Heart failure is a complex, true pandemic clinical syndrome and is responsible for 5% of hospitalizations globally. Severe heart failure can manifest as two lethal clinical entities:(1) acute cardiac decompensation with cardiogenic shock after large acute myocardial infarction with mortality rates approaching 50% or after cardiac surgery with mortality rates higher than 65% and (2) chronic destructive cardiac remodeling or acute decompensative exacerbations of cardiomyopathies with one-year mortality of approximately 80%(worse than most types of cancer). Interventional therapies aim first to improve symptoms and life expectancy in patients with severe heart failure syndrome, second to prevent left ventricular remodeling, and third to bridge patients to long-term mechanical circulatory support or transplantation. Several treatment options can be used to stabilize patients. In particular, new percutaneous mitral valve interventions and short-term circulatory support devices open up a new temporary treatment area in symptomatic Stage-D heart failure. The durable or curable surgical destination treatment will be only permanent ventricular assist devices or heart transplantation. This chapter focuses on the treatment steps and new approaches in hospitalized Stage-D heart failure patients.