Genetics and mechanism
Long QT syndrome (LQTS) is a disorder of ventricular repolarization. Loss-of-function in repolarizing potassium currents or gain-of-function in the depolarizing sodium current prolongs the action potential, lengthening the QT and creating the substrate for early afterdepolarizations and torsades de pointes.
The three common genotypes:
- LQT1 — KCNQ1, loss of slow delayed-rectifier K⁺ (IKs). Impaired QT shortening with sympathetic drive → exertional events, classically swimming.
- LQT2 — KCNH2, loss of rapid delayed-rectifier K⁺ (IKr). Events with emotional/auditory startle and postpartum.
- LQT3 — SCN5A, gain-of-function late Na⁺. Events at rest or during sleep.
ECG
- QTc by Bazett: ≥480 ms on repeated ECGs is diagnostic; ≥460 ms with symptoms is supportive. Borderline values need serial tracings and provocation.
- T-wave morphology often hints at genotype (broad in LQT1, notched/low-amplitude in LQT2, late-peaked after a long ST in LQT3).
- Macroscopic T-wave alternans signals electrical instability.
- Capture rhythm during symptoms whenever possible — pause-dependent torsades is the classic mechanism.
Diagnosis
- Repeated 12-leads with careful QT measurement (avoid counting U waves; lead II and V5 are reliable)
- Schwartz score integrates ECG, clinical, and family-history criteria
- Exercise testing — failure of the QT to shorten (or paradoxical prolongation in recovery) supports LQT1/LQT2
- Genetic testing confirms genotype and enables cascade family screening
- Exclude acquired causes first — drugs and electrolytes
Management
- Lifestyle: avoid QT-prolonging drugs (crediblemeds.org), correct/maintain K⁺ and Mg²⁺, treat fevers; genotype-specific advice (LQT1 — caution with competitive swimming/exertion; LQT2 — remove bedroom alarms/phones)
- Beta-blockers: nadolol (preferred) or propranolol — first-line for symptomatic and most asymptomatic patients; most protective in LQT1 and LQT2
- ICD: for aborted cardiac arrest, and for recurrent syncope/VT despite adequate beta-blockade
- Left cardiac sympathetic denervation (LCSD): for breakthrough events or beta-blocker intolerance
- Mexiletine: adjunct that shortens the QT particularly in LQT3
- Family screening: cascade ECG ± genetic testing of first-degree relatives
In the acute setting (torsades)
- IV magnesium first-line, even with normal magnesium
- Correct potassium to high-normal
- Increase heart rate to shorten the QT and abolish pauses — isoproterenol or temporary overdrive pacing (in acquired/pause-dependent torsades)
- Defibrillate sustained/degenerating episodes