Levosimendan has been used in Europe for the past 20 years as an intravenous inotropic treatment of acute decompensated heart failure. This expert panel with firsthand experience in its clinical efficacy summarizes this experience and the many unexplored potential uses in various conditions. Levosimendan is a pleotropic drug with multiple mechanisms of action.
Levosimendan is a K+ATP channel activator, and via this mechanism has the potential for dilating both arterial and venous blood vessels. This experiment focused on human portal veins, and compared it to another K+ATP channel activator drug cromakalim. The in vitro preparation employed pre-treating the veins with norepinephrine to simulate the physiologic environment in heart failure syndromes.
This is a summary of an FDA sponsored meeting that included academia, regulatory and industry to address the growing problem of HFpEF that currently has no identified effective treatment. This provides insight towards how the development of novel treatment will likely proceed.
This provides a summary of the use of levosimendan as an inotropic treatment of advanced heart failure from academic experts with firsthand knowledge and experience. Discussions include the relative safety of levosimendan compared to other inotropic drugs, and the chronic use in advanced disease.
An extensive review of the 20 year experience of levosimendan in Europe, covering the indicated application for use in ADHF and the experience in a multitude of other clinical situations. This is a great reference paper that covers the broad scope of preclinical and clinical features of levosimendan.
This is a report of a randomized clinical trial of oral levosimendan as a chronic treatment for HFrEF. 300 patients were included in the trial which lasted 6 months. The primary endpoint, which was not achieved, was a novel composite that included symptoms and mortality. The secondary endpoints of NT-proBNP and patient questionnaire were achieved. Serious adverse events were not encountered.
This was a small randomized clinical trial of oral levosimendan for HFrEF as an add-on medication for a 6-month period. The primary assessment was determined by echocardiography which included estimates of PCWP and tissue Doppler velocities. Both parameters improved in the levosimendan treated group compared to control.
This is a review of the role of K+ATP channels in the cardiovascular system, and the potential of K+ channel opener drugs. Included in the review is the finding that myocardial ischemia may be prevented from K+ATP channel activators, including levosimendan, via effects on cardiac mitochondria.
A review of the known vascular effects of levosimendan via K+ ATP channel activation. The author discusses how levosimendan may be effective in heart failure outside of direct inotropic actions.
A very timely review of the trials to treat PH in left heart disease (LD). PH in LHD is the most common form of PH and brings a poor prognosis by increasing the morbidity and mortality risk of this patient population. Despite apparent similarities with PAH, the current guidelines do not recommend PAH-targeted drugs for PH-LHD because of the failure of previous clinical trials in proving their safety and/or efficacy in the setting of PH-LHD. The authors state that it is imperative to further improve our understanding of the pathophysiology and underlying mechanisms of PH-LHD to develop specific therapies for this disease and by doing so, establish an evidence-based approach for the management of patients with HF developing PH.