Long QT Syndrome Treatment & Management
- Author: Ali A Sovari, MD, FACP; Chief Editor: Jeffrey N Rottman, MD more...
All patients with long QT syndrome (LQTS) should avoid drugs that prolong the QT interval or that reduce their serum potassium or magnesium level. Potassium and magnesium deficiency should be corrected.
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. 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.
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.
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.
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.
The following is a summary of guidelines for the management of patients with LQTS, as suggested by the American College of Cardiology, the American Heart Association, and the European Society of Cardiology, in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society[11, 12] :
No participation in competitive sports for patients with the diagnosis established by means of genetic testing only
Beta-blockers should be given to patients who have QTc-interval prolongation (>460 ms in women and >440 ms in men) and are recommended (class IIa) for patients with a normal QTc interval
An implantable cardioverter-defibrillator (ICD) should be used in survivors of cardiac arrest and is recommended (class IIa) for patients with syncope while receiving beta-blockers; ICD therapy can be considered (class IIb) for primary prevention in patients with characteristics that suggest high risk (including LQT2, LQT3, and QTc interval >500 ms)
Beta-blockers are effective in preventing cardiac events in approximately 70% of patients, whereas cardiac events continue to occur despite beta-blocker therapy in the remaining 30%.
Propranolol and nadolol are the most frequently used beta-blockers, though atenolol and metoprolol are also prescribed in patients with long QT syndrome (LQTS). Different beta-blockers demonstrate similar effectiveness in preventing cardiac events in patients with LQTS.
Response to beta-blocker therapy may 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 is ineffective if the event happens during sleep or arousal.
Although for years the recommended dosage of beta-blockers was relatively large (eg, propranolol 3 mg/kg/day, or 210 mg/day in a 70-kg individual), data now suggest that lower dosages have a protective effect similar to that of large ones.
Pacemakers and ICDs
The ICD has been shown to be highly effective in preventing sudden cardiac death in high-risk patients. In a 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 with 16% in non-ICD patients, during a mean 8-year follow-up. 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 is beta blockade in combination with a pacemaker 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, since some studies showed that a family history of sudden cardiac death is not an independent risk factor, some experts do not recommend ICD therapy based only on a family history of sudden cardiac death.
Early ICD therapy should be considered in high-risk patients with JLN syndrome, because the efficacy of beta-blockers has been found to be more limited in these patients.
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, 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.
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 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.
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.
Gene-specific therapy is an area under investigation in the treatment of long QT syndrome (LQTS). For example, since 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 instance, Ruan and colleagues found that mexiletine, a sodium channel blocker, can facilitate F1473 mutant protein trafficking, resulting in a net effect of further increase in sodium current and worsening of QT prolongation in a subset of patients with LQTS3 who have this specific mutation.
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.
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 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 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 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
Cisapride (Propulsid), for esophageal reflux and acid indigestion, should be avoided.
Antifungal agents to be avoided include the following:
Ketoconazole (Nizoral) - For fungal infections
Fluconazole (Diflucan) - For fungal infections
Itraconazole (Sporanox) - For fungal infections
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
Medications - For vomiting and diarrhea
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|Type of LQTS||Chromosomal Locus||Mutated Gene||Ion Current Affected|
|LQT1||11p15.5||KVLQT1 or KCNQ1 (heterozygotes)||Potassium (IKs)|
|LQT2||7q35-36||HERG, KCNH2||Potassium (IKr)|
|LQT4||4q25-27||ANK2, ANKB||Sodium, potassium and calcium|
|LQT5||21q22.1-22.2||KCNE1 (heterozygotes)||Potassium (IKs)|
|LQT6||21q22.1-22.2||MiRP1, KNCE2||Potassium (IKr)|
|LQT7 (Anderson syndrome)||17q23.1-q24.2||KCNJ2||Potassium (IK1)|
|LQT8 (Timothy syndrome)||12q13.3||CACNA1C||Calcium (ICa-Lalpha)|
|JLN1||11p15.5||KVLQT1 or KCNQ1 (homozygotes)||Potassium (IKs)|
|JLN2||21q22.1-22.2||KCNE1 (homozygotes)||Potassium (IKs)|
|Findings on physical examination usually do not indicate a diagnosis of long QT syndrome (LQTS), though some patients may present with excessive bradycardia for their age, and some patients may have hearing loss (congenital deafness), indicating the possibility of JLN syndrome. Skeletal abnormalities, such as short stature and scoliosis are seen in LQT7 (Andersen syndrome), and congenital heart diseases, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction may be seen in those with LQT8 (Timothy syndrome). Also perform the physical examination to exclude other potential reasons for arrhythmic and syncopal events in otherwise healthy people (eg, heart murmurs caused by hypertrophic cardiomyopathy, valvular defects).|
|Hinterseer et al found that increased short-term variability of QT interval, ie, STV(QT), in symptomatic patients with congenital long-QT syndrome (LQTS) could be a useful noninvasive additive marker for diagnostic screening to bridge the gap while waiting for results of genetic testing. This study is the first in humans to observe this association.|
|ECG findings *|
|450-459 in male patient||1|
|Torsade de pointes‡||2|
|Notched T wave in 3 leads||1|
|Low heart rate for age§||0.5|
|Family history ¶|
|A. Family members with definite LQTS#||1|
|B. Unexplained sudden cardiac death < 30y in an immediate family member||0.5|
|*In the absence of medications or disorders known to affect these electrocardiographic features.
†QTc calculated by Bazett's formula
§Resting heart rate below the second percentile for the age.
¶The same family member cannot be counted in A and B.
#Definite LQTS is defined by an LQTS score of more than 3 (≥4).
|Reference Range, s|
|Children and adolescents (< 15 y)||>0.46||0.44-0.46||< 0.44|