Hemodynamic tolerability and anti-ischemic efficacy of high dose intravenous diltiazem in patients with normal versus impaired ventricular function

Abstract Objectives . This study was designed to compare the acute systemic and coronary hemodynamic effects of high doses of intravenous diltiazem in patients with normal versus impaired left ventricular function, investigate the safety of this drug and compare its anti-ischemic potential in these two patient groups during pacing-induced stress. Background . Because coronary hemodynamic effects and negative inotropic properties of diltiazem are dose related, high dose intravenous diltiazem may improve anti-ischemic efficacy but may not be tolerated in patients with impaired cardiac function. Methods . High dose intravenous diltiazem, 0.4 mg/kg for 5 min followed by 0.4 mg/kg for 10 min, was administered to 23 normotensive patient's with coronary artery disease, 11 (group A) with normal and 12 (group B) with impaired ventricular function (ejection fraction Results . Diltiazem was well tolerated despite high peak plasma levels, 869 ± 152 μ/liter (group A) and 926 ± 169 μgliter (group B). It resulted in immediate but similar reductions in systemic resistance from 1,321 ± 136 (control value) to 963 ± 113 dynes·s·cm −5 (group A) and from 1,267 ± 106 to 865 ± 58 dynes ·s·cm −5 (group B) and in mean arterial pressure from 107 ± 3 to 93 ± 4 mm Hg (group A) and from 103 ± 4 to 86 ± 4 mm Hg (group B), at 5 min after diltiazem (all p 2 in group 6 and from 44 ± 4 (control value) to 49 ± 5 ml/beat per m 2 in group A, an effect that was significantly greater and more prolonged in group B than in group A. Although neither heart rate nor contractility was affected in either group, left ventricular end-diastolic pressure increased in group A (9 ± 2 mm Hg to 12 ± 1 mm Hg, p Conclusions . High dose intravenous diltiazem is well tolerated, augments coronary flow and improves left ventricular pump function, particularly in patients with preexisting ventricular dysfunction. As its anti-ischemic effects also appear more pronounced in the latter group, high dose diltiazem may be particularly useful when ventricular function is depressed, for example, during prolonged ischemia at rest.