What is long QT syndrome?

Risk Factors

Risk factors for congenital LQTS include a family history of LQTS, syncope, or unexplained sudden death. Deafness at birth is associated with one congenital form of LQTS.

Acquired, drug-induced LQTS is associated with medications that prolong the QT interval. Some patients with acquired LQTS have congenital heart defects that may increase the risk of developing the condition. Low blood levels of potassium, magnesium, or calcium may also increase the risk.

Etiology and Genetics

Inherited forms of LQTS are caused by abnormalities in the structure of the genes that form the potassium, sodium, or calcium ion channels within the heart, interrupting the normal transmission of the heart’s electrical impulses.

There are at least twelve genotypes of LQTS, with classifications based on the ion channel affected. The main forms of inherited LQTS include the autosomal dominant Romano-Ward syndrome, commonly associated with ventricular tachyarrhythmias, and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), associated with deafness at birth. Nearly 50 percent of JLNS patients have a cardiac event by age three, according to 2012 data from GeneReviews.

Two other syndromes include Andersen-Tawil syndrome (LQT7) and Timothy syndrome (LQT8), affecting the heart’s potassium and calcium ion channels, respectively. LQT7 is characterized by muscle weakness and ventricular arrhythmias. LQT8 patients may have certain congenital heart defects and features of autism or similar disorders. Patients with LQT8 have a greater risk of arrhythmias and sudden death.

LQT1, LQT2, LQT5, LQT6, LQT7, and LQT11 affect the heart’s potassium ion channel. LQT1 and LQT2 are the most frequent forms. Most LQT1 patients experience cardiac events during exercise, especially swimming, while LQT2 patients commonly experience cardiac events during emotional stress, particularly auditory stimulation.

LQT3, LQT9, LQT10, and LQT12 affect the sodium ion channel. Many LQT3 patients experience cardiac events despite beta blocker therapy, which increases the risk of life-threatening arrhythmias. Treatment with a defibrillator or pacemaker is recommended for LQT3 patients. LQT4 affects the heart’s potassium, sodium, and calcium ion channels.

Symptoms

Congenital LQTS may not be associated with any symptoms. When present, symptoms may include unexplained syncope or fainting, abnormal heart rate or rhythm, unexplained seizures, unexplained drowning or near drowning, or sudden death. Symptoms are often associated with exercise or exertion, occur at times of emotional excitement, or rarely, during sleep or when awakened suddenly.

Patients with LQTS should wear medical identification and be aware of personal symptoms, and family members should know cardiopulmonary resuscitation (CPR) and how to respond during a syncope episode.

Screening and Diagnosis

The diagnosis of LQTS is based on the patient’s medical and family history, and ECG measurement of the QT interval can confirm the diagnosis. Often, LQTS is discovered during a routine exam for another condition or after a family member has been diagnosed with the condition. Other diagnostic tests include pharmacological stress tests, ambulatory cardiac monitors, and an electroencephalogram to rule out neurological causes.

Genetic testing can identify the specific LQTS gene mutations in about 70 percent of individuals with a confirmed diagnosis. Neonatal ECG screening may aid the diagnosis in patients with a known family history.

Treatment and Therapy

Identification of the specific gene mutation can help physicians guide treatment. Changing medications may be the only treatment needed for patients with drug-induced LQTS.

Treatment includes beta blocker and potassium medications, a defibrillator or pacemaker to maintain a normal heart rhythm, and in some cases, surgery. Device therapy and surgical treatment are generally reserved for patients with a high risk of sudden death. Left-sided sympathetic denervation is the surgical treatment for LQTS in which select nerves that regulate the heart rhythm are disconnected.

Physical activity limitations may be advised, such as avoiding strenuous activities and contact sports. Avoiding stressors and other triggers may also be recommended.

Prevention and Outcomes

There is no effective means of preventing congenital forms of LQTS. Avoidance of medications that prolong the QT syndrome may reduce the risk of drug-induced LQTS, as well as help reduce the risk of dangerous heart rhythms in patients with inherited LQTS.

If undiagnosed and untreated, LQTS can be a life-threatening condition, and it is a leading cause of sudden death in otherwise healthy children and young adults. It also contributes to sudden infant death syndrome. A prompt diagnosis and proper treatment can reduce the life-threatening consequences of LQTS.

Bibliography

Crotti, L., et al. “Congenital Long QT Syndrome.” Orphanet Journal of Rare Diseases 3 (2008): 1750–1172.

Levine, E., et al. “Congenital Long QT Syndrome: Considerations for Primary Care Physicians.” Cleveland Clinic Journal of Medicine 75.8 (2008): 591–600.

"Long QT Syndrome." Mayo Clinic. Mayo Foundation for Medical Education and Research, 2014. Web. 1 Aug. 2014.

Schwartz, P. J., et al. “The Congenital Long QT Syndromes from Genotype to Phenotype: Clinical Implications.” Journal of Internal Medicine 259.1 (2006): 39–47.

Tranebjaerg, Lisbeth, Ricardo A. Samson, and Glenn Edward Green. "Jervell and Lange-Nielsen Syndrome." GeneReviews. U of Washington, Seattle, 4 Oct. 2012. Web. 1 Aug. 2014.

"What Is Long QT Syndrome?" National Heart, Lung, and Blood Institute. National Institutes of Health, 21 Sept. 2011. Web. 1 Aug. 2014.