External or internal monitoring equipment is used to automatically determine optimal programming parameters for a CRT based on externally or internally derived measurements of cardiac performance, anisotropic myocardial deformation (AMD) or both. The ideal programming parameter, operational parameter, represents optimal interval timing between multiple electrodes within the CRT, and is generated by such a closed loop control system. The closed loop system may be semi-automatic and implement connectivity to external ultrasound equipment or externally derived measurements of transthoracic impedance. Preferably, the operational parameter is determined by a closed loop system using internally derived intracardiac and intrathoracic electrograms and impedance measurements that describe cardiac performance and electromechanical dysynchrony in real time. Such a CRT has a control system that automatically optimizes performance by a system of checks and balance.