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Patients with advanced heart failure (HF) symptoms constitute stage D heart failure with high mortality and less response to conventional guideline directed medical therapies. These patients are subjected to receive non-medical therapies including heart transplant or mechanical circulatory support for increasing survival. Considering the low availability and serious complications of these strategies,effective medical therapies for this group of patients would be pivotal for decreasing mortality and morbidity of them. Angiotensin receptor neprilysin inhibitor (ARNI) is a class of drugs approved for ambulatory heart failure patients. ARNI use like other groups of heart failure drugs has not been fully evaluated in end-stage heart failure patients. Herein, we describe four inotrope-dependent heart failure patients. Initiation of ARNI in these patients, lead to discontinuation of inotrope and reducing the need for inotrope in the follow-up period.