Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO‐D registry

Abstract

Aim Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real‐life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. Methods and results Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4–26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta‐blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (−1.5) HF visit 1 year before levosimendan (−1.5) and heart rate >70 b.p.m. (−2). Patients with a score less than −1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO‐D score performed well in the ROC analysis. Conclusion In this large real‐life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO‐D Score could be of help when deciding about futile therapy in this population.

Heart failure risk scores in advanced heart failure patients: insights from the LEVO‐D registry

“…Regarding clinical and treatment variables included in the calculators, in the LEVO‐D registry, age was not related to 1‐year outcomes, reflecting the short survival expectancy of this population and neither did neurohormonal blockade use 6 . AHF patients are clearly underrepresented in pivotal HF trials, but subgroup analysis suggests that treatment effects on hard endpoints are at least attenuated 17,18 .…”

“…16 Regarding clinical and treatment variables included in the calculators, in the LEVO-D registry, age was not related to 1-year outcomes, reflecting the short survival expectancy of this population and neither did neurohormonal blockade use. 6 AHF patients are clearly underrepresented in pivotal HF trials, but subgroup analysis suggests that treatment effects on hard endpoints are at least attenuated. 17,18 On the contrary, other markers of AHF, such as prior inotropic use, impaired haemodynamic profile, HF drug down titration, worsening right ventricular function and ventricular arrhythmias/ ICD shocks are currently not included in any of the studied calculators.…”

“…Twenty‐three tertiary hospitals in Spain with a specialized or AHF unit participated in the registry, which included patients who received at least one dose of ambulatory levosimendan between 1 January 2015 and 1 September 2020. Inclusion and exclusion criteria have been previously published 6 …”

“…Inclusion and exclusion criteria have been previously published. 6 Baseline data (clinical history and treatment) was collected on the day of the first dose of levosimendan. Routine urgent laboratory data as haematinics, renal function or NT-proBNP were from the day of the first programmed levosimendan infusion.…”

“…We recently reported the largest multi-centre series of AHF patients who were not candidates to advanced therapies, treated with ambulatory periodical levosimendan infusions (LEVO-D registry), showing a significant decrease of HF events at 1 year after the first administration. 6 The need for a larger randomized study in this area is being addressed by the Repetitive Levosimendan Infusion for Patients with Advanced Chronic Heart Failure trial (LEODOR; NCT03437226), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of this therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. 7 Risk stratification has the potential to benefit patients with AHF at multiple levels, as it plays an important role in facilitating patient and provider understanding of likely outcomes, prediction of which can be suboptimal when based on holistic clinician assessment alone.…”