Although acute afterload reduction is known to improve cardiac output in patients with congestive heart failure (CHF), the effect of therapy on the atrial overload directly causing congestive symptoms has not been systematically studied. Atrial volumes and mitral and tricuspid regurgitation, in addition to left ventricular ejection fraction and indexes of left ventricular contractility (mean acceleration, ejection time and peak systolic pressure/end-systolic volume index), were measured using 2-dimensional and Doppler echocardiography and color flow imaging in 30 patients with advanced CHF, before and after acute vasodilator and diuretic therapy tailored to hemodynamic goals. Therapy increased stroke volume by 64% (36 +/- 10 to 55 +/- 14 cc), decreased right atrial pressure by 45% (15 +/- 5 to 8 +/- 4 mm Hg), systemic vascular resistance by 36% (1,700 +/- 400 to 1,030 +/- 300 dynes s cm-5) and pulmonary capillary wedge pressure by 37% (31 +/- 6 to 19 +/- 6 mm Hg) (all p less than 0.001). Echocardiography showed simultaneous reductions in left and right atrial volumes: 24 +/- 19 and 18 +/- 12%, respectively (p less than 0.001). Mitral and tricuspid regurgitation measured by color flow fraction both decreased by a mean of 44% (p less than 0.001). While ejection fraction increased from 15 +/- 5 to 19 +/- 7% (p less than 0.001), there were no changes in relatively load-independent indexes of contractility. Therefore, acute therapy with vasodilators and diuretics in advanced CHF causes reductions in atrial volumes and atrioventricular valve regurgitation that are evident from serial noninvasive studies and may play a major role in the improvement of congestive symptoms.