Lecture 7 - Channelopathies

Question 1

What causes long QT syndrome?

Answer 1

Mutations in genes which encode potassium (and sodium) ion channels
Potassium ion channels are very important in phase 3 (repolarisation), so mutations can lead to repolarisation abnormalities causing VT

Question 2

What does a long QT ECG look like?

Answer 2

Measurement of QT lands outside the normal range

Question 3

What can long QT syndrome cause?

Answer 3

‘torsades de points’ which is a variety of VT

Question 4

What is VT?

Answer 4

Ventricular tachycardia - very fast rhythm, not compatible with effective output, doesn’t give the heart chance to fill

Question 5

Does genetic abnormality = cardiac abnormality?

Answer 5

No, just because someone has genetic abnormality, it doesn’t mean they will suffer the cardiac abnormality

Question 6

What is an EAD?

Answer 6

Early after depolarisation

Question 7

What causes an EAD?

Answer 7

Abnormal potassium ion channels, so there is loss of function and repolarisation is impaired, so increased repolarisation leads to a longer QT phase, an EAD is where the cell undergoes an ap at the point of repolarisation

Question 8

What causes Brugada syndrome?

Answer 8

Sodium ion channel abnormality in right ventricular (RV) epicardium

Question 9

What does Brugada syndrome cause and in who?

Answer 9

Sudden cardiac death
Mean age of sudden death 41 +/- 15 years
Predominantly males (~75%)

Question 10

What does Brugada syndrome look like on an ECG?

Answer 10

Weird ST segment, seen in the front chest lead reading on the ECG

Question 11

What is CPVT?

Answer 11

Catecholaminergic Polymorphic Ventricular Tachycardia

Question 12

How is CPVT similar to LQT?

Answer 12

Exercise-induced syncope (loss of consciousness), seizures or sudden death

Question 13

How is CPVT different to LQT?

Answer 13

ECG at rest is typically normal

Question 14

Why is it critical to distinguish between CPVT and LQT?

Answer 14

CPVT is more arrhythmic than LQT, higher estimated fatality in CPVT

Question 15

What is a DAD?

Answer 15

Delayed after depolarisation

Question 16

What happens in a DAD?

Answer 16

The cell recovers back to RMP, then during rest phase a DAD occurs instead of waiting for the next ap

Question 17

What causes a DAD?

Answer 17

Seems to be a problem with calcium overload
Sarcoplasmic reticulum has a problem and spontaneously released calcium into the cell, an issue with ryanodine receptors
So, have spontaneous release of calcium so calcium exchanger is activated, so sodium gets brought into the cell which can build up and trigger a DAD

Question 18

What are the treatments of LQT?

Answer 18

LQT1 - Beta blockers
Avoidance of triggers 
LQT1 - swimming
LQT2 - shock 
LQT3 - sleep

Question 19

What are treatments of CPVT?

Answer 19

Beta blockers
Left cardiac sympathetic denervation - cut the sympathetic nervous supply to the heart
ICD - Implanted cardioverter defibrillator - sense abnormal heart rhythm and sends a short to restore normal rhythm

Question 20

What are treatments of Brugada syndrome?

Answer 20

ICD - Implanted cardioverter defibrillator - sense abnormal heart rhythm and sends a short to restore normal rhythm

Question 21

What is electrophysiology?

Answer 21

A wire that’s been put inside an individual’s heart, from the wire, the cardiologist is making measurements of electrical activity (basically an ECG from inside the heart)
Then can use a computer software to map the electrical activity and identify areas abnormal heart rhythm
If identify areas of abnormal activity they will destroy the area using ablation (killing defective cells), by either heating up the tissue or freezing it
This deals with the abnormal cells however it leaves scar tissue in the heart, which is another risk factor for abnormal rhythm