Every year, more than 1 million patients worldwide undergo cardiac surgery. Because of the aging of the population, cardiac surgery will increasingly be offered to patients at a higher risk of complications. The consequence is a reduced physiological reserve and hence an increased risk of mortality. These issues will have a significant impact on future health care costs because the population undergoing cardiac surgery will be older and more likely to develop postoperative complications. One of the most dreaded complications in cardiac surgery is difficult separation from cardiopulmonary bypass (CPB). When separation from CPB is associated with right-ventricular failure, the mortality rate will range from 44% to 86%. Therefore, the diagnosis and the preoperative prediction of difficult separation from CPB will be crucial to improve the selection and care of patients and to prevent complications for this high-risk patient population.