Clinical Trial
Levosimendan Improves Renal Function in Patients With Advanced Chronic Heart Failure Awaiting Cardiac Transplantation

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Abstract

Background

Long-term impact of levosimendan on renal function remains undefined. Prospectively, we evaluated effects of levosimendan on renal function in patients with advanced chronic heart failure awaiting cardiac transplantation.

Methods and Results

Of 40 patients, 20 were randomized to receive levosimendan (10-minute bolus 12 μg/kg, followed by 0.1 μg/kg/min for 24 hours; LS Group), and 20 received no levosimendan (Controls). The groups did not differ in age, heart failure etiology, left ventricular ejection fraction, and plasma brain natriuretic peptide. Patients were followed for 3 months. At baseline, the groups did not differ in serum creatinine (1.92 ± 0.13 mg/dL in LS Group versus 1.91 ± 0.12 mg/dL in Controls, P = .81) and creatinine clearance (43.7 ± 2.9 mL/min versus 43.9 ± 2.8 mL/min, P = .84). At 3 months, we found a decrease in serum creatinine and an increase in creatinine clearance in LS Group, but not in Controls, leading to a significant intergroup difference in serum creatinine (1.60 ± 0.26 mg/dL in LS Group versus 1.90 ± 0.14 mg/dL in Controls, P = .005) and creatinine clearance (53.6 ± 8.6 mL/min versus 44.0 ± 3.3 mL/min, P = .005). An improvement in creatinine ≥0.5 mg/dL occurred in 50% patients from LS Group compared with 10% of Controls (P = .005).

Conclusions

Levosimendan improves long-term renal function in advanced chronic heart failure patients awaiting cardiac transplantation.

Section snippets

Patient Population

In a prospective trial, we enrolled 40 consecutive patients with advanced chronic heart failure who were referred for cardiac transplantation listing at Advanced Heart Failure and Transplantation Program, Ljubljana University Medical Center. All patients were NYHA Class III or IV class heart failure for at least 3 months before referral, and were treated with optimal medical therapy at maximally tolerated doses according to the latest guidelines.8 Before listing, all patients were screened

Patient Characteristics

Baseline patient characteristics are presented in Table 1. The 2 groups did not differ in age, heart failure etiology, heart rate, QTc interval, sodium, left ventricular ejection fraction, or plasma brain natriuretic peptide (BNP) levels. All of the patients survived the follow-up period, and none underwent heart transplantation or implantation of a left ventricular assist device. After 3 months, we found an improvement in left ventricular ejection fraction in the LS Group, but not in Controls (

Discussion

This is the first study to date evaluating the long-term effects of levosimendan on renal function in patients with advanced heart failure listed for heart transplantation. In these patients, a 24-hour levosimendan infusion was associated with a significant improvement in renal function 1 month after therapy, with its effect persisting up to 3 months. This suggests that levosimendan may exert a sustained beneficial effect on renal function in advanced heart failure.

In patients with severe heart

Conclusions

The results of this study suggest that levosimendan exerts beneficial effects on renal function in patients with advanced chronic heart failure. Although the effects are modest, they appear to persist up to 3 months after the infusion. Further studies are needed to better define the underlying mechanisms and to determine whether or not the levosimendan-related improvement in renal function offers a survival benefit in this patient cohort.

Acknowledgments

The authors would like to thank Andreja Briski for coordinating the study and for her dedicated assistance throughout the study period.

References (21)

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