Myocardial efficiency during levosimendan infusion in congestive heart failure

Clin Pharmacol Ther. 2000 Nov;68(5):522-31. doi: 10.1067/mcp.2000.110972.

Abstract

Aims: Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure.

Methods and results: Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study. During steady-state, dynamic positron emission tomography with [11C]acetate was used to assess myocardial oxygen consumption and [15O]H2O to measure myocardial blood flow. Cardiac performance and dimensions were assessed by pulmonary artery catheterization and echocardiography. Compared with healthy volunteers, myocardial oxygen consumption during placebo was elevated in the right ventricle but comparable in the left ventricle. During administration of levosimendan, cardiac output increased by 32% (P = .002) mainly because of higher stroke volume. Coronary, pulmonary, and systemic vascular resistance values were significantly reduced. Mean myocardial blood flow increased from 0.76 to 1.02 mL/min/g (P = .033). Levosimendan was neutral on myocardial oxygen consumption and left ventricular efficiency, but it improved right ventricular mechanical efficiency by 24% (P = .012).

Conclusions: Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / therapeutic use*
  • Catheterization, Swan-Ganz
  • Coronary Vessels / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Heart Failure / diagnostic imaging
  • Heart Failure / drug therapy*
  • Hemodynamics / drug effects*
  • Humans
  • Hydrazones / administration & dosage
  • Hydrazones / therapeutic use*
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Oxygen Consumption / drug effects
  • Pyridazines / administration & dosage
  • Pyridazines / therapeutic use*
  • Simendan
  • Tomography, Emission-Computed
  • Ultrasonography

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Simendan