GENETICALLY DEFINED THERAPY OF INHERITED LONG-QT SYNDROME - CORRECTION OF ABNORMAL REPOLARIZATION BY POTASSIUM

Background Many members of families with inherited long-QT (LQT) syndr ome have mutations in HERG, a gene encoding a cardiac potassium channe l that is modulated by extracellular potassium. We hypothesized that a n increase in serum potassium would normalize repolarization in these patients. Methods and Results We studied seven subjects with chromosom e 7-linked LQT syndrome and five normal control subjects. Repolarizati on was measured by ECG and body surface potential mapping during sinus rhythm, exercise, and atrial pacing, before and after serum potassium increase. Potassium administration improved repolarization in the LQT syndrome. At baseline, LQT subjects differed from control subjects: r esting corrected QT interval QT(c), 627+/-90 versus 425+/-25 ms, P=.00 07), QT(c) dispersion (133+/-62 versus 36+/-9 ms, P=.009), QT/RR slope (0.35+/-0.08 versus 0.24+/-0.07, P=.04), and global root-mean-square QT interval (RMS-QT(c); 525+/-68 versus 393+/-22, P=.002). All LQT sub jects had biphasic or notched T waves. After administration of potassi um, the LQT group had a 24% reduction in resting QT(c) interval (from 617+/-92 to 469+/-23 ms, P=.004) compared with a 4% reduction among co ntrol subjects (from 425+/-25 to 410+/-45 ms, P>.05). The reduction wa s significantly greater in LQT subjects (P=.018). QT dispersion became normal in LQT subjects and did not change in control subjects. The sl ope of the relation between QT interval and cycle length (QT/RR slope) decreased toward normal. T-wave morphology improved in six of seven L QT subjects. The LQT group had a greater reduction in RMS-QT(c) than c ontrol subjects (P=.04). Conclusions An increase in serum potassium co rrects abnormalities of repolarization duration, T-wave morphology, QT / RR slope, and QT dispersion in patients with chromosome 7-linked LQT .