Primary Graft Dysfunction after Heart Transplantation: Optimal Timing of Levosimendan Application

Objectives: Primary graft dysfunction or even failure (PGD/PGF) heart transplantation (htx) remains a main problem causing poor outcome. Besides mechanical support, Ca 2+ sensitizers such as levosimendan play an important role and are known to improve cardiac function. Their impact on morbidity and the best time for application are still discussed controversially. Therefore, we aimed to analyze our patients particularly with regard to timing of levosimendan application.

Methods: A total of 139 patients underwent htx between 2010 and 2019 in our department, including 28 patients (22.4%) suffering from primary graft dysfunction or failure (PGD/PGF) and treated with levosimendan (group L). Patients who received the treatment within or after 48 hours after ECLS implantation form group Learly or Llate. Control group C consists of patients not treated with Ca²⁺ sensitizer postoperatively. The groups were comparable regarding further preoperative status, including cardiac function and ischemic time.

Results: 89.3% of group L were treated with extracorporeal life support (ECLS) compared to 13.4% of controls. In group Learly, 100% of patients were successfully weaned from ECLS; in group Llate, 60%; and in group C, 46.2% (p < 0.05). However, 30-day mortality was 17.9% in group L compared to 9.3% in controls (p > 0.05). One-year survival was also comparable between the groups with 73.7% in group L and 77.6% in group C.

Besides a more frequent use of postoperative ECLS, renal failure and need for resternotomy occurred significantly more often in group L compared to controls (p < 0.05). Furthermore, stay on ICU and in-hospital and duration of mechanical ventilation after htx were significantly prolonged (p < 0.05).

Patients receiving levosimendan early within the first 48 postoperative hours displayed lower 30-day mortality and an improved 1-year survival with 90% compared to 55.6% in group Llate (p > 0.05). Further postoperative complications, duration of mechanical ventilation, and stay on ICU were comparable, however, again with slightly better results for the early application.

Conclusion: We could clearly show that levosimendan application in patients with PGD/F after cardiac transplant represents a valuable treatment option to realize acceptable results in these severely affected patients. Furthermore, it is obvious that the timely decision for early treatment with Ca-sensitizer is an inevitable requirement to achieve those outcomes.