Data from Professor Gerhard Pölzl - Curated by EPG Health - Last updated 10 July 2017
Professor Gerhard Pölzl is Chief of the Heart Failure and Heart Transplant Program at the Medical University Innsbruck. His research is focused on clinical studies in advanced and chronic heart failure and on translational studies in cardiomyopathies.
He was Principal Investigator of the LevoRep clinical trial that tested the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure. He is now PI of the clinical trial LEODOR, on repetitive use of levosimendan in advanced heart failure.
This blog is focused on the therapeutic options for acute and advanced heart failure: new data, new studies, new opinions, new trends.
From 29 April to 2 May 2017 at the Palais des Congrès in Paris, the Heart Failure Association of the European Society of Cardiology held its annual meeting. Within the programme, I highlighted a series of eleven 30-minute hands-on tutorials on the use of the inodilator levosimendan in acute and advanced heart failure. These were structured in several sessions touching on the therapeutic needs and options, comorbidities, scientific evidence, guidelines, and clinical practice. The take-home message was that the inodilator levosimendan is a tolerable and valid therapeutic option for patients in advanced heart failure. Chairs and lecturers were from Austria (G. Pölzl, J. Altenberger), Italy (G. Malfatto), Hungary (Z. Papp), Finland (V-P. Harjola, M. Kivikko), Sweden (K. Karason), Greece (J. Parissis), Denmark (F. Gustafsson), and Germany (D. Kindgen-Milles, C. Tschöpe). The eleven lectures were recorded and can be now seen on the dedicated educational channel (Acute and Advanced Heart Failure Knowledge Centre).
Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalisations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes, such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalisation and improves quality of life (see journal article). A panel of 45 expert clinicians from 12 European countries met to review the literature and envision an appropriately designed and properly powered clinical trial addressing these needs. In the earlier FIGHT trial, a composite global rank score was used as primary endpoint where death, re-hospitalization and change in natriuretic peptide level were considered in a hierarchical order. The same endpoint was tested post hoc in the PERSIST and LEVOREP trials, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite endpoint in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.
Heart failure is the leading cause of adult hospitalisation in the industrialised world and imposes a substantial burden on public health. The later stages of heart failure are characterised by a steady decline in quality of life and frequent re-hospitalisation for recurrent acute symptoms.1 Most of the re-hospitalisations take place relatively soon after discharge from the index hospitalisation. About one quarter of patients are re-hospitalised within one month, and more than 60% of these are seen within 15 days after initial discharge.2
Several clinical studies have been performed on the repetitive use of intravenous levosimendan in advanced heart failure.3 Their results suggest that repeated infusions of levosimendan bring advantages to patients with advanced chronic heart failure, both as it regards mortality4 and re-hospitalisation.5 However, few of these studies were properly powered. Therefore, a larger study is needed to verify the results.
In the newly commenced LEODOR trial the efficacy and safety of intermittent levosimendan therapy, beginning during the vulnerable phase after a recent hospitalization for heart failure, is tested. The hypothesis is that, compared with placebo, repetitive administration of levosimendan in the post-acute heart failure syndrome discharge period will be associated with greater clinical stability through 14 weeks, as assessed by a composite clinical endpoint consisting of mortality, acute heart failure episodes and change in natriuretic peptide levels.
- Fruhwald S, Pollesello P, Fruhwald F. Advanced heart failure: an appraisal of the potential of levosimendan in this end-stage scenario and some related ethical considerations. Expert Rev Cardiovasc Ther. 2016;14:1335-47.
- Dharmarajan K, Hsieh AF, Lin Z, Bueno H, Ross JS, Horwitz LI, et al. Hospital readmission performance and patterns of readmission: retrospective cohort study of Medicare admissions. BMJ. 2013;347:f6571.
- Pölzl G, Altenberger J, Baholli L, Beltrán P, Borbély A, Comin-Colet J, et al. Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy. Int J Cardiol 2017;pii:S0167-5273(17)31017-3.
- Silvetti S & Nieminen MS. Repeated or intermittent levosimendan treatment in advanced heart failure: An updated meta-analysis. Int J Cardiol. 2016;202:138-43.
- Silvetti S, Belletti A, Fontana A, Pollesello P. Rehospitalization after intermittent levosimendan treatment in advanced heart failure patients: a meta-analysis of randomized trials. ESC Heart Fail 2017. doi: 10.1002/ehf2.12177.