To evaluate the short- and long-term effects of beta-adrenergic blockade (metoprolol) as well as the reaction to withdrawal and readministration of metoprolol in severe heart failure, 33 patients (25 men and eight women; mean age, 47.6 +/- 14.0 years) with dilated cardiomyopathy were studied by right and left heart catheterization, right ventricular biopsy, two-dimensional and Doppler echocardiography, and external pulse recordings. Twenty-six of 33 patients survived more than 6 months, and 24 of the 26 patients improved their functional class (from mean 3.3 to 1.8, p less than 0.0001). These 24 patients were subjected to withdrawal of metoprolol until the number of symptoms increased and deterioration occurred as observed noninvasively (group 1, n = 16), whereas the eight patients did not deteriorate during a 12-month period (group 2). During long-term treatment with metoprolol, there was an increase in ejection fraction from 0.24 to 0.42 (p less than 0.0001), whereas there was a decrease in the left ventricular (LV) end-diastolic dimension (from 7.3 to 6.4 cm, p less than 0.0001), in the grade of mitral regurgitation (from 1.7 to 0.4, p less than 0.0001), and in the grade of tricuspid regurgitation (from 0.6 to 0.05, p less than 0.007). There was a decrease in pulmonary wedge pressure (from 23.8 to 10.7 mm Hg, p less than 0.0001), LV end-diastolic pressure (from 24.1 to 13.4 mm Hg, p less than 0.002), and systolic vascular resistance (from 1,782 to 1,499 dynes/sec/cm, p less than 0.04). There was an increase in systolic blood pressure (from 116 to 132 mm Hg, p less than 0.003), cardiac index (from 2.17 to 2.58 l/min/m2, p less than 0.005), and LV stroke work index (from 31 to 65 g.m/m2, p less than 0.0001). During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001). The 12 (of 16) patients in group 1 who survived the withdrawal period had metoprolol readministered, and subsequently, ejection fraction increased (from 0.23 to 0.33, p less than 0.002). Patients had a low number of ventricular beta-adrenergic receptors compared with healthy control subjects (30.3 +/- 2.9 vs. 97.4 +/- 8.7 fmol/mg protein, p less than 0.001), but long-term treatment with metoprolol caused a moderate up-regulation (from 30.3 +/- 2.9 to 49.0 +/- 7.1 fmol/mg protein, p less than 0.05), which may facilitate a more normal response to sympathetic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
