Long QT Syndrome

• Loss of function mutations in IKs and IKr prolong QT interval and produce LQTS1 and LQT2, respectively.
• The appearance of T wave can be a clue to type of LQTS
  • symmetric, tortoise hump shaped is seen with Type 1
  • late-peaking/double hump appearance is seen with Type 2
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Diagnosis

Genetic testing

TODO

Schwartz score

• Schwartz score ≥3.5 carries a specificity of 99% for the diagnosis of LQTS.
• Genetic testing is recommended in those with Schwartz score ≥3.

LQTS Type 1

LQTS Type 2

• Caused by a loss of function mutation → blockage of IKr channel
• Most common cause of drug-induced prolonged QT syndrome as many drugs are IKr blockers
• Second most common of LQT subtypes (25-30%)
• Exacerbated by auditory stimuli 🔊
  • Events caused by alarm clocks, startle response, exercise
• Responsive to treatment with BBs and exercise restriction
• ICD indicated for:
  • female patients with LQT2
  • QTc > 500ms
  • history of syncope/SCA
• 📝 Treating a patient with K-channel blockers like sotalol or dofetilide is like giving someone LQTS type 2, i.e. like block IKr channels.

LQTS Type 3

• Caused by gain of function of INa (SCN5a)
• Third most common of LQT subtypes (5-10%), considered most lethal
• Exacerbated by bradycardia, sleep
• Events only occur during sleep, so no warning signs, often present with SCA
• Responsive to treatment with BBs and exercise restriction, less so than LQT1, new data suggest role for ranolazine, mexiletine
• Diagnostic testing with suspected ECG and genetic testing
• ICD indicated for all patients with LQT3