Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease

Summary

To assess the effects of ranolazine, a new antiischemic drug, on regional myocardium of the left ventricle, left ventricular (LV) hemodynamic and angiographic data were obtained in 15 patients with previous transmural myocardial infarction before and after intravenous infusion of ranolazine (200 or 500 µg/kg body weight). LV angiogram was analyzed by the area method and was divided into six segments. Regional LV segments were classified as normal (perfused by intact coronary vessels, n=20), ischemic (perfused by stenotic vessels but without ECG evidence suggesting myocardial necrosis, n=25), or infarcted (total coronary occlusion and with the ECG evidence for necrosis, n=45). Regional area fractional shortening, peak filling rate, and segmental wall motion during isovolumic relaxation period were analyzed. After ranolazine, regional area fractional shortening was unchanged in all segments. However, regional peak filling rate was decreased in the normal segments (1499±315 to 1368±303 mm²/sec, p<0.05). In the ischemic segments, by constrast, the administration of ranolazine significantly increased the regional peak filling rate (1050±410 to 1133±439 mm/sec, p<0.05) and regional wall lengthening during the isovolumic relaxation period (0.9±4.1% to 2.8±5.7% of end-diastolic segmental area, p<0.05), which indicates an improvement of regional diastolic function. Infarct segments were little affected by ranolazine. Thus, ranolazine improves diastolic function of the noninfarcted myocardium under chronic ischemic conditions and also may exert a mild negative lusitropic effect on the normal myocardium, although the former beneficial effect appears to be more clinically important. This finding supports the hypothesis that chronic myocardial ischemia impairs myocardial diastolic function and also opens new therapeutic perspectives.