Long QT Syndrome Treatment & Management

Updated: Nov 30, 2017
  • Author: Ali A Sovari, MD, FACP, FACC; Chief Editor: Mikhael F El-Chami, MD  more...
  • Print
Treatment

Approach Considerations

All patients with long QT syndrome (LQTS) should avoid drugs that prolong the QT interval or that reduce their serum potassium or magnesium levels. In a study of 133,359 electrocardiograms from 40,037 patients, the use of a single QT-prolonging agent increased the corrected QT (QTc) interval by 11.08 ms; when two such drugs were used, there was another 3.04 ms increase in the QTc interval relative to when a single drug was used. [4]

Potassium and magnesium deficiency should be corrected. 

Although psychoactive medications are known to have effects on the cardiovascular system, such as QT prolongation, sometimes their use may be necessary to treat psychiatric conditions. [24] To minimize the cardiovascular effects of these drugs, clinicians should carefully select appropriate patient-related drugs, closely monitor drug-specific cardiac adverse effect risks, and follow up assiduously. This process will help with early detection of adverse reactions and dose adjustments. Initiate therapy with low doses and then carefully titrate and adjust the dosing and/or drug regimen based on the patient's clinical responses. [24]

There may be an LQTS genotype-specific effect of antidepressants on the risk of arrhythmic events. In a study that evaluated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with these agents, investigators noted an increased risk of CAEs associated with antidepressant drug therapy in patients with LQT1, particularly individuals receiving selective serotonin reuptake inhibitors or antidepressants with a known risk of torsade de pointes, [25]  but there was no such associated risk in those with LQT2. Furthermore, antidepressants considered as having a "conditional risk of torsade de pointes" were not linked to a risk of recurrent CAEs in any patients from the LQT1 and LQT2 groups.

Although treating asymptomatic patients is somewhat controversial, a safe approach is to treat all patients with congenital LQTS because sudden cardiac death can be the first manifestation of LQTS.

Beta-blockers are drugs of choice for patients with LQTS. [7] The protective effect of beta-blockers is related to their adrenergic blockade, which diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.

Consultations

A cardiologist and a cardiac electrophysiologist are typically consulted when patients with LQTS are evaluated.

In families of patients with genotypically confirmed LQTS, genetic counseling of patients and family members should be considered.

Inpatient care

Patients with LQTS are frequently hospitalized in a monitored unit after they have a cardiac event (eg, syncope, cardiac arrest) to enable immediate rescue if cardiac arrhythmias recur.

Follow-up

Asymptomatic individuals with LQTS usually do not require hospitalization. However, carefully evaluate them and provide follow-up care in an ambulatory setting. A cardiologist or a cardiac electrophysiologist should examine patients with LQTS on a regular basis.

Next:

Beta-Blockers

Beta-blockers are effective in preventing cardiac events in approximately 70% of patients with long QT syndrome (LQTS), whereas cardiac events continue to occur despite beta-blocker therapy in the remaining 30%.

Propranolol and nadolol are the most frequently used beta-blockers, although atenolol and metoprolol are also prescribed in patients with LQTS. Different beta-blockers demonstrate similar effectiveness in preventing cardiac events in patients with LQTS. Nadolol is effective for reducing cardiac events in patients with LQT1 and in those with LQT2, whereas atenolol and propranolol appear to decrease this risk only for LQT1, and metoprolol does not appear to have any significant risk reduction for LQT1 or LQT2. [26] Beta-blocker therapy may not be as effective for LQT3 as for LQT1 or LQT2, but there are not enough data to make a more conclusive assessment. [26]

Response to beta-blocker therapy may also vary depending on the triggering event. A study by Goldenberg et al found that in patients with LQT1, beta-blocker therapy is effective when exercise triggers the event, but it is ineffective if the event happens during sleep or arousal. [27]

Koponen et al collected follow-up data, covering a mean of 12 years, for 316 genotyped LQT1 and LQT2 patients aged 0 to 18 years. In this pediatric group of genotyped and appropriately treated LQTS patients, they found that severe cardiac events were uncommon. [28]  In addition, treatment with beta-blocker medications reduced the risk of cardiac events and was generally well tolerated.

Previously, the recommended dosage of beta-blockers was relatively large (eg, propranolol 3 mg/kg/day, or 210 mg/day in a 70-kg individual); more recent data suggest that lower dosages have a protective effect similar to that of large dosages.

Previous
Next:

Pacemakers and ICDs

The implantable cardioverter-defibrillator (ICD) has been shown to be highly effective in preventing sudden cardiac death in high-risk patients. During a mean 8-year follow-up study of 125 patients with long QT syndrome (LQTS) who received an ICD, there was a 1.3% death rate in high-risk ICD patients, compared to 16% in non-ICD patients. [29] High-risk patients are defined as those with aborted cardiac arrest or recurrent cardiac events (eg, syncope or torsade de pointes) despite conventional therapy (ie, beta-blocker alone) and those with very prolonged QT interval (>500 ms).

An alternative treatment is beta blockade in combination with pacemaker implantation and/or stellectomy in some patients.

The use of an ICD may be considered as primary therapy if the patient has a strong family history of sudden cardiac death. However, because some studies showed that a family history of sudden cardiac death is not an independent risk factor, [30] some experts do not recommend ICD therapy based only on a family history of sudden cardiac death. [31]

Early ICD therapy should be considered in high-risk patients with Jervell and Lang-Nielsen (JLN) syndrome, because the efficacy of beta-blockers has been found to be more limited in these patients. [32]

The usefulness of implanted cardiac pacemakers is based on the premise that pacing eliminates arrhythmogenic bradycardia, decreases heart-rate irregularities (eliminating short-long-short sequences), and decreases repolarization heterogeneity, thereby diminishing the risk of torsade de pointes ventricular tachycardia. Pacemakers are particularly helpful in patients with documented pause-bradycardia–induced torsade de pointes and in patients with LQT3.

However, data indicate that cardiac events continue to occur in high-risk patients with cardiac pacing. Because newer models of ICDs include a cardiac pacing function, cardiac pacing (without defibrillators) is unlikely to be used in patients with LQTS. Pacing alone may be used in low-risk patients with LQT3.

Previous
Next:

Stellectomy

Left cervicothoracic stellectomy is another antiadrenergic therapeutic measure used in high-risk patients with long QT syndrome (LQTS), especially in those with recurrent cardiac events despite beta-blocker therapy.

Stellectomy decreases the risk of cardiac events in high-risk patients with LQTS, although it is more effective in patients with LQT1 than in those with other types of LQTS.

Although this technique decreases the risk of cardiac events, it does not eliminate the risk. Therefore, the use of an implantable cardioverter-defibrillator (ICD) is superior to cervicothoracic stellectomy. However, cervicothoracic stellectomy may be indicated in some high-risk patients and in patients who have several ICD discharges while being treated with beta blockade and an ICD.

Previous
Next:

Considerations in Physical Activity

Physical activity, swimming, and stress-related emotions frequently trigger cardiac events in patients with long QT syndrome (LQTS). Therefore, discourage patients from participating in competitive sports.

The triggering effect of exercise and tachycardia, and therefore the protective effect of beta-blockers, varies depending on the type of LQTS.

Exercise and tachycardia trigger LQT1 events. Therefore, patients with LQT1 should avoid strenuous exercise; beta-blockers are expected to provide excellent help by preventing cardiac events. Syncope and sudden cardiac death during swimming or diving are strongly related to LQT1. Therefore, patients with LQT1 should avoid swimming with no supervision. LQT2 is also exercise induced but to a lesser degree than LQT1.

Tachycardia and exercise do not trigger LQT3; events typically happen during sleep. Because tachycardia is not a trigger, the role of beta-blockers in preventing the cardiac events of LQT3 is debated. Mexiletine, a sodium channel blocker, may improve protection in this subgroup of patients. Some experts suggest the use of a beta-blocker combined with mexiletine in patients with LQT3. [33]

Previous
Next:

Gene Therapy

Gene-specific therapy is an area under investigation in the treatment of long QT syndrome (LQTS). For example, because LQT3 is associated with gain-of-function mutations in sodium channels, antiarrhythmic agents with sodium channel blocking properties have been suggested as gene-specific therapy for patients with LQTS3. Nevertheless, this area is complex and requires further investigations and studies.

For example, Ruan and colleagues found that mexiletine, a sodium channel blocker, can facilitate F1473 mutant protein trafficking, resulting in a net effect of a further increase in the sodium current and a worsening of QT prolongation in a subset of patients with LQTS3 who have this specific mutation. [34]

In a retrospective cohort study of 34 LQT3 patients, Mazzanti et al found evidence that mexiletine is an effective therapy. The median duration of oral mexiletine therapy was 36 months. Mexiletine significantly shortened QTc, reduced the percentage of patients with arrhythmic events, reduced the mean number of arrhythmic events per patient, and reduced the annual rate of arrhythmic events. [33]

Trigger-specific risk stratification and therapy have been suggested by some studies. For example, Kim and colleagues showed that certain types of mutations in LQT2 are associated with certain triggering events (exercise triggers vs arousal triggers vs nonarousal/nonexercise triggers) and that patients with exercise-related triggering events respond to the treatment with beta-blockers. [35]

Previous
Next:

Drugs To Be Avoided in LQTS

Anesthetics or asthma medication

Epinephrine (adrenaline) for local anesthesia or as an asthma medication should be avoided in patients with long QT syndrome (LQTS).

Antihistamines

Antihistamines to be avoided include the following:

  • Terfenadine (Seldane [recalled from US market]): For allergies
  • Astemizole (Hismanal [recalled from US market]): For allergies
  • Diphenhydramine (Benadryl): For allergies

Antibiotics

Antibiotics to be avoided include the following:

  • Erythromycin (E-Mycin, EES, EryPed, PCE): For lung, ear, and throat infections
  • Trimethoprim and sulfamethoxazole (Bactrim, Septra):  For urinary, ear, and lung infections
  • Pentamidine (Pentam, intravenous): For lung infections

Heart medications

Heart medications to avoid in patients with LQTS include the following:

  • Quinidine (Quinidine, Quinidex, Duraquin, Quinaglute): For heart rhythm abnormalities
  • Procainamide (Pronestyl): For heart rhythm abnormalities
  • Disopyramide (Norpace): For heart rhythm abnormalities
  • Sotalol (Betapace): For heart rhythm abnormalities
  • Probucol (Lorelco): For high triglycerides, cholesterol
  • Bepridil (Vascor): For chest pain (angina)
  • Dofetilide (Tikosyn): For atrial fibrillation
  • Ibutilide (Corvert): For atrial fibrillation

Gastrointestinal medications

Cisapride (Propulsid), for esophageal reflux and acid indigestion, should be avoided.

Antifungal drugs

Antifungal agents to be avoided include the following:

  • Ketoconazole (Nizoral): For fungal infections
  • Fluconazole (Diflucan): For fungal infections
  • Itraconazole (Sporanox): For fungal infections

Psychotropic drugs

The following psychotropic drugs should be avoided in patients with LQTS:

  • Tricyclic antidepressants (Elavil, Norpramin, Vivactil): For depression
  • Phenothiazine derivatives (Compazine, Stelazine, Thorazine, Mellaril, Trilafon): For mental disorders
  • Butyrophenones (Haloperidol): For mental disorders
  • Benzisoxazole (Risperdal): For mental disorders
  • Diphenylbutylpiperidine (Orap): For mental disorders

Medications for potassium loss

Potassium-loss medications to be avoided include the following:

  • Indapamide (Lozol): For water loss, edema
  • Other diuretics
  • Medications for vomiting and diarrhea
Previous