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Long QT Syndrome Last Updated: January 3, 2007 |
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| Synonyms and related keywords: long QT syndrome, LQTS, congenital long QT syndrome, Romano-Ward syndrome, Jervell and Lange-Nielsen syndrome, JLN syndrome, ventricular tachyarrhythmias, syncope, cardiac arrest, sudden death, Anderson syndrome, Timothy syndrome
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: Ali A Sovari, MD, Staff Physician, Department of Internal Medicine, University of Illinois College of Medicine at Urbana-Champaign Coauthor(s): Abraham G Kocheril, MD, FACC, FACP, Clinical Professor, Head of Cardiology, Department of Internal Medicine, Division of Cardiology, University of Illinois College of Medicine, Urbana-Champaign; Head, Cardiac Electrophysiology, Director, Athletes Cardiovascular Evaluation, Carle Heart Center; Ramin Assadi, MD, Staff Physician, Department of Internal Medicine, Loma Linda University; Wojciech Zareba, MD, PhD, FACC, Associate Director of Heart Research, Associate Professor, Department of Medicine, Division of Cardiology, University of Rochester Medical Center; Spencer Rosero, MD, Assistant Professor of Medicine, Department of Medicine, University of Rochester School of Medicine |
| Ali A Sovari, MD, is a member of the following medical societies:
American College of Physicians,
American Heart Association, and
American Medical Association |
| Editor(s): Justin D Pearlman, MD, ME, PhD, MA, Director of Dartmouth Advanced Imaging Center, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Brian Olshansky, MD, Professor of Medicine, Director of Cardiac Electrophysiology, Department of Internal Medicine, University of Iowa Hospitals;
Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital;
and Leonard Ganz, MD, Associate Professor of Medicine, Temple University School of Medicine; Cardiac Electrophysiologist, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Cent, West Penn Hospital |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: Long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death.
The QT interval on the ECG, measured from the beginning of the QRS complex to the end of the T wave, represents the duration of activation and recovery of the ventricular myocardium. QT intervals corrected for heart rate (QTc) longer than 0.44 seconds are generally considered abnormal, though a normal QTc can be slightly prolonged in female individuals (up to 0.46 sec). The Bazett equation is used to calculate the QTc, as follows: QTc = QT/root of the R-R interval.
To measure QT interval accurately, the relationship of QT to the R-T interval should be reproducible. This issue is especially important when the heart rate is <50 bpm or >120 bpm and when athletes or children have marked beat-to-beat variability of the R-R interval. In such cases, long recordings and several measurements are required. The longest QT interval is usually observed in the right precordial leads.
Pathophysiology: The QT interval represents the duration of activation and recovery of the ventricular myocardium. Prolonged recovery from electrical excitation increases the likelihood of dispersing refractoriness, when some part of myocardium might be refractory to subsequent depolarization.
From a physiologic standpoint, dispersion occurs with repolarization between 3 layers of the heart, and the repolarization phase tends to be prolonged in myocardium. This is why the T wave is normally wide and the interval from Tpeak to Tend (Tp-e) represents the transmural dispersion of repolarization (TDR). In LQTS, TDR increases and creates a functional substrate for transmural reentry.
In LQTS, QT prolongation can lead to polymorphic ventricular tachycardia, or torsade de pointes, which itself may lead to ventricular fibrillation and sudden cardiac death. Torsade de pointes is widely thought to be triggered by reactivation of calcium channels, reactivation of a delayed sodium current, or a decreased outward potassium current that results in early afterdepolarization (EAD) in a condition with enhanced TDR usually associated with a prolonged QT interval. TDR serves as a functional reentry substrate to maintain torsade de pointes. TDR not only provides a substrate for reentry but also increases the likelihood of EAD, the triggering event for torsade de pointes, by prolonging the time window for calcium channels to remain open. Any other condition that accelerates the reactivation of calcium channels (eg, increased sympathetic tone), increases the risk of EAD.
LQTS has been recognized as mainly Romano-Ward syndrome (ie, familial occurrence with autosomal dominant inheritance, QT prolongation, and ventricular tachyarrhythmias) or as Jervell and Lang-Nielsen (JLN) syndrome (ie, familial occurrence with autosomal recessive inheritance, congenital deafness, QT prolongation, and ventricular arrhythmias). Two other syndromes are described, namely, Andersen syndrome and Timothy syndrome, though some debate centers on whether they should be included in LQTS.
LQTS is caused by mutations of the genes for cardiac potassium and sodium or calcium ion channels; 8 genes have been identified. On the basis of this genetic background, 6 types of Romano-Ward syndrome, 1 type of Andersen syndrome and 1 type of Timothy syndrome, and types of JLN syndrome are identified (see Table 1).
Table 1. Genetic Background of Inherited Forms of LQTS (Romano-Ward syndrome: LQT1-6, Anderson syndrome: LQT7, Timothy syndrome: LQT8, and Jervell and Lang-Nielsen syndrome: JLN1-2)
| 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) |
| LQT3 |
3p21-24 |
SCN5A |
Sodium (INa) |
| 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 |
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) |
LQT1, LQT2, and LQT3 account for most cases of LQTS, with estimated prevalences of 45%, 45%, and 7%, respectively. In LQTS, QT prolongation is due to overload of myocardial cells with positively charged ions during ventricular repolarization. In LQT1, LQT2, LQT5, LQT6, and LQT7, potassium ion channels are blocked, they open with a delay, or they are open for a shorter period than they are in normally functioning channels. These changes decrease the potassium outward current and prolong repolarization.
The LQT1 gene (KVLQT1, or KCNQ1) encodes for part of the IKs slowly deactivating, delayed rectifier potassium channel. More than 170 mutations (most missense) of this gene have been reported. Their net effect is a decreased outward potassium current. Therefore, the channels remain open longer than usual, with a delay in ventricular repolarization and with QT prolongation.
The LQT2 gene (HERG, or KCNH2) encodes for part of IKr rapidly activating, rapidly deactivating, delayed rectifier potassium channel. Mutations in this gene cause rapid closure of the potassium channels and decrease the normal rise in IKr. They also result in delayed ventricular repolarization and QT prolongation. About 200 mutations in this gene have been detected.
In LQT3, caused by mutations of the SCN5A gene for the sodium channel, a gain-of-function mutation causes persistent inward sodium current in the plateau phase, which contributes to prolonged repolarization. Some loss-of-function mutations in the same gene may lead to different presentations, including Brugada syndrome. More than 50 mutations have been identified in this gene.
The LQT4 gene (ANK2, or ANKB) encodes for the ankyrin-B. Ankyrins are adapter proteins that bind to several ion channel proteins, such as the anion exchanger (chloride-bicarbonate exchanger), sodium-potassium adenosine triphosphatase (ATPase), the voltage-sensitive sodium channel (INa), and the sodium-calcium exchanger (NCX, or INa-Ca), and calcium-release channels (including those mediated by the receptors for inositol triphosphate [IP3] or ryanodine). Mutations in this gene interfere with several of these ion channels. The end result is increased intracellular concentration of calcium and, sometimes, fatal arrhythmia. Five mutations of this gene are reported. LQT4 is interesting because it provides an example of how mutations in proteins other than ion channels can be involved in the pathogenesis of LQTS.
The LQT5 gene encodes for the IKs potassium channel. Similar to LQT1, LQT5 results in a decreased outward current of potassium and in QT prolongation.
LQT6 involves mutations in the gene MiRP1, or KCNE2, which encodes for the potassium channel beta subunit MinK-related protein 1 (MiRP1). KCNE2 encodes for beta subunits of IKr potassium channels.
The LQT7 gene (KCNJ2) encodes for potassium channel 2 protein that plays an important role in inward repolarizing current (IKi), especially in phase 3 of the action potential. In this subtype, QT prolongation is less prominent than in other types, and the QT interval is sometimes in the normal range. Because potassium channel 2 protein is expressed in both cardiac and skeletal muscle, Andersen syndrome is associated with skeletal abnormalities, such as short stature and scoliosis.
Mutations in the LQT8 gene (CACNA1C) cause loss of L-type calcium current. So far, a limited number of cases of Timothy syndrome have been reported. They have been associated with abnormalities such as congenital heart disease, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction.
In patients with LQTS, a variety of adrenergic stimuli, including exercise, emotion, loud noise, and swimming may precipitate an arrhythmic response. However, it also may occur without such preceding conditions.
Drug-induced QT prolongation may also increase the risk of ventricular tachyarrhythmias (eg, torsade de pointes) and sudden cardiac death. The ionic mechanism is similar to that observed in congenital LQTS, ie, mainly intrinsic blockade of cardiac potassium efflux. In addition to the medications that potentially can prolong the QT interval, several other factors play a role in this phenomenon. Important risk factors for drug-induced QT prolongation are female sex, electrolyte disturbances (hypokalemia and hypomagnesemia), structural heart disease, and bradycardia. Some have also suggested that affected individuals have mutations that affect cardiac ion channels, altering repolarization reserve. Frequency:
- In the US: LQTS remains an underdiagnosed disorder, especially because at least 10-15% of LQTS gene carriers have a normal QTc duration.
The prevalence of LQTS is difficult to estimate. However, given the currently increasing frequency of diagnosis, LQTS may be expected to occur in 1 in 10,000 individuals.
- Internationally: The occurrence of LQTS internationally is similar to that in the United States.
Mortality/Morbidity: Mortality, morbidity, and responses to pharmacologic treatment differ in the various types of LQTS. This issue is under investigation.
LQTS may result in syncope and lead to sudden cardiac death, which usually occurs in otherwise healthy young individuals. LQTS is thought to cause about 4000 deaths in the United States each year. The cumulative mortality rate reaches approximately 6% by the age of 40 years.
Although sudden death usually occurs in symptomatic patients, it happens with the first episode of syncope in about 30% of the patients. This occurrence emphasizes the importance of diagnosing LQTS in the presymptomatic period.
- Depending on the type of mutation present, sudden cardiac death may happen during exercise, emotional stress, at rest, or at sleep.
- LQT4 is associated with paroxysmal atrial fibrillation.
- Studies have shown an improved response to pharmacologic treatment with a lowered rate of sudden cardiac death in LQT1 and LQT2 compared with LQT3.
Race: No clear evidence suggests race-related differences in the occurrence of LQTS.
Sex:
- New cases of LQTS are diagnosed in more female patients (60-70% of cases) than male patients. The female predominance may be related to the prolonged QTc (as determined by using the Bazett formula) in women compared with men and to a relatively high mortality rate in young men.
- In women, pregnancy is not associated with an increased incidence of cardiac events, whereas the postpartum period is associated with a substantially increased risk of cardiac events, especially in the subset of patients with LQT2. Cardiac events have been highly correlated with menses.
Age: Patients with LQTS usually present with cardiac events (eg, syncope, aborted cardiac arrest, sudden death) in childhood, adolescence, or early adulthood. However, LQTS has been identified in adults as late as in the fifth decade of life. The risk of death from LQTS is higher in boys than in girls younger than 10 years, and the risk is similar in male and female patients thereafter.
History: LQTS is usually diagnosed after a person has a cardiac event (eg, syncope, cardiac arrest). In some situations, LQTS is diagnosed after a family member suddenly dies. In some individuals, LQTS is diagnosed because an ECG shows QT prolongation. - A history of cardiac events is the most typical clinical presentation in patients with LQTS.
- Exercise, swimming, or emotion may trigger events, but they may also occur during night sleep.
- Triggering events are somewhat different by genotype. Patients with LQT1 usually have cardiac events preceded by exercise or swimming. Sudden exposure of the patient's face to cold water is thought to elicit a vagotonic reflex. Patients with LQT2 may have arrhythmic events after an emotional event, exercise, or exposure to auditory stimuli (eg, door bells, telephone ring). Patients with LQT3 usually have events during night sleep.
- Obtain information about hearing loss (deficit) in a patient and his or her family members to determine a possibility of JLN syndrome.
- A family history of cardiac arrest and sudden death, especially at a young age, may suggest a congenital (familial) form of LQTS.
- Analysis of repolarization duration (QTc) and morphology on the patient's ECG and on ECGs of the patient's relatives frequently leads to the proper diagnosis.
Physical: Findings on physical examination usually do not indicate a diagnosis of 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). Causes: Details of the genetic background of LQTS are presented in Pathophysiology. LQTS is caused by mutations of genes encoding for cardiac ion channel proteins that cause abnormal ion channel kinetics. Shortened opening of the potassium channel in LQT1, LQT2, LQT5, LQT6, JLN1, and JLN2 and delayed closing of a sodium channel in LQT3 overcharges a myocardial cell with positive ions.
Secondary (drug-induced) QT prolongation also may have a genetic background, consisting of predisposition of an ion channel to abnormal kinetics caused by gene mutation or polymorphism. However, data are insufficient to claim that all patients with drug-induced QT prolongation have a genetic LQTS-related mechanism. ArizonaCERT provides lists of Drugs that Prolong the Qt Interval and/or Induce Torsades de Pointes Ventricular Arrhythmia.
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DIFFERENTIALS
| Section 4 of 11 |
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Sudden Cardiac Death
Syncope
Other Problems to be Considered:
Drug-induced QT prolongation
QT prolongation in the course of other diseases (eg, myocardial infarction, cerebral hemorrhage)
Vasovagal syncope
Seizures
Other causes of syncope, cardiac arrest, or sudden death in otherwise healthy people include hypertrophic cardiomyopathy, Brugada syndrome, and arrhythmogenic right ventricular dysplasia. |
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Lab Studies:
- Routinely check serum levels of potassium (and sometimes magnesium) in patients who present with QT prolongation after arrhythmic events to eliminate secondary reasons for repolarization abnormalities.
- Genetic testing for known mutations in DNA samples from patients is becoming accessible in specialized centers. Identification of an LQTS genetic mutation confirms the diagnosis. However, a negative result on genetic testing is of limited diagnostic value because only approximately 50% of patients with LQTS have known mutations. The remaining half of patients with LQTS may have mutations of yet unknown genes. Therefore, genetic testing has high specificity but a low sensitivity.
Imaging Studies:
- Imaging studies (eg, echocardiography, MRI) may help only in excluding other potential reasons for arrhythmic events (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia) or associated congenital heart diseases in small subset of patients with LQTS, such as those with LQT8.
Other Tests:
- A presentation with syncope or sudden cardiac death and a long QT on ECG typically suggests LQTS and leads to genetic testing to diagnose the disease. However, in many patients, the presentation may not be typical. Therefore, other tests may be indicated.
- As criteria above suggest, the most helpful ECG findings are prolongation of the QT interval, torsade de pointes, T-wave alternans, and certain morphology of the T waves (wide-based T wave, and notched T wave in 3 leads). Correlation between the type of mutation and T-wave morphology has been suggested. Wide-based T waves are most frequently seen in LQT1, and notched T waves are most commonly seen in LQT2. In LQT3, T waves may appear normal with a long, isoelectric ST segment.
- Both bradycardia and tachycardia need special attention. Bradycardia is among diagnostic criteria and adds 0.5 point to the score. Tachycardia needs special attention, too, because the QTc may be overcorrected in tachycardic situation (eg, in infants).
- In patients with suspected LQTS with borderline QTc values (or even values in the reference range) on standard ECGs or patients with a score of 2-3 based on the 1993 diagnostic criteria, an analysis of the dynamic behavior of QTc duration during exercise ECG or long-term Holter monitoring may reveal maladaptation of the QT interval to changing heart rate. QTc prolongation may be evident at a fast heart rate. Ventricular arrhythmias are rarely observed during exercise testing or Holter recording in patients with LQTS.
- No evidence indicates that invasive electrophysiology with attempts to induce ventricular tachycardia facilitates diagnosis.
- Visible T wave alternans in patients with LQTS indicate an increased risk of cardiac arrhythmias (ie, torsade de pointes and ventricular fibrillation).
- Detection of microvolt T-wave alternans has low sensitivity and high specificity in diagnosing LQTS. The prognostic value of microvolt T-wave alternans has not been studied systematically.
- Pharmacologic provocation with epinephrine or isoproterenol helps in diagnosing LQTS in patients with a borderline presentation. It may also provide information regarding the type of mutation present.
- The patients with a clinical or ECG presentation of LQTS need genetic testing to identify the mutation. At present, these genetic tests are not widely available. In a patient with a high probability of LQTS, an absence of any mutation on genetic testing based on diagnostic criteria does not rule out the possibility of LQTS. The patient might have an as-yet unidentified mutation.
- It is important to review the ECGs of family members of a patient with LQTS, to obtain detail histories, and to perform physical examinations. However, an absence of ECG findings of LQTS in family members does not exclude LQTS. In the ideal setting, all family members should be tested for mutations to help limit the small but definite risk of arrhythmia and sudden cardiac death. Testing is especially relevant if the patient was exposed to a drug that prolongs the QT interval.
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TREATMENT
| Section 6 of 11 |
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Medical Care: All patients with LQTS should avoid drugs that prolong the QT interval or reduce their serum potassium or magnesium levels. 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 that diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.
- Although for years the recommended dosage of beta-blockers was relatively large (eg, propranolol 3 mg/kg/d, or 210 mg/d in a 70-kg individual), recent data suggest that dosages lower than this have a protective effect similar to that of large dosages.
- 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 beta-blockers most frequently used, though atenolol and metoprolol are also prescribed in patients with LQTS. Different beta-blockers demonstrate similar effectiveness in preventing cardiac events in patients with LQTS.
- Implanted cardioverter-defibrillators (ICDs) appear to be the most effective therapy for high-risk patients. 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).
- An alternative is beta-blockade in combination with pacemaker and/or stellectomy.
- Use of an ICD may be considered as primary therapy if the patient has a strong family history of sudden cardiac death.
- The usefulness of implanted cardiac pacemakers is based on the premise that pacing eliminates arrhythmogenic bradycardia, decreases heart-rate irregularities (eliminating short-long-short series), 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, recent 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 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, and it is more effective in patients with LQT1 than those with other types of LQTS.
- Although this technique decreases the risk of cardiac events, it does not eliminate the risk. Therefore, ICD is superior therapy to cervicothoracic stellectomy.
- 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.
- 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. Therefore, patients with LQT1 should avoid strenuous exercise, and 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 exercised induced but to 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 the 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.
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.
Activity: Physical activity, swimming, and stress-related emotions frequently trigger cardiac events in patients with LQTS. Therefore, discourage patients from participating in competitive sports. This recommendation is most important for patients with LQT1 or LQT2. See also the Medical section above.
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MEDICATION
| Section 7 of 11 |
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No treatment addresses the cause of LQTS. Antiadrenergic therapeutic measures (eg, use of beta-blockers, left cervicothoracic stellectomy) and device therapy (eg, use of pacemakers, ICDs) aim to decrease the risk and lethality of cardiac events.
Drug Category: Beta-adrenergic blocking agents -- Antiadrenergic therapy effectively protects most patients with LQTS. Beta-blockers, especially propranolol, are the drugs most frequently used in patients with LQTS. Inform patients and their family members that beta-blockers should be continued indefinitely and not stopped. Interruption in beta-blocker therapy may increase the risk of cardiac events. Drug Name
| Propranolol (Inderal) -- Decreases effect of sympathetic stimulation on heart. Decreases conduction through atrioventricular (AV) node and has negative chronotropic and inotropic effects. Consult cardiologist because dosing varies and is individualized in patients with LQTS. Patients with asthma should use cardioselective beta-blockers. Patients with LQTS who cannot take beta-blockers may require ICDs as first-line therapy. |
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| Adult Dose | 2-3 mg/kg/d PO |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities |
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| Interactions | Coadministration with aluminum salts, barbiturates, nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; cimetidine, loop diuretics, and monoamine oxidase inhibitors (MAOIs) may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase; cardiotoxicity may increase when administered concurrently with calcium channel blockers, quinidine, flecainide, and digoxin (all affect conduction) |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; should be taken by pregnant women with LQTS during pregnancy and postpartum period, when risk of cardiac events increases |
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Drug Name
| Nadolol (Corgard) -- Frequently prescribed because of long-term effect. Decreases effect of sympathetic stimulation on heart. Decreases conduction through AV node and has negative chronotropic and inotropic effects. Consult cardiologist because dosing varies and is individualized in patients with LQTS. Patients with asthma should use cardioselective beta-blockers. Patients with LQTS who cannot take beta-blockers may require ICDs as first-line therapy. |
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| Adult Dose | 20-80 mg/d PO |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock, AV conduction abnormalities |
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| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, calcium channel blockers, quinidine, flecainide, and oral contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; should be taken by pregnant women with LQTS during pregnancy and postpartum period, when risk of cardiac events increases |
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Drug Name
| Metoprolol (Lopressor) -- Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG. Consult cardiologist because dosing varies and is individualized in patients with LQTS. Patients with LQTS who cannot take beta-blockers may require ICDs as first-line therapy. |
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| Adult Dose | 50-200 mg/d PO |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock, AV conduction abnormalities |
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| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Category D in third trimester of pregnancy; beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG |
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Drug Name
| Atenolol (Tenormin) -- Selectively blocks beta1-receptors with little or no affect on beta2 types. Consult cardiologist because dosing varies and is individualized in patients with LQTS. Patients with LQTS who cannot take beta-blockers may require ICDs as first-line therapy. |
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| Adult Dose | 25-100 mg/d PO |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; congestive heart failure, pulmonary edema, cardiogenic shock, AV conduction abnormalities, heart block (without a pacemaker) |
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| Interactions | Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG |
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FOLLOW-UP
| Section 8 of 11 |
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Further 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.
- Asymptomatic individuals with LQTS usually do not require hospitalization. However, carefully evaluate them and provide follow-up care in an ambulatory setting.
Further Outpatient Care:
- A cardiologist or electrophysiologist should examine patients with LQTS on a regular basis.
Deterrence/Prevention:
- Antiadrenergic therapy (eg, beta-blockers, stellectomy) aims to prevent future cardiac events.
- Use ICDs to prevent sudden cardiac death in patients with LQTS who develop ventricular tachyarrhythmias.
- Anesthetics or asthma medication - Epinephrine (Adrenaline) for local anesthesia or as an asthma medication
- Antihistamines
- Terfenadine (Seldane [recalled from US market]) for allergies
- Astemizole (Hismanal [recalled from US market]) for allergies
- Diphenhydramine (Benadryl) for allergies
- Antibiotics
- 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
- 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)
- Gastrointestinal medications - Cisapride (Propulsid) for esophageal reflux, acid indigestion
- Antifungal drugs
- Ketoconazole (Nizoral) for fungal infections
- Fluconazole (Diflucan) for fungal infections
- Itraconazole (Sporanox) for fungal infections
- Psychotropic drugs
- Tricyclic antidepressants (Elavil, Norpramin, Vivactil) for depression
- Phenothiazine derivatives (Compazine, Stelazine, Thorazine, Mellaril, Trilafon) for mental disorders
- Butyrophenones (Haloperidol) for mental disorders
- Benzisoxazol (Risperdal) for mental disorders
- Diphenylbutylperidine (Orap) for mental disorders
- Medications for potassium loss
- Indapamide (Lozol) for water loss, edema
- Other diuretics
- Medications for vomiting and diarrhea
Complications:
- Sudden cardiac death is the most devastating complication of the disorder, especially because it frequently occurs in young individuals.
- Neurologic deficits after aborted cardiac arrest may complicate the clinical course after successful resuscitation.
Prognosis:
- The prognosis for patients with LQTS treated with beta-blockers (and other therapeutic measures if needed) is good overall. Fortunately, episodes of torsades de pointes are usually self-terminating in patients with LQTS; only about 4-5% of cardiac events are fatal.
- Patients at high risk (ie, those with aborted cardiac arrest or recurrent cardiac events despite beta-blocker therapy) have a markedly increased risk of sudden death. Treat these patients with ICDs. Their prognosis after implantation of cardioverter-defibrillators is good.
Patient Education:
- Educate patients regarding the nature of the syndrome and factors that trigger cardiac events. Patients should avoid sudden noises (eg, from an alarm clock), strenuous exercise, water activities, and other arousal factors.
- Educate patients and family members about the critical importance of systematic treatment with beta-blockers.
- Advise family members and the patient's teachers at school to undergo training in CPR.
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MISCELLANEOUS
| Section 9 of 11 |
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Medical/Legal Pitfalls:
- Failure to diagnose LQTS when the QTc clearly is prolonged
- Failure to treat patients with LQTS with beta-blockers, unless contraindicated
- Failure to educate patients and family members about potential risks associated with strenuous sport activities, interruption of beta-blocker therapy, and drugs that prolong the QT interval.
- Failure to screen for LQTS in family members of proband (ie, the first family member with the disease)
Special Concerns:
- Pregnancy is not associated with an increased incidence of cardiac events, whereas the postpartum period is associated with substantially increased risk of cardiac events, especially in the subset of patients with LQT2.
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PICTURES
| Section 10 of 11 |
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BIBLIOGRAPHY
| Section 11 of 11 |
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