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Acute and Advanced Heart Failure Blog

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 has been 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 P.I. 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.

Latest posts

2 April 2019

April 2019 post

Among the recent literature on Advanced Heart Failure which I found on PubMed, I particularly enjoyed reading the opinion paper by Burnside et al on the American Journal of Hospital Palliative Care (2019, ePub Mar 28, doi: 10.1177/1049909119838250).

The authors state that "Advanced heart failure therapies such as ventricular assist devices and home inotrope use are becoming more common. Technology advances as well as increased indications for use of such therapies is leading to a higher percentage of patients with end-stage heart failure receiving these therapies at end of life.".

In the manuscript, the authors present a case of a young man with dilated cardiomyopathy who undergoes advanced cardiac care in the setting of progressively declining cardiac function, which outlines the importance of acute care, palliative care, and hospice services being coordinated prior to and during acute-care services to provide goal-concordant and expeditious care. With advancing medical therapies for heart disease, increased coordination and collaboration of services are needed, particularly between hospice and acute-care services.

I would like also to mention the work by Shoaib et al (Int J Cardiol. 2019. ePub on Mar 15, doi: 10.1016/j.ijcard.2019.03.020) which describe the “Characteristics and outcome of acute heart failure patients according to the severity of peripheral oedema”.

The authors state that "Most trials of patients hospitalized for heart failure focus on breathlessness, but worsening peripheral oedema is also an important presentation." They investigate the relationship between the severity of peripheral oedema on admission and outcome amongst patients with a primary discharge death or diagnosis of heart failure. Of 121,214 patients taken into consideration in their research, peripheral oedema on admission was absent in 24%, mild in 24%, moderate in 33% and severe in 18%. Median length of stay was, respectively, 6, 7, 9 and 12 days (P- < 0.001), index admission mortality was 7%, 8%, 10% and 16% (P- < 0.001) and mortality at a median follow-up of 344 (IQR 94-766) days was 39%, 46%, 52% and 59%. In an adjusted multi-variable Cox model, length of hospital stay and mortality during index admission and after discharge increased progressively with increasing severity of peripheral oedema at admission.

Finally, I considered it worth of reading the small retrospective study of six patients by De Lazzari et al (Comput Methods Programs Biomed. 2019;172:117-126) who focused on how LVAD support influence ventricular energetics parameters in advanced heart failure. The analysis of ventricular energetics parameters based on external work and pressure volume area confirmed LVAD support as a beneficial therapeutic option for the patients considered eligible for this type of treatment. The authors conclude that a quantitative approach with the ability to predict outcome during patient's assessment may well be an aid and not a substitute for clinical decision-making. 



5 March 2019

March 2019 post

It’s a year since I reported on the status of the LeoDOR study (Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure) so I think it’s more than time to bring readers up to date with our progress.

Since I last wrote on this subject the protocol for the study, authored by myself and 13 distinguished colleagues, has been published [Pölzl G et al. ESC Heart Failure 2019;6(1):174-181 DOI:10.1002/ehf2.12366].

The trial’s dedicated website,, is up and running and offers information to prospective patients and investigators, including a Trial Information Sheet and Site Evaluation documents for the latter and clear plain language answers to questions such as “What is the purpose of this study” and “What does taking part in this study involve?” for the former. LEODOR researchers can keep up-to-date and exchange thoughts and information via the sharepoint facility operated via the website.

The first 10% of the planned 264 patients have been enrolled, and the dedicated Twitter feed (@LeodorTrial) has announced the participation of several centres in Germany, including Innsbruck (where the first patient was recruited), Linz, Berlin, Braunau, Kiel, Würzburg, plus Oulu (Finland), Debrecen (Hungary) and Ljubljana (Slovenia).

Underpinning and inspiring all these exertions is the fact that while findings from over 10 double-blind clinical trials or registries (including LevoRep, LION-HEART, LAICA, RELEVANT, etc.) have consistently supported the view that repeated infusion of levosimendan benefit patients with advanced heart failure, no single study has been statistically powered enough to generate conclusive results. Clearly, a larger study is needed and it is our confident hope that LeoDOR (NCT03437226) will be that trial.

LeoDOR is the first major trial of intermittent levosimendan to use a global rank score methodology to assess the impact of therapy. This global rank endpoint is a composite of: (i) time to death or urgent heart transplantation or VAD implantation: (ii) time to a non-fatal HF event requiring i.v. vasoactive therapy, and: (iii) time-averaged proportional change in NT-proBNP from baseline to 14 weeks. This novel methodology allows each patient to contribute to the overall endpoint, thereby optimizing statistical power while keeping the number of patients within manageable limits.

We’re a way off seeing the final results of LeoDOR yet and I expect to deliver more updates via this blog before that day arrives, but the study is now well and truly underway: I extend my best wishes and gratitude to all patients and investigators who have agreed to contribute to this important initiative in advanced heart failure treatment.




7 February 2019

February 2019 post

Maximizing benefits of levosimendan for patients for 30 years  - and the work continues..

If newspapers are the first draft of history for the lay public, posters and abstracts serve the same role for scientists and clinicians. We might therefore conclude that levosimendan has been making history for 30 years, since it first appeared in congress posters and abstracts in the late eighties. The volume of research material generated during those years has been quite remarkable, with many hundreds of reports being published since the start of the present century. Abstracts on levosimendan can be found at key annual congresses of scientific and clinical societies such as the ESC, the HFA, the ISICEM, the ESICM, the EACTA, the EACTS and more.

Communications at congresses on levosimendan span between preclinical pharmacology and a series of clinical investigative phases, some of which remain as interesting observations, others of which ripen into new or enlarged clinical applications or offer a side-light on contemporary clinical practice (as in the 2011 report by Dr JT Parissis et al on ” Gender-related differences in clinical phenotype and in-hospital management in patients with acute heart failure: an ALARM-HF survey sub-analysis.").

All in all, Levosimendan continues to excite the imagination of scientists and researchers in all those directions.

In the sphere of clinical development, recent years have witnessed a concentrated emphasis on exploiting the unique qualities of levosimendan to maximize benefit to patients with acute or advanced heart failure. Contributions in this area have included a large, important and still growing literature describing first-hand experience with levosimendan in the day-to-day management of these cases. As part of these investigations we have also seen in very recent years expansion of research into matters such as the impact of levosimendan on renal function in heart failure, the use of intermittent levosimendan as a bridge to heart transplant and the use of this drug in the context of ECMO treatment.

Another step in the evolution of this remarkable and versatile agent is now in progress with the recent presentation by Dr Merit Cudkowicz et al. of the protocol of the REFALS 3 trial, which will evaluate the impact of levosimendan on respiratory function in patients with acute lateral sclerosis (ALS). Details of this ambitious trial are available via ( Identifier: NCT03505021).