4- inherited cardiac conditions Flashcards
what are the types of inherited conditions?
- cardiomyopathy = something wrong with heart muscle
- channelopathy = relate mostly to ion channels and give rise to arrhythmia - not HF
- aortopathies
what are types of cardiomyopathy?
- hypertrophic cardiomyopathy (thickened muscle)
- dilated cardiomyopathy (large & weakened muscle)
- arrhythmogenic RV cardiomyopathy (specific arrhythmia that largely affects right side)
what are types of channelopathy?
- congenital long QT syndrome (delay in cardiac repolarisation, phase3)
- Brugada syndrome = abnormalities in ventricular electrical activity (coved type ST ecg)
- catecholaminergic polymorphic VT (episodes of Vtach triggered by exercise & emotional stress,high catecholamine levels when children exercise)
- Short QT syndrome (mutated K+ channels = accelerated repolarisation = risk of vfib
- Progressive familial conduction disease
- Familial AF
- Familial Wolff-Parkinson-White (WPW) syndrome = accessory pathway between atria & ventricles
how do cardiac conditions present?
- can be variable (some have normal appearance and no symptoms)
- symptoms usually relate to underlying condition e.g. arrhythmia or heart failure
what are heart rhythm related symptoms for inherited cardiac conditions?
- palpitations, presyncope, syncope, breathlessness, chest pain, sudden death
- may be sinus bradycardia or heart block eg in cLQTS; or tachyarrhythmia eg AF in Brugada syndrome or cLQTS, or ventricular arrhythmia (ventricular ectopy, VT, VF)
what are cardiomyopathy related symptoms for inherited cardiac conditions?
congestive heart failure: breathlessness, peripheral oedema, orthopnoea weakness, may be systolic HF (dilated CMPY) or diastolic heart failure (hypertrophic CMPY)
what are channelopathies?
- Mutation in genes that encode the cardiac ion channels.
- Abnormal cardiac cellular electrophysiology
- Mainly affecting repolarization
(normal cardiac structure & function)
= means develops arrhythmia both atria & ventricles
what is normal length of QT in males & females?
440 ms in males
460 ms in females (longer due to hormones)
what is congenital long QT syndrome?
when you inherit condition meaning long QT interval which is ventricular depolarisation & repolarisation
how can you inherit congenital long QT syndrome?
- 13 subtypes of LQTS each associated with different genetic mutations
- it can be inherited as autosomal dominant resulting in isolated LQT known as romano-ward syndrome
- it can be inherited as autosomal recessive - associated with deafness; jervell & lange-neilson syndrome
what is the hallmark of arrhythmia that prolongation of QT can lead to?
polymorphic VT (Torsades de Pointes VT = twisting of points)
what are associated arrhythmias observed with congenital long QT syndrome?
lone’ AF’ and heart block
what is the common primary presenting complaint with long QT syndrome?
Syncope, sudden cardiac death in children and young adults
what are triggers of torsades de pointes & syncope?
- Exercise
- Sudden auditory stimuli
- Sleep
- QT prolonging states
- Medication
- hypokalaemia
what is molecular basis of LQTS?
gene altered that affects ion channel that results in reduced or dysfunctional ionic current which means prolonged cardiac repolarisation which means QT interval prolongation and then with triggers leads to polymorphic ventricular tachycardia (changing all the time - torsades de pointes)
what is management of LQTS?
- beta blockers = very effective at reducing sudden cardiac death
- avoid QT prolongation drugs (many drugs interact with potassium ion channels like anti-histamine, anti-depressants, antibiotics etc)
- avoidance of triggers - underwater swimming, breath holding, loud sudden noises
- correction of electrolyte abnormalities, maintenance of serum K at upper limit of normal range
what is brugada syndrome?
= associated with mutations in genes that encode for cardiac channels - 12 associated genes - Cardiac sodium channel (SCN5A) and calcium channel (CACN1Ac )
- Autosomal dominant: Adults, 8x males
= underlying pathology involves a faulty sodium channel
what is result of brugada syndrome? (on ECG?)
- risk of polymorphic ventricular tachycardia, VF
- atrial fibrillation common
- ST elevation and (right bundle branch block) RBBB in V1-V3
- ECG findings may be intermittent, change over time
- Diagnostic ECG changes may seen only with provocative testing with flecainide or ajmaline (drugs that block the cardiac sodium channel)
what does brugada syndrome look like on ECG?
ST elevation with partial bundle branch pattern
what are triggers of ventricular fibrillation?
- usually rest or sleep
- fever
- excessive alcohol, large meals
- genotype & family history of sudden cardiac death does not influence prognosis
what is management of brugada syndrome?
- Avoidance of drugs that may induce Brugada changes on ECG.
- Avoidance of excessive alcohol and large meals.
- Prompt treatment of fever with anti-pyretic medications
- ICD if ventricular arrhythmia
what drugs should be avoided with brugada syndrome?
- Anti-arrhythmic drugs (beta blockers may aggravate ECG changes, therefore only under supervision).
- Psychotropics
- Analgesics
- Anaesthetics
what is most common gene responsible for
a) hypertrophic cardiomyopathy
b) dilated cardiomyopathy
c) arrhythmogenic RV cardiomyopathy
a) myosin binding protein, C - MYBPC3
b) lamin A/C - LMNA
c) desmoglein 2 - DSG2
what type of genes most commonly have mutation causing hypertrophic cardiomyopathy?
sarcomeric gene
what are different clinical presentations for hypertrophic obstructive cardiomyopathy?
- sudden death
- heart failure
- angina
- atrial fibrillation
- asymptomatic
what is management for dilated cardiomyopathy?
same as for heart failure (4 pillars)
what type of mutations in dilated cardiomyopathy tend to be malignant?
Titin and lamin C mutations
what is arrhythmogenic RV cardiomyopathy?
Fibro-fatty replacement of cardiomyocytes in the RV.
- caused by autosomal dominant mutations in the genes for desmosomal proteins; autosomal recessive mutations in nondesmosomal genes
what is importance of pre-symptomatic identification?
- sudden cardiac death may be first presentation so want to identify before that
- young age group at risk
- effective therapies are available →lifestyle changes, beta blockers, ICDs
- family members may also be at risk
what are important notes about lifestyle for long QT syndrome?
- Diet: potassium rich foods (bananas, beans, oranges, green leafy vegetables, nuts)
- Caution if diarrhea, vomiting
- Underwater breath holding.
- Avoiding sudden loud noises.
what is important lifestyle notes about brugada syndrome?
- Excessive alcohol
- Prompt treatment of fevers
is exercise still good for inherited cardiac conditions?
yes - even though risk of sudden cardiac death at certain levels
- Prevention of cardiovascular disease, diabetes, hypertension, certain cancers.
- Psychological well being: depression, anxiety, mood.
- Physical inactivity is the 4th leading cause of death, 10% of premature death worldwide
what is S-ICD?
subcutaneous ICD = you put them just under the skin and can give out shock if needed, doesn’t give ATP so if needs pacing not good but if just needs shock if heart attack then good
- Prevention of vascular complications
- Better cosmetic and functional outcome
- Lead extraction safe
what is problem of transvenous ICD for inherited cardiac conditions?
- High risk of vascular and cardiac complications in life time of patient
- Cosmetic and functional issues related to ICD position e.g. seat belts, shoulder bags, ports etc
- Lead extraction has high risk of mortality and morbidity
what are the first steps after sudden cardiac death?
- Making the diagnosis (DNA retention for genetic post-mortem)
- Assessing relatives for the disease and risk
- Prevention of further events (clinical and genetic testing of family members)
why not just do cascade screening of young people for inherited cardiac conditions?
not cost effective, lots of false positives - doesn’t prevent sudden deaths
what are inherited cardiac conditions issues in the young?
- Psycho-social impact
- Lifestyle
- School
- Sports
- Pregnancy
- ICD therapy
- Employment
- Life-insurance
- Diagnosis and management : multidisciplinary approach
