What is the diagnostic approach for long QT syndrome?

Diagnosis of Long QT Syndrome

Long QT syndrome is diagnosed when a confirmed pathogenic LQTS mutation is identified regardless of QT duration, or clinically when QTc ≥460 ms is found on repeated ECGs in patients with unexplained syncope (after excluding secondary causes of QT prolongation). 1

Electrocardiographic Criteria

Definitive ECG Diagnosis

• QTc ≥480 ms on repeated 12-lead ECGs in the absence of secondary causes establishes the diagnosis clinically 1
• A QTc ≥500 ms is considered unequivocal LQTS regardless of family history or symptoms 1
• QTc ≥460 ms with unexplained syncope is sufficient for diagnosis 1

Borderline Cases (QTc 440-480 ms)

• Require detailed assessment including family history, personal history of syncope, and additional testing 1
• Serial ECG measurements are essential, as QTc can vary over time 1
• T-wave morphology abnormalities (notched T waves in precordial leads) support the diagnosis 1

Important Caveat

• A small percentage of LQTS patients have QTc <440 ms, so normal QT does not absolutely exclude the diagnosis 1

Genetic Testing

In patients with clinically diagnosed LQTS, genetic counseling and genetic testing are recommended (Class I recommendation) 1

• Identifies disease-causing mutations in approximately 75% of cases 1
• Three main genes (KCNQ1, KCNH2, SCN5A) account for 90% of genetically positive cases 1
• For first-degree relatives of patients with a causative LQTS mutation, genetic counseling and mutation-specific testing are recommended 1

Comprehensive Diagnostic Workup

Essential Initial Steps

1. Obtain detailed family history specifically asking about:

   • Early sudden death in family members 1
   • Fainting spells or syncope 1
   • Seizures or misdiagnosed epilepsy 1
   • Congenital deafness (suggests Jervell and Lange-Nielsen syndrome) 1

2. Exclude secondary causes of QT prolongation:

   • QT-prolonging medications 1
   • Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) 1
   • Structural heart disease via echocardiography 1
   • Maternal autoimmune antibodies (anti-Ro/SSA, anti-La) in neonates 1

Additional Diagnostic Testing

Ambulatory ECG monitoring, positional ECG recording (lying and immediately standing), and exercise treadmill testing can be useful for establishing diagnosis and monitoring therapy response (Class IIa recommendation) 1

• 24-hour Holter monitoring identifies:

  • T-wave alternans 1
  • Complex ventricular arrhythmias 1
  • Marked QTc prolongation during daily activities 1

• Exercise testing enhances diagnostic accuracy:

  • Inadequate QT shortening during exercise suggests LQTS 1
  • QTc typically prolongs in LQT1, remains unchanged in LQT2, and shortens excessively in LQT3 1

Family Screening

• ECGs should be obtained from parents and siblings when LQTS is suspected 1
• Cascade screening of family members is essential given autosomal dominant inheritance (50% risk for offspring) 1

Risk Stratification Features

Highest Risk Indicators

• QTc approaching 600 ms 1
• T-wave alternans 1
• 2:1 AV block secondary to QT prolongation 1
• Hearing loss (Jervell and Lange-Nielsen syndrome) 1
• History of cardiac arrest or syncope 1

Genotype-Specific Risk

• LQT2 and LQT3 genotypes carry higher risk 1
• Females with LQT2 genotype are particularly high-risk 1
• Symptom onset before age 10 years indicates elevated risk 1

Neonatal-Specific Approach

For neonates with QTc >440 ms:

• Repeat ECG after a few days to confirm the finding 1
• If second ECG shows QTc ≥500 ms, the infant is very likely affected and should be treated 1
• For QTc 470-500 ms, perform all diagnostic procedures and plan third ECG within one month 1
• Note that even infants with very prolonged QTc may normalize over time, requiring ongoing surveillance 1