Comparative effects of nicorandil with isosorbide mononitrate on cardiac sympathetic nerve activity and left ventricular function in patients with ischemic cardiomyopathy

Abstract

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves left ventricular (LV) remodeling after myocardial infarction in rat models. However, the effects of chronic nicorandil therapy on cardiac sympathetic nerve activity in patients with ischemic cardiomyopathy have not been determined. Thirty-six patients with ischemic cardiomyopathy (LV ejection fraction [LVEF] < 40%) who underwent successful revascularization procedure before 6 months were treated by standard conventional therapy. Eighteen patients were randomized to additionally receive nicorandil (15 mg/d), whereas the other 18 patients received isosorbide mononitrate (40 mg/d). The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy before and 6 months after treatment. Left ventricular end-diastolic volume (LVEDV) and LVEF were determined by echocardiography. Total defect score, H/M ratio, WR, LVEDV, and LVEF at baseline were similar for both groups. After treatment, in patients receiving nicorandil, TDS decreased from 50 +/- 6 to 40 +/- 11 (P < .005), H/M ratio increased from 1.68 +/- 0.23 to 1.79 +/- 0.26 (P = .005), and WR decreased from 46% +/- 9% to 40% +/- 12% (P < .005). In addition, LVEDV decreased from 178 +/- 31 to 157 +/- 30 mL (P < .0005), and LVEF increased from 33% +/- 6% to 39% +/- 7% (P < .05). In patients receiving isosorbide mononitrate, no significant changes were observed in these parameters. Moreover, there was a significant correlation between the percent change of LVEF and that of TDS from baseline to 6 months in the patients receiving nicorandil (r = -0.569, P < .05). The present study demonstrates improvements in cardiac (123)I-MIBG scintigraphic and echocardiographic parameters with nicorandil treatment. These findings indicate that nicorandil can improve cardiac sympathetic nerve activity and LV function in patients with ischemic cardiomyopathy.