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Circulatory Support with Extracorporeal Membrane Oxygenation and/or Impella for Cardiogenic Shock During Myocardial Infarction

Mourad, Marc*; Gaudard, Philippe*,†; De La Arena, Pablo*; Eliet, Jacob*; Zeroual, Norddine*; Rouvière, Philippe; Roubille, François†,§; Albat, Bernard; Colson, Pascal H.*,¶

doi: 10.1097/MAT.0000000000000704
Adult Circulatory Support

Temporary mechanical circulatory support (TCS) is recommended for patients with profound cardiogenic shock (CS). Extracorporeal membrane oxygenation (ECMO) and Impella are possible TCS devices, but the device choice and the implantation timing are not definitely established, specifically during acute myocardial infarction. We have analyzed the respective use of ECMO or Impella (2.5, CP, or 5.0) for CS following acute myocardial infarction, from a cohort of patients who underwent TCS within 72 hours after admission for emergency percutaneous coronary intervention (PCI) from January 2009 to April 2015. Among 88 TCS-treated patients, 42 had early TCS: 23 ECMO and 19 Impella. Cardiac management, including PCI, was similar between the two groups, but ECMO patients were sicker than Impella patients (higher blood lactate level at ICU admission, higher vasoactive-inotroic and ENCOURAGE scores before TCS implantation, p ≤ 0.02). Three patients (7%) have had TCS implantation before admission, but TCS was implanted mostly in cathlab (43%, 1 during PCI, 13 just after PCI) or soon after ICU admission (50%, n = 21). Modification of the initial TCS choice was required in 10 cases (24%) for assistance upgrading in case of Impella (n = 4) or for left ventricle unloading in case of ECMO (n = 6). Extracorporeal membrane oxygenation is the technique of choice in case of profound CS, whereas Impella devices seem more appropriate for less severe hemodynamic compromise. Interestingly, the combination of both techniques may help to overcome the limits inherent to each device.

From the *Department of Anesthesiology and Critical Care Medicine, Arnaud de Villeneuve Academic Hospital, CHU Montpellier, France

PhyMedExp, University of Montpellier, Montpellier, France

Department of Cardiac Surgery, Arnaud de Villeneuve Academic Hospital, Montpellier, France

§Department of Cardiology, Arnaud de Villeneuve Academic Hospital, Montpellier, France

Endocrinology Department, Institut de Génomique Fonctionnelle, University of Montpellier, Montpellier, France.

Submitted for consideration March 2017; accepted for publication in revised form September 2017.

Disclosure: The authors have no conflicts of interest to report.

M.M. and P.G. contributed equally to this work. M.M. supervised all aspects of the study, contributed to analyze the data, participated in interpreting the results, performed statistical analysis, and drafting the article. P.C. was involved in results interpretation, drafting, and revising of the article. P.D.L.A. contributed to data acquisition and analysis. J.E., N.Z., P.R., B.A., P.G. were involved in revising the article.

Correspondence: Pascal Colson, Département d’Anesthésie Réanimation Arnaud de Villeneuve, CHU Montpellier, 371 avenue Doyen Giraud, F-34295 Montpellier, France. Email:

Incidence of cardiogenic shock (CS) after acute myocardial infarction (AMI) is around 5–15%.1 , 2 Cardiogenic shock remains the leading cause of death following AMI, with high mortality rates (40–50%) despite early revascularization.1 , 2 Intravenous inotropic agents (like dobutamine) may be considered to increase cardiac output, but this treatment is challenged by temporary circulatory support (TCS).3–5 Temporary mechanical circulatory support after AMI should be now considered for any acute hemodynamic compromise (class of recommendation IIa, level of evidence B or C, for american college of cardiology and american heart association (ACC AHA) 2013 guidelines or european society of cardiology (ESC) 2016 guidelines, respectively).6–8

Micro-impeller (Impella) and peripheral veno-arterial extracorporeal membrane oxygenator (ECMO) are the most used devices.9 , 10 Extracorporeal membrane oxygenation offers a full circulatory support and has been applied in all CS etiologies.11–13 The Impella devices (2.5, CP, or 5.0) are catheter-mounted micro-axial rotary blood pumps, designed for short-term TCS. The Impella device is inserted via a femoral or axillary artery back to the aorta, and the impeller is positioned across the aortic valve. Blood is aspirated in the left ventricular (LV) and expelled into the ascending aorta at flows ranging from 2.5 to 5.0 l/min. Impella provides a selective left heart assistance with LV unloading, which improves myocardial recovery in experimental conditions.14 However, data allowing an evidence-based choice of TCS device are missing, and most publications report TCS use in very heterogeneous population.11–18 There is no randomized controlled study comparing ECMO versus Impella, but such a comparison might not be clinically relevant since the devices are quite different. Indeed, their technical specificities suggest distinct and complementary indications.

Owing to these device characteristics, our heart team used ECMO or Impella as TCS in patients admitted for emergency percutaneous coronary intervention (PCI) for AMI with CS. This work aims therefore at evaluating the relevance of the device selection and the implantation timing.

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From January 2009 to April 2015, patients who were admitted to the intensive care unit (ICU) for CS treated with TCS in the context of AMI were retrospectively analyzed. In order to have a homogeneous study population, delayed TCS after AMI (> 72 hours) or after CS onset (> 48 hours), refractory cardiac arrest before TCS, mechanical AMI complication (ventricular septal defect, papillary muscle rupture), aortic valve pathology (stenosis or regurgitation), early surgical revascularization, or a specific condition (septic shock, cardiac surgery, myocardial trauma) were excluded. Moreover, Impella was not implanted in case of mural thrombus in the left ventricle.

Montpellier Academic Hospital institutional review board approved the study, which waived the need for patients’ informed consent because of the retrospective, observational nature of the study.

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Acute Myocardial Infarction Management

All patients with AMI, diagnosed according to international recommendations, underwent PCI (see Supplementary Material 1, Supplemental Digital Content, They received antiplatelet therapy and anticoagulation with unfractionated heparin.

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Cardiogenic Shock Management

Cardiogenic shock was defined by sustained hypotension and reduced estimated cardiac output (low LV ejection fraction and low Doppler aortic Velocity Time Integral as assessed by experienced echocardiographer) despite adequate intravascular volume on quick echocardiography check (see supplementary material 2, Supplemental Digital Content, Temporary mechanical circulatory support was inserted when aortic Velocity Time Integral was less than 5 cm, left ventricle ejection fraction (EF) < 20%, and E wave of mitral Doppler inflow was more than 1 m/s), either in case of failure of medical treatment including inotropes and vasopressors or in case of very severe cardiac dysfunction at echocardiography, therefore bypassing inotrope treatment.

Device selection resulted from a multidisciplinary agreement between cardiologists, intensivists, and cardiac surgeons (heart team). The indication of each device as first TCS was based on device characteristics and severity of the CS. There was no formal age limit, but patients older than 75 years were eligible to TCS, in the absence of previous morbidity, provided sufficient cardiac recovery was likely.

Extracorporeal membrane oxygenation was inserted through peripheral, percutaneously or surgically femoro-femoral veno-arterial cannulae and was selected in case of very severe, life-threatening CS. The Impella “2.5” and “CP” were inserted percutaneously through femoral artery. Impella 2.5 device was substituted by CP since March 2014 when this model became available in our center. Impella “5.0” required surgical cut down of femoral or axillary artery. Impella devices were selected in less severe CS.

Moreover, in case of LV overload during ECMO (severe pulmonary edema, left heart cavities distension with spontaneous contrast on echocardiography, or loss of left ventricle ejection), LV unloading was provided by Impella or intra-aortic balloon pump (IABP) in case of Impella contraindication. In case of persistent circulatory shock with Impella, including refractory right ventricular (RV) dysfunction despite inhaled nitric oxide, inotrope and vasopressor, assistance upgrading consisted in adding an ECMO.

Temporary mechanical circulatory support was implanted in cathlab or in operating room. For each device, the lower pump flow necessary to maintain adequate tissue perfusion was wanted (meaning SvcO2 > 65% and correction of metabolic acidosis).

The TCS weaning process followed a stepwise decrease of the pump speed with echocardiography, clinical, and biological monitoring. When TCS weaning was not possible, bridging to long-term left ventricular assist device or heart transplantation was considered, provided there was not severe multiorgan failure.

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Patient and procedural characteristics were collected retrospectively. Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score were calculated at ICU admission and the ENCOURAGE mortality risk score19 at TCS implantation. The following data were recorded at ICU admission and during first 48 hours of TCS: vasoactive-inotropic score as defined as dose of dobutamine (μg/Kg/min) + (dose of epinephrine [μg/Kg/min] + dose of norepinephrine [μg/Kg/min]) × 100, inotrope score defined as dose of dobutamine (μg/Kg/min) + (dose of epinephrine [μg/Kg/min]) × 10020 , 21 and blood lactate levels.

The main outcome variables included death before or less than 24 hours after TCS removal, cardiac outcome in TCS survivors (cardiac recovery; bridge to left ventricular assist device; bridge to heart transplantation), ICU discharge, hospital discharge, and 6-month mortality rate.

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Statistical Analysis

Continuous variables are presented as median (interquartile range) and categorical variables as number (percentage). Paired Wilcoxon tests were used to describe evolution of clinical, biological, and echocardiographic variables during TCS. Based on the first TCS device used, the study population was divided into two groups, ECMO (ECMO-G) and Impella (Impella-G). Group comparison used Wilcoxon rank-sum test and chi-square tests or Fisher exact tests when appropriate. Statistical significance was defined as p < 0.05. Analyses were performed using the R Core Team 2015 (R Foundation for statistical Computing, Vienna, Austria).

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Patient Selection

During the study period, 88 patients required TCS after AMI, 42 of them met the criteria of early TCS for CS shortly after AMI (Figure 1); 23 patients (55%) were first treated with ECMO (ECMO-G) and 19 (45%) with Impella (Impella-G). There were no significant differences between groups for the management of myocardial infarction (Table 1).

Table 1

Table 1

Figure 1

Figure 1

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Hemodynamic Management

Twenty-one patients (50%) had preserved hemodynamic stability at PCI admission, but 18 of them (86%) developed CS during PCI (Table 2). The treatment included mechanical ventilation (MV) (98%) and inotropic support (76%), but TCS was anticipated in 10 patients (24%) because of threatening hemodynamic collapse. Of note, 24 patients (60%) experienced transient cardiac arrest.

Table 2

Table 2

Extracorporeal membrane oxygenation were inserted percutaneously in seven of the 23 patients. Impella support consisted in “5.0” in seven patients (three femoral access, four axillary access), “CP” in seven patients and “2.5” in five patients.

During TCS, devices needed to be combined in 10 patients (24%) (Figures 1 and 2). In the ECMO-G, six patients (26%) needed an LV discharge with Impella and one patient had IABP because of LV thrombus. Insertion of the Impella device was made 20 (8–25) hours after TCS start, for 7.5 (5–13) days and consisted in 2 “2.5” and 4 “5.0”. In the Impella-G, four of the 19 patients (21%), all treated with percutaneous models (three “CP” and one “2.5”), needed additional support with ECMO, including two refractory RV dysfunctions. Extracorporeal membrane oxygenation was initiated 8 (1–15) hours after Impella insertion and maintained for 9 (6–11) days.

Figure 2

Figure 2

Temporary mechanical circulatory support provided rapid improvement of the patients “clinical condition without significant difference between both groups.” Blood lactate level decreased significantly and was normalized at 24 hours reaching 1.8 (1.3–2.7) mmol/L and 1.7 (1.2–2.7) mmol/L for ECMO-G and Impella-G, respectively (p < 0.01, from before TCS implantation in both groups). In the same time, inotrope score decreased significantly and was reduced to almost zero in ECMO-G (1 [0–5]) and Impella-G (0 [0–2]; [p < 0.001, from before TCS implantation in both groups]). Vasoactive-inotrope score decreased significantly in both groups at 48 hours (36 [7–56] and 20 [0–34] for ECMO-G and Impella-G, respectively [p < 0.01, from before TCS implantation in both groups]).

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There was no significant difference between groups regarding device complications or mortality in ICU and at 6 months (TABLES 3, 4). However, device dysfunction was reported only with Impella 2.5 (two of five). Six (32%) Impella-G patients were extubated during TCS; TCS duration and ICU stay were similar in both groups.

Table 3

Table 3

Table 4

Table 4

In both groups, mortality was found lower than the predicted mortality according to the ENCOURAGE score. In the ECMO-G, mortality rate at 30 days was 30% (predicted 72%), and 48% at 6 months (predicted 80%). In the Impella-G, 37% at 30 days (predicted 65%), and 42% at 6 months (predicted 75%).

A switch to Impella alone was made in five of the 10 patients with combined ECMO and Impella. In this subcategory of patients, two died under TCS, one was weaned from both devices at the same time, and two were weaned from Impella before ECMO.

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The study shows that, in a homogeneous population of patients admitted for PCI for AMI, the initial TCS, ECMO or Impella can be adapted to the patient clinical condition according to CS severity.

In case of profound CS, ECMO is a safe option and very effective circulatory support,12 , 22 , 23 which justified its preferred used in the most severe patients of the series.9 Contrary to most published cohorts,23 , 24 we excluded ECMO insertion under CPR to avoid the effect of the cardiac arrest itself, which is independently associated with mortality.11 This exclusion may explain a lower incidence of mortality in our series than in other published reports.23 , 24 However, the CS cases were quite severe, even worst in the ECMO-G, as attested by serum lactate, the vasopressor dose, which gave a high ENCOURAGE score. Among the markers of CS severity, a high lactate level seems a strong indicator in favor of ECMO selection. Indeed, 75% of the ECMO patients had a blood lactate level above 4.8 mmol/L. Nevertheless, we observed a lower mortality rate than the predicted value by the ENCOURAGE score. This low mortality rate may result from the very early initiation of the circulatory assistance in the course of the CS.

Impella 5.0 seems an interesting option for more stable conditions.25 It provided adequate blood flow in all cases, without ECMO rescue support. However, the insertion requires a surgical access that may limit its use to specific centers. Conversely, percutaneous Impella provided inadequate circulatory support in 33% patients. These observations are in agreement with previously published data showing that Impella 2.5 may be not efficient enough as circulatory support.16 , 18 Nevertheless, two of the four patients had refractory RV dysfunction, which might have been observed also with Impella 5.0. Therefore, percutaneous Impella can be considered as an adequate first TCS device, keeping ECMO addition as a secondary option. Impella is a less complex technique (nonsurgical approach, no perfusionist needed), therefore theoretically accessible in many cardiac centers without surgery facilities.

A distinctive feature of our report is the association of ECMO and Impella as a backup strategy in 24% patients. These results highlight the need for combining the two devices in selected situations. Impella ensured successful LV unloading in a significant proportion of ECMO patients (26%), as already reported25; ECMO was added for complementary circulatory support in 21% of Impella patients. The device association should be an integral part of any TCS strategy, possibly through a regional health-care networking, in order to fulfill the two conditions that are equally important for improving survival in CS complicating AMI. First, TCS must be implanted before multiple organ failure; second, PCI should not be delayed as it improves long-term survival.26 The challenge is actually to make compatible the two timing constraints.

Early initiation of TCS before PCI may be beneficial in AMI patients because it may enable a complete revascularization, with better outcome.26–28 This improved revascularization could be even more beneficial in patients developing CS after AMI. Elevated LV filling pressures and low coronary blood flow aggravate myocardial ischemia, a high-risk clinical scenario for PCI.10 In our experience, CS during PCI exposes patients to a high risk of refractory cardiac arrest (15% of the whole population of 88 patients in the flowchart, Figure 1). Conversely, a high survival rate has been already reported either with ECMO or Impella when applied before PCI for CS complicating AMI.15–17

In our series, half of the patients were admitted for PCI without CS, and hemodynamic instability occurred in a great proportion in the cathlab (43%), which means that patient selection for TCS before PCI is quite difficult. Further studies are needed to identify cardiogenic “pre-shock” patients, or to find out criteria to anticipate TCS. For these patients, percutaneous Impella could be the preferred option. Of note in our series, percutaneous Impella CP was the easiest device to be inserted, more quickly than ECMO or Impella 5.0. Otherwise, urgent TCS implantation would remain the only possible alternative, during PCI or soon after, with the available device on site, although ECMO is obviously the TCS of reference in very serious conditions, including cardiac arrest.13

The retrospective, single-center nature, and the sample size of this study are important limitations. However, selection of patients receiving TCS for severe CS early after AMI, excluding patients under CPR, offers a homogeneous study population contrary to numerous other series published to date. Moreover, to our knowledge, it is the first study on TCS in AMI undergoing emergent PCI showing the potential indication of mixing various devices.

In conclusion, based on distinctive indications and possible association of devices, ECMO or Impella are quite suitable in AMI with acute CS. However, implantation timing is more crucial than the device choice, especially in emergency. Combination of the two techniques could be stratified in a predefined strategy, according to center competency, device availability, and eventually structured in a networking including primary to tertiary cardiac centers.

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myocardial infarction; temporary circulatory support; extracorporeal membrane oxygenation; cardiogenic shock

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