In ER, the Patient was initially found to be combative but hemodynamically stable. 12 lead EKG showed presence of long corrected QT interval of 710 msec, and presence of U waves correlating with his low potassium levels of 3.1. The urine toxicology screen was positive for cocaine. Patient’s mental status rapidly improved and in a span of few hours he was able to provide coherent history. Suddenly, he was found to have a seizure-like activity in the ER. Monitor revealed a wide complex, polymorphic ventricular tachycardia, which reverted to sinus rhythm in a span of few seconds. After the initial episode, patient had 2 more episodes of ventricular tachycardia in the next few minutes, which resolved spontaneously after lasting for a duration of 5-7 seconds.

Patient was initially intubated and transferred to Cardiac Care Unit (CCU). Serial EKG’s done in the CCU did reveal a prolonged QTC which gradually decreased to normal duration over a span of 2 days. Given the history of sudden cardiac deaths in the family and seizure like episodes in the patient, diagnosis of Congenital long QT syndrome was entertained and an Epinephrine induced QT stress test was planned.

Initial EKG before the start of epinephrine stress test showed a QTc of 440 msec, patient was started on Epinephrine infusion at rate of 0.25 micrograms/Kg/min for 10 mins under continuous EKG monitoring. QTc at end of this period did show a prolongation to 570 msec after which rate of epinephrine was increased to 0.5 mcg/kg/min for another 5 minutes, at end of which QTc prolonged to 600 msec. The test was deemed positive and was stopped at this point of time. Patients QTc rapidly reverted to pre test level after epinephrine was stopped.

The congenital LQTS is a potentially life threatening condition, caused by mutations in genes encoding cardiac ion channels which result in prolongation of ventricular action potential. Genetic screening of symptomatic patients or their asymptomatic family members may identify patients at risk for life threatening arrhythmias and the type of LQT as it has important implications in the management. Out of the several forms of congenital LQTS, three forms LQT1, LQT2, and LQT3 have been well characterized. These three forms have also been described on the basis of their specific EKG morphology. Recent investigations suggest that even in patients with acquired LQTS (e.g. resulting from intake of QT-prolonging medicines), there are clinically silent gene mutations that lead to overt QT prolongation only with exposure to QT- prolonging medications (4-6).This explains why some patients seem to be more prone than others to have QT prolongation at a given dose of QTProlonging drugs, even after adjustment for other factors that could prolong QT-interval.

According to Pfizer Tikosyn program, the QTc should be no more than 500 msec in the presence of ventricular conduction abnormality (7). This guidance may be used until a standard method is established for the measurement. Treatment with beta-blockers can reduce this risk. The clinical course of the congenital LQTS is influenced largely by the gene affected (8). While cardiac events are more frequent and occur at a younger age in patients with LQT1 and LQT2, they are potentially more fatal in patients with genotype LQT3. Patients with LQT1 and LQT2 genotype typically benefit from high dose beta-blocker therapy (9, 10). However, patients with LQT3 are at higher risk at lower heart rates and potentially may benefit from pace maker therapy. In addition, they shorten their QT-interval more with sodium channel blockers (11).

Provocative tests using catecholamine or exercise testing have long been considered to unmask some forms of congenital LQTS (12). Recent preliminary data by Ackerman et al. have suggested the usefulness of an epinephrine test to unveil concealed LQT1 syndrome (13). An epinephrine provocative test should only be done by cardiologists, under enough preparation of intravenous beta-blockers and direct cardioverter for unintentionally induced ventricular fibrillation.

Both experimental and clinical studies have suggested a differential response of action potential duration (APD) and QT interval to sympathetic stimulation among LQT1, LQT2, and LQT3 (14). Persistent and paradoxical prolongation of APD and QT interval at steady state conditions of catecholamines is reported in LQT1 syndrome. Under normal conditions, betaadrenergic stimulation is expected to increase net outward repolarizing current, owing to larger increase of outward currents, including Ca-activated slow component of the delayed rectifier potassium current (IKs) and Ca-activated chloride current, than that of an inward current, Na/Ca exchange current (INa-Ca), resulting in an abbreviation of APD and QT interval. A defect in IKs in the LQT1 syndrome could account for failure of betaadrenergic stimulation to abbreviate APD and QT interval, resulting in a persistent and paradoxical QT prolongation under sympathetic stimulation (14). In LQT2 syndrome, catecholamines are reported to initially prolong but then abbreviate APD and QT interval, probably because of an initial augmentation of INa-Ca and a subsequent stimulation of IKs. In contrast to the LQT1 and LQT2 syndromes, catecholamines are reported to constantly abbreviate APD and QT interval as a result of a stimulation of IKs in the LQT3 syndrome, because an inward late sodium current (INa) was augmented in this genotype. The epinephrine test may be applied not only for unmasking silent mutation carriers with LQT1 syndrome but also for predicting genotypes.