Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization

Masaki Yamauchi, Eiichi Watanabe, Kenji Yasui, Hiroshi Takeuchi, Toshiaki Terasawa, Ken Sawada, Hitoshi Hishida, Itsuo Kodama

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Backgrounds: 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. Methods and 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 (QTpeak, QTend), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QTpeak and QTend 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≥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). Conclusion: 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.

Original languageEnglish
Pages (from-to)92-97
Number of pages6
JournalInternational Journal of Cardiology
Volume103
Issue number1
DOIs
Publication statusPublished - 03-08-2005

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Mexiletine
Ventricular Premature Complexes
Long QT Syndrome
Anti-Arrhythmia Agents
Electrocardiography
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Yamauchi, Masaki ; Watanabe, Eiichi ; Yasui, Kenji ; Takeuchi, Hiroshi ; Terasawa, Toshiaki ; Sawada, Ken ; Hishida, Hitoshi ; Kodama, Itsuo. / Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization. In: International Journal of Cardiology. 2005 ; Vol. 103, No. 1. pp. 92-97.
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abstract = "Backgrounds: 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. Methods and 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 (QTpeak, QTend), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QTpeak and QTend 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≥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). Conclusion: 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.",
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Prevention of ventricular extrasystole by mexiletine in patients with normal QT intervals is associated with a reduction of transmural dispersion of repolarization. / Yamauchi, Masaki; Watanabe, Eiichi; Yasui, Kenji; Takeuchi, Hiroshi; Terasawa, Toshiaki; Sawada, Ken; Hishida, Hitoshi; Kodama, Itsuo.

In: International Journal of Cardiology, Vol. 103, No. 1, 03.08.2005, p. 92-97.

Research output: Contribution to journalArticle

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AU - Yamauchi, Masaki

AU - Watanabe, Eiichi

AU - Yasui, Kenji

AU - Takeuchi, Hiroshi

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AU - Hishida, Hitoshi

AU - Kodama, Itsuo

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N2 - Backgrounds: 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. Methods and 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 (QTpeak, QTend), and the interval from T-wave peak to T-wave end (TPE) against preceding respective RR intervals of sinus beats. Both the QTpeak and QTend 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≥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). Conclusion: 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.

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