LONG QT SYNDROME

✓ Medically ReviewedDISEASEID: MDBT0172🚨 TRIAGE: EMERGENCYICD-10: I45.8

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Definition

CLINICAL DEFINITION

Long QT Syndrome (LQTS) is a primary electrical disorder of the heart characterised by delayed ventricular repolarisation, manifesting as a prolonged QT interval on the electrocardiogram (ECG). It is associated with a high risk of syncope, seizures, and sudden cardiac death due to polymorphic ventricular tachycardia, specifically Torsades de Pointes.

IN PLAIN ENGLISH

Long QT Syndrome is a condition where the heart muscle takes longer than normal to recharge between beats. This delay can cause dangerous, fast, and irregular heart rhythms that may lead to fainting or sudden cardiac arrest.

COMMON MISCONCEPTION / WHAT IT DOES NOT MEAN

Long QT Syndrome is NOT simply a prolonged QT interval caused by medications, electrolyte imbalances, or structural heart disease, which are classified as acquired QT prolongation rather than the inherited syndrome. It is also NOT a structural heart defect like hypertrophic cardiomyopathy.

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Word Breakdown

=The QT interval on an electrocardiogram representing ventricular depolarisation and repolarisation

syndrome

=A group of signs and symptoms occurring together (from Greek 'syndrome', the concurrence of symptoms)

Literal Meaning: A syndrome of a prolonged QT interval

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Abbreviations

LQTS=Long QT Syndrome — the standard abbreviation for the condition

QTc=Corrected QT interval — the primary electrocardiographic measurement used for diagnosis

TdP=Torsades de Pointes — the characteristic polymorphic ventricular tachycardia associated with LQTS

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Synonyms & Variants

Romano-Ward syndrome›Jervell and Lange-Nielsen syndrome›

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Category-Specific Context

As a Disease, LQTS represents a spectrum of inherited or acquired channelopathies affecting cardiac ion channels. It is classified by genetic subtype (LQT1 to LQT17), with LQT1, LQT2, and LQT3 accounting for the vast majority of cases, each having distinct triggers for arrhythmic events.

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Clinical Context & Usage

CLINICAL SETTINGS

Cardiology ClinicEmergency DepartmentGenetics Counselling ServicePaediatric Cardiology UnitIntensive Care Unit

USAGE & DOCUMENTATION NOTES

Clinicians document the corrected QT interval (QTc) in milliseconds (ms) and note the specific genetic subtype if known (e.g., LQT1). Risk stratification often involves noting the Schwartz score. Documentation frequently includes triggers for previous syncopal episodes, such as exercise or auditory stimuli, and a list of avoided medications.

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Primary Causes & Pathophysiology

PATHOPHYSIOLOGY

LQTS is caused by loss-of-function mutations in potassium channel genes (e.g., KCNQ1, KCNH2) or gain-of-function mutations in sodium channel genes (e.g., SCN5A), which delay the repolarisation phase of the cardiac action potential. This prolongs the QT interval on the surface ECG and increases the transmural dispersion of repolarisation. The prolonged repolarisation creates a vulnerable window where early afterdepolarisations (EADs) can trigger re-entrant circuits, initiating Torsades de Pointes, a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and cause sudden cardiac death.

PRIMARY CAUSES

Loss-of-function mutations in KCNQ1 (LQT1)

Reduces the slow delayed rectifier potassium current (IKs), delaying repolarisation especially during sympathetic stimulation like exercise.

Loss-of-function mutations in KCNH2 (LQT2)

Reduces the rapid delayed rectifier potassium current (IKr), increasing susceptibility to arrhythmias triggered by sudden auditory stimuli or emotional stress.

Gain-of-function mutations in SCN5A (LQT3)

Increases the late inward sodium current (INa), prolonging the action potential plateau phase and causing arrhythmias predominantly during sleep or rest.

Autosomal recessive inheritance with deafness (Jervell and Lange-Nielsen syndrome)

Biallelic mutations in KCNQ1 or KCNE1 profoundly impair potassium channels in both the heart and the stria vascularis of the inner ear.

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Drug-Induced Causes

💊 Class III antiarrhythmics (e.g., sotalol, amiodarone, dofetilide) ↗

Mechanism: Block the rapid delayed rectifier potassium current (IKr), directly prolonging the action potential duration.

→ Discontinue the offending agent immediately; monitor ECG continuously and correct hypokalaemia or hypomagnesaemia.

💊 Macrolide and fluoroquinolone antibiotics (e.g., erythromycin, moxifloxacin) ↗

Mechanism: Off-target blockade of the hERG potassium channel (IKr), leading to delayed ventricular repolarisation.

→ Stop the antibiotic, switch to a non-QT-prolonging alternative, and monitor for Torsades de Pointes.

💊 Antipsychotics (e.g., haloperidol, ziprasidone, thioridazine) ↗

Mechanism: Blockade of cardiac potassium channels, particularly IKr, increasing the risk of TdP especially with IV administration or electrolyte imbalances.

→ Withdraw the drug, administer intravenous magnesium sulphate if TdP occurs, and consider temporary overdrive pacing.

💊 Tricyclic antidepressants (e.g., amitriptyline, imipramine) ↗

Mechanism: Inhibit multiple ion channels including potassium channels, prolonging the QT interval and widening the QRS complex.

→ Discontinue medication, support airway and breathing, and treat arrhythmias with magnesium and sodium bicarbonate if QRS is widened.

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Epidemiology

Prevalence:Congenital LQTS has an estimated prevalence of approximately 1 in 2,000 to 1 in 2,500 individuals in the general population. Acquired QT prolongation is significantly more common, affecting up to 1–2% of hospitalised patients depending on medication exposure and comorbidities.

Age Group:Congenital forms often present in childhood, adolescence, or young adulthood, though they can remain asymptomatic until later in life. Jervell and Lange-Nielsen syndrome presents in infancy or early childhood with profound sensorineural deafness and high-risk cardiac events.

Sex Predilection:Female

Geographic Distribution:Globally distributed across all ethnic groups. Certain founder mutations exist in specific populations, such as the KCNQ1 mutation in certain isolated communities, but no broad geographic restriction applies to the syndrome as a whole.

Red Flags & Triage ★

TRIAGE LEVEL

🚨 EMERGENCY

DO NOT MISS — LIFE-THREATENING PRESENTATIONS

Unexplained syncope or seizure in a young patient with a family history of sudden cardiac death — raises high suspicion for an inherited channelopathy like LQTS and requires a screening ECG and cardiology referral.
Torsades de Pointes in a patient with acquired QT prolongation — requires immediate intravenous magnesium sulphate and withdrawal of the offending agent; do not use amiodarone or other QT-prolonging antiarrhythmics for chemical cardioversion.

URGENT EVALUATION TRIGGERS

QTc interval > 500 ms on a screening ECG, requiring immediate cardiology evaluation for risk stratification.
Any episode of syncope, especially during exercise, swimming, or in response to a sudden loud noise.
Palpitations associated with presyncope or a documented run of non-sustained ventricular tachycardia.

Contraindications & Precautions

CONTRAINDICATIONS

QT-prolonging medications — strictly contraindicated
including specific antiarrhythmics
antibiotics
antipsychotics
and antiemetics (refer to CredibleMeds lists).
Competitive sports and intense isometric exercise — particularly contraindicated in LQT1 due to the high risk of catecholamine-triggered arrhythmias.
Hypokalaemia and hypomagnesaemia — must be avoided as low serum potassium and magnesium exacerbate repolarisation delay and trigger Torsades de Pointes.

SPECIAL PRECAUTIONS

Avoid sudden loud noises (e.g.
alarm clocks
loud telephones) especially in LQT2
as auditory stimuli can trigger arrhythmias.
Ensure all healthcare providers
including dentists and anaesthetists
are aware of the diagnosis to avoid inadvertent administration of QT-prolonging anaesthetic or antiemetic agents.
Maintain strict electrolyte balance during intercurrent illnesses
particularly gastroenteritis with vomiting or diarrhoea
to prevent secondary QT prolongation.

Complications

DOWNSTREAM CLINICAL COMPLICATIONS

Torsades de Pointes — a polymorphic ventricular tachycardia that can cause syncope or degenerate into ventricular fibrillation.
Ventricular fibrillation — a chaotic
life-threatening rhythm leading to sudden cardiac arrest if not immediately defibrillated.
Sudden cardiac death — particularly in young
otherwise healthy individuals
often occurring during exercise
emotional stress
or sleep depending on the genetic subtype.
Misdiagnosis as a seizure disorder — anoxic seizures caused by transient cerebral hypoperfusion during arrhythmias are frequently mistaken for primary epilepsy.

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Reference Ranges

NORMAL RANGEThe normal corrected QT interval (QTc) is typically < 440 ms in adult males and < 460 ms in adult females. In children aged 1–15 years, a QTc < 440 ms is generally considered normal.

CRITICAL (PANIC) VALUEA QTc > 500 ms is associated with a markedly increased risk of Torsades de Pointes and sudden cardiac death, requiring immediate risk stratification, medication review, and optimisation of beta-blocker therapy or consideration of an implantable cardioverter-defibrillator (ICD).

UNIT OF MEASUREMENTMilliseconds (ms) for the QT and QTc intervals.

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Confused With (LASA & DDx) ★

LEXICAL (LASA) — SIMILAR NAMES

Short QT Syndrome

Opposite electrophysiological phenotype characterised by an abnormally short QT interval (< 340 ms) and increased risk of atrial and ventricular fibrillation.

Brugada Syndrome

Another inherited primary arrhythmia syndrome causing sudden cardiac death, but characterised by ST-segment elevation in right precordial leads rather than QT prolongation.

Long QT interval (acquired)

Often confused with the syndrome; acquired prolongation is secondary to drugs or electrolytes and lacks the primary genetic basis of Long QT Syndrome.

CLINICAL DIFFERENTIAL DIAGNOSES (DDx)

Vasovagal syncope

Key Distinguishing Feature: Typically preceded by a prodrome (nausea, diaphoresis) and associated with hypotension and bradycardia, with a normal baseline QTc interval.

Epilepsy

Key Distinguishing Feature: Seizures in LQTS are actually anoxic seizures secondary to cerebral hypoperfusion during TdP; true epilepsy has abnormal EEG findings and normal cardiac evaluation.

Hypertrophic cardiomyopathy

Key Distinguishing Feature: Causes sudden cardiac death and syncope but is characterised by left ventricular hypertrophy on echocardiography and different ECG findings, not isolated QT prolongation.

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Clinical Pearls

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Always calculate the corrected QT interval (QTc) using Bazett's formula (QTc = QT / √RR) or Fridericia's formula, as the raw QT interval varies with heart rate. A QTc > 480 ms in the presence of unexplained syncope is highly suggestive of LQTS.

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Beta-blockers are the cornerstone of therapy for LQT1 and LQT2, significantly reducing the risk of cardiac events. Nadolol and propranolol are preferred over metoprolol or atenolol due to their longer half-lives and more consistent protection.

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In LQT3, where events often occur during sleep or rest, sodium channel blockers like mexiletine may be used in addition to beta-blockers to shorten the QT interval. This targeted therapy addresses the specific gain-of-function mutation in the SCN5A gene responsible for the prolonged inward sodium current.

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Misdiagnosis as epilepsy is a common and dangerous pitfall; anoxic seizures caused by transient cerebral hypoperfusion during Torsades de Pointes can look identical to primary generalised tonic-clonic seizures on initial presentation. An ECG is mandatory for any young patient presenting with a first-time seizure.

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Acquired QT prolongation is a medical emergency if Torsades de Pointes develops. Intravenous magnesium sulphate is the first-line treatment even if serum magnesium levels are normal, as it stabilises the cardiac membrane and suppresses early afterdepolarisations.

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Example Usage & SOAP

CLINICAL SENTENCE

"The patient, a 16-year-old female with a history of exercise-induced syncope, was found to have a QTc of 520 ms on her resting ECG, prompting urgent referral to the inherited arrhythmia clinic for genetic testing and initiation of nadolol."

IN A SOAP NOTE

S: 14-year-old male presents with a syncopal episode while swimming, which resolved spontaneously after 30 seconds. No preceding prodrome. O: BP 110/70, HR 68 regular. ECG shows sinus rhythm with a QT interval of 480 ms and QTc of 510 ms. T-wave morphology is broad-based. A: Suspected Long QT Syndrome type 1 (LQT1) given the exercise trigger and ECG findings. P: Admit for continuous telemetry monitoring. Start oral nadolol. Order comprehensive LQTS genetic panel. Strict avoidance of competitive sports and QT-prolonging medications. Consult paediatric cardiology for consideration of ICD.

DIFFERENTIAL DIAGNOSIS CONTEXT

Differential for prolonged QTc and syncope: (1) Congenital Long QT Syndrome — supported by family history, specific triggers (exercise, auditory), and genetic mutations; (2) Acquired QT prolongation — review medication list (macrolides, antipsychotics) and check electrolytes (K+, Mg2+, Ca2+); (3) Vasovagal syncope — typically has a prodrome and normal QTc; (4) Structural heart disease (e.g., HCM, ARVC) — ruled out via echocardiography and cardiac MRI; (5) Seizure disorder — normal EEG and post-ictal state without cardiac trigger.

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Classifications & Scoring

SCORING TOOL

Schwartz Score

Evaluates the clinical probability of congenital LQTS by assigning points for QTc duration, Torsades de Pointes, T-wave alternans, notched T-waves, low heart rate for age, syncope, and family history.

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Prognosis

SHORT-TERM OUTCOME

With appropriate beta-blocker therapy and avoidance of triggers, the short-term risk of cardiac events is significantly reduced. Untreated or non-compliant patients face a high risk of recurrent syncope and sudden cardiac arrest.

LONG-TERM PROGNOSIS

The long-term prognosis for treated patients with congenital LQTS is generally excellent, with life expectancy approaching that of the general population. Untreated patients, especially those with Jervell and Lange-Nielsen syndrome or a history of cardiac arrest, have a significantly higher long-term mortality rate.

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References & Coding

ICD-10 DIAGNOSTIC CODE

I45.8

LITERATURE CITATIONS & GUIDELINES

[1]Priori SG et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm. 2013;10(12):1932-1963.

[2]Wilde AAM et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases. Heart Rhythm. 2022;19(11):e169-e220.

[3]Schwartz PJ et al. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993;88(1):368-374.

MEDICAL DISCLAIMER — This content is intended for educational purposes and qualified healthcare professionals only. Always refer to current clinical diagnostic criteria, institutional protocols, and official guidelines. Medobo is not responsible for clinical decisions made based on this content.