Effect of Mibefradil on Left Ventricular Diastolic Function in Patients with Congestive Heart Failure

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Abstract
Calcium antagonists have antihypertensive and antianginal properties. In heart failure, however, their use can be hazardous, as systolic function can deteriorate. This may not be true of the new calcium antagonist mibefradil, which has a new chemical structure. Calcium antagonists may also be beneficial for diastolic left ventricular function in coronary artery disease. To investigate the possible effects of mibefradil on diastolic left ventricular function, we performed the present study 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 nuclear angiographic parameters included ejection fraction (EF), peak ejection rate (PER), and peak filling rate (PFR). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were also obtained. Group I (5 patients) received placebo medication; group IIA (6 patients) received mibefradil 6.25, 12.5, or 25 mg/day; and group IIB (4 patients) received mibefradil 50 or 100 mg/day. Measurements were made before and after the first dose and after 1 week of treatment before and after the final dose. Mibefradil clearly decreased HR (repeated-measures analysis of variance p < 0.05). No statistically significant effects of mibefradil were noted on SBP or DBP or on systolic and diastolic left ventricular function. In our study conditions, mibefradil caused no worsening of systolic function and preserved diastolic function in short-term treatment of patients with decreased EF and heart failure.

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