To the Editor:
We read with interest the article by Llorens-Soriano et al,1 in which they report their experience with levosimendan and conclude that it is a safe and effective therapeutic option for the treatment of acute heart failure (AHF) in hospital emergency departments. The purpose of this letter is to reflect on certain aspects of the above mentioned article.
In the first place, there are notable differences between the indications for levosimendan in the clinical practice guidelines2 and the protocol followed by the authors.1 Whereas the guidelines recommend its use in heart failure with symptomatic reduced cardiac output secondary to left ventricular dysfunction with no severe hypotension, the authors of the above mentioned study consider its use in multiple clinical situations, including AHF with a left ventricular ejection fraction (LVEF) >45% and hypotension, or shock.
To date, no scientific evidence is available regarding the use of levosimendan in patients with AHF and conserved systolic function. It is therefore surprising that more than 40% of the patients included in the study belonged to this subgroup. The administration of levosimendan is known to produce a reduction in peripheral vascular resistance and an improvement in the parameters of diastolic function.3 However, at the present time diuretics and vasodilators have been shown to be highly effective in these patients and currently form the treatment of choice in this context.4 Additionally, the results of the study offer serious doubts about their scientific validity: the lack of a control group, the inconsistency of the inclusion criteria (not all the patients received diuretics), the low risk profile of the study population (only 30% had acute pulmonary edema), and the lack of precision in the definition used for "lack of response to the drug" are all important aspects that should have been taken into account. The clinical practice guidelines2 contraindicate the use of levosimendan in patients with cardiogenic shock. Nonetheless, recent studies in patients with ischemic cardiogenic shock and low cardiac output after heart surgery have shown promising results.5,6
In our opinion, levosimendan should be used after optimal patient selection, which requires suitable coordination between the various different services. To this extent, an echocardiogram may prove extremely useful. The following factors have recently been suggested to be associated with a favorable therapeutic response7: decompensated chronic heart failure, ischemic
etiology, NYHA Class III/IV, absence of concomitant treatment with vasodilators or antiarrhythmic drugs, and systolic blood pressure >100 mm Hg. Another important aspect to consider is the dosage of this drug. In the REVIVE and SURVIVE studies, the relative depletion of intravascular volume secondary to diuretic therapy, together with the administration of a high loading dose, favors the onset of hypotension and is probably associated with worse survival.8 The authors of this study, like us, are in favor of using a more flexible dose of levosimendan depending on the hemodynamic status of the patient, as well as its early use in order to avoid situations of excessive volume depletion caused by the use of diuretics.
In conclusion, we would like to emphasize the need for adequate identification of those patients who might benefit from this promising drug, which, pending the results of further studies, should have its use restricted to the indications already approved in consensus guidelines. Additionally, it would seem reasonable to perform an echocardiogram prior to the administration of this drug and to have better co-ordination between the various hospital services involved in treating these patients.