Long QT Syndrome (LQTS)

Congenital or acquired adrenergic-induced ventricular arrhythmias.

Romano-Ward Syndrome; Long QT Syndrome (1-2-3-4-5); Prolonged QT Interval Syndrome; Protracted QT; QT Interval Prolongation; QT Prolongation Syndrome; Ventricular Fibrillation Prolonged QT Interval Syndrome.

Seven different genetic defects have been identified, all involving potassium and sodium transmission.

LQT1 is the most common type. It corresponds to a defect of chromosome 11, encoding for the potassium channel.

LQT2 is the second most common form of LQTS. It is reported to be a defect on chromosome 7, again encoding for the potassium channel. LQT1 and LQT2 are thought to represent 95% of all cases of LQTS. The standard treatment for LQT1 and LQT2 is β-adrenergic blockade, which has been confirmed to reduce mortality.

LQT3 represents 3 to 4% of cases and corresponds to a defect on chromosome 3. It is encoding the sodium channel. β-Blockade is contraindicated in this type of LQTS because bradycardia can further prolong the QT interval and lead to ventricular arrhythmias. Therefore, it has been suggested that increasing the heart rate probably would be beneficial in LQT3.

LQT4, LQT5, and LQT6 all involve defects on the potassium transmission and are located on chromosomes 4, 21, and 21, respectively. They are very rare.

LQT7 (Andersen Cardiodysrhythmic Periodic Paralysis Syndrome) is discussed in Section A under this name.

All types are characterized by a corrected QT interval of at least 440 ms on the electrocardiogram. The manifestation is recurrent syncope associated with documented ventricular arrhythmia and sudden death.

1:10,000 in the general population (= 90% of congenital LQTS).

Romano-Ward by autosomal dominant inheritance. LQT1 has been mapped to chromosome 11. Other mutated genes located on chromosomes 3, 6, and 11 may contribute to or cause LQTS.

Long QT syndrome results from structural of acquired/transient (therapeutic) abnormalities in the potassium channels of the heart.

Acquired LQTS may be caused by the following:

• Drugs: A list of drugs known or suspected to prolong the QT interval is given in Table L-4. A more extensive list of drugs that prolong the QT interval can be found on the web site of either The University of Arizona Center for Education and Research on Therapeutics at http://qtdrugs.org or http://www.torsades.org
• Electrolyte Disturbances: Acute or chronic hypokalemia, chronic hypocalcemia, and chronic hypomagnesemia.
• Associated Medical Conditions: Atrioventricular block, sick sinus syndrome, myocarditis, hyperparathyroidism, hypothyroidism, subarachnoid hemorrhage, encephalitis, head trauma, starvation, and anorexia nervosa.

Congenital LQTS presents a large genetic heterogeneity: at least six genes have been identified that code for subunits of K or Na ionic channels. Six genotypes have been identified for the Romano-Ward syndrome (LQTS 1-6). Mutations have been identified in the KVLQT1, HERG, and KCNE1 genes (coding for a K+ channel controlling cardiomyocyte repolarization during phases 3 and 4 of the cardiac muscle action potential). A mutation of the SCN5A gene has been identified and affects Na+ influx during phase 1 of depolarization.

Patient history, family history. Corrected QT (QTc) greater than 0.46 seconds has a positive predictive value greater than 90%. A QTc greater than 0.42 seconds needs to be taken in context of history. Some patterns of repolarization abnormalities reflected by T-wave morphology on surface ECG (wide base, double hump) could indicate which mutation is involved.

Forty percent of patients remain asymptomatic. Ten percent of patients will have as first clinical sign, a cardiac arrest. Symptoms include syncope, “epilepsy,” and palpitations precipitated by stressful events (intense emotion or physical activity). Swimming appears to be a potent trigger. Sudden death or cardiac arrest secondary to ventricular dysrhythmia can be the presentation. ECG findings include long QTc interval (QTc = QT interval/square root of R-R interval) calculated in lead II or V5 and abnormal T-wave morphology. Ventricular dysrhythmias, torsades de pointes, and ventricular tachycardia are common causes of collapse. Medical management includes beta blockade, pacemaker insertion, implantable cardioverter-defibrillator placement, and rarely left stellate ganglion excision/ablation. Genotyping may allow targeting drugs at specific ion channels in the future.

Full history regarding episodes of collapse and current medical management. Check pacemaker specifications if present. Exclude obvious signs of endocrine disease. Review drug history for medications associated with the syndrome. Check Na, K, Ca, and Mg electrolytes. Correct abnormalities preoperatively. Review ECG. Continue beta blockade preoperatively (IV if necessary). Check QT duration on ECG in infants presenting with deafness or syndactyly. Defibrillator cardiac and resuscitation drugs should be present in the same room as the patient. Preoperative laboratory investigations must include kalemia, magnesemia, and calcemia, which can increase arrhythmia.

Death can occur at any age and at any stage of anesthesia. Increased rhythm troubles are observed with light anesthesia, hypoxemia, hypercarbia, and hypocarbia. Tracheal intubation and extubation should be performed with deep anesthesia. The number of episodes of induced arrhythmias during induction and intubation is given in Table L-5. Prevent any electrolytic disorders. Premedication is desirable to prevent any stress to the patient. Hypoglycemia has been reported after preoperative fasting associated with beta blockade. Monitor blood glucose and consider administration of dextrose-containing fluids. Full monitoring preinduction! Aim to minimize surges in endogenous catecholamines. Cover stress response to laryngoscopy. Prevent hypocalcemia and hypokalemia. Ensure optimal postoperative analgesia.

Although thiopental, succinylcholine, and propofol all increase QT interval in normal patients, the effect is least with propofol. Because sevoflurane prolongs QT interval in both normal and congenital LQTS patients, it should be used very cautiously. Esmolol should be available at induction. Magnesium sulfate should be used to treat torsades de pointes. Ketamine and pancuronium are contraindicated because of their sympathomimetic effects. Vasopressors are relatively contraindicated. Halothane is contraindicated because of sensitization of myocardium.

Avoid drugs known to prolong QT duration (see Table L-4). Stellate ganglion block should be considered in patients who are at particularly high risk for arrhythmia. Treatment of cardiac ventricular arrhythmia can include β-adrenergic blockade, internal atrial pacing, isoproterenol (increases heart rate to reduce QT interval), and cardioversion.

Jervell and Lange-Nielsen Syndrome (JLN 1-2): Two genotypes have been described; one results in mutation of the cardiac potassium channel KCNQ1 (K channel involved in phase 3 of cardiac action potential). This gene is involved in endolymph homeostasis explaining the association of the syndrome with deafness. Although congenital LQTS typically occurs in patients with normal cardiac morphology, a new variant with congenital heart disease and bilateral syndactyly has been described. Epidural anesthesia has been used successfully for cesarean section in Jervell and Lange-Nielsen syndrome: lidocaine might be a better choice than bupivacaine. No experience with ropivacaine or levobupivacaine have been reported.

Andersen Cardiodysrhythmic Periodic Paralysis Syndrome: Characterized by the clinical triad of potassium-sensitive periodic paralysis (low, normal, or high potassium levels), ventricular arrhythmias (bigeminy, long QT interval, ectopy, and bidirectional ventricular tachycardia), and dysmorphic facial features. Sudden death has been reported. Andersen syndrome must not be confused with Andersen disease (glycogen storage disease type IV).

Periodic Paralysis (PP): Congenital abnormality in membrane electrolyte conductance leading to episodic muscle weakness.

Thyrotoxic Periodic Paralysis: Acquired disorder characterized by intermittent episodes of muscle weakness alternating with periods of normal muscular function. Occurs during hyperthyroidism and thyrotoxicosis. During attacks, hypokalemia is present. May be precipitated by low plasma concentration of insulin. Occurs predominantly in Asian males but has been found in Latin American males.