Potassium in Long QT Syndromes

Abstract

fects are mediated mostly by the rapidly activating delayed rectifi er potassium current (I Kr ) that is paradoxically increased when extracellular potassium is increased [9] . When KCNH2, the gene coding for the -subunit of I Kr , was fi rst linked to the congenital long QT syndrome, the cornerstone for gene-specifi c therapy was laid [10] . Compton et al. [11] where the fi rst to systematically study the effects of potassium supplementation in patients with congenital long QT syndrome. They showed that acute intravenous potassium supplementation (increase 6 1.5 mEq/l) led to a 24% reduction in QTc in 7 patients carrying mutations in KCNH2 (LQT2) compared to a 4% reduction in 5 control probands [11] . This study was followed by a recent study testing a 4-week oral potassium administration (accompanied by high-dose spironolactone) in 8 patients with mutations in KCNH2 that demonstrated an increase in serum potassium from 4.0 8 0.3 to 5.2 8 0.3 mEq/l resulting in a decrease in QTc from 526 8 94 to 423 8 36 ms [12] . In this issue of Heart Drug , Christiansen et al. [13] report the case of a female patient that had been resuscitated several times at the age of 5–6 years while bathing at the beach. She had experienced several syncopal events at the age of 35 when ECG revealed broad T and U waves, and had been treated successfully with potassium salts and ammonium chloride for more than 35 years until she was diagnosed with a known mutation in KCNQ1 (G306R) that has been found to exhibit a dominant negLong QT syndrome is considered as a genetically heterogeneous disease caused by defects predominantly in genes coding for myocardial ion channels with a natural history ranging from sudden death in infancy to asymptomatic longevity [1] . Congenital long QT syndrome serves as a model disease for understanding arrhythmogenesis in the context of altered repolarization. Besides mutations that directly affect cardiac repolarization, a number of additional factors, e.g. female gender, left ventricular hypertrophy, and heart failure, drugs, and hypokalemia have been linked to QT prolongation and risk of arrhythmias. The concept of reduced repolarization reserve as the basis for individual susceptibility to arrhythmias in the context of QT prolongation [2] has been confi rmed in several studies [3, 4] and applies for the congenital long QT syndrome as well as for other causes of QT prolongation, e.g. hypertrophy, heart failure and QT-prolonging drugs. Current evidence suggests that reduced repolarization reserve is caused by mutations in disease genes (familial LQTS) and may be subclinical until unmasked by extrinsic triggers (e.g. drugs and hypokalemia) [5] . Potassium has been linked to cardiac arrhythmias for almost a century, and its effects on the QT interval have been previously shown. Potassium supplementation may have arrhythmia-suppressing properties [6, 7] and the potential mechanism being the shortening of cardiac action potentials [8] . Today, it is widely accepted that these efPublished online: January 19, 2005