Genetics of Arrhythmias Flashcards
what is a channelopathy?
a pathology within the cardiac ion channels - affect sNa usually
give some examples of channelopathies, 7
- Congenital long QT syndrome
- Catecholaminergic polymorphic ventricular tachycardia
- Short QT syndrome
- Brugada syndrome
- Progressive familial conduction disease
- familial AF
- Familial WPW
give some examples of cardiomyopathies, 3
- Hypertrophic cardiomyopathy
- Arrhythmogenic right ventricular cardiomyopathy
- dilated Cardiomyopathy
how do you make the diagnosis for arrhythmogenic inherited caridac conditions?
- DNA retention for genetic post-mortem
- clinical and genetic testing of family members
it is not just the patient that needs to be treated - you need to_____ the whole family and may give ________ treatment
it is not just the patient that needs to be treated - you need to screen the whole family and may give prophylactic treatment
cascade screeening Produces a greater rate of case identification than _______ _______ screening
Produces a greater rate of case identification than general population screening
Once a diagnosis is confirmed in an individual, testing is extended to ___ degree and ____ degree relatives.
Once a diagnosis is confirmed in an individual, testing is extended to first degree and second degree relatives.
Polymorphic VT (Torsades de pointes) triggered by _______ stimulation is an example of a congenital ______
Polymorphic VT (Torsades de pointes) triggered by adrenergic stimulation is an example of a congenital LQTS
what do people with congenital LQTS present with (uncommonly though)
- syncope 5%
- SCD in untreated LQTS 0.33-0.9%
there are ____ subtypes of LQTS
13
give an example of an autosomal dominant isolated LQT
romano-ward syndrome
give an example of an autosomal dominant LQT with extra cardiac features?
Anderson-Tawil Syndrome, Timothy syndrome
give an example of an autosomal recessive LQT with associated deafness
: Jervell and Lange-Nielsen syndrome
in LQTS there is a mutation causing a slower flow of ions such as ___- out of the heart
K
QT prolongation triggers _______ VT
polymorphic
LQTS diagnosed with either
- QT >____ ms in repeated 12 lead ECG or
- LQTS risk score >___
QTS diagnosed with either
QT >480 ms in repeated 12 lead ECG or
LQTS risk score >3
look at the schwarz score for the diagnosis of lQTS
LQTS is diagnosed in the presence of a confirmed pathogenic LQTS mutation, irrespective of QT duration
LQTS __ is the most common type of LQTS, what does the ECG show?
LQTS 1
ECG shows high T wave
what risk factors increased risk of SCD in LQTS?
- age dependent
- gender- more common in males (preadolescent) and females (adults)
- increased QT duration
- prior syncope and response to b blockers
what are the 2 broad management areas in LQTS?
risk stratification
treatment
how are the risks of LQTS avoided?
- avoid QT prolonging drugs
- correct electrolyte imbalances
- avoid genotype specific triggers for arrhythmias
what is a genotype specific trigger in LQTS 1?
strenuous swimming
what is a genotype specific trigger in LQTS 2?
loud noises
what is a new oral therapy for LQTS?
long term oral K improves repolarisation with HERG mutations
what are the arrhythmias risks associated with brugada?
polymorphic VT and VF
AF
if you see a young person with AF, this about _____syndrome
brugada
what are the ECG features of brugada?
ST elevation and RBBB in V1-3
ECG findings for brugada may be ____, change over time
ECG findings for brugada may be intermittent, change over time
Diagnostic ECG changes for brugada may seen only with provocative testing with ______ or _____ (drugs that block the cardiac _____ channel)
Diagnostic ECG changes for brugada may seen only with provocative testing with flecainide or ajmaline (drugs that block the cardiac sodium channel)
there are ___ associated genes for brugada?
12
what are the two of the channles that may be affected?
Cardiac sodium channel (SCN5A) and calcium channel (CACN1Ac )
brugada is predominantly Autosomal ________: causing faulty ___ channels
brugada is predominantly Autosomal dominant:
Na
consider ____ ______disease in all with unexplained syncope
consider primary electrical disease in all with unexplained syncope
how is brugada diagnosed?
ST elevation in one or more leads among the right precordial leas V1 and V2 occuring either spontaneoulsy r with drugs provoeked
what triggers VF in brugada?
- usually rest or sleep
- fever
- excessive alcohol, large meals
what are the management areas for brugada?
risk stratification
ICD implantatins
what triggers should be avoided in brugada?
- avoidance of drugs that may induce ST SEGMENT ELEVATION (AADs, psychotropics, analgesics, anaesthetics)
- avoidance of excessive alcohol and large meals
- fever- antipyretics promptly used
ICD is recommended in brugada people if: 2 things
they are survivors of CA
they have documenter spontaneous sustained VT
what is catecholaminergic polymorphic VT?
Adrenergic induced bidirectional and polymorphic VT, SVTs, triggered by emotional stress, physical activity.
what is the prevalence of CPVT?
1 in 1000
what would be seen on ECG and ECHO for CPVT?
may be normal
autosomal dominant CPVT shows a mutation in the ______ receptor
ryanodine type 2 channel
what is the ryanodine receptor responsible for ?
Ca induced Ca release from the sarcoplasmic reticulum
autosomal recessive CPVT shows a mutation in the ____ ______ gene (CASQ2)
cardiac calsequestrin
what are the main areas of management for CPVT?
risk stratification
- treatment
- preventon
what should be done to avoid risks for CPVT>
- avoid competative sports
- avoid strenuous exercise and stressful environments
what treatment should be considered for CPVT>
- b blockers
- ICD - in addition to b blockers
what are the indications for ICD in CPVT?
- if had CA
- recurrent syncope
- polymorphic/ bidirectional VT despite optimal therapy
what prevention should be used for CPVT and for who?
B blockers should be considered for genetically positive family members even after a negative exercise test
when should flecainide be used for CPVT?
- in addition to b blockers in those who experience episodes as above, when there are risks/contraindications for an ICD
- in addition to b blockers in CPVT patients and carriers of an ICD to reduce appropriate ICD shocks
what is arrhythmogenic right ventricular cardiomyopathy?
this is a fibro-fatty replacement of cardiomyocytes
in ARVC there is LV involvement in >__% cases
50%
in ARVC the autosomal dominant mutations are in the genes for _____ proteins
desmosomal
in ARVC the autosomal recessive mutations are in the genes for _____ proteins
nondesmosomal
what are the risk factors for SCD in ARVC? 7
- family history of premature SCD
- severity of RV and LV function
- frequent non-sustained VVT
- ECG: QRS prolongation
- VT induction on EPS
- male gender
- Age of presentation
what should be avoided in ARVC?
competitive sport
what treatment should be used for ARVC patients with frequent PVC and NSVT?
b blockers at maximum tolerated dose
when should ICD be used in ARVC?
for people with aborted SCD ad haemodynamically poorly tolerated VT
when should amiodarone be sued in ARVC?
improves symtopms in PVC or NSVT who can’t have b blockers
when should catheter ablation be used in ARVC?
for those who have frequent PVC orVT which is unresponsive to medical therapy
what are some complications associated with transvenous leads for ICD implantation? 9
Endocarditis Perforation Hemothorax Pneumothorax Thromboembolic events Vascular complications Lead fractures Lead extraction complications Lead dislodgement
when venous access is difficult ______ ICD may be used
subcutaneous
