Key Facts

Long QT syndrome (LQTS) is a disorder of myocardial repolarisation characterised by a prolonged QT interval on the ECG, predisposing to polymorphic VT (Torsades de Pointes), syncope, and sudden cardiac death. It may be congenital (inherited channelopathy) or acquired (drugs, electrolytes).

Epidemiology

• Congenital LQTS: estimated prevalence 1 in 2,000
• Acquired LQTS: far more common, primarily drug-induced
• Women have a longer baseline QTc and are at higher risk of drug-induced TdP
• Leading cause of sudden cardiac death in young people with structurally normal hearts

Aetiology

Congenital:

• LQT1 (KCNQ1 - IKs channel): ~40% of cases; triggered by exercise/swimming
• LQT2 (KCNH2/HERG - IKr channel): ~30% of cases; triggered by sudden auditory stimuli
• LQT3 (SCN5A - sodium channel gain-of-function): ~10%; events at rest/sleep

• 15 genes identified; some rare subtypes

Acquired:

• Drugs: antiarrhythmics (sotalol, amiodarone), antibiotics (macrolides, fluoroquinolones), antipsychotics, antiemetics (domperidone, ondansetron), methadone
• Electrolytes: hypokalaemia, hypomagnesaemia, hypocalcaemia
• Metabolic: hypothyroidism, anorexia nervosa, starvation
• Bradycardia, hypothermia

Pathophysiology

• Prolonged repolarisation increases the vulnerable period for early afterdepolarisations (EADs)
• EADs can trigger Torsades de Pointes (polymorphic VT in the context of long QT)
• Transmural dispersion of repolarisation creates substrate for re-entry
• LQT1/LQT2: potassium channel dysfunction (reduced repolarising current)
• LQT3: sodium channel gain-of-function (persistent depolarising current)

Typical Presentation

• Syncope: sudden, often without warning; may be triggered by exercise (LQT1), emotion/startle (LQT2), or occur during sleep/rest (LQT3)
• Seizures (may be misdiagnosed as epilepsy)
• Cardiac arrest/sudden death (may be first presentation)
• Family history of sudden death, 'drowning', or 'epilepsy'

Genotype-Phenotype Correlations

• LQT1: swimming, exertion triggers; broad-based T waves on ECG
• LQT2: sudden auditory stimuli (alarm clocks, phones); low-amplitude notched T waves
• LQT3: rest/sleep events; late-onset peaked T waves with long ST segment

Red Flags

• QTc >500 ms on resting ECG
• Syncope during exercise, emotional stress, or sleep
• Family history of unexplained sudden death <40 years
• Prior episode of Torsades de Pointes or VF
• Jervell-Lange-Nielsen: sensorineural deafness + long QT (severe phenotype, high risk)

Bedside

• 12-lead ECG: measure QTc (Bazett formula); T-wave morphology analysis
• Serial ECGs: QTc may vary; prolongation may be intermittent

Bloods

• U&Es: potassium, magnesium, calcium
• TFTs: hypothyroidism
• Drug screen: if acquired cause suspected

Imaging

• Echocardiography: exclude structural heart disease

Special Tests

• Exercise testing: QTc fails to shorten or paradoxically prolongs with exercise in LQTS (especially LQT1)
• Holter monitor: capture QTc variability, T-wave alternans
• Genetic testing: LQT1-3 genes (KCNQ1, KCNH2, SCN5A); guides therapy and family screening
• Schwartz diagnostic score: clinical criteria combining ECG, symptoms, and family history
• Epinephrine QT stress test: can unmask borderline LQTS

Non-pharmacological

• Avoid QT-prolonging drugs (www.crediblemeds.org)
• Correct electrolytes: maintain K⁺ >4.0 mmol/L, Mg²⁺ >0.8 mmol/L
• Genotype-specific lifestyle advice:
  • LQT1: avoid competitive swimming and strenuous exercise
  • LQT2: avoid sudden auditory stimuli (e.g., alarm clocks by the bed)
  • LQT3: may benefit from higher heart rates (exercise may be protective)

Pharmacological

• Beta-blockers (first-line for all congenital LQTS):
  • Nadolol 1-2.5 mg/kg/day (preferred - once daily, non-selective)
  • Propranolol 2-4 mg/kg/day (alternative)
  • Reduces cardiac events by ~60-70%
  • Most effective in LQT1, less effective in LQT3
• Mexiletine (sodium channel blocker): useful in LQT3 (shortens QT by reducing late INa)
• Magnesium sulphate IV 2g: acute treatment for TdP

Surgical/Interventional

• ICD: indicated for:
  • Cardiac arrest survivors (secondary prevention)
  • Recurrent syncope despite beta-blockers
  • High-risk features (QTc >500 ms, LQT3, Jervell-Lange-Nielsen)
• Left cardiac sympathetic denervation (LCSD): reduces events by ~50%; considered when beta-blockers fail or ICD not feasible

Referral Criteria

• All suspected LQTS: referral to inherited cardiac conditions clinic
• Genetic testing and counselling for patient and family
• First-degree relative screening: ECG + genetic testing if mutation identified
• Sudden death in a young family member: referral for cardiac screening of relatives

• Untreated symptomatic LQTS: ~5% annual risk of sudden death
• Beta-blocker therapy reduces events by 60-70%; mortality reduced to <1% per year
• ICD nearly eliminates SCD risk (inappropriate shocks are a significant morbidity)
• LQT1 with beta-blockers: lowest event rate (~1% per year)
• LQT3: highest per-event lethality, less responsive to beta-blockers
• Jervell-Lange-Nielsen: most severe phenotype, higher mortality despite treatment
• Gene-negative LQTS (clinical diagnosis): generally better prognosis

Schwartz Diagnostic Score for LQTS

Genotype-Specific Triggers