Optimization plays a fundamental role in patients with INTERMACS levels 3–4 because there is more time for planning the implant [54, 55]. Preoperative optimization is in continuous interplay with haemodynamics, because low cardiac output and RV failure or fluid overload are key targets of treatment. In these perspectives, their potential for improvement and timing are pivotal. Indeed, the interaction between the RV and end-organ function is to be acknowledged because the latter is a risk factor for RV failure. At baseline, organ function should be routinely assessed with standard parameters; therefore, haemodynamic evaluation and the potential for its management with a tailored pharmacological or short-term MCS device should follow. Optimization does not mean normalization; a positive trend following specific treatment is to be taken as a goal. Similarly, no conclusion about reversibility of organ dysfunction can be drawn until cardiac output and filling pressures have been optimized. As a general rule, recent onset HF and young age may be associated with a higher probability of recovery of end-organ dysfunction if cardiac output is restored.