The deleterious consequences of biventricular dysfunction with elevated venous pressure in heart failure patients are increased mortality and impaired function of end-organs such as the kidneys and liver. For these patients, a heart transplant becomes the only viable option if they fail optimal medical treatment, as they are not suitable candidates for long-term mechanical circulatory support. Medical management of these patients involves lowering the ventricular afterload with vasodilator drugs while awaiting a transplant. We hypothesized that when venous pressure is elevated prior to transplant, vasodilation increases cardiac output but leads to a significant drop in mean perfusion pressure (the difference between mean arterial pressure and venous pressure), resulting in compromised end-organ function and consequent unfavourable outcomes even after heart transplantation. To investigate our research hypothesis, we utilized pre-transplant clinical data from 250 heart transplant recipients, post-transplant survival information and a sophisticated mathematical model to simulate cardiovascular hemodynamics. Our research found that in patients with high venous pressure, low mean perfusion pressure is a risk factor for post-transplant survival due to end-organ dysfunction, especially in those with a higher body surface area. The mathematical model demonstrated that in biventricular dysfunction with high venous pressure, vasodilation increases the cardiac output but lowers the mean perfusion pressure significantly, particularly in patients with higher body surface area. Adding an Intra-aortic balloon pump counter-pulsation to vasodilation increases cardiac output while maintaining perfusion pressure simultaneously and confers a substantial hemodynamic benefit in this setting. These findings emphasize the importance of reevaluating vasodilator therapy guidelines in heart failure. Focusing on a more individualized therapeutic approach to vasodilation that considers venous pressure and body surface area, in addition to the already established patient-specific factor of systolic blood pressure, is crucial to improve patient outcomes. Transitioning from analysis of heart transplantation outcomes, the subsequent phase of our research focuses on improving the diagnosis of heart failure patients through hemodynamic monitoring. We have developed a mathematical model-based approach to non-invasively predict the patient-specific left ventricular pressure-volume loop in the ICU setting, and it was validated in silico. While these results are promising, future clinical trials are needed to confirm these findings in actual patients. This study serves as a proof of concept for designing and implementing such clinical trials.