Long QT syndrome

Congenital long QT syndrome (LQTS) is a genetic disorder with prolongation of the QT interval on the electrocardiogram (ECG) and life-threatening cardiac arrhythmias occurring especially under conditions of physical or emotional stress (2).

CLINICAL FEATURES

LQTS is characterised by prolongation of the QT interval on the ECG, causing arrhythmic episodes such as torsades de pointes ventricular tachycardia and ventricular fibrillation. These lead to syncope or even sudden cardiac death. The majority of patients with LQTS are asymptomatic and are either discovered incidentally based on ECG, family history, or having survived an episode of syncope or severe ventricular arrhythmias (1).

The pathogenesis of LQTS is due to defects in the cardiac ion channels involved in the control of ventricular repolarisation (5). Depending on mutation, patients can be divided into different genetic subgroups, major three of them being LQT1, LQT2 and LQT3. Still, 30–35% of patients with a definite clinical diagnosis of LQTS are not positively genotyped to any subgroup.

Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner (3). For LQT1 patients the most life-threatening events occur during sympathetic activation such as emotional arousal and exercise (especially competetive sports and swimming). The cardiac events for LQT2 and LQT3 patients show a different pattern, with most events occurring at rest or during sleep. LQT2 patients are particularly sensitive to startling and sudden noises.

Long QT syndrome can also be acquired due to drugs, primarily antiarrhythmics, antidepressants, and phenothiazides (see: List of drugs prolonging QT interval). This should be taken into consideration when prescribing any medication to LQTS patient. In addition, hypokalemia, hypomagnesemia, and hypocalcemia can also cause prolongation of the QT interval. These drugs and electrolyte abnormalities play a major triggering role in ventricular arrhythmias and sudden cardiac deaths in patients with the inherited LQTS.

MANAGEMENT

Most importantly, patients diagnosed with LQTS should not take drugs that prolong the QT interval. They should also be carefull with conditions that might cause elecrolyte abnormalities.

With few possible exceptions, every patient diagnosed as having LQTS should receive -blocker therapy (4). Implantable cardioverter-defibrillators and left cardiac sympathetic denervation are also good choices of therapy for some patients.

Existing therapies are very effective, but mortality is high among untreated, symptomatic individuals.

LIST OF ABBREVIATIONS

(1)   Roberts, R., (2006) Genomics and Cardiac Arrhythmias, J Am Coll Cardiol. 47: 9-21
(2)   Schwartz , P.J., et al. (1975) The long Q-T syndrome. Am Heart J  89: 378–390
(3)   Schwartz, P.J., et al. (2001) Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 103: 89-95.
(4)   Schwartz, P.J., (2005) Management of long QT syndrome, Nat Clin Pract Cardiovasc Med. 2: 346-51
(5)   Wang, Q., et al. (1995b) Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 4:1603-7.

LIST OF QT PROLONGING DRUGS:

Antiarrhythmic drugs
disopyramide
dofetilide
ibutilide
procainamide
quinidine
sotalol
amiodarone
flecainide

Antihistamines
difenhydramine
terfenadine
astemizole
combination drugs which contain pseudoephedrine
terfenadine

Antimicrobics
erythromycin
chlarithromycin
other macrolide antimicrobics at least when used simultaneously with antihistamines or amiodarone
halofantrine
sulfonamides
pentamidine
sparfloxacin

Others
cisapride
sildenafile
tamoxifen
methadone
domperidone
droperidol

Drugs which may cause hypokalemia
several diuretics
corticosteroids
beta-2 adrenergic agonists

For updated list, see http://www.arizonacert.org/