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Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Purpose of Review: Patients with acute pulmonary edema are often treated with noninvasive ventilation (NIV). There are essentially two modalities used in this setting: continuous positive airway pressure and bilevel pressure support ventilation. The clinical impact of these techniques and the subset of patients who can benefit from their application have not been definitely established., Recent Findings: The main advantage of the use of NIV in patients with severe acute pulmonary edema is to avoid intubation by more effectively decreasing respiratory distress with respect to conventional oxygen therapy. These beneficial effects were demonstrated in three meta-analyses including nearly 900 patients. Although neither technique was superior to the other in the comparative analysis, a tendency to reduce hospital mortality was observed, which was statistically significant for continuous positive airway pressure. However, unpublished data from a large multicenter trial comparing both modalities of NIV to conventional treatment in emergency departments did not confirm these results. Recent research has pointed out a clear advantage when the treatment is initiated early in the prehospital setting., Summary: Although in acute pulmonary edema NIV is more effective in improving respiratory distress than conventional oxygen therapy and reduces the necessity of intubation, the subset of patients who can best benefit from these techniques in terms of mortality still warrant further investigation.

Background: Dyspnea is a key target in both clinical management and clinical trials of acute heart failure syndromes and its relief important to patients, clinicians, investigators, and regulatory approval agencies. Despite its importance, the impact of early therapy on dyspnea is not well known. The severity of dyspnea may also be influenced by the conditions under which it is measured (ie, sitting up or lying down). URGENT Dyspnea (Ularitide Global Evaluation in Acute Decompensated Heart Failure) is a prospective multicenter study designed to address these issues., Methods and Results: Consenting adult patients with dyspnea secondary to acute heart failure syndromes are eligible. Patients must be interviewed within one hour of first physician evaluation, typically in an emergency department or acute care setting, with dyspnea assessed by the patient using both a 5-point Likert scale and 10-point visual analog scale in the sitting (60 degrees) and then supine (20 degrees ) position if symptomatically able. Improvement of dyspnea by change in Likert and visual analog scale scores at 6 h is the primary endpoint., Conclusions: Timing of dyspnea measurement and the conditions under which it is measured may influence dyspnea severity and this may have significant implications for future acute heart failure syndromes clinical trial design that target dyspnea.