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

4 November 2019

November 2019 post

In a recent expert opinion paper by Farmakis et al., published on Int J Cardiol (doi: 10.1016/j.ijcard.2019.09.005; PMID: 31615650) the authors summarized the proceedings of a meeting organized by the Heart Failure Clinic, Attikon University Hospital, Athens, Greece on the topic “A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure”.

Experts from 21 countries (Austria, Belgium, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Poland, Russia, Slovenia, Spain, Sweden, Switzerland, and Turkey) attended and reached a consensus

In a nutshell, inotropes increase cardiac output by enhancing cardiac contractility through different mechanisms of action, but they also bear variable vasodilatory or vasoconstrictive effects depending on agent and dosage. They constitute an important tool for the treatment of patients with acute heart failure (AHF) or advanced heart failure (AdHF), as they are often effective in improving hemodynamics and symptoms. However, their administration has been associated with increased short and long-term mortality due to frequent adverse effects, but also due to their improper use. The classes of inotropes currently used in HF are the β-adrenergic receptor agonists including dopamine, dobutamine and the catecholamines norepinephrine and epinephrine, the PDE III inhibitor milrinone and the calcium sensitizer levosimendan.

In AHF, inotropes are indicated with a IIb recommendation by the ESC guidelines only for patients with peripheral hypoperfusion because of low cardiac output. Identifying patients with truly low cardiac output in need of inotropic support can be challenging, while selecting the proper agent according to patients’ clinical profile and limiting infusion to the shortest time and lowest dose possible are important to optimize inotrope use. Levosimendan bears some advantages in this setting, especially for its beneficial effects in presence of beta-blockers, and its positive renal effects.

In AdHF, inotropic agents are required for the relief of persistent symptoms and the improvement of quality of life. Day clinic-based or home-based repetitive infusions may reduce hospital admission, which is a key factor in the quality of live and perhaps overall prognosis of the disease. Levosimendan bears an advantage in this setting due to its long-acting active metabolite.

The paper provides a practical approach to the three main steps required for the optimal use of inotropes in heart failure, namely (i) the identification of the right patient, (ii) the choice of the proper inotrope and (iii) the definition of the adequate weaning time.

The effects of inotropes on QoL in general, remain poorly defined, and more studies on this important and clinically meaningful aspect of AHF and AdHF patient care are warranted.

4 October 2019

October 2019 post

At the European Society of Cardiology Congress in Paris, the results of the GALACTIC trial were reported by Prof. Müller (Basel). Early intensive vasodilation using personalized high doses of nitrates, oral hydralazine and rapid up-titration of ACE inhibitors or angiotensin II receptor blockers did not improve 180-day mortality in a cohort of 781 acute heart failure patients. This trial is notable, among other things, for the fact that short-term use of conventional “tried and tested” (and extremely cheap) vasodilators, administered in an intensive regime and at high dose was just as ineffectual at influencing longer-term mortality as novel agents such as ularitide and serelaxin.

The inability to demonstrate survival benefit even from drugs that are established as part of the therapeutic armamentarium for AHF highlights some fundamental issues contributing to the paucity of new drug therapies in recent decades: for example, are we targeting the wrong pathological processes in our drug development programmes or are we privileging inappropriate endpoints in clinical trials and thus hampering the regulatory approval of useful new agents?

The general lack of evidence for an ongoing survival benefit from acute-phase treatments for AHF requires some reflection. While perhaps not fully subscribing to its philosophical outlook we find much to agree with in the views of McCullough [McCullough, P.A. How Trialists and Pharmaceutical Sponsors Have Failed Us by Thinking That Acute Heart Failure Is a 48-Hour Illness. Am J Cardiol 2017, 120, 505–508.], who has argued that AHF (and by extension AdHF) is a situation often long in the making and that to expect any therapy administered for <48 h to make a robust difference to survival or rehospitalization many months after the index admission is to misunderstand the pathophysiology of these conditions.

Hospitalization for heart failure, whether as a presentation of AHF or a decompensation in the context of AdHF, results in a down-shift in the trajectory of the syndrome that is associated with worsening outcomes and patient quality of life and increased costs of care. Medical progress to address these challenges has substantially stalled in the past 20 years but advances in data technology and analytics, along with developments in clinical trials design now offer opportunities to re-envision heart failure as a complex pathophysiological continuum in ways that may help to bring a new generation of therapies into clinical use. Meanwhile it would be advisable for the clinicians to evaluate if the nearly total absence of evidence of benefit with some of the traditional i.v. drugs used in AHF and AdHF (such as the catecholamines) warrants their elimination from routine use in favor of treatments where such evidence has been accrued.

10 September 2019

September 2019 post

ESC Congress 2019 was an astonishing success: over 32000 visitors at a program spanning from Saturday Aug 31 to Wednesday Sept 4 and focused on the best and latest science with renowned leaders in cardiovascular medicine. Being the largest such gathering in the world, ESC displayed more than 500 sessions during the five-day conference.

It is one of the professional events I cannot afford to miss: it is exciting to be part of a congress that covers so many interesting topics in cardiology. Everything is here together – science, practice, exhibitions, interesting people. A unique opportunity to get connected with experts coming from all over the world and present original research. At ESC Congress, I had the opportunity to keep abreast of the latest news in cardiology and talk about the results of my own research to colleagues from many other countries: ESC Congress did definitely provide a stimulus for my further research and practical work in my practice.

Now – after such a great moment - I strongly suggest everyone to review the ESC365 Congress resources: slides, videos and abstracts from ESC 2019.

Among the highlights, a satellite symposium was held in “The HUB Duras” on Monday Sept 2 from 13:00 to 13:45 on “Inodilators in Acute and Advanced Heart Failure” (John T PARISSIS (Athens, Greece) and Francesco FEDELE (Roma, Italy), as chairs, while the lectures and discussions were held by Finn GUSTAFSSON (Copenhagen, Denmark), Veli-Pekka HARJOLA (Helsinki, Finland), yours truly Gerhard PÖLZL (Innsbruck, Austria), Josep COMIN-COLET (Hospitalet De Llobregat, Spain), Piergiuseppe AGOSTONI (Milan, Italy), and Carsten TSCHOEPE (Berlin, Germany).

As it regards the LEODOR study (“repetitive use of levosimendan in advanced heart failure patients”), an investigator meeting was held to discuss about the progress in initiation of the centers and enrollment of the patients.