Cardiac Channelopathies Flashcards
How many people per year die of sudden cardiac arrest in the UK?
70,000
How many sudden cardiac arrest cases are caused by ischaemic heart disease?
60% - in the other 40% there is no detectable cause
Long and Short QT syndrome generally affect what?
Ventricular myocyte action potentials
What are the normal segments of an ECG and what do the show?
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
Which interval changes in long/ short QT syndrome?
The QT interval changes - shorter or longer
What are the stages of a ventricular action potential?
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
What is the normal QT time interval at rest?
0.36s
In patients with long QT syndrome what is their QT time interval?
0.45s or longer
In patients with short QT syndrome what is their QT time interval?
0.34s or less
Why can beats be skipped in long QT syndrome?
The SAN is firing normally but the ventricles have not fully repolarised so a beat is missed
What is triggered activity?
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
What is an addition ectopic beat?
Extra contraction of the myocytes which can cause ventricular tachycardia -> ventricular fibriliation -> sudden cardiac arrest
What is ventricular fibrilation?
A complete lack of coordination of the contraction of cells
What is Re-entrant excitation?
Not seen across all layers of the myocytes - triggering of extra activity only in some parts of the muscle
What is spatial dispersion?
Only certain parts of the myocytes are impacted
What is temporal dispersion?
Extra electical acvitivty of the heart but only at certain times
What are the possible symptoms felt by a patient with long QT syndrome?
Syncope (fainting)
Palpitations
Some patients have no ‘warning signs’
In long QT syndrome, what increases the chances of sudden cardiac arrest?
Exercise
Diving into cold water
What is torsades de pointes?
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.
What is the incidence of long QT synrdrome?
1:10,000 - 1:15,000
How many forms of long QT syndrome are there?
12
Which gene is mutated in long QT type 1 and what is its incidence?
KCNQ1
Mutation in Kv7.1a
Loss of function = no IKs current
Incidence is 30-35%
Which gene is mutated in long QT type 2 and what is its incidence?
KCNH2
Mutation in Kv11.1a
Loss of function = no Ikr current
Incidence is 25 - 30%
Which gene is mutated in long QT type 3 and what is its incidence?
Gain of function in voltage gated sodium channel
Incidence is 5-10%
Which gene is mutated in long QT type 4 and what is its incidence?
Loss of function in ankyrin B
Incidence is 1-2%
Which gene is mutated in long QT type 5 and what is its incidence?
Loss of function in Mink - contributes to IKs
Mink is a B subunit which regulates Kv7.1 by forming a complex
Incidence is 1%
Long QT1 and 5 are also associated with what and why?
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
Gain in function of sodium or calcium channels prolongs what?
The plateau phase (depolarisation)
How can long QT syndrome be treated?
B blockers
Atenolol
Negative chronotrophic and ionotrophic actions
How many types of short QT syndrome are there?
5
Males make up for how much of short QT syndrome cases?
75%
Which gene is mutated in short QT type 1?
Kv.11.1a - gain of function mutation
Affects IKr
KCNH2
Which gene is mutated in short QT type 2?
KCNQ1
KV7.1a - gain of function
Affects IKs
Which gene is mutated in short QT type 3?
KCNV2
Kir2.1 gain of function
Affects IKi
Which gene is mutated in short QT type 4?
CACNAIC
CaV1.2a - loss of function
Affects ICa
Which gene is mutated in short QT type 5?
CACNB2
CaV1.2B2 - loss of function
Affects ICa
What is the treatment for short QT syndrome?
Implant a defibrillator
Quinide - potassium channel blocker slows down repolarisation
