Basics
Description
Long QT syndrome (LQTS) is characterized by prolongation of the QT interval on the surface electrocardiogram (ECG), syncope, and sudden death as a result of malignant ventricular arrhythmias. The electrical instability is due to an abnormality of ventricular repolarization associated with a cardiac ion channelopathy. ‚
Epidemiology
Prevalence
Prevalence of LQTS is estimated to be approximately 1 in 2,500. ‚
Risk Factors
Genetics
- Autosomal dominant (Romano-Ward syndrome)
- Autosomal recessive, sometimes associated with congenital nerve deafness (Jervell and Lange-Nielsen syndrome)
- Genetic linkage analysis studies have demonstrated that >400 genetic mutations among 13 cardiac ion channel genes account for nearly 3/4 of LQTS.
- Genotype-phenotype " “based research studies have identified gene-specific electrocardiographic profiles, gene-specific arrhythmia triggers, gene-directed treatment strategies, and gene-specific risk stratification.
General Prevention
- Preventive measures focus on screening for the electrocardiographic abnormality, especially in individuals who appear to be at risk of having the diagnosis.
- Patients who have been diagnosed are advised to avoid exposure to stimulants, medications that are known to prolong the QT interval or provoke ventricular arrhythmias, and situations that may aggravate the cardiac rhythm or induce torsades de pointes.
Pathophysiology
Two hypotheses have been proposed to explain the pathogenesis of congenital LQTS syndrome: ‚
- An abnormality or imbalance in sympathetic innervation to the heart, which helps explain the findings of sinus bradycardia, abnormal repolarization, adrenergic dependence of arrhythmias, and response to adrenergic antagonist medications associated with the syndrome
- Intrinsic cardiac ion (potassium and sodium) channel defects appear to be the mechanism responsible for cardiac repolarization abnormalities. Because some identified gene mutations that result in congenital LQTS occur at loci that also encode a cardiac ion channel protein, ion channel dysfunction has been proposed as the intrinsic abnormality that is responsible for abnormal repolarization.
Diagnosis
History
- Notable findings include the following:
- Palpitations
- Presyncope
- Syncope
- These symptoms may be related to provocative stimuli, especially emotional or physical stress. Any use of medications known to prolong the QTc interval should be noted.
- Most importantly, a thorough family history for arrhythmia, syncope, epilepsy, or sudden unexplained death should be obtained.
Physical Exam
Findings are usually normal, but bradycardia may be present. ‚
Diagnostic Tests & Interpretation
Lab
- The Bazett formula: QTc = QT/(square root of RR interval). Generally, a QTc >480 msec is considered abnormal, although some clinicians allow a slightly longer QTc for infants <6 months of age.
- Some clinicians believe that the QTc should not be corrected at heart rates <60 beats per minute (bpm). The measurement should be taken in lead II without significant sinus arrhythmia.
- Children frequently have a prominent U wave. It should generally be included in the measurement of the QTc if it exceeds 1/2 the amplitude of the T wave.
- A single measured prolonged QTc interval does not confirm the diagnosis of LQTS.
- T-wave alternans on an electrocardiographic recording is diagnostic.
- Since 2004, genetic testing has been available as a commercial diagnostic test. Unfortunately, only up to 3/4 of all genetic causes of LQTS have been identified, so false-negative genetic testing is possible.
- Clinical scoring systems may help stratify patients into high, moderate, and low probability of having the diagnosis, based on symptoms, family history, and ECG findings.
Imaging
ECG ‚
- Atrioventricular block can be seen on the ECG in infants with relatively rapid heart rates and P waves that occur during the prolonged repolarization period (QT interval) of ventricular refractoriness.
Echocardiogram ‚
- The echocardiogram usually demonstrates normal cardiac structure and function.
Diagnostic Procedures/Other
Other tests that may help confirm the diagnosis include the following: ‚
- 24-hour ambulatory Holter monitoring
- This recording may disclose asymptomatic ventricular ectopy or arrhythmias, T-wave alternans, or variability in the QTc interval during different periods of the day.
- Exercise stress testing may also be helpful in identifying ventricular arrhythmias or prolongation of the QTc interval, particularly during the recovery phase.
Differential Diagnosis
- Congenital LQTS is most commonly misdiagnosed as vasovagal syncope or a seizure disorder. All patients who have a syncopal event or who are diagnosed with epilepsy should have a baseline screening ECG.
- Sudden infant death syndrome (SIDS) may be related to congenital LQTS. Some studies have demonstrated that mutations of ion channel proteins that cause LQTS have been found in SIDS victims. QT interval prolongation may be subtle, such that ¢ ˆ ¼10% of affected patients may have a normal result on routine ECG and ¢ ˆ ¼40% may have only borderline prolongation of the QT interval.
- Acquired forms of LQTS should be differentiated from the congenital and inherited form. Acquired LQTS may be due to the following:
- Electrolyte abnormalities: hypokalemia, hypocalcemia, hypomagnesemia, and metabolic acidosis
- Toxins: organophosphates
- Central nervous system trauma
- Malnutrition: anorexia
- Primary myocardial disease: myocarditis, ischemia, cardiomyopathy
- Medication
- Cardiac medications: quinidine, procainamide, disopyramide, sotalol, and amiodarone
- Antibiotics/antifungals: erythromycin, trimethoprim " “sulfamethoxazole, pentamidine, ketoconazole, and fluconazole
- Psychotropic medications: tricyclic antidepressants, phenothiazines, and haloperidol
- Antihistamines: terfenadine, astemizole, diphenhydramine
- Gastrointestinal: cisapride
Treatment
Medication
- The primary therapy is Ž ²-blockade, most commonly with propranolol or nadolol. Metoprolol and perhaps atenolol are less effective for this diagnosis.
- Class Ib antiarrhythmic medications (e.g., mexiletine) are also used in patients with congenital LQTS, especially in those with documented ventricular arrhythmia.
- Anti-arrhythmic medications generally do not help treat patients with acquired LQTS, but the administration of magnesium sulfate may be beneficial.
Additional Treatment
General Measures
Patients are usually treated based on symptoms and the clinical severity of the disease. ‚
Additional Therapies
Implantable cardioverter-defibrillators (ICDs) are usually reserved for older children and adolescents who have significant symptoms, documented ventricular arrhythmias, or other significant risk factors for sudden death. ‚
Surgery/Other Procedures
- Occasionally, implantation of a permanent pacemaker is indicated based on the theory that the tachyarrhythmias (e.g., torsades de pointes) are dependent on bradycardia and/or pauses. Rarely, pacemaker implantation may be necessary to support the low heart rate that occurs as a result of Ž ²-blocker therapy. Newborns and infants with a very prolonged QT interval, atrioventricular block, and low ventricular rates are historically treated with a pacemaker.
- An ICD may be recommended for patients thought to be at higher risk of developing ventricular arrhythmias.
- Left stellate ganglionectomy is performed to potentially eliminate the hyperactive left sympathetic ganglion output that has been proposed as a mechanism of ventricular arrhythmias. This treatment option is not universally accepted.
Inpatient Considerations
Initial Stabilization
Most clinicians treat diagnosed asymptomatic children with medications because of a high incidence of sudden death that occurs as the first symptom. ‚
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Follow-up outpatient appointments should review new or recurrent symptoms, including palpitations, near syncope or syncope, and the efficacy and adverse effects of medical therapy.
- ECG may demonstrate a normal or prolonged QTc.
- Follow-up 24-hour ambulatory Holter monitor recordings and exercise stress tests may help assess the adequacy of Ž ²-blocker therapy and identify ventricular arrhythmias.
- All family members of the patient should have an ECG as a minimum screening measure.
Prognosis
- Children have a higher incidence of sudden death than adults, which may reflect an inherent bias because adult patients have already survived childhood. The risk of cardiac events is higher in boys before puberty and in women during adulthood.
- Pediatric patients with greatest risk for sudden death are those with QTc >600 msec. Gender, environmental factors, genotype, and therapy are other factors that influence the clinical course.
- A particular clinical phenotype may be caused by different genetic substrates, whereas a single gene can cause very different phenotypes, even within the same family, by acting through different pathways.
- Without treatment, mortality is 21% within 1 year from the first syncope. With proper treatment, mortality has been estimated at 1% during 15-year follow-up. Ž ²-blocker therapy has been shown to reduce the incidence of sudden death.
- Current research may lead to the development of therapy specific to the precise ion channel defect.
Complications
- Complications, especially in untreated patients, include the following:
- Ventricular tachyarrhythmias, specifically torsades de pointes
- Syncope
- Sudden death
- In patients with the congenital and inherited form of the condition, asymptomatic family members may be affected.
Additional Reading
- Ackerman ‚ MJ. Genotype-phenotype relationships in congenital long QT syndrome. J Electrocardiol. 2005;38(Suppl 4):64 " “68. ‚ [View Abstract]
- Hedley ‚ PL, J ƒ ¸rgensen ‚ P, Schlamowitz ‚ S, et al. The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat. 2009;30(11):1486 " “1511. ‚ [View Abstract]
- Morita ‚ H, Wu ‚ J, Zipes ‚ DP. The QT syndromes: long and short. Lancet. 2008;372(9640):750 " “763. ‚ [View Abstract]
- Priori ‚ SG, Napolitano ‚ C, Vicentini ‚ A. Inherited arrhythmia syndromes: applying the molecular biology and genetic to the clinical management. J Interv Card Electrophysiol. 2003;9(2):93 " “101. ‚ [View Abstract]
- Priori ‚ SG, Schwartz ‚ PJ, Napolitano ‚ C, et al. Risk stratification in the long QT syndrome. N Engl J Med. 2003;348(19):1866 " “1874. ‚ [View Abstract]
- Roden ‚ DM. Clinical practice. Long-QT syndrome. N Engl J Med. 2008;358(2):169 " “176. ‚ [View Abstract]
- Schwartz ‚ PJ, Crotti ‚ L, Insolia ‚ R. Long-QT syndrome: from genetics to management. Circ Arrhythm Electrophysiol. 2012;5(4):868 " “877. ‚ [View Abstract]
Codes
ICD09
ICD10
SNOMED
- 9651007 Long QT syndrome (disorder)
- 442917000 Congenital long QT syndrome
- 442946007 Aquired long QT syndrome
FAQ
- Q: Should activity be restricted in patients with congenital LQTS?
- A: Because sudden rises in serum catecholamine levels may precipitate symptoms, it is appropriate to restrict competitive and vigorous athletics. Symptomatic patients may require greater restrictions. Documentation of appropriate Ž ²-blockade by a lower maximal heart rate at peak exercise on follow-up exercise stress test may be helpful.
- Q: If someone is identified as having LQTS, should family members be evaluated?
- A: Yes, with a high degree of suspicion. Most cases of congenital LQTS are inherited in an autosomal dominant pattern, so that each child of an affected parent has a 50% chance of having the gene. This does not predict severity of symptoms, but parents, all siblings, and children of patients should be examined with an ECG, Holter monitor, and exercise stress test. These studies may help reveal an abnormal QTc interval in suspected family members.