Long QT Syndrome - September 2007
Electrical activity of the heart is due to flow of ions (potassium, sodium and calcium) through “ion channels” across cardiac cells. Dysfunction of ion channels shows up on the surface electrocardiogram as prolongation of the QT interval (time marking onset of ventricular depolarization and end of repolarization). Abnormal prolongation of QT interval (see definition below) is a surrogate for disturbed electrical activity of the heart and an indicator of a propensity to have lethal ventricular arrhythmias including the classic Torsade de Pointes (Figure 1). This is referred to as long QT syndrome (LQTS).
Measuring QT Interval
Measuring a patient’s QT interval on a 12 lead electrocardiogram is simple but requires attention to detail. The number of small boxes (each box = 0.04 milliseconds) between the start of the QRS complex and the end of the T wave on the isoelectric point in lead II (or any other limb lead) are counted. The product of the number of small boxes and 0.04 derives QT interval. A correction is made for the heart rate using Bazett’s formula (Figure 2) referred to as corrected QT interval (QTc). RR interval is derived by measuring the time interval between 2 preceding R waves using the same method.
Diagnosing LQTS
While a QTc greater than 480 milliseconds is clearly abnormal, we recommend consultation with a pediatric cardiologist when QTc is greater than 450 milliseconds in boys and 460 milliseconds in girls.
LQTS is encountered in clinical practice as:
1. An incidental finding on an electrocardiogram.
2. A presentation with palpitation, syncope, seizures, near or sudden cardiac death.
3. Prolonged QT interval on screening and surveillance electrocardiograms during therapy with agents known to cause LQTS.
LQTS may be an acquired or an inherited condition.
Acquired LQTS is reversible when exposure to the causative agent (Table I) ceases.
Inherited LQTS
Inherited LQTS is due to mutation of genes coding for the ion channels resulting in altered protein infrastructure of the ion channels. The incidence is 1:5000. About 200 different mutations of these genes have been found so far. There is some variation of the electrocardiographic findings and patient symptoms depending upon which gene and which mutations are involved. In order of frequency, LQT1 due to gene mutation KCNQ1 (KVLQT1) or KCNE1 (MinK) is the most frequent (55-60%) followed by LQT2 due to HERG or KCNE2 (MiRP1) mutations (35-40%) and LQT3 from SCN5A mutations (3-5%).
Newborn infant and long QT
Newborn infants may exhibit prolongation of QT interval in the first week of life that is transient and secondary to developmental status of autonomic cardiac innervation. On the other hand, there is a growing body of evidence that up to 10% of sudden infant death syndrome is due to fatal arrhythmias secondary to LQTS. At the present time justification for universal newborn screening electrocardiograms remains unclear.
Treating Patients with inherited LQTS
Symptomatic patients should be treated with beta-blocker drug therapy which is very well tolerated. The goal of therapy is resolution of symptoms and ECG changes. Beta-blockers are effective in the LQT1 patients and are the treatment of choice. Patients with LQT3 due to sodium channel abnormalities may require agents affecting the sodium channel such as mexilitine. In patients with LQT2, potassium administration has been shown to shorten QT duration. For patients presenting with near sudden death or who continue to have syncope in spite of medications, an implantable defibrillator is indicated. This may particularly be the case in patients with LQT3.
Asymptomatic individuals should be on beta-blocker therapy as they have a significant chance of subsequently developing symptoms including sudden death. Medication is not curative; but protective while being taken. The protective effect of beta blocker therapy ceases upon discontinuation of therapy, exposing the individual to risk for sudden death.
With proper treatment, individuals with LQTS can participate in recreational sports. Competitive sports are contraindicated as symptoms are often precipitated by physical exertion and/or emotions. Family members should learn CPR to be able to provide immediate resuscitation effort.
References
1. Moss, AJ: JAMA, Volume 289 (16) April 23/30, 2003, 2041-2044
2. Arnestad, M et al. Circ 2007; 115:361-367
This information provided by Nikola Tede, M.D. and Kalyani Trivedi, M.D., Pediatric Cardiology, California Pacific Medical Center Department of Pediatrics. www.cpmc/pediatrics