Cardiac Channelopathies

Question 1

How many people per year die of sudden cardiac arrest in the UK?

Answer 1

70,000

Question 2

How many sudden cardiac arrest cases are caused by ischaemic heart disease?

Answer 2

60% - in the other 40% there is no detectable cause

Question 3

Long and Short QT syndrome generally affect what?

Answer 3

Ventricular myocyte action potentials

Question 4

What are the normal segments of an ECG and what do the show?

Answer 4

P wave -atrial depolarisation
QRS complex - ventricular depolarisation
T wave - ventricular repolarisation
PR interval - start of atrial depolarisation to the start of ventricular depolarisation
Q-T interval - Start of ventricular depolarisation to the end of ventricular repolarisation
The T-P interval -Time between the end of ventricular repolarisation and the start of a new cardiac cycle

Question 5

Which interval changes in long/ short QT syndrome?

Answer 5

The QT interval changes - shorter or longer

Question 6

What are the stages of a ventricular action potential?

Answer 6

1) Large increase in sodium permeability occurs as well as a small increase in potassium permeability
2) Voltage gated calcium channels open = plateau
3) Potassium channels drive repolarisation

Question 7

What is the normal QT time interval at rest?

Answer 7

0.36s

Question 8

In patients with long QT syndrome what is their QT time interval?

Answer 8

0.45s or longer

Question 9

In patients with short QT syndrome what is their QT time interval?

Answer 9

0.34s or less

Question 10

Why can beats be skipped in long QT syndrome?

Answer 10

The SAN is firing normally but the ventricles have not fully repolarised so a beat is missed

Question 11

What is triggered activity?

Answer 11

Where after depolarisation occurs in the ventricles myocytes reach threshold. The sodium channels may get to a closed state and ready to respond before repolarisation is finished so the sodium channels may reactivate again

Question 12

What is an addition ectopic beat?

Answer 12

Extra contraction of the myocytes which can cause ventricular tachycardia -> ventricular fibriliation -> sudden cardiac arrest

Question 13

What is ventricular fibrilation?

Answer 13

A complete lack of coordination of the contraction of cells

Question 14

What is Re-entrant excitation?

Answer 14

Not seen across all layers of the myocytes - triggering of extra activity only in some parts of the muscle

Question 15

What is spatial dispersion?

Answer 15

Only certain parts of the myocytes are impacted

Question 16

What is temporal dispersion?

Answer 16

Extra electical acvitivty of the heart but only at certain times

Question 17

What are the possible symptoms felt by a patient with long QT syndrome?

Answer 17

Syncope (fainting)
Palpitations
Some patients have no ‘warning signs’

Question 18

In long QT syndrome, what increases the chances of sudden cardiac arrest?

Answer 18

Exercise

Diving into cold water

Question 19

What is torsades de pointes?

Answer 19

Specific form of polymorphic ventricular tachycardia in patients with a long QT interval
Characterized by rapid, irregular QRS complexes, which appear to be twisting around the ECG baseline
Arrhythmia may cease spontaneously or degenerate into ventricular fibrillation.

Question 20

What is the incidence of long QT synrdrome?

Answer 20

1:10,000 - 1:15,000

Question 21

How many forms of long QT syndrome are there?

Answer 21

12

Question 22

Which gene is mutated in long QT type 1 and what is its incidence?

Answer 22

KCNQ1
Mutation in Kv7.1a
Loss of function = no IKs current
Incidence is 30-35%

Question 23

Which gene is mutated in long QT type 2 and what is its incidence?

Answer 23

KCNH2
Mutation in Kv11.1a
Loss of function = no Ikr current
Incidence is 25 - 30%

Question 24

Which gene is mutated in long QT type 3 and what is its incidence?

Answer 24

Gain of function in voltage gated sodium channel

Incidence is 5-10%

Question 25

Which gene is mutated in long QT type 4 and what is its incidence?

Answer 25

Loss of function in ankyrin B | Incidence is 1-2%

Question 26

Which gene is mutated in long QT type 5 and what is its incidence?

Answer 26

Loss of function in Mink - contributes to IKs Mink is a B subunit which regulates Kv7.1 by forming a complex Incidence is 1%

Question 27

Long QT1 and 5 are also associated with what and why?

Answer 27

Deafness The stria vascularis secretes potassium into the endolymph The endolymph is bordered by hair cells and Reissner's membrane If potassium is not secreted Reissner's membrane collapses = no endolymph = deafness

Question 28

Gain in function of sodium or calcium channels prolongs what?

Answer 28

The plateau phase (depolarisation)

Question 29

How can long QT syndrome be treated?

Answer 29

B blockers Atenolol Negative chronotrophic and ionotrophic actions

Question 30

How many types of short QT syndrome are there?

Answer 30

5

Question 31

Males make up for how much of short QT syndrome cases?

Answer 31

75%

Question 32

Which gene is mutated in short QT type 1?

Answer 32

Kv.11.1a - gain of function mutation Affects IKr KCNH2

Question 33

Which gene is mutated in short QT type 2?

Answer 33

KCNQ1 KV7.1a - gain of function Affects IKs

Question 34

Which gene is mutated in short QT type 3?

Answer 34

KCNV2 Kir2.1 gain of function Affects IKi

Question 35

Which gene is mutated in short QT type 4?

Answer 35

CACNAIC CaV1.2a - loss of function Affects ICa

Question 36

Which gene is mutated in short QT type 5?

Answer 36

CACNB2 CaV1.2B2 - loss of function Affects ICa

Question 37

What is the treatment for short QT syndrome?

Answer 37

Implant a defibrillator | Quinide - potassium channel blocker slows down repolarisation