Background:The myocardial performance index (MPI) has emerged as a Doppler-derived index for global ventricular function capable of estimating combined systolic and diastolic performance. While several studies have reported its load-dependency, responses of the MPI to various hemodynamic changes have not been fully characterized.Methods and Results:The response characteristics of the MPI were examined and compared with ejection fractions (EF) by changing hemodynamic parameters within the physiological range in a lumped parameter model of the cardiovascular system. At baseline, the MPI was 0.42 and the EF was 0.68. Heart rate increase resulted in a decrease in EF and an increase in the MPI. Reduction in end-systolic elastance decreased EF and increased the MPI. Volume overload and ventricular stiffening did not affect EF but paradoxically reduced the MPI. Increased afterload due to higher systemic resistance resulted in a decrease in EF and increase in the MPI, but afterload increase caused by reduced arterial compliance led to a decrease in both EF and MPI. These MPI characteristics caused paradoxical improvement of the MPI during disease progression of chronic heart failure in a simulation of mitral regurgitation.Conclusions:The MPI is affected by a wider variety of hemodynamic parameters than EF. In addition, it is predicted to decrease paradoxically with volume overload, reduction in arterial compliance, or ventricular diastolic stiffening. These MPI characteristics should be considered when assessing cardiovascular dynamics using this index. (Circ J 2016; 80: 148–156)