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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

1 November 2017

November 2017 post

Acute heart failure and renal function: an organ interplay not to be underestimated.

In “Cardiorenal Syndrome” by Ronco et al. (JACC 2008;52:1527-39) the authors identified 5 subtypes of cardio-renal syndrome (CRS) with distinctive pathophysiologies and described the nature of the co-dependencies of cardiac and renal dysfunction.

 

This mattered in 2008 and it matters today because, as Ronco and colleagues noted in their preamble, “A diseased heart has numerous negative effects on kidney function but, at the same time, renal insufficiency can significantly impair cardiac function.”

 

It matters also because of the numbers of patients affected and the consequences of CRS for patients with acute heart failure. Researchers in the Atherosclerosis Risk in Communities (ARIC) Study Community Surveillance programme have reported that “Severely reduced eGFR (<30 ml/min/1.73m2) was observed in ~30% of acute decompensated heart failure cases”.1 Elsewhere it has been reported that type-1 CRS (kidney injury secondary to acute cardiogenic shock or acute decompensation of chronic heart failure) “accounted for more than half of all mortality”.2  Age or geographical location are no protection from these malign effects.3,4

 

Both in 2008 and again more recently,5 Dr Ronco and colleagues called attention to the possible conceptual differences between chronic kidney disease and worsening renal function in acute heart failure and suggested that these may represent “different pathophysiological mechanisms in the setting of acute heart failure”. Multiple pathways that might contribute to these differences have been proposed.5,6

 

All of this is a reminder that the interplay between the acutely compromised heart and the kidneys is complex, with huge scope for variations of relevant pathophysiology between cases. Identifying the optimal treatment for individual cases is a correspondingly complex and demanding task.

 

In the therapeutic palette, levosimendan seems a reasonable option, in cases where cardiac output is compromised.7 In a tutorial lecture at the recent ESICM-LIVES congress in Vienna, Prof. Sven-Erik Ricksten (Sahlgrenska University Hospital, Gothenburg, Sweden) showed a profound difference in the effects of levosimendan vs dobutamine on glomerular filtration (see HERE) which would justify the selection of levosimendan as inotrope of choice for treatment of heart failure with concomitant renal failure.

 

References:

1. Matsushita K et al. PLoS One. 2017;12(8):e0181373.
2. Pimienta González R et al. PLoS One. 2016;11(12):e0167166.
3. Saiki H et al. Heart Vessels. 2016;31(8):1313-8.
4. Sliwa K et al. Eur Heart J. 2013;34(40):3151-9.
5. Palazzuoli A et al. Eur Heart J Acute Cardiovasc Care. 2016;5(8):534-548.
6. Obi Y et al. Cardiorenal Med 2016;6:83-98
7. Yilmaz MB et al. Cardiorenal Med 2016;6:83-98.

6 October 2017

October 2017 post

What could be worse than heart failure? Perhaps advanced heart failure. The ESC and other expert cardiology groups have produced precise technical definitions of “advanced heart failure” but for many patients affected those definitions perhaps miss the central experience: every aspect of life as you know it and cherish it starts to slide from your grasp as your heart falters repeatedly and each recovery leaves you weaker and less independent than before.

We are not entirely without options for these critically vulnerable patients. Ivabradine may benefit the patient with tachycardia; even digoxin may retain a role for rate regulation in atrial fibrillation and for symptom relief. For selected patients with a strong renal dimension to their situation rolofylline, empagliflozin, or serelaxin may bring benefit though full characterization those drugs and their target populations is desirable.

For acute exacerbations of heart failure we face an emerging alphabet soup of natriuretic peptides (ularitide, cenderitide), beta-arrestin-biased angiotensin II type 1 receptor ligands (TRV120027), nitroxyl donors (CXL-1020, CXL-1427), soluble guanylate cyclase modulators (cinaciguat, vericiguat) and short-acting calcium channel blockers (clevidipine), in addition to familiar names such as nicorandil.

Increasingly there is the option of a left ventricular assist device (LVAD), which in an era when demand consistently exceeds supply is becoming a destination therapy for many patients who might otherwise qualify for a heart transplant.

It remains the case, however, for many patients whose condition continues to deteriorate even though they have “maxed out” on diuretics, beta-blockers and treatments directed at the rennin-angiotensin-aldosterone axis (including perhaps the combined angiotensin receptor blocker and neprilysin inhibitor LCZ696) that inotrope therapy is a key resource in gaining time and preserving quality of life while decisions are taken about heart transplantation, mechanical support or perhaps palliative care.

Conventional inotropes such as dobutamine or milrinone may improve symptom control but appear to do so at the expense of worsened mortality. In this landscape levosimendan stands out as a therapy that preserves or enhances ventricular function in an energy-neutral way and does not make patients choose between more life or better life – they can have both.

11 September 2017

September 2017 post

ESC 2017 in Barcelona

The annual congress of the European Society of Cardiology (in Barcelona, from the 26th to the 30th of August) was a unique occasion for updating our knowledge on Acute and Advanced Heart Failure. At “Village 9” the sessions were focused on Heart Failure, with insights on Pathophysiology and mechanisms, Epidemiology, prognosis and outcome, ventricular function & hemodynamics, Drug treatment, etc. Also in some of the very popular “Hubs” the sessions were often touching intriguing themes such “Can we teach heart failure drugs new tricks?”. Several Pharmaceutical Industries had organized either satellite symposia or series tutorials to complement the general program, and the daily agendas of the attendees went easily overbooked. In the field of Advanced Heart Failure, a series of hands-on tutorials was organized by Orion Pharma on the use of inodilators. The three days program included lectures by 14 European speakers (from Spain, Italy, Germany, France, Greece, Austria, Finland, and Russia) on the use of inodilators for correcting hemodynamic dysfunction and ameliorating symptoms in patients with advanced heart failure. Their main conclusion was that the calcium sensitizer and potassium channel opener drug family can be considered as a safe solution to achieve inodilation. 

Also the poster session was rich and stimulating. To be noticed, the first report of the RELEVANT-HF clinical trial on repetitive levosimendan in advanced refractory heart failure was presented by the Italian group of Prof. Fabrizio Oliva.  They concluded that, in patients with ARHF, scheduled repeated LEVO infusions resulted in a decrease in hospital admissions for worsening HF, expressed as proportion of days spent in hospital in the 6 months after with respect to the 6 months before start of planned treatment.

Finally, the Investigator Meeting of the LEODOR study (Repetitive Levosimendan infusions for patients with advanced chronic heart failure) was also held in Barcelona in occasion of the ESC congress. The study just started and over 30 centers are currently enrolling.