Although vasodilators improve cardiac output in severe left ventricular (LV) failure, the degree to which reduction in mitral regurgitation (MR) contributes to this response is unknown. In the present study, nitroprusside-induced changes in forward cardiac output were compared with simultaneous radionuclide LV output in 14 patients with severe LV systolic dysfunction in the absence of known primary valvular disease. Regurgitant output was estimated as LV output minus forward output and regurgitant fraction was calculated as regurgitant output/LV output. At rest, LV ejection fraction averaged 0.16 +/- 0.04 (mean +/- standard deviation). Patients were classified into 2 groups based on regurgitant fraction at rest. Group I (n = 5) had little or no detectable valvular regurgitation, with regurgitant fraction less than 0.10; group II (n = 9) had evidence of MR with regurgitant fraction greater than 0.30. Nitroprusside increased forward cardiac output in all patients in both groups, but this effect was significantly greater in group II (64 +/- 34%) than in group I (31 +/- 17%) (p less than 0.01). Nitroprusside decreased regurgitant fraction in all group II patients, with mean regurgitant fraction decreasing from 0.44 +/- 0.12 to 0.26 +/- 0.15 (p less than 0.005). Thus, a large percentage of patients with severe LV systolic dysfunction have clinically relevant MR, defined as a regurgitant fraction greater than 0.30. Nitroprusside has a greater effect on forward cardiac output in patients with LV failure and MR than in patients with comparable ventricular dysfunction in the absence of detectable MR.(ABSTRACT TRUNCATED AT 250 WORDS)