Changes in Stressed Blood Volume with Levosimendan in Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction: Insights Regarding Mechanism of Action From the HELP Trial

Levosimendan is a K+-ATPase activator, cardiac myofil-ament Ca2+sensitizer, and phosphodiesterase inhibitor with positive inotropic effects and vasodilatory properties in the pulmonary and systemic circulation, all of which are poten-tial therapeutic targets for patients with pulmonary hyper-tension and heart failure with preserved ejection fraction (PH-HFpEF).1 In the recent multicenter, double-blind, pla-cebo-controlled Hemodynamic Evaluation of Levosimen-dan in Patients with HFpEF (HELP) study, a weekly infusion of levosimendan decreased the pulmonary capil-lary wedge pressure (PCWP) and central venous pressure, and was associated with a significant increase in 6-minute walk distance.2 However, the mechanism(s) underlying lev-osimendan's effects were not elucidated fully. The purpose of this report is to integrate hemodynamic and echocardio-graphic data from the HELP study to determine which car-diovascular effects of levosimendan contributed to the finding of decreased right and left heart filling pressure in PH-HFpEF.