Six weeks of once-weekly levosimendan infusion did not significantly reduce exercise-PCWP compared with placebo (-1.4 mm Hg; 95% CI: -7.8 to 4.8; p=0.65) in patients with PH-HFpEF.
RCT (n=37)
Double-blind
Does weekly levosimendan infusion reduce exercise-PCWP in patients with PH-HFpEF?
In patients with PH-HFpEF, 6 weeks of weekly levosimendan infusion did not significantly reduce exercise-PCWP but did improve 6-minute walk distance and PCWP across all exercise stages.
Mean Difference: -1.4 (95% CI -7.8–4.8)
p-value: p=0.65
OBJECTIVES: The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). BACKGROUND: There are no proven effective treatments for patients with PH-HFpEF. METHODS: Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. RESULTS: Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (-1.4 mm Hg; 95% confidence interval CI: -7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (-3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. CONCLUSIONS: Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF HELP; NCT03541603).
Burkhoff et al. (Wed,) conducted a rct in Pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF) (n=37). Levosimendan vs. Placebo was evaluated on Exercise-PCWP at 6 weeks (MD -1.4 mm Hg, 95% CI -7.8 to 4.8, p=0.65). Six weeks of once-weekly levosimendan infusion did not significantly reduce exercise-PCWP compared with placebo (-1.4 mm Hg; 95% CI: -7.8 to 4.8; p=0.65) in patients with PH-HFpEF.