EFFECT OF MIBEFRADIL ON LEFT-VENTRICULAR DIASTOLIC FUNCTION IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Calcium antagonists have antihypertensive and antianginal properties. In heart failure, however, their use can be hazardous, as systolic fun ction can deteriorate. This may nor be true of the new calcium antagon ist mibefradil, which has a new chemical structure. Calcium antagonist s may also be beneficial for diastolic left ventricular function in co ronary artery disease. To investigate the possible effects of mibefrad il on diastolic left ventricular function, we performed the present st udy as a multicenter, double-blind, placebo-controlled, multiple-dose safety trial. Fifteen patients with New York Heart Association (NYHA) class II or III for dyspnea and depressed ejection fraction (<40%) due to a previous myocardial infarction were investigated. The measured n uclear angiographic parameters included ejection fraction (EF), peak e jection rate (PER), and peak filling rate !PFR). Systolic and diastoli c blood pressure (SEP, DBP) and heart rate (HR) were also obtained. Gr oup I (5 patients) received placebo medication; group IIA (6 patients) received mibefradil 6.25, 12.5, or 35 mg/day, and group IIB (4 patien ts) received mibefradil 50 or 100 mg/day, Measurements were made befor e and after the first dose and after 1 week of treatment before and af ter the final dose. Mibefradil clearly decreased HR (repeated-measures analysis of variance p < 0.05). No statistically significant effects of mibefradil were noted on SEP or DBP or on systolic and diastolic le ft ventricular function. In our study conditions, mibefradil caused no worsening of systolic function and preserved diastolic function in sh ort-term treatment of patients with decreased EF and heart failure.