ARTICLE: Thiele H, Zeymer U, Akin I, et. al, for the ECLS-SHOCK Investigators. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. N Engl J Med. 2023;389(14):1286-1297.
OBJECTIVE
To determine whether early extracorporeal life support (ECLS) plus standard medical therapy versus standard medical therapy alone would improve survival in patients with acute myocardial infarction (MI) complicated by cardiogenic shock
BACKGROUND
Cardiogenic shock occurs in up to 10% of patients with acute MI and is the main cause of death among these patients. Traditional management involves immediate revascularization, but mortality remains upwards of 40-50% within 30 days.1 New efforts to improve mortality among these patients in the last 10 years involve the application of venoarterial extracorporeal membrane oxygenation or extracorporeal life support (ECLS).2 The idea is that the mechanical circulatory and respiratory support provided by ECLS allows for perfusion of the body despite the severe shock state and buys time for immediate revascularization or other definitive management to occur. Interest in ECLS also increased after studies showed a lack of survival benefit for the intra-aortic balloon pump as the former standard of hemodynamic support.3
There are only three small randomized control trials and observational studies that have looked at the use of ECLS in cardiogenic shock resulting from acute MI.4-7 The risk of device-associated local and systemic complications of ECLS like bleeding, stroke, limb ischemia and hemolysis may potentially outweigh the hemodynamic benefits of ECLS. This study tested the hypothesis that early routine ECLS treatment compared to usual medical therapy alone would result in improved survival in patients with acute MI complicated by cardiogenic shock for whom revascularization was planned.
DESIGN
This was an international multicenter (44), investigator-initiated, randomized open-label trial in Germany and Slovenia. It was conducted from June 2019 - November 2022. Design of the trial was published previously.
Immediately after evaluation of eligible patient’s coronary anatomy via coronary angiography, patients were randomized into a 1:1 ratio to receive either ECLS implantation plus usual medical therapy or usual medical therapy. Revascularization therapy applied to both groups, and though percutaneous coronary intervention (PCI) is the preferred method, immediate coronary artery bypass grafting (CABG) was performed if the patient was not suitable for PCI.
Patients in the ECLS group had ECLS initiated during the index catheterization, preferably before PCI. The use of an antegrade arterial femoral sheath was strongly recommended to reduce risk of acute lower limb ischemia. Crossover from control group to ECLS group was avoided. Therefore, patients who needed escalation of care based on specific predefined criteria were allowed to utilize other devices such as intra-aortic balloon pump or a microaxial transvalvular flow pump. Those predefined criteria include severe hemodynamic instability with impending hemodynamic collapse, in increase in the arterial lactate level of more than 3 mmol/L during a 6-hour interval, or an increase in vasopressor use by 50% from baseline to maintain a mean arterial blood pressure of more than 65 mmHg.
INCLUSION CRITERIA
Patients between 18-80 years of age with acute MI complicated by cardiogenic shock and planned for early revascularization either by PCI or CABG. Cardiogenic shock was defined as:
- Systolic blood pressure < 90 mmHg for more than 30 min or initiation of vasopressors to maintain systolic pressure > 90 mmHg
- Arterial lactate level > 3 mmol/L
- AND signs of impaired organ perfusion with at least one of the following: altered mental status, cold or clammy skin and limbs, or urine output < 30 mL/hr
EXCLUSION CRITERIA
Patients who have had:
- Cardiopulmonary resuscitation (CPR) > 45 minutes before randomization
- Mechanical etiology of the cardiogenic shock
- Severe peripheral vascular disease precluding insertion of ECLS cannulas
PRIMARY OUTCOME
- Death from any cause at 30 days
SECONDARY OUTCOMES
- Key secondary outcomes:
- Time until hemodynamic stabilization
- Length of ICU stay
- Incidence of acute renal failure warranting renal-replacement therapy
- Incidence of recurrent myocardial infarction
- Rehospitalization for congestive heart failure
- Other secondary outcomes:
- Initiation and duration of catecholamine therapy
- Use and duration of mechanical ventilation
- Poor neurologic outcome as defined by a Cerebral Performance Category (CPC) score of 3 or 4 at 30 days (CPC ranges from 1-5, with scores of 3, 4, and 5 suggesting severe neurologic disability, persistent vegetative state, or brain death, respectively)
- Safety outcomes:
- Moderate or severe bleeding (type 3 to 5 according to the Bleeding Academic Research Consortium [BARC] criteria)
- Stroke or systemic embolization
- Peripheral ischemic vascular complications necessitating surgical or interventional therapy
KEY RESULTS
A total of 420 patients were enrolled, 3 patients who did not provide consent (2 from ECLS and 1 from control) were excluded. Of these, 209 patients were assigned to the ECLS group and 208 patients to the control group. Patients in both groups had similar baseline characteristics. The median age was 63 years of age with a predominance of men (81.3%). Two thirds of the patients presented with STEMI and the left anterior descending artery was the most common infarct site (in 47.6%). Approximately 2/3 of the patients had multivessel disease. A total of 77.7% of the patients underwent cardiopulmonary resuscitation before randomization. The median lactate level before revascularization was 6.9 mmol/L. Revascularization by PCI was performed in the majority of the patients (96.6%). Use of catecholamines was well balanced between the groups, but dobutamine was noted to be used more frequently in the ECLS group.
In the ECLS group, ECLS was initiated during the index catheterization in 192 patients (91.9%). ECLS was not initiated in 17 patients, including 4 patients who died before initiation. The median duration of ECLS therapy was 2.7 days. Use of at least one left ventricular unloading strategy was reported in 5.8% of the patients in the ECLS group.
In the control group, ECLS was initiated in 26 patients (12.5%), including 22 patients within 24 hours after randomization and 4 patients afterward. A total of 28 patients (15.4%) received mechanical circulatory support other than ECLS, primarily with the use of a microaxial transvalvular device.
Primary Outcome
Death from any cause at 30 days occurred in 100/209 patients (47.8%) in the ECLS group and 102/208 patients (49.0%) in the control group (relative risk [RR], 0.98; 95% confidence interval [CI], 0.80 to 1.19; P=0.81).
Secondary and Safety Outcomes
There were no statistically significant differences observed between the treatment groups regarding any of the key or other secondary outcomes listed above.
There was an increased risk of bleeding in the ECLS group (RR, 2.44; 95% CI, 1.50 to 3.95) and increased risk of peripheral ischemic vascular complications warranting surgical or interventional therapy in the ECLS group (RR, 2.86; 95% CI, 1.31 to 6.25) versus the control group. There was no statistically significant difference for stroke or systemic embolization between the two groups.
LIMITATIONS
- Mortality in the ECLS group may have been skewed due to the greater risk of complications (bleeding and peripheral vascular complications requiring intervention)
- During this study, only 5.8% of patients in the ECLS group had concomitant use of an active left ventricular unloading strategy which recent nonrandomized studies have indicated as a potential benefit when combined with ECLS (ECLS is associated with increased LV afterload due to retrograde aortic flow)
- Dobutamine was used more frequently in the ECLS group which may suggest an increase in LV afterload and an increase in oxygen consumption and related adverse effects
- To increase generalizability, the study included more patients who underwent cardiopulmonary resuscitation before randomization, which may confound the results with competing risk of cerebral injury in these patients
- Unable to blind clinicians
- A total of 39 patients crossed over between the groups
- The 44 centers reported moderate and high volume of ECLS use, therefore there may be differences in experiences and comfort for clinicians and ECLS techniques
EM TAKE-AWAYS
This trial did not show a significant difference in 30-day mortality or other pre-specified outcomes between ECLS and standard management in patients with infarct-related cardiogenic shock and was instead associated with increased complications (eg, bleeding). Consider holding off early application of VA-ECMO in patients who can be stabilized with medical therapy.
REFERENCES
- Thiele H, Ohman EM, de Waha-Thiele S, Zeymer U, Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J. 2019;40(32):2671-2683.
- Becher PM, Schrage B, Sinning CR, et al. Venoarterial Extracorporeal Membrane Oxygenation for Cardiopulmonary Support. Circulation. 2018;138(20):2298-2300.
- Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet (London, England), 2013;382(9905):1638-1645.
- Ostadal P, Rokyta R, Karasek J, et al. Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock: Results of the ECMO-CS Randomized Clinical Trial. Circulation. 2023;147(6):454-464.
- Brunner S, Guenther SPW, Lackermair K, et al. Extracorporeal Life Support in Cardiogenic Shock Complicating Acute Myocardial Infarction. J Am Coll Cardiol. 2019;73(18):2355-2357.