The inodilator levosimendan in acute and advanced heart failure

The articles collected in this Supplement emerged from a series of tutorials delivered at the annual congress of the Heart Failure Association of the European Society of Cardiology (ESC) held in May 2016 in Florence, Italy. It was quickly apparent to those who contributed to the tutorials that the themes explored merited the attentions of a wider audience and that publication in a European Heart Journal Supplement was an appropriate vehicle for achieving that goal. As Guest Editor of this Supplement, I wish to thank my fellow contributors for their willing cooperation in this project.

One of the salient facts to emerge from the original tutorials is that late-stage heart failure is a complex entity with a variable presentation and an often unpredictable trajectory.

We would all, I imagine, like to believe that we can recognize a case of late-stage heart failure when we encounter one but the plurality of terms attached to the situation—including ‘late-stage heart failure’, ‘advanced heart failure’, ‘end-stage heart failure’, perhaps even ‘terminal-stage heart failure’—is an immediate reminder that this may not always be the case, or that at the very least we may reach importantly different views about the nature of the clinical problem that confronts us and the appropriate response. Recent ESC guidelines have provided valuable advice in this area but we have some way to travel to arrive at a fully systematic and evidence-based approach.

What we can say already, however, is that at the centre of these situations is a patient in low spirits and perhaps approaching the end of life, and that as physicians one of our first responsibilities, as eloquently asserted by my colleague and co-author Professor Alexander Reinecke, is pity for our patient.

Pity may take many forms but for a patient whose life and circumstances are increasingly and probably irreversibly defined by the symptoms of their condition and the limitations on life imposed by those symptoms, making successful efforts to preserve or maintain physical capacity and help them engage with life as a person and not just as ‘a difficult case’ are a goal of undeniable significance. Levosimendan, a first-in-class inodilator that enhances cardiac contractility through calcium sensitization and exerts vasodilator and cardioprotective effects via adenosine triphosphate-dependent potassium channels in vascular smooth muscle cells and mitochondria, is one of the options that can be drawn on in this situation.

It must be acknowledged, as it is at several places in this Supplement, that the evidence base for levosimendan as a palliative care measure is indicative or suggestive rather than conclusive. However, when heart failure has advanced beyond the boundaries of control achievable by conventional and established therapies additional measures are required. As Professor Simon Matskeplishvili commented during his original tutorial, drawing on a remark attributed to former US Secretary of State Dr Henry Kissinger, the absence of alternatives clears the mind wonderfully.

Lack of viable alternatives is not, however, a justification for uncritical or indiscriminate use of any medical intervention. It is partly in recognition of this fact that several of the essays in this collection address in detail the practicalities of how to use and administer levosimendan to these often severely ill patients. This guidance comes from colleagues who have first-hand experience in the use of levosimendan in settings of advanced and serious heart failure and who can comment with authority on its utility, its benefits and its limitations, of which inevitably there are some.

The overall verdict from these essays is that levosimendan remains a work in progress in this area of heart failure management but that it is one with some proven value and much interesting potential. The results of ongoing controlled trials and other investigations may be expected to illuminate that potential and will help to define the place of levosimendan in the evolving discipline of palliative care for advancing heart failure.