Noninvasive assessment of clinical response to oral propranolol therapy

Nineteen patients with severe but stable angina pectoris entered a double blind controlled study to evaluate the effect of orally administered propranolol on exercise tolerance measured with a bicycle ergometer, and left ventricular function measured by echocardiography and systolic time intervals. In the group treated with propranolol the dose was increased from 80 to 320 mg/day. Studies including determination of propranolol blood levels were obtained before treatment and for each dose of propranolol. With propranolol, 80 mg/day, total work performance increased by 128 percent from 765 plus or minus 125 before treatment to 1,792 plus or minus 285 kilopond-meters (mean plus or minus standard error) (P less than 0.01). With 160 mg of propranolol daily, total work performance decreased, but remained higher than at control levels. In the group given propranolol, left ventricular function decreased progressively with increasing doses of the drug. As measured from the echocardiogram, maximal endocardial posterior wall velocity decreased 42 percent, from 72 plus or minus 7 to to 41 plus or minus 4 mm/sec (P less than 0.02); ejection fraction decreased 13 percent, from 0.68 plus or minus 0.01 to 0.59 plus or minus 0.01; and end-diastolic bolume increased 28 percent, from 79 plus or minus 11 to 102 plus or minus 9 ml/m2 (P less than 0.05). The preejection period and the ratio between preejection period and left ventricular ejection time significantly increased with progessive dose increments. There was no correlation between blood level of propranolol and improved work performance. Exercise tolerance was maximally improved with doses of 80 to 160 mg/day. At higher dose levels left ventricular function deteriorated and exercise work decreased. Noninvasive assessment of left ventricular function proved more valuable than determination of drug blood levels in managing patients with angina pectoris and provided a guide to optimal adjustment of dosage.