Long QT and Brugada syndromes Flashcards
What are the cardiac channelopathies?
- Long QT Syndrome
- Short QT syndrome
- Brugada Syndrome
- Progressive Cardiac Conduction Disease
- Catecholaminergic Polymorphic Ventricular Tachycardia
- Progressive Cardiac Conduction Disease
What defines Long QT syndrome?
- Prevalence 1 in 2000
- Heritable
- Normal cardiac structure
- Diagnosed using ECG
- ECG characteristics QTc prolongation T wave abnormalities Torsades de Pointes - most feared sequalae Delayed Cardiac Repolarisation
What does the balance between inward and outward current determine?
Duration of the action potential plateau, and the QT interval
Problem arises due to changes within hearts action potential
Outward current: Positively charged potassium leaving the cell
Inward current- sodium entering cell, leading to membrane resting potential more positive
Decreased outward current or increased Inward current = prolonged action potential duration, prolonged QT interval
Phase 0— cardiac depolarisation due to sodium rushing into cell, leading to resting membrane potential to become more positive
Cardiac repolarisation mainly phase 3 due to opening of potassium channel, potassium leaves cell causing cell membrane potential to become more negative back to baseline
How is LQTS diagnosed?
Schwartz score 2011: Diagnose condition based on combination of factors including ECG, family history and clinical history
Normal QTc intervals for male= below 440 millisecond and 460 for female
LQTS risk score 4 (≥3.5 high probability)
What are the key genes involved in LQTS?
KCNQ1- Long QT1. Potassium channel gene. Encodes the potassium channel responsible for the slow ratifying outward current potassium.
KCNH2- Long QT2. Encodes different potassium by similarly this is potassium that leaves the cell. Thus if there is a disruption in the outward transit of potassium , this prolongs time taken for the cell to depolarise manifesting as prolonged QT.
SCN5A- Long QT3. Encodes voltage gated sodium channel, responsible for phase zero of the cardiac action potential. This has several different diverse pleiotropic effects as also implicated in other disorders. Chief principle disorder is Brugada syndrome
In longQT a loss of function mutation in KCNQ1 or KCNH2 gene leads to impaired function of ion channel, prolongation of QT interval and the consequences that result from prolonging cardiac repolarisation which are mainly ventricular arrythmias
SCN5A- Gain of function, prolonged or late sodium current which continues to enter cell outside of phase zero of the action potential, sodium enters when cell is depolarising and therefore increases time for both depolarisation and repolarisation
Yield of genetic testing is based upon clinical likelihood of having condition
The sensitivity falls to 30% with ‘intermediate’ probability of LQTS
What are the expert consensus recommendations for comprehensive or LQT1-3 targeted LQTS testing?
- Recommended for any patient with strong clinical index of suspicion based on clinical history, ECG, family history and expressed ECG phenotype – schwarz score
- Recommended for any asymptomatic patient with QT prolongation in absence of other clinical conditions that may prolong the QT interval on serial 1—lead ECGs >480ms (prepuberty) or >500ms adults
- May be considered for any asymptomatic patient with otherwise idiopathic QTc values >460ms (prepuberty) or >480ms (adults)
Mutation-specific genetic testing is recommended for family members and other appropriate relatives following identification of the LQTS-causative mutation in an index case.
What did Ackerman 2011 - Genetic Testing for Long QT Syndrome - Distinguishing Pathogenic Mutations from Benign Variants find?
Type, frequency, and location of mutations across KCNQ1, KCNH2 and SCN5A were compared between 388 unrelated “definite” (clinical diagnostic score > 4 and/or QTc > 480 ms) cases of LQTS and over 1300 healthy controls for each gene
Mutations were 10× more common in cases than controls. Missense mutations were the most common, accounting for 78%, 67%, and 89% of KCNQ1, KCNH2, and SCN5A in cases and >95% in controls. Non-missense mutations have an EPV >99% regardless of location
Mutations were discovered in cases throughout all regions of the KCNH2-encoded Kv11.1 potassium channel. Missense mutations discovered in controls localized only to Kv11.1’s N- and C-termini.
248 mutations (180 distinct: 129 missense mutations, 51 radical) were found among 224 of the 388 LQTS cases (58%). Only 79 unique mutations (77 missense) were found across the three genes among the > 1300 controls
The relative frequency of mutations discovered in the N-terminus and C-terminus in cases versus controls was 2.7× and 3.8× respectively.
Many genetically confirmed with Long QT syndrome have a normal QT interval
True or false
True
Qtc in families often does not present incomplete penetrance
True or false
False, often does
How does LQT1 and 2 differ?
Each genotype has a subtle difference in phenotype
LQT1- associated with arrythmias at times of exertion
LQT2- associated with times of anxieties, event acoustic triggers such as a door bell ringing
Athletes with long Qt syndrome can participate in all competitive sports, provided they have been treated.
True or false
True
What is the main treatment for LQTS?
Main treatment used are beta blockers- able to suppress arrythmias and also blunts high heart rate
Genetic test confirming LQT1 indicates that competitive sport is allowed.
True or false
False
No competitive sport is allowed
What is Brugada Syndrome?
First described in 1992
- SUDs
- Hereditary
SCD Adult male in sleep
Prevalence 1:2000 - 1:5000
Polymorphic VT and VF
PAF in 10%
Structurally normal heart. RVOT myopathy
Characteristic ECG - transient and concealed
Ajmaline is a drug used for what?
Unmask brugada syndrome using ECG
