Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia

The effects of oral mexiletine on left ventricular (LV) election fraction (EF) and ventricular arrhythmias--and a possible relation between these effects--were evaluated during 3 months of therapy in 29 patients with chronic ventricular premature complexes VPCS) and a moderately reduced to normal LVEF by 24-hour Holter monitoring and by radionuclide ventriculography at rest and during maximum tolerable exercise testing. After an average titration period of 13 days, a mean daily mexiletine dose of 739 mg was maintained throughout the treatment. At the end of titration and after 3 months of treatment, patients with a baseline LVEF [is less than or equal to] 40% (group 2) responded with a median reduction of the hourly VPC rate by 90 and 81%, respectively, compared with 79 and 72% in those with a baseline LVEF >40% (group 1). Couplets and runs of ventricular tachycardia were almost completely suppressed in nearly all patients. A single patient had a proarrhythmic increase in VPCs during treatment. Compared with baseline, there were no significant changes in resting or exercise LVEF after 1 or 3 months of treatment in either of the 2 groups of patients. No correlation was found between treatment-induced changes in arrhythmia frequency and in resting EF. No symptoms of congestive heart failure developed. The study confirms that long-term use of mexiletine is efficacious and relatively free of cardiac depressant effects even in patients with diminished LV function. (Am J Cardiol 1990;66:1222-1227)
Treatment of ventricular arrhythmias, abnormal heartbeats originating in the ventricles, are very difficult to treat if the patients have poor left ventricle function or chronic congestive heart failure. These patients do not respond well to antiarrhythmic drugs and are more likely to experience drug-induced worsening of the arrhythmia. However, mexiletine, an antiarrhythmic drug, has not demonstrated adverse effects on patients with a history of heart attack, left ventricular dysfunction, or congestive heart failure. This study of 29 men assessed the effects of mexiletine on left ventricular function and the suppression of ventricular premature complexes (VPCs), a type of abnormal heart rhythm. The results confirmed that left ventricular ejection fraction (LVEF), the proportion of blood that is ejected by contraction of the left ventricle, was not significantly affected by mexiletine. Of the six antiarrhythmic drugs recently tested, mexiletine had the second lowest incidence (after lorcainide) of new or worsened congestive heart failure. Those patients with a baseline LVEF below 35 percent (normal is 65 percent) did not develop symptoms or signs of congestive heart failure while taking mexiletine. Those patients who had more severely impaired left ventricles originally had more VPCs per hour, and had a greater than average reduction while taking mexiletine than patients with less damage. However, there was no relation between the magnitude of the treatment effect on left ventricular function and the degree of suppression of VPCs, which contradicts other studies. This study confirms that long-term oral mexiletine treatment works well, and has few heart depressant effects in men with diminished left ventricular function. (Consumer Summary produced by Reliance Medical Information, Inc.)