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) ejection 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 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 greater than 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. 