By Arnaldo Lopez Ruiz, MD, and Miguel Quintana, MD, FACC
Dr. Lopez Ruiz is Attending Physician, Division of Critical Care, AdventHealth Medical Group, AdventHealth Orlando, FL. Dr. Quintana is Director, Institute Cardiovascular, Migone Hospital, Asunción, Paraguay.
SYNOPSIS: The use of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with acute myocardial infarction-related cardiogenic shock who underwent early revascularization did not result in improved mortality at 30 days and resulted in more major bleeding and peripheral vascular complications.
SOURCE: Thiele H, Zeymer U, Akin I, et al. Extracorporeal life support in infarct-related cardiogenic shock. N Engl J Med 2023;389:1286-1297.
Extracorporeal life support (ECLS) using venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly seen in the management of acute myocardial infarction-related cardiogenic shock (AMI-CS), despite a lack of convincing evidence regarding its effect on short-term and long-term mortality.1 This was an open-label, multicenter trial performed in Germany and Slovenia. Patients with AMI-CS for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was all-cause mortality at 30 days. The safety outcomes included bleeding, stroke, and peripheral vascular complications that warranted interventional or surgical therapy.
A total of 420 patients (mean age 62 years, interquartile range [IQR], 56-69 years) were randomized, and 417 patients were included in the final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 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). The mechanical ventilation median duration was seven days (IQR, 4-12 days) in the ECLS group and five days (IQR, 3-9 days) in the control group (median difference one day; 95% CI, 0 to 2 days). The safety outcome involving moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group vs. 9.6% in the control group (RR, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications that warranted intervention occurred in 11.0% vs. 3.8%, respectively (RR, 2.86; 95% CI, 1.31 to 6.25).
In patients with AMI-CS with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy compared to those who received medical therapy alone.
COMMENTARY
Progression to cardiogenic shock (CS) in those patients with AMI occurs in up to 10% to 15% of patients and is the main reason for high mortality among this population.1 Factors such as low baseline ejection fraction, multivessel coronary artery disease, moderate to advanced chronic obstructive pulmonary disease, and delayed time to reperfusion/revascularization have been shown to contribute to the progression to CS in patients with AMI.2,3 Current treatment for this complication is limited to immediate revascularization of the culprit coronary lesion to improve clinical outcomes. However, despite the availability of diverse mechanical circulatory devices (MCS), including VA-ECMO, the mortality for AMI-CS remains high at 40% to 50% within 30 days.1
In this trial, patients 18-80 years of age with AMI-CS and planned for early revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were eligible for inclusion. The study defined CS as systolic blood pressure (SBP) less than 90 mmHg for more than 30 minutes (or the initiation of catecholamines to maintain an SBP of more than 90 mmHg), arterial lactate level greater than 3 mmol/L, and signs of organ hypoperfusion with at least one of the following: altered mental status, cold/clammy skin and limbs, and urine output less than 30 cc/hour. Some of the most relevant baseline characteristics of the patients before randomization in this trial were: 66% of the patients presented with ST-elevation myocardial infarction (STEMI); 77% required resuscitation before randomization, with a median time until return of spontaneous circulation (ROSC) of 20 minutes; 35% of the patients had two-vessel disease, and 30% had triple vessel disease, with the left descending coronary artery involved in 46% of the patients; the median left ejection fraction was 30%; the median admission lactate level was 6.9 mmol/L; and the severity of CS based on the Society for Cardiovascular Angiography and Interventions (SCAI) classification was stage C for 49% of patients and stage E for 32% of patients, correlating to an expected in-hospital mortality of 12.5% and 67%, respectively.4
Despite the increasing use of ECLS in patients with AMI-CS, this larger trial failed to demonstrate survival benefit of VA-ECMO in AMI-CS. Although the duration of mechanical ventilation and stay in the ICU were longer in the ECLS group, there were no differences in the frequency of renal replacement therapy, repeat revascularization, myocardial reinfarction, rehospitalization for congestive heart failure, or poor neurologic outcome. However, moderate or severe bleeding and peripheral ischemic complications were more frequent in the ECLS group.
There are many possible reasons for the absence of benefits of ECLS in AMI-CS. First, at least 32% of the patients (those in CS stage E) had a very high risk for poor outcomes, and this may have been unlikely to be modified by ECLS.5 Second, despite a similar rate of bleeding and peripheral vascular complications as reported in previous VA-ECMO trials, these events occurred in patients who were sicker at baseline and may have contributed to less benefit in this group. Third, the longer duration of mechanical ventilation in the ECLS group may have had a negative effect on outcomes. Fourth, peripheral insertion of VA-ECMO is associated with increased left ventricular (LV) afterload. Recent studies have shown clinical benefits of percutaneous unloading LV devices in addition to VA-ECMO as compared to VA-ECMO alone.6,7 In this trial, only 5.8% of patients in the ECLS group received an unloading device, and probably a larger proportion of patients had evidence of increased afterload given the increased use of dobutamine in the ECLS group compared to control (43% vs. 30%). Fifth, as mentioned, the higher frequency of dobutamine in the ECSL group may have contributed to increased myocardial oxygen consumption.8 Finally, the high incidence of resuscitation with the competing risk of cerebral injury may have diminished the possibility that ECLS positively influenced prognosis.
The lack of an apparent mortality benefit appeared to be consistent across multiple subgroup analyses, including those analyses according to sex, age, the presence or absence of diabetes, STEMI or non-STEMI, anterior MI, a lactate level greater than 6 mmol/L, or receipt of cardiopulmonary resuscitation. Of note, the study did not include a subgroup analysis according to shock-severity stage. The lack of a mortality benefit with ECLS in this study is consistent with the findings of other randomized trials of mechanical circulatory support devices in patients with MI and CS.3-9
If the goal of using ECLS is to improve the 30-day mortality, the available evidence should steer intensivists away from its early routine implementation for all or even most patients with AMI-CS. For some patients in this population, ECLS is necessary and lifesaving, but the results of this study do not indicate which ones benefit. For now, the best approach may be to reserve the early initiation of ECLS for those patients with AMI-CS in whom the likely benefits more clearly outweigh the potential harms and in those in whom a long-term support strategy (LV assist device or heart transplant) is available and reasonable.
REFERENCES
- Thiele H, Ohman EM, de Waha-Thiele S, et al. Management of cardiogenic shock complicating myocardial infarction: An update 2019. Eur Heart J 2019;40:2671-2683.
- Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999;341:625-634.
- Samsky MD, Morrow DA, Proudfoot AG, et al. Cardiogenic shock after acute myocardial infarction: A review. JAMA 2021;326:1840-1850.
- Jentzer JC, van Diepen S, Barsness GW, et al. Cardiogenic shock classification to predict mortality in the cardiac intensive care unit. J Am Coll Cardiol 2019;74:2117-2128.
- Marashly Q, Taleb I, Kyriakopoulos CP, et al. Predicting mortality in cardiogenic shock secondary to ACS requiring short-term mechanical circulatory support: The ACS-MCS score. Catheter Cardiovasc Interv 2021;98:1275-1284.
- Schrage B, Becher PM, Bernhardt A, et al. Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: Results from an international, multicenter cohort study. Circulation 2020;142:2095-2106.
- Russo JJ, Aleksova N, Pitcher I, et al. Left ventricular unloading during extracorporeal membrane oxygenation in patients with cardiogenic shock. J Am Coll Cardiol 2019;73:654-662.
- van Diepen S, Katz JN, Albert NM, et al. Contemporary management of cardiogenic shock: A scientific statement from the American Heart Association. Circulation 2017;136:e232-e268.
- Henry TD, Tomey MI, Tamis-Holland JE, et al. Invasive management of acute myocardial infarction complicated by cardiogenic shock: A scientific statement from the American Heart Association. Circulation 2021;143:e815-e829.
