A new oral therapy for long QT syndrome: Long-term oral potassium improves repolarization in patients with HERG mutations

Objectives We sought to determine whether oral potassium supplementation safely increases serum K+ and results in sustained improvement of repolarization parameters in long QT syndrome type 2 (LQT2) subjects. Background Mutations in HERG (LQT2), the gene encoding the rapid delayed rectifier K+ current IKr, account for a significant proportion of congenital long QT syndrome (LQTS). The magnitude of IKr is paradoxically increased by an increase in extracellular K+. We tested the hypothesis that long-term oral potassium supplementation results in a mild, sustainable increase in serum K+ that improves repolarization abnormalities in subjects with LQT2. Methods After an initial evaluation consisting of electrocardiography, electrolytes, blood urea nitrogen, and creatinine, escalating doses of potassium chloride (KCl) and spironolactone were administered to eight subjects with six distinct HERG mutations. Medications were continued for four weeks, at which time, the final evaluation was undertaken. Beta-adrenergic blocking therapy was maintained. Results The subjects ranged in age from 11 to 52 years. The average daily KCl and spironolactone dose was 3.3 ± 1.5 mEq/kg and 3.5 ± 1.2 mg/kg, respectively, and this regimen resulted in an increase in serum K+ from 4.0 ± 0.3 to 5.2 ± 0.3 mEq/l. There were no serious complications associated with therapy. The increase in serum K+ resulted in a decrease in the corrected QT interval from 526 ± 94 to 423 ± 36 ms (mean ± SD; lead V2). Both QT dispersion and T-wave morphology improved in most subjects. Conclusions Long-term oral potassium administration increases serum K+ in patients with LQT2. This can be achieved safely and results in improvement in repolarization. Further studies are warranted to determine whether this will reduce the incidence of life-threatening events in LQTS patients.