Long QT Syndrome

1. Long QT Syndrome Teresa Menendez Hood M.D.

2. LQTS :Facts • Abnormalities of ion channels that result in long QT intervals ( prolongation of phase III-time for repolarization) and predispose to polymorphous ventricular tachycardia (“Torsade de Pointe”) • Common cause of sudden death in children and young adults • 1:7000 births • In the US it causes ~ 5% of the SCD/year • Symptoms include syncope or SCD usually with physical activity or emotional stress

3. LQTS:Facts • Prolonged recovery from electrical excitation contributes to increased likelihood of dispersion of refractoriness. • Consequently, the wave of excitation may pursue a distinctive pathway around a focal point in myocardium (circus reentrant rhythm), leading to polymorphous ventricular tachycardia……. syncope and possibly sudden death.

4. LQTS:Facts • QT prolongation in LQTS is due to overload of myocardial cells with positively charged ions during ventricular repolarization (not enough K+ getting out or too much Na+ in ) • In LQT1, LQT2, LQT5, and LQT6 types, potassium ion channels are blocked or they open with a delay or are open for a shorter period than in normally functioning channels, leading to decreased potassium outward current and prolonged repolarization. In LQT3, caused by mutations of the SCN5A sodium channel gene, persistent inward sodium current contributes to prolonged repolarization.

5. LQTS:Facts • Syncope often misdiagnosed as vasovagal or epilepsy • Family history is important-ask about deafness and SCD <30 years of age • 1/3 of patients with LQTS are asymptomatic • 10% of patients will have a normal QT interval • Rule out drug induced LQT and other causes of SCD in young patients(HCM,Brugada,ARVD) • Treatment is BB +/- ICD

6. LQTS:Facts • Gender differences :SCD- males-higher risk during childhood with mean age 13 of SCD and females have higher risk in adulthood with mean age of 20 of SCD • Women are twice as likely to be symptomatic and develop TdP than their male counterparts (the estrogen?) • Competitive sports should be avoided • Most episodes result in syncope with only 5% resulting in SCD • EP studies are not helpful

7. LQTS: Facts • Inherited/Congenital :first described in 1957 with an autosomal dominant type (Romano Ward) and an autosomal recessive type (Jervell Lange-Nielsen). In the 1990s the genetic mutations have been linked to at least 6 genes and 2 ion channels. • JLN-deafness, auto R, rare (<1% of all LQTS);needs to be homozygous and involves K consduction in the cilia of the ear • RW-common,hearing is normal,auto D

8. LQTS:Facts • With treatment, can lower the mortality from 10% at 10 years to <1% • BB prevent symptoms is 70% of patients • ICD’s are indicated for those who have not responded to BB • TdP:Acutely need to treat with defibrillation, IV magnesium, consider temporary pacing if bradycardic ,and remove offending drugs • Need to avoid drugs which can further prolong the QT-www.qtdrugs.org

9. LQTS: The EKG • Measure the QT corrected via the Bazett’s formula and look for T-wave abnormalities • Do not rely on the automated QTc from the computer read EKG • T wave abnormalities : wide based, double hump, T-U complex, low amplitude • Do an EKG on the parents and siblings • Take an average of 3 QTc intervals

11. LQTS: Calculating the QTc • Bazett: 1920 QTc=QT/square root of the RR • Corrects QT for the heart rate-there is normally an inverse relation…as one goes up/the other goes down and vice versa • Abnormal if QTc in males >470 ms and females of > 480 ms • Borderline prolonged QTc 450-470 ms • Average QTc for someone with the LQTS is 490 ms

12. LQTS: Nomogram

13. LQTS:Genetics • Not all is known… since 40% of families with LQTS have not yet been linked to the known genetic causes • LQT1-LQT7 • All encode for K channels except LQT3 which is linked to the Na channel-very good test question….

14. LQTS: Geneticstype/gene/chromosome/comment • LQT1; KCNQ1 (KvLQT1); 11Trigger: Stress ;Iks;associated with JLN • LQT2; KCNH2 (hERG); 7; Trigger: Noise ;Ikr…… • LQTS1 and 2 = 87% of known LQTS • LQT3 ; SCN5A ; 3; Trigger: Sleep, rest. Beta blocker therapy seems to be the less effective ;Ina…8% of known LQTS • LQT4 ?????

15. LQTS:Genetics type/gene/chromosome/comment • LQT5 ; KCNE1 ; 21 ; Associated to the JLN;Iks • LQT6 ; KCNE2-MiRP1 ; 21 ; Triggers: certain drugs, exercise;Ikr • LQT7 ; KCNJ2 ; 17 ; Associated to the Andersen syndrome (periodic paralysis and skeletal developmental abnormalities)

16. Diagnostic Criteria for LQTS • 1. EKG findings • QTc • >480 3 • 460-470 2 • 450 (male) 1

17. Diagnostic Criteria for LQTS • Torsdade De Pointes 2 • T-wave alternans 1 • Notched T wave in 3 leads 1 • Low heart rate for age 0.5

18. Diagnostic Criteria for LQTS • Clinical History • Syncope with stress 2 • without stress 1 • Congenital deafness 0.5

19. Diagnostic Criteria for LQTS • Family history • Definite LQTS 1 • Unexplained SCD in immediate family member that is less than 30 years of age 0.5

20. Diagnostic Criteria for LQTS • <1 points low probability • 2-3 points intermediate probability • >4 points high probability

21. Risk stratification in the LQTS • Those at highest risk (>50%) of having a cardiac event are those with QTc at rest of >500 msec and females • Those at lowest risk are those with QTc < 500 msed and males • Those with LQT3 have less events, but when they occur..they are more lethal

22. El FIN