13th March 2024

Long QT syndrome

Pathophysiology

Long QT syndrome (LQTS) can be congenital or acquired and is characterised by a prolonged QT interval on electrocardiogram (ECG) as a result of prolonged ventricular repolarisation. 

The QT interval on an ECG can be adjusted to estimate the QT interval at a heart rate of 60 beats per minute; this is known as the corrected QT (QTc) and is used to measure QT length. QTc is prolonged if > 440 ms in men or > 460ms in women.

Acquired LQTS can be due to medications or electrolyte abnormalities as well as due to forms of bradyarrhythmia. However, the focus of this section is on congenital LQTS.

Congenital LQTS occurs in around 1 in 2000 people worldwide and results from genetic mutations coding for ion channels responsible for prolonging myocardial repolarisation, which in turn prolongs QT interval. A prolonged QT interval or corrected QT (QTc) can result in arrhythmias, most commonly a form of polymorphic ventricular tachycardia called torsades de pointes. Although multiple genes have been identified in congenital LQTS, three genes account for as many as 80-95% of cases, which are shown below.

Clinical features

Congenital LQTS can be split syndromes based on the phenotype:

Typically, LQTS presents by the time someone is 30 years old. Presentation may be with syncope or syncope followed by seizures. Symptoms, including chest pain, breathlessness or palpitations, will usually precede syncopal episodes. There may be distinct triggers (see above), such as swimming or being startled. Sudden cardiac arrest is an uncommon but possible presentation of LQTS. All of these cardiac events are the result of arrhythmias caused by a prolonged QT interval.

Some people with congenital LQTS are asymptomatic and remain so throughout their lives. Diagnosis may occur through screening of an affected family member.

Diagnostics

Diagnosis of congenital LQTS involves the following:

• ECG to look at the corrected QT (QTc) and T wave morphology
• Ruling out secondary causes of QT prolongation
• 24 ambulatory ECG monitoring
• Exercise stress test for exercise-associated arrhythmias

If congenital LQTS is suspected, then the Schwartz score is calculated to look at the likelihood of a congenital LQTS diagnosis. This looks at ECG findings and factors, including the patient’s clinical history and family history. A score of 3.5 points and above is classed as high risk, and the likelihood of the patient having congenital LQTS is 80%. Intermediate risk is classed as 1.5 to 3 points, and these individuals require genetic testing to evaluate if this is congenital. If the patient scores 0-1 points, then they are classed as low risk, and genetic testing should not be performed.

Management

All patients should be advised on avoiding medications that may prolong the QT interval, such as tricyclic antidepressants. Patients should replace electrolytes if experiencing vomiting or diarrhoea, as hypokalaemia and hypomagnesemia can increase the risk of a prolonged QT interval. Patients should also avoid competitive sports.

Regardless of whether patients are symptomatic or not, a beta blocker, usually propranolol or nadolol, should be started to prevent ventricular tachyarrhythmias. 

In addition, those with congenital LQTS who have not had a cardiac event but are at high risk (QTc >500ms in those with LQT1 or 2, or men with LQT3 with a QTc >550 ms) or in any patient with congenital LQTS who has experienced a previous cardiac event, should be considered for the following treatments:

1st line treatments in conjunction with beta-blockers:

• Implantable cardioverter-defibrillator (ICD) if they have had a previous cardiac event, recurrent syncope on beta blockers or Jervell and Lange-Nielsen syndrome
• Mexiletine can be considered in individuals with LQT3

2nd line treatment in conjunction with beta-blockers:

• Left cervicothoracic sympathectomy (resection of lower half of left stellate ganglion as well as other thoracic ganglia to partially denervate the heart) can be considered in those unable to tolerate beta blockers; those receiving multiple ICD shocks, recurrent syncope despite beta blockers or Jervell and Lange-Nielsen syndrome.

3rd line treatment in conjunction with beta-blockers:

• Permanent pacemaker can be considered alongside beta blockers if a patient has ongoing symptoms despite cervicothoracic sympathectomy.

Patients should have minimum annual ECG monitoring as well as an ECG check after starting or dose adjustment of beta blockers. Exercise testing or Holter monitoring can be used to assess adequate beta-blockade after starting beta blockers.

References

• UpToDate – Congenital long QT syndrome 
• BMJ Best Practice – Long QT syndrome
• Life in the Fastlane – https://litfl.com/qt-interval-ecg-library/