Oral levosimendan improves cardiac function and hemodynamics in patients with severe congestive heart failure

Levosimendan, a new calcium sensitizer, was administered orally to 10 patie nts with severe congestive heart failure (CHF), who had a mean baseline pul monary capillary wedge pressure (PCWP) of 22 mm Hg and a left ventricular e jection fraction of 23%, Each-patient received 3 escalating doses of 1 mg, 2 mg, and 4 mg of levosimendan within 18-24 hours in an open-label pilot st udy. After administration of a I-mg dose of levosimendan, PCWP decreased by 18% (p = 0.002) and cardiac output increased by 22% (p = 0.005), Diastolic blood pressure was decreased by about 5 mm Hg, Plasma catecholamine levels were unaffected, Plasma concentrations of levosimendan were unexpectedly l ow after administration of the 2-mg dose, and responses were weak, This was probably due to delayed drug absorption and altered baseline hemodynamics caused by ingestion of a meal before drug intake. The 4-mg dose of levosime ndan was associated with a 27% increase in cardiac output (p = 0.009). PCWP showed only a small decrease, probably a result of relatively law baseline values (carryover from previous doses). Right atrial pressure decreased su bstantially by 40%, Heart rate increased by only 1-8 beats/min after admini stration of the 1- and 4-mg doses of levosimendan, It is concluded that ora l levosimendan has favorable cardiac and hemodynamic effects in patients wi th severe CHF, and that these effects are similar to those seen after intra venous dosing with levosimendan in this patient group. (C) 1999 by Excerpta Medica, Inc.