Levosimendan is a K+-ATPase activator, cardiac myofilament Ca2+-sensitizer, and phosphodiesterase inhibitor with positive inotropic effects and vasodilatory properties in the pulmonary and systemic circulation, all of which are potential therapeutic targets for patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF) [ [1] Gorter TM Obokata M Reddy YNV Melenovsky V Borlaug BA. Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease.

European heart journal. 2018; 39: 2825-2835

]. In the recent multicenter, double-blind, placebo-controlled Hemodynamic Evaluation of Levosimendan in Patients with HFpEF (HELP) study, a weekly infusion of levosimendan decreased pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) and was associated with a significant increase in six-minute walk distance [ [2] Burkhoff D Borlaug BA Shah SJ Zolty R Tedford RJ Thenappan T et al. Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial.

JACC Heart Fail. 2021; 9: 360-370

]. However, the mechanism(s) underlying levosimendan's effects were not fully elucidated. The purpose of this report is to integrate hemodynamic and echocardiographic data from the HELP study to determine which cardiovascular effects of levosimendan contributed to the finding of decreased right and left heart filling pressure in PH-HFpEF.