A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations.
OBJECTIVE
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 V(2)). 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.
Etheridge
Susan P
SP
Primary Children's Medical Center and the Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, Utah 84113, USA. pcether@ihc.com
Compton
Steven J
SJ
Tristani-Firouzi
Martin
M
Mason
Jay W
JW
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins; D002648:Child; D004268:DNA-Binding Proteins; D019587:Dietary Supplements; D004232:Diuretics / Q000008:administration & dosage; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011189:Potassium Chloride / Q000008:administration & dosage*; D017680:Potassium Compounds / Q000008:administration & dosage*; D013148:Spironolactone / Q000008:administration & dosage; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D004232:Diuretics; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D017680:Potassium Compounds; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D013148:Spironolactone; D011189:Potassium Chloride