The pathophysiology of advanced valvular heart disease and its clinical implications were analyzed. The study was undertaken primarily on 153 recent patients with implantation of central flow valves. The operative mortality rate was 3.9%, with deaths except one related to LOS. There was a higher incidence of LOS in left ventricular volume-overloaded hearts, and a much higher incidence in patients associated with TR: 70% of TR cases with RVEDP higher than 15 mmHg developed LOS. Cardiac contractile reserve proved to be useful index for predicting immediate postoperative and long-term results; less favorable results were indicated in patients with PWE below 10 mm even after epinephrine infusion. In volume-overloaded hearts, the muscle cell diameter of the left ventricle increased proportionally to the dimension of the left ventricle, with interstitial fibrosis representing irreversible morphological change. Patients with a prolonged indocyanine green disappearance rate showed fibrosis of the liver and were complicated more frequently by LOS, hepatic and renal disturbance and increased mortality. Patients with cardiac cachexia were liable to develop LOS postoperatively, and preoperative GIK therapy appeared to be effective in improving depressed metabolism and hemodynamics, except in patients with severe TR.