Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization.
BACKGROUND
Antiarrhythmic potential of mexiletine in patients with congenital and acquired long-QT syndrome (LQTS) has been attributed to a reduction of transmural dispersion of repolarization (TDR). A similar mechanism could be involved in the antiarrhythmic activity of the drug in patients with normal QT intervals, but the issue remains to be investigated.


RESULTS
We analyzed 24-h Holter ECG recordings from 17 patients in sinus rhythm showing premature ventricular complexes (PVCs) with normal QT intervals (age, 62+/-10 years, mean+/-S.D.). Treatment of the patients with oral mexiletine (300 mg/day for 21-40 days) resulted in a significant reduction of PVCs (from 13899+/-18887 to 6949+/-12822 beats/24 h, p<0.01). Rate-dependent behavior of ventricular repolarization was analyzed by plotting QT intervals (QT(peak), QT(end)), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QT(peak) and QT(end) tended to be shortened by mexiletine at RR intervals from 600 ms to 1000 ms, although the changes did not reach statistical significances. TPE, which reflects TDR, was shortened significantly at relatively long RR intervals (by 14+/-9% at RR of 900 ms, p<0.05). There was a linear relationship between the percentage shortening of TPE and the percentage reduction of PVCs (r=0.86, p<0.04). TPE> or =70 ms was significantly associated with PVC suppression >75% with an odds ratio of 0.60 (95% confidence interval 0.36-0.98, per 1 ms increment).


CONCLUSIONS
Inhibitory effect of mexiletine against PVCs in patients with normal QT intervals is mediated at least in part by a reduction of TDR. Mexiletine may be effective in patients exhibiting longer baseline TPE.
Yamauchi
Masaki
M
Department of Cardiology, Gifu Shakai Hoken Hospital, Kani, Japan.
Watanabe
Eiichi
E
Yasui
Kenji
K
Takeuchi
Hiroshi
H
Terasawa
Toshiaki
T
Sawada
Ken
K
Hishida
Hitoshi
H
Kodama
Itsuo
I
D000200:Action Potentials / Q000502:physiology; D000284:Administration, Oral; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D018879:Ventricular Premature Complexes / Q000503:physiopathology / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine