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Three Part Question

Patient group: [Patients undergoing cardiac bypass surgery and severe left ventricular dysfunction (LVEF <35%]

Intervention: [Levosimendan infusion or IABP]

Outcomes: [Cardiac index, Troponin levels, length of ICU stay]

Clinical Scenario

A 78 year old male patient was undergoing an urgent cardiopulmonary bypass operation after a coronary angiogram revealed severe triple vessel disease. He also suffers from multiple co-morbidities and his ECHO revealed an ejection fraction of 25%. The cardiothoracic registrar suggests using a levosimendan infusion instead of an intra-aortic balloon pump. You wonder whether there is any evidence for this treatment.

Search Strategy

Search Strategy Medline (1950 – December week 1 2016) was searched via an Ovid interface: [Levosimendan] and [Intra-aortic balloon pump OR IABP OR Balloon pump] and [cardiac surgery].

Search was limited to English language and Humans 

Search Outcome

Medline: 216 references were found, of which 4 were felt to be relevant to the question. 2 were found to be duplicates. No relevant Cochrane reviews were identified.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lomivorotov et al. 2012 Russia	90 patients with coronary artery disease and left ventricular ejection fraction <35% who underwent surgery with cardiopulmonary bypass	Prospective randomized trial	Cardiac troponin I level – 6 hours post op	Significantly lower in the levosimendan group compared to the IABP group (p=0.048)	Significantly more females in the levosimendan group. Relatively small number of patients in each group.
			Cardiac index	Cardiac index significantly lower in the IABP group than the levosimendan group.
			Intensive care stay	The intensive care unit stay was significantly shorter in the levosimendan group than in the IABP group (p = 0.001)
Severi et al 2011 Italy	22 patients with coronary artery disease and left ventricular ejection fraction of <35% scheduled to undergo coronary artery bypass surgery.	Case matched study	Intensive care stay	The length of intensive care unit stay was reduced in patients receiving levosimendan (median, 2.5; range, 1-3 days) compared with those receiving an IABP (median, 5; range, 3-6 days; p = 0.01). No deaths occurred in the levosimendan group; 1 patient died in the intra-aortic balloon pump group.	Not randomised. Very small numbers.

Comment(s)

With the rise of interventional cardiology, patients with a significantly higher cardiac risk profile are increasingly being referred for cardiac surgery1. There is ample data to support the use of both levosimendan and IABP to increase the cardiac output in a low cardiac output state (LCOS)2. Unlike traditional inotropic agents, levosimendan works primarily by sensitizing the myocytes to calcium, thereby increasing the contractile force and cardiac output3. It also induces the opening of potassium ATP-channels resulting in systemic and coronary vasodilatation improving both cardiac blood supply and reducing the afterload4. The IABP has become ubiquitous in the therapy of heart failure following cardiac surgery. It is a mechanical device which serves to increase coronary perfusion during the diastolic phase and subsequently reduce the afterload during systole. Although it has been widely used in this patient group since its introduction to clinical practice, there are several IABP-related complications, with the frequency being quoted as being between 0.9 – 13%5. Levosimendan has the obvious advantage of not having to insert a large foreign body into the aorta. Despite this, only one RCT and one case matched study was found that focused on comparing the two treatments. Both papers highlight the reduced intensive care stay for patients in the levosimendan group and Lomivorotov also reports the reduced troponin levels and increased cardiac index in the levosimendan group. However, both authors concede that the single centre nature and small sample sizes of their studies limits the generalizability and statistical power of their results. The abundance of data supporting the use of IABP already, may make it ethically difficult to perform RCT’s with levosimendan infusion, particularly as the subpopulation in question is far sicker and older than the normal surgical patient. Furthermore, the high cost of levosimendan and the fact that it does not currently have a product license in the UK add further barriers to continued research. Nevertheless, both papers suggest that levosimendan infusion is as clinically effective if not better than IABP and have rightly suggested further clinical trials to elucidate the difference between the two.

Clinical Bottom Line

Currently there is no definitive evidence to support the use of levosimendan over IABP in cardiac surgical patients with reduced LVEF.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Vladimir V. Lomivorotov, MD, PhD, Vladimir A. Boboshko, MD, Sergey M. Efremov, MD, PhD, Igor A. Kornilov, MD, PhD, Alexandr M. Chernyavskiy, MD, PhD, Vladimir N. Lomivorotov, MD, PhD, Lubov G. Knazkov Levosimendan Versus an Intra-Aortic Balloon Pump in High-Risk Cardiac Patients Journal of Cardiothoracic and Vascular Anesthesia Vol 26, No 4 (August), 2012: pp 596-603
2. Luca Severi, MD, Angela Lappa, MD, Giovanni Landoni, MD, Lucio Di Pirro, MD, Sacha Jerome Luzzi, MD, Patrizia Caravetta, MD, Pierluigi Cipullo, MD, and Antonio Menichetti, MD Levosimendan Versus Intra-aortic Balloon Pump in High-Risk Cardiac Surgery Patients Journal of Cardiothoracic and Vascular Anesthesia Vol 25, No 4 (August), 2011: pp 632-636