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CLINICAL RESEARCH: ELECTROPHYSIOLOGIC DISORDERS

A new oral therapy for long QT syndrome

Long-term oral potassium improves repolarization in patients with HERG mutations

Susan P. Etheridge, MD, FACC^*,*, Steven J. Compton, MD, FACC, Martin Tristani-Firouzi, MD^* and Jay W. Mason, MD, FACC

^* Primary Children's Medical Center and the Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Alaska Heart Institute, Anchorage, Alaska, USA
Division of Cardiology, University of Kentucky, Lexington, Kentucky, USA

Manuscript received December 12, 2002; revised manuscript received July 6, 2003, accepted July 7, 2003.

^* Reprint requests and correspondence: Dr. Susan P. Etheridge, University of Utah and Primary Children's Medical Center, 100 North Medical Drive, Salt Lake City, Utah 84113, USA.
pcsether{at}ihc.com

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 I_Kr, account for a significant proportion of congenital long QT syndrome (LQTS). The magnitude of I_Kr 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.

Abbreviations and Acronyms   HERG = human ether-a-go-go related gene   IKr = rapidly activating delayed rectifier K+ current   LQTS = long QT syndrome   LQT2 = long QT syndrome type 2   QTc = corrected QT interval

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