{"doi":"10.1016/j.jchf.2021.01.015","title":"Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF","abstract":"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. 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Chung","orcid":"0000-0002-9443-3274","position":10,"is_corresponding":false},{"id":645123,"name":"Farhan Raza","orcid":"0000-0001-5750-2034","position":11,"is_corresponding":false},{"id":334555,"name":"David T. Majure","orcid":"0000-0002-8951-0079","position":12,"is_corresponding":false},{"id":255092,"name":"Gregory D. Lewis","orcid":"0000-0001-8108-8240","position":13,"is_corresponding":false},{"id":645124,"name":"Ioana R. 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