Long QT Syndrome

Last Updated on by frcemuser

Long QT syndrome (LQTS) is a genetic or acquired condition characterised by a prolonged QT interval on the surface ECG and is associated with a high risk of sudden cardiac death due to ventricular tachyarrhythmias or torsades de pointes.

Causes

  • Congenital LQTS
    • Mutations within 13 identified genes result in a variety of channelopathies affecting myocardial repolarisation, thus prolonging the QT interval
  • Acquired LQTS
    • Drugs: e.g. quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, tricyclic antidepressants, and methadone
    • Electrolyte imbalances: in particular hypokalaemia, hypomagnesaemia, and hypocalcaemia
    • Bradyarrhythmias: any sudden bradycardia or AV nodal block may result in QT prolongation or pause-dependent QT prolongation
    • CNS lesions: such as intracranial haemorrhage (especially subarachnoid haemorrhage) and ischaemic strokes
    • Malnutrition: liquid protein diet, starvation

Clinical features

  • LQTS commonly presents in young people with cardiac arrest or unexplained syncope and is frequently misdiagnosed as epilepsy. It should therefore be considered in all such presentations and a thorough history, including a review of premonitory symptoms and a corroborative history, is essential as it can help to differentiate between cardiac syncope, epilepsy, and other causes of syncope, some of which may be benign conditions. Cardiac syncope is characterised by premonitory symptoms such as palpitations, chest pain, and dyspnoea. During the syncopal episode, pallor and cyanosis are common features, and the recovery period is brief and characterised by flushing.
  • Both congenital and acquired LQTS may present with palpitations secondary to premature ventricular contractions (PVC) and tachyarrhythmias including torsades de pointes.
  • Acquired LQTS secondary to electrolyte imbalance may present with associated symptoms of hypokalaemia, hypomagnesaemia, and/or hypocalcaemia.
  • Complete AV block may present with palpitations, syncope or presyncope, angina, and symptoms of reduced cardiac output (cold and clammy extremities, fatigue, listlessness, poor effort tolerance, dizziness, confusion, hypotension, oliguria).
  • LQTS may also be discovered as an incidental ECG finding during the routine investigation of an unrelated presenting complaint such as a cardiac murmur.
  • Drugs known to prolong the QT interval or cause depletion of potassium and/or magnesium may precipitate symptoms in patients with congenital LQTS or be the primary cause of acquired LQTS.

Diagnosis

  • The diagnosis of LQTS is not straightforward, as nearly 2.5% of the normal population may have a mildly prolonged QT interval, and nearly 25% of patients genotypically positive for LQTS may have normal-appearing QT intervals.
  • A resting ECG is crucial in the diagnosis of LQTS and should be undertaken in all suspected cases in order to confirm QT interval prolongation, help identify the LQTS subtype, and uncover any causative or contributory reversible factors. In a patient with documented LQTS, it is very important to obtain ECGs from parents, siblings, and especially any family member with presyncope or syncope.
  • The QT interval, measured from the onset of the initial wave of the QRS complex to where the T wave returns to the isoelectric baseline, is the ECG representation of ventricular depolarisation and subsequent repolarisation and may be measured in any lead in which it looks prolonged. The most commonly used formula to calculate the QTc is Bazett’s formula: QT divided by the square root of the RR interval, where all intervals must be in seconds. The RR interval is the interval between each QRS complex, and should ideally be that immediately preceding the QT interval and averaged for 3 to 5 complexes. QTc is prolonged if > 440ms in men or > 460ms in women. QTc > 500 is associated with increased risk of torsades de pointes.
  • Complete AV block, which can result in prolongation of the QT interval, or pause-dependent QT prolongation, resulting in acquired LQTS, shows characteristic ECG changes: sinus rhythm with normal atrial rate (represented by P-wave rate); no relationship between P waves and QRS complexes; widening of the QRS complex and ventricular rate (represented by QRS complex rate) <50 bpm.
  • The Schwartz criteria are diagnostic criteria for LQTS and are distinct from the criteria used to risk-stratify patients with known LQTS. The criteria are based on ECG findings (length of QTc, presence of torsades de pointes, visible T-wave alternans, presence of notched T waves, low heart rate for age in children), clinical history (presence of syncope, congenital deafness), and family history (of LQTS or sudden cardiac death). Patients with 4 or more points have a high probability of having LQTS, those with 2 or 3 points have an intermediate probability, and those with 1 or no points have a low probability of having LQTS.

Further investigations

  • Hypokalaemia, hypomagnesaemia, and hypocalcaemia may precipitate symptoms in patients with unrecognised congenital LQTS or be the primary cause of acquired LQTS. Serum electrolytes should therefore be measured in all patients found to have a prolonged QT interval on ECG.
  • All patients with suspected or confirmed congenital LQTS should undergo Holter monitoring, allowing evaluation of the behavior of the QT interval during bradycardia (at night), tachycardia and sudden pauses.┬áHolter monitoring may allow the clinician to identify non-sustained ventricular arrhythmias in patients with LQTS who are asymptomatic, thereby assisting the decision-making process as to whether medical and/or device therapy should be initiated.
  • All patients with suspected or confirmed congenital LQTS should undergo an exercise tolerance test to identify abnormal QT interval prolongation during exercise and recovery.
  • Echocardiography is helpful to assess for and rule out regional wall motion abnormalities suggestive of myocardial scarring or infarction. It is also helpful in ruling out and characterising valvular stenotic or regurgitant lesions. This investigation should be carried out in patients with suspected structural heart disease as suggested by a history of CAD, MI, or valvular heart disease requiring surgical correction.
  • Determination of the patient’s genotype should be undertaken in patients with suspected congenital LQTS.

Management

  • Patients with LQTS may be risk-stratified for the probability of a future cardiac event (syncope, cardiac arrest, or sudden death) according to genotype, sex, age, and length of the corrected QT interval (QTc). It is also important to take into consideration any history of past symptoms when assessing the patient’s risk of a future cardiac event.
  • The mainstay of treatment for LQTS, unless there is an identifiable reversible cause, is lifestyle modification and beta-blocker therapy with the implantation of a cardioverter-defibrillator (ICD) in patients who have had a previous cardiac arrest and in those continuing to have symptoms despite beta-blockade.
  • Lifestyle modification comprises the following measures:
    • Competitive sports or similar extreme exertion should be avoided.
    • All patients must avoid other sympathomimetics and factors that may prolong the QT interval.
    • Electrolyte losses due to vomiting, diarrhoea, or excessive sweating should be replaced with electrolyte solutions in order to avoid hypokalaemia and hypomagnesaemia.
  • Beta-blocker therapy
    • As ventricular arrhythmias may arise during a state of high adrenergic tone, particularly increasing the occurrence of afterdepolarisations, beta-blockers are used to blunt adrenergic stimulation. Beta-blockers themselves will not shorten the QT interval, but their use is thought to prevent ventricular tachyarrhythmias. The efficacy of beta-blockade may be assessed with exercise tolerance testing to ensure that the heart rate response is blunted.
  • Implantable cardioverter-defibrillator (ICD)
    • ICDs are now considered first-line therapy for:
      • Patients who have had a previous cardiac arrest
      • Those with recurrent arrhythmic syncope despite beta-blocker therapy
      • Patients who cannot tolerate beta-blockers or in whom beta-blockers are contraindicated
      • High-risk patients (QTc >500 ms in men or women with LQT1 and LQT2, and in men with LQT3)
      • Patients with a QTc >550 ms
  • Management of Torsade de Pointes:
    • Stop QT prolonging drugs
    • Correct electrolyte abnormalities
    • Give magnesium sulphate 2 g IV over 10 mins
    • Obtain expert help
    • Arrange immediate synchronised cardioversion if adverse features develop

Other ion channelopathies

  • Brugada syndrome
  • Progressive cardiac conduction defect (PCCD)
  • Catecholaminergic polymorphic ventricular tachycardia (CPVT)
  • Short QT syndrome (SQTS)
  • Idiopathic ventricular fibrillation (without Brugada ECG changes)

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