Effects of Long-term Treatment With Calcium Antagonists on Left Ventricular Diastolic Function in Stable Angina and Heart Failure

The appearance of impaired left ventricular diastolic function in chronic ischemic heart disease often precedes systolic dysfunction. Myocardial ischemia and increased calcium loading have been implicated in the genesis of increased left ventricular stifness. We have assessed the effects of long-term therapy with different classes of calcium channel-blocking drugs on left ventricular peak filling rate in patients with chronic stable angina and congestive heart failure secondary to ischemic heart disease. Therapeutic effects of nicardipine (30 mg t.i.d.), nisoldipine (10 mg b.i.d.), and verapamil (120 mg t.i.d.) (4 weeks) have been assessed on radionuclide left ventricular diastolic filling parameters in patients with chronic stable angina using placebo-controlled studies. All three drugs significantly improved exercise capacity as compared with placebo. Verapamil produced significant improvements in peak filling rate (p<0.005), time to peak filling rate (p<0.01), and first one-third filling fraction (p<0.005), whereas nicardipine only improved peak filling rate (p<0.005); neither drug altered the mean ejection fraction (n=20). Nisoldipine did not significantly alter diastolic filling parameters or ejection fraction (n=10). Nisoldipine and digoxin were also assessed in congestive heart failure (New York Heart Association [NYHA] classes II and III) associated with ischemic heart disease (n=26) (open parallel design). Neither produced significant alterations in peak filling rate and ejection fraction after 3 months of therapy. In a preliminary study of patients with moderately severe ischemic heart failure (NYHA classes 111 and IV), however, nicardipine produced significant improvements in ejection fraction, relative cardiac output, and peak filling rate after 4 weeks of long-term therapy (20–40 mg t.i.d.) (n=7). Calcium antagonists vary significantly in their ability to improve diastolic filling abnormalities in patients with ischemic heart disease despite pharmacological similarities.