15 - LQT Syndromes Flashcards
What are top 7 causes of sudden cardiac death in young people?
- Hypertrophic Cardiomyopathy (#1 in NA)
- RV Dysplasia (ARVC) (#1 in italy) (arrhythmogenic Right Ventricular Cardiomyopathy)
- Brugada Syndrome (#1 in Southeast asia)
- CPVT (catecholaminergic polymorphic ventricular tachycardia)
- Coronary Anomalies/Premature CAD (coronary artery disease)
- Long QT syndromes
- Short QT syndromes
Label the heart:
A) SA Node
B) Atria
C) AV Node
D) Purkinje
E) Ventricle
Where is the action potential seen in the image?
Label 0-4
Atria
0 - upstroke
1 - initial repolarization
2 - plateau
3 - Late repolarization
4 - rest (diastole)
The action potential in the image is seen in which area of the heart?
Label 0, 3, 4
What is important about phase 4?
SA Node
0 - Upstroke
3 - late repolarization
4 - depolarization in SA nodal cells
Phase 4 depolarization in SA nodal cells = pacemaker activity
SA node >> Atrial > Ventricle
Which area of the heart would create the action potential in the image?
Label 0-4
What is the arrow representing?
Ventricle
0 - upstroke
1 - Initial repolarization
2 - plateau
3 - late repolarization
4 - rest (diastole)
Arrow - transient outward K+ current through Ito channels = repolarizing - contributes to initial repolarization phase 1
Which ion channels contribute to depolarization?
- Ca++
- Na+
- Move into the cell
Nernst potential of:
- Ca++
- Na+
- Cl-
- K+
Nernst potential of:
- Ca++
- +150mV
- Na+
- +70mV
- Cl-
- -30 to -65mV
- K+
- -98mV (Resting Em)
Movement of ____ out of the cell causes ______
Movement of K+ out of the cell causes repolarization
There is constant recycling of ___ channels with every heart beat
There is constant recycling of Ca++ channels with every heart beat
Why does hyperkalemia cause QRS widening and asystole (eg lethal KCl injection)?
As serum potassium levels increase to greater than 6.5mM, the rate of phase 0 (upstroke/depolarization) of the action potential decreases leading to a longer action potential and, in turn, a widened QRS complex and prolonged PR interval
- delayed intraventricular and atrioventricular conduction
PR interval of ECG is related to ______ (ion moving)
PR interval of ECG is related to Na+ moving into cell - depolarization
The QRS interval of the ECG is related to which phase of the AP
ion moving in/out
The QRS interval of the ECG is related to action potential depolarization
The T wave of the ECG is associated with ________
ion moving in/out
The T wave of the ECG is associated with ventricular repolarization
K+ moving out of cell
What does the QT interval represent?
The time for both ventricular depolarization and repolarization to occur - estimates the duration of an average ventricular AP
Complete the table
K+ currents move _____ and cause _____. They are present in which phases of the ventricular AP?
K+ currents move outward and cause repolarization. They are present in which phases of the ventricular AP?
- Phase 1 - Ito
- Phase 2/phase 3 - IKr , hERG
- Phase 3 - IKs
- Phase 4 - IK1
Ito - transient outward K+ current
IKr , hERG - Rapidly activating delayed rectifying K+ current
IKs - Slowly activating delayed rectifying K+ current
IK1 - Inward rectifying K+ channels
What are the following channels and when are they active during ventricular AP?
- Ito
- IKr , hERG
- IKs
- IK1
Ito - transient outward K+ current
IKr , hERG - Rapidly activating delayed rectifying K+ current
IKs - Slowly activating delayed rectifying K+ current
IK1 - Inward rectifying K+ channels
- Phase 1 - Ito
- Phase 2/phase 3 - IKr , hERG
- Phase 3 - IKs
- Phase 4 - IK1
Na+ currents move _____ and cause _____. They are present in which phases of the ventricular AP?
Na+ currents move inward and cause depolarization. They are present in which phases of the ventricular AP?
Phase 0
Ca++ currents move _____ and cause _____. They are present in which phases of the ventricular AP?
Ca++ currents move inward and cause depolarization. They are present in which phases of the ventricular AP?
Phase 2 (phase 1 according to slide 11) (plateau phase)
L-type Ca++ channel (ICa,L)
Na+ current is a ______ current (phase _\_ of AP) Cardiac Sodium current is important for: (2)
Na+ current is a depolarizing current (phase 0 of AP) Cardiac Sodium current is important for: (2)
- AP duration (and QTc interval)
- Rapid Conduction eg. Purkinje fibres
Ca2+ current is a _____ current (phase __ of AP)
Cardiac Calcium current is important for: (2)
Ca2+ current is a depolarizing current (phase 1 of AP) (also phase 2 - plateau phase - very important for excitation contraction-coupling)
Cardiac Calcium current is important for:
- AP duration (and QTc interval)
- Triggers excitation-contraction coupling
K+ current is a _____ current (phase ___ of AP) Cardiac Potassium current is important for: (2)
K+ current is a repolarizing current (phase 2/3 of AP) Cardiac Potassium current is important for: (2)
- AP duration (and QTc interval)
- Repolarization
In 1957, Jervell and Lange-Nielsen reported a syndrome of congenital sensory deafness with a prolonged QT interval in four children: ______________
In 1957, Jervell and Lange-Nielsen reported a syndrome of congenital sensory deafness with a prolonged QT interval in four children: autosomal recessive…..LQT1 (and 5)
Romano–Ward syndrome is an ________ form of the long-QT syndrome NOT associated with deafness …higher incidence than JLN (jervell and Lange-Nielsen) syndrome, but affected persons generally have milder symptoms…….due to _______
Romano–Ward syndrome is an autosomal dominant form of the long-QT syndrome NOT associated with deafness …higher incidence than JLN (jervell and Lange-Nielsen) syndrome, but affected persons generally have milder symptoms…….due to LQT2, LQT3 and LQT4
What drugs case acquired LQT syndrome?
- Blockers of K+ channels (eg Quinidine)
- Decrease surface expression
How is LQT syndrome diagnosed?
LQT1,2 results from a (__∆ _____)
LQT1,2 results from a (-∆ repolarizing currents) (K+ current, Ik)
What causes LQT3 in AP?
+∆ depolarizing currents (Na+, current, INa)
What is torsade de pointes? What causes it?
TdP = polymorphic ventricular tachycardia with a twisting QRS morphology associated with a prolonged QT (LQT) interval
- triggered by reactivation of Ca++ channels, reactivation of a delayed sodium current, or a decreased outward potassium current that results in early afterdepolarization (EAD)
Label the image
Electrophysiological basis for LQT3 syndrome
Which ion channels are associated with LQT syndromes? (gene and protein)
- LQT1
- LQT2
- LQT3
- LQT4
- LQT5
- LQT6
- LQT7
- LQT8 (+LQT9, 10)
Which ion channels are associated with LQT syndromes?
- LQT1
- gene: KCNQ1 (KVLQT1)
- Protein: IKsK+ channel alpha subunit
- LQT2
- gene: KCNH2 (HERG)
- protein: IKrK+ channel alpha subunit
- LQT3
- gene: SCN5A
- protein: INaNa+ channel alpha subunit
- LQT4
- gene: ANKB
- protein: Ankyrin-B
- LQT5
- gene: KCNE1 (minK)
- protein: IKsK+ channel beta subunit
- LQT6
- gene: KCNE2 (MiRP1)
- protein: IKrK+ channel beta subunit
- LQT7
- gene: KCNJ2
- protein: IKr2.1K+ channel alpha subunit
- LQT8 (+LQT9, 10)
- gene: CACNA1
- protein: Cav1.2 Ca++ channel alpha subunit
Genotype-specific ECG changes:
Which chromosome is involved in the following LQT syndromes? Which LQT type are shown?
- Chromosome 3
- LQT3
- Flat ST segment with normal T-waves
- Chromosome 2
- LQT2
- bifib T waves
- LQT2
- Chromosome 11
- LQT1
- peak and broad T waves
How would you recognize LQT2 caused by chromosome 7?
Bifib T-waves
How would you recognize LQT1 in Chromosome 11?
Peak and broad T-waves
How would you recognize a LQT3 in chromosome 3?
Flat ST segment with Normal T-waves
Gain of function mutation in I<u>Na</u> causes _____
Gain of function mutation in I<u>Na</u> causes LQT3
Loss of function mutation in IKr and IKs causes ________
Loss of function mutation in IKr and IKs causes LQT2 and 1
The image shows?
LQT3 syndrome
- QT interval longer than in LQT1 and LQT2
- HR increases
- QT inverval shortens more in LQT3
- Late appearance of T wave
fill in the table
3 methods to manage LQT1 and 2 syndromes
- K+ and MG++ supplementation
- Beta-blocker
- ICD (implantable cardioverter-defibrillator)- if symptomatic and/or aborted SCD (sudden cardiac death)
Management of LQT3 Syndrome (3)
- Bradycardia dependent i.e. unlike LQT1 and 2; avoid beta-blockers
- ICD (implantable cardioverter-debrillator)
- Class I anti-arrhythmic eg. mexilitine (Sodium Channel Blockers)
How to recognize LQT7 on ECG?
- A triad of K+-sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features
- T and U form a continuum - resultant of one and the same process: Repolarization of the Ventricular Myocardium
The image shows:
Short QT1 syndrome
SQTS1,2,3 caused by __∆ repolarizing current
SQTS1,2,3 caused by +∆ repolarizing current
SQTS4,5 caused by __∆ depolarizing current
SQTS4,5 caused by -∆ depolarizing current
What are the 3 gain of function mutations in K+ channels associated with?
IKr
IKs
IK1
- IKr = SQT1 (LQT2)
- IKs = SQT2 (LQT1)
- IK1 = SQT3 (LQT7)
What are the 3 gain of function mutations in K+ channels associated with?
IKr
IKs
IK1
- IKr = SQT1 (LQT2)
- IKs = SQT2 (LQT1)
- IK1 = SQT3 (LQT7)
Management of Short QT syndromes
_____ is the therapy of choice in patients with syncope and a positive family history of SCD
ICD is the therapy of choice in patients with syncope and a positive family history of SCD
ICD therapy in patients with a short QT syndrome has an increased risk for inappropriate shock therapies due to _______
ICD therapy in patients with a short QT syndrome has an increased risk for inappropriate shock therapies due to possible T wave oversensing
How is Quinidine used for Short QT syndromes?
Quinidine (IKr blocker) causes QT prolongation
QTc increased from 263 +/- 12ms to 362+/- 25ms
Management of Short QT syndromes
_______ is particularly important because SQT1 patients are at risk of sudden death from birth, and ICD implant is not feasible in very young children
Quinidine is particularly important because SQT1 patients are at risk of sudden death from birth, and ICD implant is not feasible in very young children
