Cardiology - QT Channelopathies Flashcards
When do you do genetic testing?
- ANY patient with strong suspicion
- Family hx
- Asymptomatic with QTc>500ms
CONSIDER if QTc >480ms
What channelopathies result from mutations in SCN5A?
SCN5A encodes a Na channel on Ch3
GAIN: LQT3
LOSS: Brugada and Lenegres
What channelopathies result from mutations in KCNQ1?
KCNQ1 encondes K channel on Ch11
GAIN: Familial AF and SQTS
LOSS: LQT1
What channelopathies result from mutations in KCNH2?
KCNH2 encodes K channel on Ch7
GAIN: SQTS
LOSS: LQT2
What does SCN5A encode?
SCN5A encodes Na channel on Ch 3
What does KCNQ1 encode?
KCNQ1 encodes K channel on Ch 11
What does KCNH2 encode?
KCNH2 encodes K channel on Ch7
Antiarrythmics that cause long QT?
ANTI-ARRYTHMICS:
- Class IA: quinidine / procainamide
- Class III: sotolol / amiodarone
Antibiotics/Infection Drugs that cause long QT?
Macrolides: erythromycin, clarithromycin and azithromycin
Fluoroquinolones: levofloxacin and moxifloxacin
Bactrim
Clindamycin
Pentamidine
Chloroquine
Antifungals: ketoconazole / intraconazole
Antivirals: amantadine
Antihistamines that cause long QT?
Terfenedine
Diphenhydramine
Antipsychotics that cause long QT?
Haloperidol
Ziprasidone
Tricyclics and Tetracycline antidepressants
Other medications that cause long QT?
- Cholinergic antagonists: cisapride / organophosphates
- Citrate (ie post massive blood transfusion)
- Cocaine
- Methadone
- Fluoxetine
Which electrolyte abnormalities cause long QT?
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
Which endocrine conditions cause long QT?
Hypothyroidism HyPERparathyroidism Pheochromocytoma HyPERaldosteronism Hypothermia
Which intracranial causes cause long QT?
SAH Thalamic haematoma CVA Encephalitis Head injury
Which nutritional disorders cause long QT?
Anorexia nervosa Starvation Liquid protein diet Gastroplasty and ileojujunal bypass Coeliac disease
Definition of a long QTc?
Females >460ms
Males >440ms
Of LQT1, LQT2 and LQT3 what proportion of Long QT syndromes do they make?
LQT1 = 45% LQT2 = 45% LQT3 = 7%
What is the mutation in LQT1
Mutation in K channel
Autosomal DOMINANT heterozygotic
Mutation in either:
KVLQT1 or KCNQ1 on Ch11
If someone has the homozygous mutation seen in LQT1 what do they have?
LQT1 is a mutation in either KVLQT1 or KCNQ1 on Ch11.
It is heterozygous autosomal dominant.
If they are homozygous then JERVELL-LANG-NIELSEN syndrome
What is the mutation in LQT2?
Mutation in K channel
Autosomal DOMINANT of either:
HERG or KCNH2 genes on Ch7
What mutation in LQT3?
Mutation in Na channel
Autosomal DOMINANT of SCN5A on Ch3
What is the Romano Ward Syndrome?
Autosomal DOMINANT
VT and QTc prolongation
Mutation in: ANK2 / KCNE1 / KCNE2 / KCNQ1 / SCN5A
What is the Jervell-Lang-Nielsen Syndrome?
Autosomal RECESSIVE
VT and QTc prolongation
PLUS SENSORINEURAL HEARING LOSS
Mutation in KCNE1 or KCNQ1
Jervell-Lang-Nielsen and Romano-Ward result in which cardiac abnormalities?
How do you tell them apart?
JVN is Autosomal RECESSIVE
And associated with sensorineural deafness
Romanoward is Autosomal DOMINANT
They both result in VT and QTc prolongation
What triggers LQT1?
Exercise, swimming, sudden exposure of face to cold
What triggers LQT2?
Emotion and loud noises
What triggers LQT3?
Sleep
Which Long QT Syndrome is triggered by Exercise, swimming, sudden exposure of face to cold
LQT1
Which LQTS is triggered by Emotion and loud noises
LQT2
Which LQTS is triggered by sleep
LQT3
What classifies a Long QT Syndrome as HIGH risk?
If QTc >500ms and:
- LQT1
- LQT2
- Male LQT3
What classifies a Long QT Syndrome as INTERMEDIATE risk?
If QTc>500ms AND female LQT3
or
If QTc <500 and:
- Female LQT2
- Female LQT3
- Male LQT3
What classifies a Long QT Syndrome as LOW risk?
If QTc <500 and:
- Male LQT2
- LQT1
If you are LQT1 what risk are you?
Low risk
If you are LQT2 what risk are you?
FEMALE:
If QTc <500 then intermediate
If QTc >500 then high
MALE:
If QTc <500 then low
If QTc >500 then high
If you are LQT3 what risk are you?
FEMALE: Intermediate
MALE:
If QTc <500 then intermediate
If QTc >500 then high
How do you manage Long QT Syndrome?
- IV magnesium if torsades
- Beta blocker
- prevents cardiac events in 70%
- propranolol and nadolol most use
- greatest benefit in LQT1
ICD (**UNLESS low risk and no history of VT)
Avoid competitive sports and medications that prolong QT
NO ROLE for PPM
Which Betablocker must be avoided in Long QT Syndrome?
Sotalol (can exacerbate the QTc prolongation)
Where do beta blockers have the greatest benefit in Long QT syndrome?
In LQT1
Short QT Syndrome:
Definition and mutation
Short QTc <350ms
Autosomal DOMINANT gain of function mutation in K channel
Short QT Syndrome:
Clinical features:
HIGH risk of sudden cardiac death
Also associated with:
AF
Polymorphic VT
Management of short QT syndrome
ICD in EVERYONE
Non-genetic causes of long QT?
- Hypokalaemia
- Hypomagnesaemia
- Hypocalcaemia
- Hypothermia
- Myocardial ischaemia
- Post cardiac disease
- Raised ICP
- Drugs
Antipsychotic drugs that prolong QT?
Chlorpromazine Haloperidol Droperidol Quetiapine Olanzapine Amisulpride
Antiarrythmics that prolong the QT?
Type 1A:
- quinidine
- procainamide
- disopyramide
Type 1C:
- flecainide
Type III:
- sotolol
- amiodarone
Tricyclic Antidepressants that prolong the QT?
Amitryptiline Imipramine Doxepin Nortryptyline Desipramine
Other antidepressants (not TCAs) that prolong the QT?
Citalopram and escitalopram
Venlafaxine
Bupropion
Moclobemide
Antihistamines that prolong the QT?
Loratadine
Terfanidine
Other drugs (not psych or antihistamines or arrythmics) that prolong the QT?
Chloroquine
Hydroxychloroquine
Quinine
Macrolides: erythromycin and clarithromycin
Non-genetic causes of short QT?
Hypercalcaemia
Digoxin
