Levosimendan improves renal function in acute decompensated heart failure: possible underlying mechanisms.

AIMS: The cardio-renal syndrome plays a critical role in acute heart failure (HF). Levosimendan, an inodilator drug, has a positive but controversial effect on kidney. Our aim was to evaluate its effects on both renal and systemic haemodynamic parameters as well as on renal function, explaining the possible mechanisms involved. METHODS AND RESULTS: Patients with acute decompensated HF, moderate renal impairment, wedge pressure >20 mmHg and EF <40% were eligible. Twenty-one patients were randomized to infusion of levosimendan or placebo, on top of standard therapy. Systemic haemodynamic parameters (wedge and cardiac output) were evaluated at baseline and at 8, 16, 24, 48, and 72 h. An intravascular renal artery Doppler exam was performed at baseline, after levosimendan bolus, and 1 h thereafter. Renal blood flow, glomerular filtration rate (GFR), cystatin C, blood urea nitrogen (BUN), urinary output, sodium excretion, and plasma sodium were measured. The effect of levosimendan was beneficial and significantly different from placebo on several renal and cardiac parameters. Specifically, the levosimendan and placebo group exhibited significantly different changes over time in GFR (P = 0.037), renal blood flow (P = 0.037), and renal artery diameter (P = 0.033), with ensuing improvements in serum levels of BUN (P = 0.014), creatinine (P = 0.042), and cystatin C (P = 0.05). Concomitantly, levosimendan provided a significant increase in urine output up to 72 h (P = 0.02). These beneficial results on renal parameters were accompanied by similarly significant and favourable changes in cardiac index (P = 0.029) and PCWP (P < 0.001). CONCLUSION: Levosimendan, in acute decompensated HF, has an immediate renoprotective effect, mediated by an increase in renal blood flow, due to a selective renal arterial and venous vasodilating action. TRIAL REGISTRATION: NCT00527059.

Role of ion channels in coronary microcirculation: a review of the literature.

In normal coronary arteries, several different mechanisms of blood flow regulation exist, acting at different levels of the coronary tree: endothelial, nervous, myogenic and metabolic regulation. In addition, physiologic blood flow regulation is also dependent on the activity of several coronary ion channels, including ATP-dependent K(+) channels, voltage-gated K(+) channels and others. In this context, ion channels contribute by matching demands for homeostatic maintenance. They play a primary role in rapid response of both endothelium and vascular smooth muscle cells of larger and smaller arterial vessels of the coronary bed, leading to coronary vasodilation. Consequently, an alteration in ion channel function or expression could be directly involved in coronary vasomotion dysfunction.

Cost-effectiveness of levosimendan in patients with acute heart failure.

Heart failure is a major public health problem because of its high prevalence and impact on mortality, morbidity, quality of life, and social costs. The aim of this analysis was to estimate the effects of the novel inodilator levosimendan versus standard inotropic therapy (ST) of dobutamine in acute heart failure. A study population of 292 patients with acute heart failure was derived from an observational registry of patients referred to our department. Of these, 147 patients received iv levosimendan (0.05-0.1 µg·kg·min for 24 hours), and 145 patients were treated with ST. Duration of hospitalization, survival at 1 month, and the rehospitalization rate during the year after the index hospitalization were evaluated. Cost-effectiveness analysis was performed. The mean length of hospitalization was 12.08 and 13.57 days in the levosimendan and ST groups, respectively (P < 0.05). Rehospitalization rates were lower in the levosimendan group at 6 months (1.44% vs. 2.3%; P < 0.05) and 12 months (7.6% vs. 14.3%; P < 0.05). Mortality rate at 1 month was 2.1% versus 6.9% in the levosimendan and ST groups, respectively (P < 0.05). The per-capita cost of treatment with levosimendan was €78.86 higher than that with ST during the first hospitalization but €280.22 lower when the rehospitalization rate was considered.