Author + information
- Stefan Brunner, MD,
- Sabina P.W. Guenther, MD,
- Korbinian Lackermair, MD,
- Sven Peterss, MD,
- Martin Orban, MD,
- Anne-Laure Boulesteix, PhD,
- Sebastian Michel, MD,
- Jörg Hausleiter, MD,
- Steffen Massberg, MD∗ (, )@LMU_Uniklinikum and
- Christian Hagl, MD
- ↵∗University Hospital Munich, Department of Medicine I, Marchioninistrasse 15, 81377 Munich, Germany
Despite multimodal treatment of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI), the outcome remains poor. Large retrospective analyses and animal models suggest that extracorporeal life support (ECLS) in CS-complicating AMI improves outcome (1). However, to date, no randomized controlled trials assessing the effectiveness of ECLS in this setting exist, and evidence levels of current guidelines in support of ECLS are low (2).
In this monocentric, open-label, randomized controlled, phase IV study, 42 patients with CS-complicating AMI were randomly assigned to ECLS (SCP, LivaNova, Munich, Germany; ECLS group, n = 21) or no mechanical circulatory support (control group, n = 21). CS was defined according to criteria derived from previous CS trials (3). All patients were expected to undergo early revascularization and to receive the best available medical therapy. The primary endpoint was left ventricular ejection fraction (LVEF) after 30 days. Main secondary endpoints included 30-day all-cause mortality and safety assessments.
Lachin’s procedure using the Mann-Whitney U test (4) was used for the primary analysis: deceased patients received the worst ranks based on survival time; surviving patients were ranked by LVEF. Assuming a probability of 0.74 that an ECLS patient is ranked better than a control (corresponding to a between-group LVEF difference of 5% for survivors, with an SD ± 5.5%), 21 patients per group are needed to achieve 80% power with α = 0.05.
Median age was 62 years (interquartile range [IQR]: 50 to 68 years) for ECLS patients and 70 years (IQR: 60 to 74 years) for control patients (p = 0.02). Lactate levels before randomization were 4.8 mmol/l (IQR: 2.7 to 8.5 mmol/l) and 5.4 mmol/l (IQR: 3.3 to 9.2 mmol/l), respectively (p = 0.44). A total of 95% of patients had been resuscitated before randomization. The number of diseased vessels was higher in the control group (p = 0.003).
The primary study endpoint, LVEF at 30 days, was similar among surviving patients in the ECLS group (50.0% [IQR: 44.0% to 59.0%]) and in the control group (50.8% [IQR: 47.2% to 60.6%]; Lachin p = 0.86) (Figure 1A). Thirty-day all-cause mortality was 19% in the ECLS group and 33% in the control group (log rank test p = 0.37) (Figure 1B). Secondary endpoints, including pH values, lactate levels after 24 h, and cumulative catecholamine dosages, were similar between groups. Additional analyses with respect to process-of-care outcomes showed significantly longer intensive care unit stays and durations of mechanical ventilation for ECLS patients when considering survivors only (p = 0.03 and p < 0.001, respectively).
There were no significant differences between the ECLS and the control group with respect to rates of stroke (ECLS 5% vs. control 5%; p = 1.0), peripheral ischemic vascular complications (10% vs. 0%; p = 0.49), life-threatening, severe, or moderate bleeding complications (19% vs. 14%; p = 1.0), sepsis (43% vs. 33%; p = 0.75), reinfarction (10% vs. 5%; p = 1.0), and stent thrombosis (10% vs. 5%; p = 1.0).
The primary endpoint LVEF at 30 days as a surrogate of myocardial regeneration was not significantly different between both groups. The unexpectedly good recovery of LVEF in our entire cohort impedes confirmation of a potential benefit of ECLS therapy. Among others, a potential explanation for the preservation of LVEF in both groups may be the high proportion of patients presenting with CS after pre-hospital resuscitation. During resuscitation, global myocardial ischemia results in a transient contractile impairment, known as “post-cardiac arrest syndrome,” resolving without specific treatment (5). Therefore, clinical presentation of post-cardiac arrest syndrome may overlap with AMI-CS.
We observed a numerical difference in mortality without statistical significance; however, this study was not powered for this clinically important endpoint.
Study outcomes may have been influenced by increased afterload caused by ECLS therapy, and further by differences in baseline characteristics.
In conclusion, this first randomized trial on ECLS treatment in patients with CS-complicating AMI could demonstrate feasibility of this therapy, but the study failed to demonstrate an impact on LVEF at 30 days. This raises an urgent call for randomized controlled trials assessing survival as primary endpoint.
Please note: This study was funded by LivaNova (Munich, Germany). Dr. Hausleiter has relationships with Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Clinical Study of Extra-Corporal Life Support in Cardiogenic Shock Complicating Acute Myocardial Infarction [ECLS-SHOCK]; NCT02544594)
- 2019 American College of Cardiology Foundation
- Aubin H.,
- Petrov G.,
- Dalyanoglu H.,
- et al.
- O'Gara P.T.,
- Kushner F.G.,
- Ascheim D.D.,
- et al.
- Kern K.B.,
- Hilwig R.W.,
- Rhee K.H.,
- Berg R.A.