Cardiology - QT Channelopathies

Question 1

When do you do genetic testing?

Answer 1

• ANY patient with strong suspicion
• Family hx
• Asymptomatic with QTc>500ms

CONSIDER if QTc >480ms

Question 2

What channelopathies result from mutations in SCN5A?

Answer 2

SCN5A encodes a Na channel on Ch3

GAIN: LQT3
LOSS: Brugada and Lenegres

Question 3

What channelopathies result from mutations in KCNQ1?

Answer 3

KCNQ1 encondes K channel on Ch11

GAIN: Familial AF and SQTS
LOSS: LQT1

Question 4

What channelopathies result from mutations in KCNH2?

Answer 4

KCNH2 encodes K channel on Ch7

GAIN: SQTS
LOSS: LQT2

Question 5

What does SCN5A encode?

Answer 5

SCN5A encodes Na channel on Ch 3

Question 6

What does KCNQ1 encode?

Answer 6

KCNQ1 encodes K channel on Ch 11

Question 7

What does KCNH2 encode?

Answer 7

KCNH2 encodes K channel on Ch7

Question 8

Antiarrythmics that cause long QT?

Answer 8

ANTI-ARRYTHMICS:

• Class IA: quinidine / procainamide
• Class III: sotolol / amiodarone

Question 9

Antibiotics/Infection Drugs that cause long QT?

Answer 9

Macrolides: erythromycin, clarithromycin and azithromycin

Fluoroquinolones: levofloxacin and moxifloxacin

Bactrim
Clindamycin
Pentamidine
Chloroquine

Antifungals: ketoconazole / intraconazole
Antivirals: amantadine

Question 10

Antihistamines that cause long QT?

Answer 10

Terfenedine

Diphenhydramine

Question 11

Antipsychotics that cause long QT?

Answer 11

Haloperidol
Ziprasidone
Tricyclics and Tetracycline antidepressants

Question 12

Other medications that cause long QT?

Answer 12

• Cholinergic antagonists: cisapride / organophosphates
• Citrate (ie post massive blood transfusion)
• Cocaine
• Methadone
• Fluoxetine

Question 13

Which electrolyte abnormalities cause long QT?

Answer 13

Hypokalaemia
Hypomagnesaemia
Hypocalcaemia

Question 14

Which endocrine conditions cause long QT?

Answer 14

Hypothyroidism
HyPERparathyroidism
Pheochromocytoma
HyPERaldosteronism
Hypothermia

Question 15

Which intracranial causes cause long QT?

Answer 15

SAH
Thalamic haematoma
CVA
Encephalitis
Head injury

Question 16

Which nutritional disorders cause long QT?

Answer 16

Anorexia nervosa
Starvation
Liquid protein diet
Gastroplasty and ileojujunal bypass
Coeliac disease

Question 17

Definition of a long QTc?

Answer 17

Females >460ms

Males >440ms

Question 18

Of LQT1, LQT2 and LQT3 what proportion of Long QT syndromes do they make?

Answer 18

LQT1 = 45%
LQT2 = 45%
LQT3 = 7%

Question 19

What is the mutation in LQT1

Answer 19

Mutation in K channel
Autosomal DOMINANT heterozygotic

Mutation in either:
KVLQT1 or KCNQ1 on Ch11

Question 20

If someone has the homozygous mutation seen in LQT1 what do they have?

Answer 20

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

Question 21

What is the mutation in LQT2?

Answer 21

Mutation in K channel
Autosomal DOMINANT of either:
HERG or KCNH2 genes on Ch7

Question 22

What mutation in LQT3?

Answer 22

Mutation in Na channel

Autosomal DOMINANT of SCN5A on Ch3

Question 23

What is the Romano Ward Syndrome?

Answer 23

Autosomal DOMINANT
VT and QTc prolongation

Mutation in: ANK2 / KCNE1 / KCNE2 / KCNQ1 / SCN5A

Question 24

What is the Jervell-Lang-Nielsen Syndrome?

Answer 24

Autosomal RECESSIVE
VT and QTc prolongation
PLUS SENSORINEURAL HEARING LOSS

Mutation in KCNE1 or KCNQ1

Question 25

Jervell-Lang-Nielsen and Romano-Ward result in which cardiac abnormalities? How do you tell them apart?

Answer 25

JVN is Autosomal RECESSIVE And associated with sensorineural deafness Romanoward is Autosomal DOMINANT They both result in VT and QTc prolongation

Question 26

What triggers LQT1?

Answer 26

Exercise, swimming, sudden exposure of face to cold

Question 27

What triggers LQT2?

Answer 27

Emotion and loud noises

Question 28

What triggers LQT3?

Answer 28

Sleep

Question 29

Which Long QT Syndrome is triggered by Exercise, swimming, sudden exposure of face to cold

Answer 29

LQT1

Question 30

Which LQTS is triggered by Emotion and loud noises

Answer 30

LQT2

Question 31

Which LQTS is triggered by sleep

Answer 31

LQT3

Question 32

What classifies a Long QT Syndrome as HIGH risk?

Answer 32

If QTc >500ms and: - LQT1 - LQT2 - Male LQT3

Question 33

What classifies a Long QT Syndrome as INTERMEDIATE risk?

Answer 33

If QTc>500ms AND female LQT3 or If QTc <500 and: - Female LQT2 - Female LQT3 - Male LQT3

Question 34

What classifies a Long QT Syndrome as LOW risk?

Answer 34

If QTc <500 and: - Male LQT2 - LQT1

Question 35

If you are LQT1 what risk are you?

Answer 35

Low risk

Question 36

If you are LQT2 what risk are you?

Answer 36

FEMALE: If QTc <500 then intermediate If QTc >500 then high MALE: If QTc <500 then low If QTc >500 then high

Question 37

If you are LQT3 what risk are you?

Answer 37

FEMALE: Intermediate MALE: If QTc <500 then intermediate If QTc >500 then high

Question 38

How do you manage Long QT Syndrome?

Answer 38

- 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

Question 39

Which Betablocker must be avoided in Long QT Syndrome?

Answer 39

Sotalol (can exacerbate the QTc prolongation)

Question 40

Where do beta blockers have the greatest benefit in Long QT syndrome?

Answer 40

In LQT1

Question 41

Short QT Syndrome: | Definition and mutation

Answer 41

Short QTc <350ms Autosomal DOMINANT gain of function mutation in K channel

Question 42

Short QT Syndrome: | Clinical features:

Answer 42

HIGH risk of sudden cardiac death Also associated with: AF Polymorphic VT

Question 43

Management of short QT syndrome

Answer 43

ICD in EVERYONE

Question 44

Non-genetic causes of long QT?

Answer 44

- Hypokalaemia - Hypomagnesaemia - Hypocalcaemia - Hypothermia - Myocardial ischaemia - Post cardiac disease - Raised ICP - Drugs

Question 45

Antipsychotic drugs that prolong QT?

Answer 45

``` Chlorpromazine Haloperidol Droperidol Quetiapine Olanzapine Amisulpride ```

Question 46

Antiarrythmics that prolong the QT?

Answer 46

Type 1A: - quinidine - procainamide - disopyramide Type 1C: - flecainide Type III: - sotolol - amiodarone

Question 47

Tricyclic Antidepressants that prolong the QT?

Answer 47

``` Amitryptiline Imipramine Doxepin Nortryptyline Desipramine ```

Question 48

Other antidepressants (not TCAs) that prolong the QT?

Answer 48

Citalopram and escitalopram Venlafaxine Bupropion Moclobemide

Question 49

Antihistamines that prolong the QT?

Answer 49

Loratadine | Terfanidine

Question 50

Other drugs (not psych or antihistamines or arrythmics) that prolong the QT?

Answer 50

Chloroquine Hydroxychloroquine Quinine Macrolides: erythromycin and clarithromycin

Question 51

Non-genetic causes of short QT?

Answer 51

Hypercalcaemia | Digoxin