Congenital Long QT Syndrome (Long QT Syndrome – LQTS): Updated Overview
Congenital Long QT Syndrome (LQTS) is an inherited channelopathy characterized by prolongation of the QT interval on the ECG and a predisposition to malignant ventricular arrhythmias, particularly torsades de pointes, which may cause syncope, seizures, or sudden cardiac death in individuals with structurally normal hearts.
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1. Pathophysiology
LQTS results from mutations in genes encoding cardiac ion channels, leading to altered ventricular repolarization.
The basic mechanism involves:
- reduction of repolarizing potassium currents, or
- increase in late sodium or calcium currents
This prolongs phase 3 of the ventricular action potential, which appears as QT interval prolongation on the ECG.
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2. Genetics
More than 15 genes have been associated with LQTS, but three subtypes account for approximately 90% of genetically identified cases.
| Subtype | Gene | Channel | Clinical characteristics |
|---|---|---|---|
| LQT1 | KCNQ1 | IKs (K⁺) | Events triggered by exercise, particularly swimming |
| LQT2 | KCNH2 (HERG) | IKr (K⁺) | Arrhythmias triggered by sudden auditory stimuli |
| LQT3 | SCN5A | INa (Na⁺) | Events occurring during rest or sleep |
The most common inheritance pattern is autosomal dominant, known as Romano-Ward syndrome.
A rare form includes:
- Jervell and Lange-Nielsen syndrome, characterized by congenital deafness and autosomal recessive inheritance.
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3. Epidemiology
- Estimated prevalence: approximately 1 in 2000 individuals.
- Many patients remain asymptomatic and are identified only through ECG screening or family evaluation.
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4. Diagnosis
Diagnosis is based on ECG findings, clinical history, and genetic testing.
Main diagnostic criteria
1. Prolonged QTc
- ≥480 ms on repeated ECG recordings
2. Arrhythmic syncope
3. Family history of LQTS or premature sudden death
4. Positive genetic test
A commonly used scoring system is the Schwartz score, which combines:
- QTc duration
- clinical history
- family history.
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5. Clinical manifestations
The most common presentations include:
- syncope triggered by stress, exercise, or emotional stimuli
- unexplained seizures
- sudden cardiac death, particularly in young individuals
The characteristic arrhythmia is:
- torsades de pointes associated with prolonged QT
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6. Treatment
Treatment aims to reduce the risk of fatal ventricular arrhythmias.
1. Beta-blockers (first-line therapy)
Particularly effective in LQT1 and LQT2.
Commonly used agents include:
- nadolol
- propranolol
2. Implantable cardioverter-defibrillator (ICD)
Indicated in:
- survivors of cardiac arrest
- recurrent syncope despite beta-blocker therapy.
3. Left cardiac sympathetic denervation
May be considered in high-risk patients refractory to pharmacological therapy.
4. Genotype-specific therapies
Example:
- mexiletine or ranolazine in LQT3, as they reduce the late sodium current.
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7. Important preventive measures
Patients with LQTS should:
- avoid QT-prolonging medications
- correct hypokalemia and hypomagnesemia
- avoid excessive bradycardia
- consider family genetic screening
Databases such as CredibleMeds are widely used to identify drugs associated with QT prolongation.
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8. Prognosis
With appropriate diagnosis and treatment, the risk of sudden cardiac death is significantly reduced.
Patients treated with beta-blockers and specialized follow-up generally have excellent long-term survival.
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References
1. Schwartz PJ, Crotti L, Insolia R. Long-QT syndrome: from genetics to management. Circulation. 2012.
2. Priori SG et al. ESC Guidelines for the management of ventricular arrhythmias and sudden cardiac death. European Society of Cardiology. 2022.
3. Ackerman MJ et al. HRS/EHRA/APHRS expert consensus statement on inherited arrhythmia syndromes. Heart Rhythm.
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