestive of HOCM?
Often asymptomatic, but may have:
- Exertional dyspnoea
- Angina
- Syncope - typically following exercise
- Sudden death (most commonly due to ventricular arrhythmias), arrhythmias, heart failure
- Ejection systolic murmur
What conditions is HOCM associated with ?
- Friedreich’s ataxia
- Wolff-Parkinson White
What are the ECG changes suggestive of HOCM?
- Left ventricular hypertrophy
- non-specific ST segment and T-wave abnormalities, progressive T wave inversion may be seen
- deep Q waves
- atrial fibrillation may occasionally be seen
What is the treatment of HOCM?
- Amiodarone for arrhythmias
- Beta-blockers or verapamil for symptoms
- Cardioverter defibrillator if high risk of SCD
What is the most common cause of sudden cardiac death in the young?
HOCM
What is Arrhythmogenic right ventricular cardiomyopathy (ARVC)?
It is an autosomal dominant inherited cardiovascular disease which may present with syncope or sudden cardiac death.
What is the second most common cause of SCD in the young after HOCM?
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
What are the main mutations which cause ARVC & its underlying pathophysiology
- Mutations in the genes encoding desmosomes (PKP2, DSG2 & DSP)
- The right ventricular myocardium is replaced by fatty and fibrofatty tissue
What are the clinical features suggestive of AVRC?
- palpitations
- syncope
- sudden cardiac death
What are the typical ECG changes suggestive of AVRC?
- T wave inversion typically in V1-3
- A terminal notch in the QRS complex
What is the management of AVRC?
- Drugs: sotalol is the most widely used antiarrhythmic
- Catheter ablation to prevent ventricular tachycardia
- ICD
Define what dilated cardiomyopathy is
This is a dilated flabby heart of unknown cause
What are the potential causes of dilated cardiomyopathy ?
- Idiopathic: the most common cause
- myocarditis: e.g. Coxsackie B, HIV, diphtheria, Chagas disease
- ischaemic heart disease
- peri or post-partum
- HTN
- iatrogenic: e.g. doxorubicin
- substance abuse: e.g. alcohol, cocaine
- X-linked disorders e.g. duchennes
Describe the pathophysiology of dilated cardiomyopathy ?
- dilated heart leading to predominately systolic dysfunction
- all 4 chambers are dilated, but the left ventricle more so than right ventricle
What are the features suggestive of dilated cardiomyopathy ?
- classic findings of heart failure
- systolic murmur: stretching of the valves may result in mitral and tricuspid regurgitation
- S3
- ‘balloon’ appearance of the heart on the chest x-ray
Once a diagnosis is confirmed in an individual of an inherited cardiac condition what is then done ?
Cascade screening:
- Once a diagnosis is confirmed in an individual, testing is extended to 1st & 2nd degree relatives.
- If relatives test positive, their 1st & 2nd degree relatives are tested, and so on.
