European Experience on the Practical Use of Levosimendan in Patients with Acute Heart Failure Syndromes

Abstract

The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and postinterventional myocardial dysfunction ( Levosimendan is a new calcium-sensitizing drug that opens adenosine triphosphate-dependent potassium (K ATP ) channels with effects that increase myocardial contraction and cause vasodilation. Compared with other agents for acute heart failure syndromes (AHFS), its main potential advantages are the improvement of myocardial contractility without increasing oxygen requirements, reduction of ventricular preload, and an antistunning, anti-ischemic effect by opening K ATP channels. [1][2][3] This pharmacologic profile of levosimendan offers new therapeutic possibilities in patients with AHFS. In initial dose-finding 4,5 and therapeutic trials, 6 a rapid and prolonged hemodynamic improvement with an increase in cardiac index, reduction of pulmonary capillary wedge pressure (PCWP), and reduction of peripheral vascular resistance without proarrhythmic effects were documented. Furthermore, positive effects on long-term survival up to 6 months were observed. 6,7 Levosimendan is registered for clinical use in several countries in Europe, South America, and Asia. There are an increasing number of reports on practical experiences and therapeutic successes in different clinical situations. In this article, we summarize recent publications on therapeutic indications, dose schedules, outcomes, and tolerance. MethodsClinical reports on levosimendan therapy in patients with severe decompensated acute or chronic heart failure (HF), cardiogenic shock after myocardial infarction (MI), or cardiac interventions and perioperative administration are reviewed. These publications were mostly smaller randomized or observational trials, with good descriptions of patient inclusion criteria, levosimendan administration, and methods of clinical and/or hemodynamic evaluation. Therapeutic Efficacy of Levosimendan in Acute Heart Failure SyndromesDecompensated low-output heart failure: Decompensated low-output HF is the best documented therapeutic indication for levosimendan administered as a single intravenous infusion lasting 6 to 24 hours. Patients included in the dose-finding and comparative clinical trials 4 -6 were characterized by dyspnea (New York Heart Association [NYHA] functional class III to IV) and signs of venous and pulmonary congestion accompanied by peripheral vasoconstriction. Hemodynamic inclusion criteria were reduced cardiac index (Ͻ2.5 L/min per m 2 ) and increased PCWP (Ͼ16 mm Hg). Patients with systolic blood pressure Ͻ90 mm Hg were excluded in these initial ...

Levosimendan Produces an Additional Clinical and Hemodynamic Benefit in Patients With Decompensated Heart Failure Successfully Submitted to a Fluid Removal Treatment

“…Previous studies have demonstrated the beneficial clinical and hemodynamic effects of levosimendan in patients with decompensated HF [6][7][8][9][10][11][12][13][14] and with left ventricular dysfunction after ST segment elevation myocardial infarction, [15][16][17] so that in recent European Society of Cardiology guidelines it has been recommended with a class IIa, level of evidence B indication. 18 The effective role of levosimendan in the treatment of decompensated congestive HF has not been completely clarified, however, especially in relation to the exact time in which to start using this drug in the pharmacologic sequence of a patient's treatment.…”

Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study)

“…Levosimendan reduces elevated pulmonary capillary wedge pressure and increases cardiac output 10 The beneficial haemodynamic effects of levosimendan, unlike those of dobutamine, are not attenuated by the concomitant use of β‐blockers,10 which makes the drug specifically suitable for use in chronic HF. Levosimendan offers renal protection and increases peripheral organ perfusion 30 Previous studies in severe HF patients such as REVIVE‐I and II revealed a higher rate of clinical improvement in levosimendan‐treated patients than in placebo patients 31.…”

Pharmacologic therapies for acute cardiogenic shock

“…After 180 days, there was no difference in all-cause mortality [12]. The recommended dose is 0.05-0.2 mg/kg/min, but levosimendan is not recommended in systolic blood pressures <90 mmHg [19]. At 5 days after randomization patients in the levosimendan group had better symptoms, lower serum B-type natriuretic peptide levels and shorter length of hospital stay compared with placebo.…”