Myocardial efficiency during levosimendan infusion

Abstract

Levosimendan (LS) is a novel agent indicated for the treatment of acute decompensated heart failure. It has a dual mechanism of action, increasing cardiac contractility without increasing myocardial oxygen demand as well as demonstrating vasodilator properties. This double-blind, randomised, cross-over trial was conducted to assess the effects of LS on myocardial energetics in patients (n = 8) with New York Heart Association functional class III and IV heart failure. Patients initially received either placebo or intravenous LS (18 μg/kg bolus, followed by a continuous infusion of 0.3 μg/kg/min for 5 hours). The following day, patients who had received LS were given placebo and vice versa. Cardiac loading conditions and cardiac output (CO) were assessed using a Swan-Ganz catheter, thermodilution and echocardiography. Dynamic positron emission tomography (PET) with 11C-acetate and 15O-H2O was used to measure myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF), respectively. Myocardial efficiency was calculated as (heart rate × stroke volume × arterial pressure) / ventricular oxygen consumption. CO increased by 32% (P = 0.002) in patients receiving LS, mainly because of an increase in stroke volume. LS significantly reduced pulmonary capillary wedge pressure by 29% (P = 0.013), systemic vascular resistance by 26% (P < 0.001) and pulmonary vascular resistance by 28% (P = 0.025). Mean MBF was 0.76 ml/min/g with placebo and 1.02 ml/min/g with LS (P = 0.033). LS did not increase MVO2 significantly (8%). Left ventricular efficiency was comparable in LS-treated and placebo-treated patients, while right ventricular efficiency was improved by 24% (P = 0.012) with LS. In conclusion, LS as well as having beneficial haemodynamic effects, also has an energetically favourable profile.