Levosimendan therapy and mortality predictors in end-stage heart failure patients beyond advanced therapeutic options

Background Heart failure (HF) patients ineligible for heart transplantation or mechanical circulatory support present unique therapeutic challenges requiring innovative approaches. At our center, we've implemented comprehensive care strategies including intermittent levosimendan therapy, which enables effective symptom control, improves quality of life, and facilitates personalized end-of-life planning for these complex patients. This integrated approach aims to reduce unnecessary hospitalizations while optimizing pharmacological management in this high-risk population. Purpose To identify mortality predictors in advanced HF patients excluded from definitive therapies who receive intermittent levosimendan, and to evaluate the effectiveness of our integrated care approach. Methods This retrospective single-center study analyzed 39 advanced HF patients who initiated intermittent levosimendan therapy (2017-2023). All patients were deemed unsuitable for transplantation or ventricular assist devices. We collected comprehensive baseline data and tracked outcomes through December 2024. Statistical analysis included Cox proportional hazards regression with NT-proBNP stratified by quartiles. Results In our cohort (mean age 78.4±12.6 years, 84.6% male), 21 patients (53.8%) died during follow-up. Non-survivors were older (84.0±6.8 vs. 71.8±14.6 years, p=0.031) with worse renal function (eGFR 35.7±10.9 vs. 56.1±26.0 mL/min, p=0.008). SGLT2 inhibitor use was significantly higher among survivors (55.6% vs. 19.1%, p=0.018). Notably, while 81% of deaths were cardiovascular, our integrated care approach enabled 33% of patients to die at home and 29% in appropriate care facilities, with only 38% requiring hospitalization at end-of-life. This highlights our center's effective home-based management programs and advanced care planning. Cox regression identified two significant mortality predictors: age (HR 1.06, p=0.046) and NT-proBNP >7200 pg/mL (HR 3.70, p=0.043). Treatment with at least one neuro-hormonal therapy (HR 0.21, p=0.104) – including angiotensin receptor neprilysin inhibitors, ACE inhibitors, ARBs, or SGLT2 inhibitors – showed potential protective association with mortality. Conclusion Our findings demonstrate that intermittent levosimendan can be effectively incorporated into comprehensive care strategies for patients with limited therapeutic options. The ability to facilitate end-of-life care at home for one-third of our patients reflects successful implementation of integrated care pathways and effective coordination between hospital and community resources. Age and elevated NT-proBNP emerged as critical mortality predictors that can help clinicians stratify risk and tailor treatment intensity. The potential survival benefit associated with SGLT2 inhibitors represents a promising therapeutic opportunity and warrants further investigation.