Inherited Cardiac Conditions Flashcards
what can an arrhythmia be?
a common manifestation of many genetic conditions
inherited arrhythmia syndromes
inherited cardiomyopathies
inherited multi-system diseases with CVS involvement
myotonic dystrophy
2 types of arrhythmogenic inherited cardiac conditions
channelopathies
cardiomyopathies
channelopathies examples
congenital long QT syndrome brugada syndrome catecholaminergic polymorphic ventricular tachycardia (CPVT) short QT syndrome progressive familial conduction disease familial AF familial WPW
cardiomyopathies examples
hypertrophic cardiomyopathy
arrhythmogenic right ventricular cardiomyopathy
dilated cardiomyopathy
channelopathies
arrhythmogenesis is related to ion current imbalance and development of early and late depolarisations
transmural ADP dispersion
cardiomyopathies
arrhymogenesis related to scar/electrical barrier formation and subsequent re-entry
summation of all ion currents across the cell membrane
the surface ECG
after depolarisations
abnormal depolarisations of cardiac myocytes that interrupt phase 2,3 or 4 of the cardiac AP
can lead to triggered activity seen as sustained cardiac arrhythmia
when are early afterdepolarisations?
during phase 2 or 3
what causes early afterdepolarisations
an increase in frequency of abortive APs before normal repolarisation is completed
what can EADs lead to?
torsades de pointes
why would phase 2 be interrupted by an EAD?
augmented opening of calcium channels
why would phase 3 be interrupted by an EAD?
opening of sodium channels
when do delayed afterdepolarisations occur?
during phase 4, after repolarisation is completed but before another action potential would normally occur via the normal conduction system of the heart
why do DADs occur?
due to elevated cystolic calcium concentrations
the overload of the SR may cause spontaneous Ca2+ release after repolarisation, causing the released Ca2+ to exit the cell through the 3Na+/Ca2+ exchanger
this results in a net depolarising current
when are DADs seen?
digoxin toxicity
bidirectional ventricular tachycardia
catecholaminergic polymorphic ventricular tachycardia (CPVT)
what is the mechanism of QT prolongation?
less repolarising current prolongs ADP
-or-
more depolarising current prolongs ADP
congenital LQTS
polymorphic VT (torasades de pointes) triggered by adrenergic stimulation syncope risk associated with severity of QT prolongation
autosomal dominant LQTS
isolated LQT- romano-ward syndrome
extra cardiac features- anderson-tawil syndrome, timothy syndrome
autosomal recessive LQTS
associated with deafness; jervell and lange-neilsen syndrome
LQTS diagnosis
QTc >480 ms in repeated 12-lead ECGs or LQTS risk score >3
confirmed pathogenic LQTS mutation irrespective of the duration
QTc >460 ms in repeated 12-lead ECGs in patients with an unexplained syncopal episode in the absence of secondary causes for QT prolongation
risk of sudden cardiac death in LQTS
age dependant gender - pre-adolescent males - adult females increasing QT duration prior syncope response to beta blockers
risk management in LQTS
avoidance of QT prolonging drugs
correction of electrolyte abnormalities
avoidance of genotype-specific triggers eg strenuous swimming and exposure to loud nosies
brugada syndrome
risk of polymorphic VT, VF
atrial fibrillation common
ST elevation and RBBB in V1-V3
ECG findings may be intermittent and change over time
diagnostic ECG changes may seen only with provocative testing with flecainide or ajmaline
autosomal dominant
usually adult males
VF triggers in brugada syndrome
rest or sleep
fever
excessive alcohol, large meals
risk management in brugada syndrome
avoidance of drugs that may induce ST segement elevation in right precordial leads
avoidance of excessive alcohol intake and large meals
prompt treatment of any fever with antipyretic drugs
ICD implantation in brugada syndrome
survivors of cardiac arrest or have documented sustained VT
spontaneous diagnostic type I ECG pattern and history of syncope
drugs to avoid in brugada syndrome
anti-arrhythmic drugs
psychotropics
analgesics
anaesthetics
catecholaminergic polymorphic ventricular tachycardia
adrenergic induced bidirectional and polymorphic VT, SVTs, triggered by emotional stress, physical activity
normal ECG and ECHO
autosomal dominant catecholaminergic polymorphic ventricular tachycardia
ryanodine receptor mutation
recessive catecholaminergic polymorphic ventricular tachycardia
cardiac calsequestrin gene
CPVT risk management
avoidance of competitive sports, strenuous exercise and stressful environments
B blockers
ICD implantation in CPVT
cardiac arrest
recurrent syncope
polymorphic/ bidirectional VT despite optimal therapy
flecainide
patients with CPVT where there are risks/contraindications for an ICD
complications associated with transvenous leads
endocarditis perforation haemothorax pnemothorax thromboembolic events vascular complications lead fractures lead extraction complications lead dislodgement
S-ICD
an alternative to transvenous defibs in patients with an indication for an ICD when pacing therapy for bradycardia, cardiac resynch or antitachycardia pacing is not needed
hypertrophic cardiomyopathy
mutation in sarcomeric genes
HOCM clinical presentations
sudden death
heart failure end stage HF
atrial fibrillation
dilated cardiomyopathy
more males than females
sarcomere and desosomal genes/ laminA/C and desmin if there is conduction disease, dystophin if X linked
lamin A/C
progressive dilated cardiomyopathy atrioventricular block (first degree heart block) SVT and VA high risk of sudden death sometimes neuromuscular symptoms
arrhythmogenic right ventricular cardiomyopathy
fibro-fatty replacement of cardiomyocytes
LV involvement
mutations in arrhythmogenic right ventricular cardiomyopathy
autosomal dominant in the genes for desmosomal proteins
autosomal recessive mutations in nondesmosomal genes
risk of sudden death in ARVC
family history severity of RV and LV function frequent non-sustained VT QRS prolongation VT induction on EPS male age
risk management in ARVC
avoidance of competitive sports B blcokers ICD implantation amiodarone catheter ablation
cascade screening
Produces a greater rate of case identification than general population screening.
Once a diagnosis is confirmed in an individual, testing is extended to first degree and second degree relatives.
If relatives test positive,
their first and second degree
relatives are approached and
offered testing, and so on
