Background: Myocardial recovery may occur in patients with heart failure who are receiving left ventricular assist-device support, but identification of candidates for device removal remains challenging. We hypothesized that on-line quantitative echocardiography during trials of decreased device support alone or in combination with exercise cardiopulmonary testing can assess cardiac recovery to predict successful device removal. Methods: We studied 18 patients with severe heart failure, aged 45 +/- 19 years, who received 234 +/- 169 days of assist-device support as a bridge to transplantation. We used echocardiographic automated border detection from mid-ventricular short-axis images and non-invasive arterial pressure to measure beat-to-beat responses in 2 to 5 minute trials of decreased device flow. We also assessed maximal oxygen consumption in 14 patients who could exercise. Results: Six patients experienced myocardial recovery and underwent successful device removal; 12 remained device dependent. With transient, low assist-device flow, patients with device removal had increased echocardiographic stroke area of 27% +/- 36% vs -24% +/- 12% (p < 0.05) and fractional area change of 51% +/- 13% vs 23% +/- 11% (p < 0.05) in the patients who were device dependent. Estimates of pre-load-adjusted maximal power, a relatively load-independent index, were 6.7 +/- 2.1 mW/cm(4) in patients with successful device removal vs 1.2 +/- 1.2 mW/cm(4) in patients who were device dependent (p < 0.005). Maximal oxygen consumption was 17.2 +/- 1.4 ml/kg/min in patients with myocardial recovery vs 13.1 +/- 1.9 ml/kg/min in patients who were device dependent (p < 0.005) and correlated with pre-load-adjusted maximal power (r = 0.89, p < 0.001). Maximal oxygen consumption >16 ml/kg/min, increased stroke area, >40% increase in fractional area change, or pre-load-adjusted maximal power >4.0 mW/cm(4) with low device flow were associated with successful device removal (P < 0.05). Conclusions: On-line quantitative echocardiography alone or combined with exercise cardiopulmonary testing can assess myocardial recovery of patients receiving left ventricular assist-device support and has the potential to identify patients who are clinical candidates for device removal.