Approach
Given the increasing prevalence of LQTS and the associated risk of sudden cardiac death, primary care providers are likely to find themselves encountering challenging management decisions.
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.
Acquired LQTS
In acquired LQTS, management involves thorough assessment in order to identify and remove or treat the causative factor.
Drug history should be taken to identify and remove drugs known to prolong the QT interval or cause depletion of potassium and/or magnesium, including quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, tricyclic antidepressants, and methadone.[21][22] Credible Meds (Arizona CERT): drugs that prolong the QT interval Opens in new window
Serum electrolytes should be measured and corrected, in cases of hypokalaemia, hypomagnesaemia, and hypocalcaemia; the goals of therapy include achieving a 'high normal' potassium (of at least 4.0 to 4.5 mEq).
Follow-up serial, periodic ECG monitoring is recommended until the QT interval has normalised.
Any sudden bradycardia or atrioventricular (AV) nodal block may result in QT prolongation or pause-dependent QT prolongation. If an identifiable cause is not present, treatment involves implantation of a pacemaker (temporarily if the bradycardia or AV block improves, permanently if symptomatic bradycardia or AV block persists).
Beta-blocker therapy, and lifestyle modification with avoidance of any further QT-prolonging drugs and monitoring, are indicated if removal of the causative drug is not possible due to medical necessity.
Prophylactic treatment with beta-blockers and lifestyle modification are not indicated in these patients if the QT-prolonging agent is identified and removed.
Cardiac events may include syncope, ventricular tachyarrhythmias, torsades de pointes, or cardiac arrest. For details of management, see Sustained ventricular tachycardias and Cardiac arrest.
Some patients with acquired LQTS may ultimately be diagnosed with congenital LQTS, and they should be managed as other patients with congenital LQTS (e.g., with beta-blockers, lifestyle modifications, and consideration of ICD).
Congenital LQTS without previous cardiac event
Treatment of congenital LQTS in patients without a previous cardiac event (e.g., syncope, ventricular tachyarrhythmias, torsades de pointes, or cardiac arrest) is dependent on whether the patient is at low- or high-risk of events.
Low risk (probability of first cardiac event before age 40 of <49%) is defined as: men or women with LQT1 or LQT2 and QTc <500 ms; men with LQT3 and QTc <500 ms; women with LQT3 (irrespective of level of QTc prolongation).
High risk (probability of first cardiac event 50% or higher) is defined as: men or women with LQT1 or LQT2 and QTc ≥500 ms; men with LQT3 and QTc ≥500 ms.[29]
The 1-2-3 LQTS risk calculator is an alternative risk stratification tool that estimates the 5-year risk of life-threatening arrhythmias for patients with LQTS based on QT interval and genotype; it may assist in the identification of patients who would benefit from ICD placement.[2][48]
Low risk:
Lifestyle modification and monitoring
Patients with LQT1 are at increased risk with activities that increase sympathetic activation, such as swimming, emotional stress, and exercise; they should avoid swimming unless cleared by LQTS experts, and should avoid extreme exertion until under optimal therapy and fully counselled.[5]
Patients with LQT2 are at high risk if woken from sleep or disturbed by a sudden noise.[5] Removal of alarm clocks and telephones from bedrooms is recommended.[5]
In general, competitive sports or similar extreme exertion should be avoided by patients with LQTS. However, patients who wish to engage in competitive sports should be referred for expert evaluation for risk stratification.[3] In one retrospective analysis of a cohort of patients with genotype-positive LQTS who were treatment-adherent, their participation in competitive or recreational sports was not associated with cardiac events or death.[49] Activities that are of low risk include golf, curling, cricket, billiards, or bowling.[50] Non-competitive swimming, especially for LQT1 patients, must be limited and, if performed, should be done under close supervision. Selected low-risk patients without a history of exercise-induced symptoms may be considered for sports participation in consultation with an expert in LQTS and with careful education and consideration of options.[51]
All patients must avoid other sympathomimetics and factors that may prolong the QT interval, such as drugs including quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, tricyclic antidepressants, and methadone.[21][22] Credible Meds (Arizona CERT): drugs that prolong the QT interval Opens in new window Consult a drug formulary for a full list of drugs that prolong the QT interval.
Electrolyte loss due to vomiting, diarrhoea, or excessive sweating should be replaced with electrolyte solutions in order to avoid hypokalaemia and hypomagnesaemia. Patients with LQT2 particularly require adequate potassium levels, and oral supplementation may be beneficial.[5]
Beta-blockers
The mainstay of medical treatment for patients with congenital LQTS is beta-blocker therapy, ideally non-selective beta-blockers (e.g., nadolol, propranolol).[2] As ventricular arrhythmias may arise during a state of high adrenergic tone, particularly increasing the occurrence of afterdepolarizations, 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, although they may provide less protection to patients with LQT3. Data from one study show that beta-blocker therapy reduces the risk of life-threatening cardiac events in females with LQT3; however, efficacy in males could not be determined conclusively because of the low number of events.[52]
The efficacy of beta-blocker therapy may be assessed with exercise tolerance testing to ensure the heart rate response is blunted.
Although no randomized controlled trials exist, observational data suggest a strong mortality benefit with beta-blocker therapy.[28][53]
Beta-blocker therapy should also be considered in patients with a normal QTc interval in the presence of a pathogenic mutation.[2]
High risk:
Lifestyle modification and monitoring: the recommendations are the same as for low-risk patients.
Beta-blockers: the recommendations are the same as for low-risk patients.
Implantable cardioverter-defibrillator (ICD): in Jervell and Lange-Nielsen syndrome and in certain very high-risk patients with LQT1, LQT2, or LQT3, ICD can be considered but expert consultation should be sought first.[2] This should include a discussion regarding the risks of not having an ICD and the advantages/disadvantages of an ICD, single- or dual-chamber depending on the individual patient and following specialist cardiologist or electrophysiologist advice.
Mexiletine: should be considered in patients with confirmed LQT3, especially those with syncope or ICD shocks despite beta-blocker therapy; use in other genotypes is being investigated.[5][54][55] Oral testing should be carried out to ensure that the QTc is shortened by at least 40ms before prescribing mexiletine long term.[2] There is currently no evidence on whether mexiletine should be given alone or in combination with beta-blocker therapy for patients with LQT3.[2]
Left cardiac sympathetic denervation: may be considered in patients with recurrent syncope despite treatment with beta-blockers or in those requiring multiple appropriate ICD shocks.[2] It may also be an option in patients who are deemed not to be ideal candidates for an ICD, such as children, due to the physical limitations of age and height and the psychological distress of ICD shocks.
Congenital LQTS with previous cardiac event
Cardiac events may include syncope, ventricular tachyarrhythmias, torsades de pointes, or cardiac arrest. For details of management, see Sustained ventricular tachycardias and Cardiac arrest.
Lifestyle modification
Required in all patients with congenital LQTS; the recommendations are the same as for patients without a previous cardiac event.
Beta-blocker therapy
Required in all patients with congenital LQTS; the recommendations are the same as for patients without a previous cardiac event.
Implantable cardioverter-defibrillator (ICD)
Use of an ICD, in conjunction with beta-blockers, has proven invaluable in the treatment of patients with LQTS who have recurrent arrhythmic syncope or documented torsades de pointes despite optimally dosed beta-blocker therapy.[2][56][57]
ICDs are now considered appropriate therapy for:
Patients who have had a previous cardiac arrest[2]
Those with recurrent arrhythmic syncope despite beta-blocker therapy, or in those whom beta-blocker therapy is contraindicated or not tolerated[2]
Some patients with high-risk LQTS, especially patients with LQT2 or those with multiple mutations[58]
Jervell and Lange-Nielsen syndrome.
Mexiletine
Should be considered in patients with confirmed LQT3, especially those with syncope or ICD shocks despite beta-blocker therapy; use in other genotypes is being investigated.[2][5][54][55]
Left cardiac sympathetic denervation
Sometimes called stellate ganglionectomy, this procedure involves surgical resection of the lower half of the left stellate ganglion along with several other thoracic ganglia (T2 to T4) in an attempt to partially denervate the heart.[59]
This procedure is available at specialised medical centres and referral should be considered for:
Patients who cannot tolerate beta-blockers or in whom beta-blockers are contra-indicated[2]
Those with recurrent arrhythmic syncope despite beta-blocker therapy[2]
Patients receiving multiple ICD shocks[2]
Patients in whom ICD implantation is contraindicated or declined[2]
Children in whom an ICD, due to the physical limitations of age and height and the psychological distress of ICD shocks, is not appropriate
Jervell and Lange-Nielsen syndrome.
Development of a minimally invasive thoracoscopic approach makes left cardiac sympathetic denervation a more attractive option for these patients. Left cardiac sympathetic denervation is well tolerated and does not negatively affect cardiovascular performance.[2] Side effects may occur with this treatment though, and breakthrough events occur in half of the patients after the procedure.[2][60]
Permanent pacemaker
When combined with beta-blockers, atrial (or, less optimally, ventricular) pacing, which prevents bradycardia, may facilitate the up-titration of beta-blockers to more effective antiarrhythmic doses and can also serve to prevent pause-dependent torsades de pointes.[61]
A permanent pacemaker in conjunction with beta-blocker therapy should be considered if:
The patient continues to have symptoms despite a left cardiac sympathetic denervation
There is a lack of surgical experience in thoracoscopic left cardiac sympathetic denervation (and the patient declines referral to a specialised centre).
However, no randomised study exists comparing the efficacy of pacemakers combined with beta-blockers versus ICDs in preventing symptoms in patients with LQTS. Pacemakers are infrequently used in LQTS given the similar risks of indwelling leads that an ICD system has and lack of back-up defibrillation.
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